Access to side branches with a sharply angulated origin: usefulness of a specific wire for chronic occlusions

INTRODUCTION

In-stent restenosis (ISR) is a common problem in the routine clinical practice regarding percutaneous coronary intervention (PCI), and its management is associated with high rates of target lesion revascularization (TLR).1 Together with the implantation of a new everolimus drug-eluting stent, the PCI with drug-coated balloon (DCB) is the strategy of choice to treat ISR after bare-metal stent (BMS) and drug-eluting stent (DES) implantation, and has a class I indication after confirmation that it can reduce the rate of TLR at the follow-up without having to implant a new layer of metal into the artery.2-5 Despite of this, TLR is still high in the long-term (up to 20% at 3 years),6-11 which is suggestive that new strategies may be needed to improve these results.

The cutting balloon (CB) consists of small blades or nitinol bands on its surface to optimize the predilatation of coronary lesions by performing controlled fractures of the atheromatous plaque. Compared to the plain old balloon angioplasty, its use for the management of ISR is associated with structural changes of the neointima and acute improvements of the lumen area,12 although no angiographic or clinical benefit has been reported in the mid-term.13,14

The efficacy of the DCB depends on the transfer of drug from the surface of the balloon to the tissue where it exerts it antiproliferative effect.15 Theoretically speaking, greater the neointimal disarrays are associated with more effective transfers and smaller issue thickness. As a matter of fact, preclinical studies have suggested a greater effect of DCB inhibiting neointimal growth.16 This greater disarray and reduction of the neointima can be achieved using a CB before the DCB.

Although this hypothesis has not been confirmed in animal models in the short-term,17 the strategy has shown better angiographic results in the mid-term (6 to 8 months) (significant reduction of binary restenosis), but no effect on TLR or clinical events at the 1-year follow-up.18 No long-term results have been published on the use of this strategy.

Our objective was to assess the very long-term results of the use of CB plus DCB to treat ISR.

METHODS

Retrospective registry of cohorts of real-world patients with, at least, 1 ISR treated with DCB at a single high-volume PCI center (> 800/year) and a 5-year follow-up. Two different cohorts were defined based on the use of CB prior to the PCI with DCB (C_DCB) or standard DCB (S_DCB). The C_DCB cohort was defined by the use of, at least, 1 cutting balloon (Flextome Cutting Balloon, Boston Scientific, United States) or 1 scoring balloon (ScoreFlex, OrbusNeich, China). The use of the CB was left to the operator’s discretion. The ISR was defined as an angiographic stenosis > 50% in 2 different orthogonal radiographic projections inside the stent or < 5 mm from its borders plus symptoms of angina or objective confirmation of myocardial ischemia or fractional flow reserve/positive instantaneous wave-free ratio. Lesions were treated with 2 types of drug-coated balloons based on their availability at the time: the SeQuent Please (B. Braun Surgical, Germany) or the Pantera Lux (Biotronik, Switzerland). Data on the long-term progression of patients with ISR treater with the SeQuent Please DCB in this cohort regardless of the use of CB were reported beforehand.19

Exclusion criteria were cardiogenic shock or cardiac arrest in the index event, the presence of ≥ 3 layers of metal in the lesion with ISR and a contraindication to dual antiplatelet therapy with acetylsalicylic acid and a P2Y₁₂ inhibitor for, at least, a month.

The clinical and procedural characteristics were obtained from the center and the cath lab databases. The coronary study of the lesions was performed with the Xcelera system (Philips, The Netherlands) using the projection with the highest degree of stenosis. The Mehran classification of ISR was used to categorize the lesions.20 The strategy of the procedure including the use and type of CB was left to the operator’s criterion. DCB dilatation lasted for, at least, 60 seconds at nominal pressure. The PCI, management, and previous and later treatment of the patients was performed based on the routine clinical practice.

The study was conducted in observance of the criteria established at the Declaration of Helsinki and the International Council on Harmonization Good Clinical Practice guidelines (ICH-GCP). Also, it was authorized by Hospital Clínico Lozano Blesa (Zaragoza, Spain) management and ethics committee. No informed consents were needed given the retrospective nature of the study. A 5-year long follow-up period was arranged. Every follow-up was performed by checking the electronic database of the regional healthcare system where all the patient’s clinical events were thoroughly detailed. Data were anonymized through internal numerical identification at the cath lab.

All events were defined in a standard way according to the ARC-2 consensus.21 The primary endpoint was the need for TLR with a clinically indicated DCB at 5 years and estimated on the overall number of all target lesions. Clinically indicated TLR was defined as a new-onset ISR > 70% or > 50% of the target lesion in the presence of ischemic symptoms, a positive inducible ischemia on stress testing dependent on the vessel or fractional flow reserve values ≤ 0.80 or instantaneous wave-free ratio values ≤ 0.89.

Secondary endpoints were the presence or lack of target vessel revascularization, and target vessel myocardial infarction (according to the universal definition22), all-cause mortality, death due to cardiac causes (acute myocardial infarction, severe arrhythmia, heart failure, unwitnessed or unknown death) or cardiovascular death (cardiac or stroke induced or due to other cardiovascular processes), BARC type ≥ 3 bleeding, stroke (new neurologic deficit > 24 h duration) or a composite endpoint of target lesion failure (TLR + target vessel myocardial infarction + cardiovascular death), target vessel failure (target vessel revascularization + target vessel myocardial infarction + cardiovascular death) or patient-oriented composite endpoint (any revascularization + acute myocardial infarction + stroke + overall death). These endpoints were estimated on the overall number of patients. Definitive or probable stent thrombosis was also defined based on the ARC-2 criteria and estimated on the overall number of lesions.

Data mining and analysis were performed using the SPSS 19.0. statistical software (IBM, United States). Quantitative variables were expressed as mean and standard deviation. Qualitative variables were expressed as relative percentage. The cumulative incidence of the endpoints at the follow-up was also estimated. The variables and the group endpoints studied were compared on a bivariate analysis using the chi-square test (or Fisher’s exact test, when appropriate) or the Student t test regarding the quantitative variables. Cox regression analysis was performed to estimate the primary endpoint predictors (including the variables associated with P values < .1). Survival was analyzed using the Kaplan-Meier method to build the cumulative incidence curve of time to the primary endpoint based on the strategy of treatment used. P values < .05 were considered statistically significant.

RESULTS

A total of 107 ISRs were treated with DCBs in 95 procedures performed on 91 patients from January 2010 through December 2015 (in 4 patients the PCI with DCB was repeated at the follow-up, in 1 case using a different DCB on the same previously treated lesion). A total of 51 lesions (42 patients) were treated with a PCI plus CB + DCB (C_DCB), and 56 lesions (49 patients) with standard DCB (S_DCB). A total of 53 lesions were treated with the SeQuent Please device, and 54 with the Pantera Lux. The cutting balloon and the scoring balloon were used in 36 and 15 lesions, respectively.

The study cohorts were similar regarding the clinical characteristics (table 1), and the lesion and procedural characteristics (table 2). Some of the differences reported in the C_DCB group where that radial access was more common, and the size of the stent and minimum lumen diameter were greater, although with a similar percent diameter stenosis of the lesion before and the after the PCI. Patients had a high prevalence of cardiovascular risk factors including diabetes in 35% of the cases. A total of 47 new coronary angiographies were performed at the follow-up. In 29 of these the target lesion had good results. The rate of new coronary angiography was similar in both groups (44.6% vs 41.2% in the C_DCB group. P = .71). A total of 18 TLRs were performed at the follow-up (16.8%) of which 17 were treated with a PCI (16 stent-in-stent), and 1 with coronary artery bypass graft. The rate of TLR was numerically lower in the C_DCB group at 1 (3.9% vs 7.1%; P = .68) and 3 years (9.8% vs 17.9%; P = .23). Compared to the S_DCB strategy, the use of the C_DCB reduced the 5-year rate of TLR although not statistically significant (9.8% vs 23.2%; OR, 0.36; 95% confidence interval [95%CI], 0.19-1.09; P = .05). The Kaplan-Meier analysis of the cumulative incidence curve revealed the differences seen at the 5-year follow-up (log-rank test, P = .05) with a similar 1-year event rate and curve separation consistent with the passing of the follow-up period (figure 1).

Table 1. Baseline characteristic of the patients

	S_DCB	C_DCB	P
	N = 49 patients/ 56 lesions	N = 42 patients/ 51 lesions
Age	68.9 ± 11.3	67.7 ± 10	.58
Male	85.7% (35)	83.3% (35)	.75
Arterial hypertension	26.8% (14)	23.8% (10)	.6
Dyslipidemia	46.9% (23)	28.6% (12)	.7
Smoking	61.2% (30)	57.1% (24)	.69
Diabetes	37.5% (21)	35.3% (18)	.81
AF in oral anticoagulants	22.4% (11)	19% (8)	.38
Previous myocardial infarction	55.1% (27)	50% (21)	.62
Previous coronary artery bypass graft	6.1% (3)	4.8% (2)	1
CKD (GFR < 60mL/min)	32.7% (16)	33.3% (14)	.94
LVEF (%)	54 ± 10	55 ± 9	.51
AF, atrial fibrillation; CKD, chronic kidney disease; GFR, glomerular filtration rate; LVEF, left ventricular ejection fraction.

Table 2. Lesion and procedural characteristics

	S_DCB	C_DCB	P			S_DCB	C_DCB	P
	N = 49 patients/ 56 lesions	N = 42 patients/ 51 lesions				N = 49 patients/ 56 lesions	N = 42 patients/ 51 lesions
Procedural characteristics					Lesion characteristics
Clinical signs			.87		Location of ISR			.35
Stable angina	55.4% (31)	56.9% (29)			LAD	53.6% (30)	45.1% (23)
Unstable angina/NSTEACS	41.1% (23)	41.2% (21)			LCX	23.2% (13)	15.7% (8)
STEACS	3.6% (2)	2% (1)			RCA	16.1% (9)	31.4% (16)
Radial access	55.4% (31)	78.4% (40)	.01		LMCA	5.4% (3)	3.9% (2)
DCB caliber (mm)	3.03 ± 0.37	3.15 ± 0.42	.13		Coronary artery bypass graft	1.8% (1)	3.9% (2)
DCB length (mm)	20.2 ± 5.8	19.5 ± 4.7	.53		Mehran's angiographic classification of ISR pattern			.42
DCB inflation pressure (atm)	14 ± 3	14 ± 3	.81		IA	1.8% (1)	3.9% (2)
CB caliber (mm)	N/A	2.93 ± 0.45			IB	3.6% (2)	0% (0)
CB length (mm)	N/A	8 ± 3			IC	41.1% (23)	49% (25)
CB inflation pressure (atm)	N/A	14 ± 3			ID	1.8% (1)	3.9% (2)
NCB	53.6% (30)	70.6% (36)	.07		II	21.4% (12)	27.5% (14)
NCB caliber (mm)	3.12 ± 0.42	3.28 ± 0.43	.14		III	21.4% (12)	11.8% (6)
NCB length (mm)	13.2 ± 3.1	12.6 ± 3.8	.65		IV	8.9% (5)	3.9% (2)
NCB inflation pressure (atm)	18 ± 4	18 ± 3	.74		ISR based on type of stenting			.4
Intracoronary imaging	8.9% (5)	5.9% (3)	.55		BMS	53.6% (30)	37.3% (19)
Multivessel disease	62.7% (32)	47.7% (21)	.14		DES	33.9% (19)	45.1% (23)
Complete revascularization	82.4% (42)	93.2% (41)	.13		DES in BMS	8.9% (5)	11.8% (6)
P2Y12 inhibitor			.64		DES in DES	3.6% (2)	5.9% (3)
Clopidogrel	88.2% (45)	81.6% (36)			Time from implantation	4.1 ± 4.8	3.8 ± 5	.69
Prasugrel	3.9% (2)	4.5% (2)			Bifurcation	32.1% (18)	23.5% (12)	.32
Ticagrelor	7.8% (4)	13.6% (6)			Stent caliber (mm)	2.96 ± 0.43	3.1 ± 0.56	.02
Duration of dual antiplatelet therapy			.27		Stent length (mm)	22.4 ± 6.5	22.8 ± 7.1	.75
1 month	3.9% (2)	2.3% (1)			Reference diameter (mm)	2.98 ± 0.48	3.12 ± 0.53	.16
3 months	21.6% (11)	9.1% (4)			Minimum lumen diameter (mm)	0.73 ± 0.51	0.68 ± 0.5	.67
6 months	21.6% (11)	34.1% (15)			Length (mm)	13.2 ± 5.6	11.7 ± 5.3	.18
12 months	52.9% (27)	54.5% (24)			Stenosis (%)	72 ± 18	75 ± 16	.3
					Minimum lumen diameter post-PCI (mm)	2.43 ± 0.46	2.77 ± 0.62	.002
					Acute lumen gain (mm)	1.7 ± 0.64	2.08 ± 0.83	.01
					Stenosis post-PCI (%)	14 ± 5	14 ± 6	.45
					Final TIMI grade 3 flow	98.2% (55)	100% (51)	1
BMS, bare-metal stent; CB, cutting balloon; DCB, drug-coated balloon; DES, drug-eluting stent; ISR, in-stent restenosis; LAD, left anterior descending coronary artery; LCX, left circumflex artery; LMCA, left main coronary artery; NCB, non-compliant balloon; NSTEACS, non-ST-segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; RCA, right coronary artery; STEACS, ST-segment elevation acute coronary syndrome; TIMI, Thrombolysis in Myocardial Infarction.

Figure 1. Kaplan-Meier analysis of the 5-year cumulative incidence of target lesion revascularization. DCB, drug-coated balloon.

The 5-year cumulative incidence of secondary endpoints is shown on table 3. The incidence rate of target vessel-related composite endpoints (target lesion failure and target vessel failure) was numerically lower in the C_DCB group although not statistically significant. No differences were found in the remaining secondary endpoints. The overall mortality rate at the follow-up was 31.8% (n = 19) being neoplasms the most common cause (n = 7). The incidence rates of stroke and patient-oriented composite endpoint were high (10.9% and 51.6%, respectively), which was consistent with an old cohort with high cardiovascular risk. No cases of definitive or probable stent thrombosis were seen at the follow-up.

Table 3. 5-year cumulative incidence of primary and secondary endpoints

	S_DCB	C_DCB	P
	N = 49 patients/ 56 lesions	N = 42 patients/ 51 lesions
Primary endpoint
TLR (clinically justified)	23.2% (13/56)	9.8% (5/51)	.05
Secondary endpoints
Target vessel revascularization	28.6% (16/56)	17.6% (9/51)	.18
Any revascularization	28.6% (14/49)	26.2% (11/42)	.8
Target vessel myocardial infarction	7.1% (4/56)	5.9% (3/51)	.79
Myocardial infarction	18.3% (9/49)	7.2% (3/42)	.19
Death due to cardiac causes	4.1% (2/49)	4.8% (2/42)	1
Cardiovascular death	16.3% (8/49)	11.9% (5/42)	.54
Overall mortality	36.7% (18/49)	26.2% (11/42)	.28
Stroke	10.2% (5/49)	11.9% (5/42)	.55
BARC type 3-5 bleeding	7.1% (4/49)	3.9% (2/42)	.68
Target lesion failure	37.5% (21/56)	25.5% (13/51)	.18
Target vessel failure	41.1% (23/56)	25.5% (13/51)	.08
POCE	53.1% (26/49)	50% (21/42)	.77
BARC, Bleeding Academic Research Consortium; DCB, drug-coated balloon; POCE, patient-oriented composite endpoints; TLR, target lesion revascularization.

A Kaplan-Meier subanalysis based on ISR after BMS or DES implantation showed that the C_DCB strategy consistently reduced the 5-year rate of TLR in half with both types of stent although not statistically significant (figure 2).

Figure 2. Kaplan-Meier analysis of the 5-year cumulative incidence of target lesion revascularization based on whether the stent is made out of metal or is drug-eluting. BMS, bare-metal stent; DCB, drug-coated balloon, DES, drug-eluting stent.

Aside from the C_DCB no association was found between the variables and the 5-year rate of TLR except for the location of ISR that was 100% in cases found in coronary artery bypass graft stents (3 cases) compared to 14.4% in cases found in the native coronary tree (P = .003). The 5-year rate of TLR was similar in diabetic patients (17.9% vs 16.2%; P = .81) in the ISR of DESs (17.2% vs 16.3%; P = .9) and in stents < 3 mm (12.9% vs 18.4%; P = .58) without any differences based on the type of DCB used (Sequent, 20.4% vs Pantera, 13.2%; P = .32). In the Cox regression analysis, the use of the C_DCB was not an independent predictor of TLR at 5 years being the ISR of a coronary artery bypass graft the only independent predictor (OR, 5.4; 95%CI, 1.5-19.8; P = .01).

DISCUSSION

As far as we know, the study presented here is the first one to confirm:

Compared to the plain old balloon angioplasty for the management of ISR, the CB achieves greater lumen areas because it breaks down the elastic and fibrotic continuity of the neointima by reducing its integrity and resistence.12 However, this acute angiographic improvement is not associated with lower but high rates of TLR (18% to 29%) at the 1-year follow-up.13,14 Similarly, in our series, the use of the CB is associated with a significant increase of minimum lumen diameter and acute gain after the procedure (table 2) despite the fact that the caliber of non-compliant balloons and DCBs was similar between both groups. Although stent diameter was slightly larger in the C_DCB group, the final percent stenosis did not change significantly between both groups; still, this may be an important piece of information in our results since the size of the vessel has been described as an independent predictor of new restenosis.23

The use of the DCB to treat ISR is something common after several meta-analyses revealed that, together with DES implantation with in-stent everolimus, this strategy is the most effective one to avoid new revascularizations.2-4 Afterwards, in the RIBS IV (with DES) and RIBS V (with BMS) clinical trials Alfonso et al. proved the long-term superiority of DES implantation with in-stent everolimus.8,9,24 However, the philosophy of not adding a new metal layer (or delay it through time) and questions associated with its long-term safety10,11 have turned DCB implantation into a common practice to treat ISR. Added to the RIBS IV-V studies, other trials have reported on the long-term effectiveness of DCB (PEPCAD7 with BMS, and PEPCAD-DES6 and ISAR-DESIRE 310 with DES). Overall, in these 5 studies, a total of 94 TLRs were reported in 524 ISRs treated with DCB, which is a 3-year rate of TLR of 17.9%. These results are accurately reproduced in our S_DCB cohort with rates high enough to justify looking into ways to improve the efficacy of DCBs.

The efficacy of DCBs is based on a transfer of the drug to the neointima of ISR where it exerts its antiproliferative effect. The proper preparation of the lesion by reducing neointimal thickening and increasing the surface of contact with the balloon is the key to achieve successful DCB implantations.15 Preclinical studies suggest that greater neointimal disarrays can increase the release and retention of the drug into the tissue, thus increasing its effects.16 Considering the greater acute lumen gain and controlled disarray that the CB provides, results can improve if used together with the DCB. This hypothesis was put to the test, but not proven, in a preclinical trial. The reason was that the use of the CB was not associated with a lower neointimal volume or acute lumen loss. Nonetheless, this assessment was made was very early (28 days).17

The synergistic effects of CB plus DCB were also confirmed by Scheller et al.25 in the PATENT-C trial. They took a different angle and studied the addition of an antiproliferative drug (paclitaxel) to the scoring balloon that reduced the 1-year rate of TLR significantly (3% vs 32%; P = .004). This information is consistent with the 1-year rate of TLR of 3.9 seen in our C_DCB cohort. From a new and different angle too, while still observing the philosophy of not leaving any material behind in the long-term after the PCI, Alfonso et al. conducted the RIBS VI Scoring trial and analyzed the impact of a CB before bioresorbable scaffold implantation to treat ISR. However, the 1-year rate of TLR was not reduced (9.8 vs 11.1%).26

Two randomized clinical trials have assessed the effect of CB implantation before DCB implantation to treat ISR. Aoki et al.27 found no angiographic differences at the 8-month follow-up in the ELEGANT trial. However, this was a comparative study vs a non-compliant balloon. Kufner et al.18 specifically tested the effects of CB implantation in the ISAR-DESIRE 4 trial. The primary endpoint was an angiographic result that confirmed that this strategy effectively reduced binary ISR at the 6 to 8-month follow-up. However, no differences were seen when the clinical events or TLR were assessed at the 1-year follow-up (16.2% vs 21.8%; P = .26). Qualitatively speaking, these results are consistent with what our series described because, although long-term benefits were reported, the 1-year rate of TLR did not change between our groups. No long-term data have ever been published so our cohort cannot be compared to corroborate the benefits described. Quantitatively speaking, we saw differences in the 1-year rate of TLR, much lower in our study (3.9% vs 7.1%). Three may be the reasons for this. In the first place, the scheduled angiographic assessment of the ISAR-DESIRE 4 trial because if we look at the Kaplan-Meier analysis of the TLR, in this study more clinical events were reported at the 6 to 8-month follow-up (when the angiographic assessment occurred). This is suggestive of a TLR guided by angiographic criteria (the so-called oculodilatory reflex) and not clinically justified as it was the case in our series. Secondly, the exclusive use of the scoring balloon vs the predominant use of the CB in our series since the CB achieves greater neointimal disarray and larger residual lumen diameters, thus increasing the efficacy of the DCB. Thirdly, the exclusive management of ISR after DES implantation vs ISR after any other type of stent implantation (BMS or DES) of our series since different authors have proposed the lower efficacy of the DCB to treat ISR after DES implantation.11,28 Based on this previous knowledge a subanalysis of the C_DCB strategy based on the type of stent used was conducted (figure 2). A consistent efficacy both in BMSs and DESs was seen with a similar 5-year rate of TLR in both subgroups (10.5% and 9.4% respectively)

Treating ISR with DCBs is a safe strategy associated with very low rates of stent thrombosis (around 1%) at the long-term follow-up.11 The role that a greater CB-induced neointimal tissue disarray plays in the appearance of thrombotic phenomena on the lesion is unknown. Consistent with the mid-term results of theISAR-DESIRE 4 trial, in our series, long-term target lesion thrombosis is null, which is a guarantee that the use of C_DCB is safe.

Limitations

Our study has several limitations. It is a retrospective, observational, and single-center study. Although the use of the DCB is the treatment of choice for the management of ISR in our center, it is possible that patients with more unfavorable ISR may have been excluded for having been treated with a DES. The use of intracoronary imaging was limited and the characterization of ISR could have given relevant information on the therapeutic strategy used and its long-term results. The size of the sample was not big enough to obtain powerful evidence. A larger sample size and longer follow-up is, therefore, guaranteed.

CONCLUSIONS

In a real-world cohort, changing the neointima of ISR with CB plus DCB vs standard DCB reduces the 5-year rate of TLR although not statistically significant. The benefit of this strategy is evident in the long-term and consistent between ISR after BMS and DES implantation.

FUNDING

None whatsoever.

AUTHORS’ CONTRIBUTIONS

J.A. Linares Vicente: study design, data mining, and analysis and writing of the manuscript. J.R. Ruiz Arroyo: data and critical review of the manuscript. A. Lukic, B. Simó Sánchez, and O. Jiménez Meló: data mining. A. Riaño Ondiviela, P. Morlanes Gracia, and P. Revilla Martí: data mining.

CONFLICTS OF INTEREST

None reported.

REFERENCES

INTRODUCTION

Drug-eluting stents (DES) are one of the greatest advances in the percutaneous treatment of coronary artery disease. These devices have consistently shown lower rates of revascularization of the treated vessel in a wide range of clinical situations, and have become the treatment of choice.1 However, the risk of late and very late stent thrombosis arose with first-generation DES,2 and, to this date, it is still a matter of concern.3 This phenomenon has been associated with side effects to the drug (impairing the proliferation of new endothelial cells), the polymer, the stent platform or a combination of them on the vessel wall, leading to delayed or incomplete endothelialization, persistent inflammatory reactions, and the development of neo-atherosclerosis. New DES have been developed with superior efficacy in terms of abolishing the need for revascularization, but with the reassurance of much lower rates of stent thrombosis, the most dreadful clinical manifestation of suboptimal vessel healing. The Angiolite stent (iVascular, Spain) is a thin-strut cobalt-chromium sirolimus-eluting stent with biostable coating made of 3 layers: acrylate to ensure adhesion to the metal surface, fluoroacrylate loaded with sirolimus (1.4 µg/mm2), and a top layer of fluoroacrylate for drug release control (> 75% elution within the first month).

The Angiolite stent was initially tested in a pre-clinical model with very promising results,4 with an equivalent antiproliferative response, and a better healing pattern compared to the XIENCE stent (Abbott Vascular, United States). Subsequently, a first-in-human study5 (ANCHOR study) proved a powerful inhibition of neointimal hyperplasia as seen on the OCT: The Angiolite stent efficiently inhibited the proliferative response (vessel area stenosis, 4.4% ± 11.3%), in- stent late lumen loss at 6 months (0.07 mm ± 0.37 mm), and had a low rate of strut malapposition (1.1% ± 6.2%). Finally, the ANGIOLITE study,6 a randomized clinical trial, compared the Angiolite stent to the XIENCE stent in 223 patients (randomization with a 1:1 allocation ratio). In this study, the primary endpoint, the 6-month in-stent late lumen loss, was non-inferior in the Angiolite group (0.04 mm ± 0.39 mm) compared to the XIENCE group (0.08 mm ± 0.38 mm). The stent received the CE marking (Conformité Européenne) for its routine use. Therefore, we designed the present observational, prospective, registry to endorse the previous results in the routine clinical practice, with wider indications for use.

METHODS

Study design

The EPIC02-RANGO study was designed as a prospective, single-arm, multicenter, observational registry for the evaluation of the safety and efficacy profile of the Angiolite stent in unselected patients representative of the routine clinical practice. The study design was approved by all investigators and the sponsor as well. A reference ethics committee approved the protocol and the informed consent forms; local ethics committees were informed that this study would be conducted in their centers in compliance with the national legislation. The study was conducted and monitored by an independent contract research organization. The authors of this original manuscript independently conducted the data final analysis, interpreted the study results, and drafted/wrote this original manuscript. The sponsor was informed on the status of the study and the final results, but had no further participation.

Selection of the study population

To be enrolled in the study, subjects should met all the 3 following inclusion criteria: ≥ 18 years-old; treated with percutaneous coronary intervention (PCI) with at least 1 Angiolite stent; and have received proper information and signed the corresponding informed consent.

To guarantee a real-world population, non-stringent exclusion criteria were applied. Subjects were only excluded from the study if they met any of the following exclusion criteria: contraindication to dual antiplatelet therapy; established cardiogenic shock; unlikely to complete the scheduled follow-up; or formal refusal to participate in the study.

The PCI (predilatation, invasive imaging, postdilatation, planning, and final performance) was left at the discretion of the operator, and was indicative of the real-world use of the stents. Medical treatment during and after the procedure, including antiplatelet regime and duration, also followed the standard local practices; however, we suggested the investigators to follow the guidelines available on the management of these patients.1,7

Endpoints

The primary endpoint was target lesion failure (TLF) at 6, 12, and 24 months defined as cardiovascular death, target vessel myocardial infarction or clinically driven target lesion revascularization.

 

 

In all cases, myocardial infarction refers to spontaneous infarction only. Two subgroups were predefined: patients with diabetes, and patients with Angiolite stents placed in small vessels (stent diameter ≤ 2.5 mm).

Sample size calculation

We conducted an exploratory analysis that rendered a population of 640 patients (with an estimated loss to follow-up of 10%). This sample size produces a 2-sided 95% confidence interval with a precision equal to 1.75% when the TLF rate is 4.86%. This value was obtained from the data published from different contemporary stents9-17 (table 1 of the supplementary data).

Table 1. Baseline and clinical characteristics

	Total N = 646	Angiolite only population N = 426
Age (years old)	66.41 ± 11.93	65.72 ± 11.98
Male sex	495 (76.6%)	320 (75.1%)
Cardiovascular risk factors & history
Hypertension	402 (62.2%)	254 (59.6%)
Dyslipidemia	385 (59.6%)	251 (58.9%)
Diabetes mellitus*	199 (30.8%)	119 (27.9%)
Current smoker	182 (28.2%)	127 (29.8%)
Chronic kidney disease	46 (7.1%)	25 (5.9%)
Peripheral vascular disease*	44 (6.8%)	23 (5.4%)
Previous stroke	28 (4.3%)	17 (4.0%)
Previous myocardial infarction	119 (18.4%)	73 (17.1%)
Previous coronary surgery	20 (3.1%)	13 (3.1%)
Previous PCI	131 (20.3%)	78 (18.3%)
Atrial fibrillation	34 (5.3%)	20 (4.7%)
Heart failure	46 (7.1%)	32 (7.5%)
Valvular heart disease ≥ grade III	16 (2.5%)	7 (1.6%)
PCI indication
NSTEMI	220 (34.1%)	141 (33.1%)
STEMI	149 (23.1%)	112 (26.3%)
Stable angina	120 (18.6%)	68 (16.0%)
Unstable angina (negative biomarkers)	72 (11.1%)	51 (12.0%)
Silent myocardial ischemia	32 (5.0%)	19 (4.5%)
Other	53 (8.2%)	35 (8.2%)
NSTEMI, non-ST-elevation acute myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction. * Significant differences between patients with the Angiolite stent only vs patients with any stents in addition to the Angiolite, P < .05. Data are expressed as no. (%) or mean ± standard deviation.

Population analysis

The primary safety and efficacy analysis considered all patients who received the Angiolite stent only except for those who withdrew their consent. The secondary analysis was performed on all patients included in the study who received, at least, 1 Angiolite stent plus another different stent except for those who withdrew their consent.

Clinical events committee

An independent data and safety monitoring board reviewed the cumulative safety data to safeguard the well-being of the participants. All events were remotely monitored by a contract research organization. The clinical events committee reviewed, adjudicated, and classified all adverse events. The 5 members of the clinical events committee were not affiliated to the centers that participated in the study.

A total of 90 random patient audits (14% of the global population) were conducted at 4 centers, including the top 3 recruiters. The result of these audits detected 9 unreported events, most of them corresponded to scheduled procedures that required admission (non-cardiac surgeries and 2 scheduled PCI cases). None of the events associated with these audits corresponded to events classified as primary or secondary endpoints.

Descriptive statistics

All continuous variables were summarized using the following descriptive statistics: n (based on the number of recorded data values for each parameter), mean, standard deviation, 95% confidence interval for the mean, median, interquartile range [Q1, Q3], maximum, and minimum. The frequency and percentages (based on the number of recorded data values for each parameter) of the observed values are reported for all categorical measures. In general, all data are listed, and sorted by study site, and subject.

Statistical methods

Regarding the continuous variables, results were expressed as mean ± standard deviation. Variables were compared using an independent t test or the Mann-Whitney test, when applicable. Categorical variables are expressed as counts and percentages and compared using the chi-square test or Fisher’s exact test. Variables were compared between patients with only the Angiolite stent versus patients with other stents in addition to the Angiolite one. The clinical variables at 6, 12, and 24 months were expressed as counts and percentages. Time-to-event hazard curves were expressed as Kaplan-Meier estimates.

These methods were applied for the entire cohort and the 2 predefined subgroups, when appropriate: patients with diabetes, and patients with small vessel lesions (stent diameter ≤ 2.5 mm).

The statistical software SAS Version 9.4 was used for all statistical analyses, listings, tabulations, and figures.

RESULTS

A total of 654 patients were recruited from 16 academic medical centers in Spain and Portugal from June 2017 through July 2018. A total of 8 patients were excluded for not meeting the selection criteria (2 in whom the Angiolite stent was not intented to be used, 5 duplicated patients with staged, planned, procedures, and 1 patient without any data available). Therefore, the population analyzed consisted of 646 patients (figure 1); a total of 426 patients were treated with Angiolite stents only (primary analysis).

Figure 1. Flow chart of the study.

The baseline characteristics and clinical data, as well as the angiographic and procedural features are shown on table 1 and table 2, respectively. Noteworthy, the population has a high-risk profile with a remarkable prevalence of previous myocardial infarction (18.4%), previous coronary revascularization (23.4%), clinical presentation as ST-segment elevation myocardial infarction (23.1%), and multivessel disease (47.8%).

Table 2. Angiographic and procedural features

	Total N = 646	Angiolite only population N = 426
Coronary angiography
Radial approach	585 (90.6%)	396 (93.0%)
Extension of the disease
No. of diseased vessels*
1	337 (52.2%)	289 (67.8%)
2	198 (30.7%)	92 (21.6%)
3	111 (17.1%)	45 (10.6%)
Left main coronary artery*	29 (4.5%)	12 (2.8%)
Proximal LAD disease	179 (27.7%)	110 (25.8%)
Diffuse disease*	128 (19.8%)	63 (14.8%)
No. of lesions per patient*	1.98 ± 1.24	1.51 ± 0.90
No. of treated lesions per patient*	1.68 ± 0.95	1.25 ± 0.53
No. of stents per patient*	1.80 ± 1.11	1.24 ± 0.55
Index procedure
Revascularization
Complete	489 (75.7%)	331 (77.7%)
Functional	84 (13.0%)	51 (12.0%)
Intravascular imaging
IVUS	15 (2.3%)	5 (1.2%)
OCT	12 (1.9%)	7 (1.6%)
Staged revascularization*	85 (13.2%)	26 (6.1%)
IVUS, intravascular ultrasound; LAD, left anterior descending coronary artery; OCT, optical coherence tomography. * Significant differences between patients with the Angiolite stent only vs patients with any stents in addition to the Angiolite, P < .05. Data are expressed as no. (%) or mean ± standard deviation.

The mean ± standard deviation number of lesions per patient was 1.98 ± 1.2, the mean number of treated lesions per patient was 1.68 ± 0.9 with a mean number of stents per patient of 1.80 ± 1.1. These numbers were significantly lower among patients treated with the Angiolite stent and consistent with the different patient profile. Table 3 summarizes the characteristics and treatment of each individual lesion. Interestingly, Angiolite stents were more frequently used to treat the infarct-related artery compared to other stents in our population. Subsequently, lesions with thrombus were more common in the group treated with Angiolite stents only while severe calcification was more prevalent in the entire group. Procedural complications occurred in 10 patients, 7 of them associated with Angiolite stents: 1 uncrossable lesion, 1 guidewire-related distal perforation, 1 severe no-reflow phenomenon, and 4 cases of dissection, 2 of them treated with additional stents. The procedural and device success rates were 99.7% and 99.2%, respectively. In more complex anatomic scenarios, specifically lesions with moderate/severe calcification, the procedural and device success rates stayed high (99.6% and 99.3%, respectively). Those rates were 100% in the subgroup of lesions at bifurcations or at left main coronary artery level.

Table 3. Characteristics and treatment of each individual lesion

	Total L = 1083 (84.9% of all lesions)	Angiolite only population L = 531 (82.5% of all lesions)
Vessel
Left anterior descending territory	459 (42.4%)	236 (44.4%)
Right coronary territory	327 (30.2%)	172 (32.4%)
Circumflex territory	273 (24.9%)	112 (21.2%)
Left main coronary artery	19 (1.8%)	5 (0.9%)
Other	5 (0.7%)	6 (1.1%)
AHA/ACC Classification*
A	95 (8.8%)	68 (12.8%)
B1	355 (32.8%)	193 (36.3%)
B2	429 (39.6%)	185 (34.8%)
C	204 (18.8%)	85 (16.0%)
Lesion characteristics
Thrombus*	145 (13.4%)	91 (17.1%)
Stent at the infarct-related artery*	366 (33.8%)	249 (46.9%)
Severe calcification*	85 (7.8%)	22 (4.1%)
Restenotic lesion treated	37 (3.4%)	22 (4.1%)
Chronic total coronary occlusion	37 (3.4%)	20 (3.8%)
Lesion at bifurcation	108 (10.0%)	47 (8.9%)
Severe tortuosity	142 (13.1%)	62 (11.7%)
Vessel diameter (mm)	2.91 ± 0.55	2.91 ± 0.53
Lesion length (mm)*	19.47 ± 9.80	17.56 ± 8.26
Pre-dilatation*	786 (72.6%)	363 (68.4%)
Scoring balloon	45 (4.2%)	11 (2.1%)
Cutting balloon	28 (2.6%)	8 (1.5%)
Rotational atherectomy	27 (2.5%)	9 (1.7%)
Thrombectomy*	75 (6.9%)	48 (9.0%)
Stents implanted	S = 1160	S = 529
No. of stents per lesion	1.07 ± 0.45	1.00 ± 0.35
Characteristics of the stent*
Type = Angiolite stent	784 (67.6%)	529 (100.0%)
Stent diameter (mm)	2.99 ± 0.51	2.99 ± 0.46
Stent length (mm)	21.38 ± 8.51	20.34 ± 7.03
Maximum pressure (atm)	14.61 ± 2.48	14.69 ± 2.46
Stent crossing the lesion at the 1st attempt	1067 (98.5%)	527 (99.2%)
Lesions at bifurcation	104 (96.3%)	45 (95.7%)
Moderate or severe calcification	268 (97.1%)	75 (97.4%)
Left main coronary artery	19 (100%)	5 (100%)
Postdilatation	284 (26.2%)	149 (28.1%)
Balloon diameter (mm)	3.24 ± 0.62	3.25 ± 0.53
Type of balloon, non-compliant	186 (67.4%)	112 (76.7%)
ACC, American College of Cardiology; AHA, American Heart Association; L, lesions; S, stents. * Significant differences between patients with the Angiolite stent only vs patients with any stents in addition to the Angiolite, P < .05. Data are expressed as no. (%) or mean ± standard deviation.

The 6-month and 1-year follow-ups were good, with only 9 (1.4%) and 12 (1.9%) patients lost to follow-up, respectively. At the 1-year follow-up, 368 patients (59.6%) were still on dual antiplatelet therapy; this rate dropped to a 15.5% at the 2-year follow-up. During the established follow-up period (2 years for all patients), only 13 patients (2%) were lost. In the global population, at 2 years, the rates of TLF, target vessel failure, and MACE were 3.4%, 4.3%, and 9.6%, respectively. Two of the 9 cases of TLF were not associated with Angiolite stents but with other stents implanted. The rate of definite/probable stent thrombosis was 0.9%; all patients were on dual antiplatelet therapy when the event occurred. Interestingly, 4 cases appeared during the first week of follow-up, 1 case within the first month, and only 1 case of stent thrombosis after 6 months (268 days). Table 4 and figure 2 summarize the individual event rate and timing.

Table 4. Outcomes in the global population

Total population (N = 646)	6-month follow-up	1-year follow-up	2-year follow-up
Death	11 (1.7%)	17 (2.6%)	31 (4.8%)
Cardiovascular death	6 (0.9%)	8 (1.2%)	11 (1.7%)
Myocardial infarction	11 (1.7%)	16 (2.5%)	20 (3.1%)
Target vessel myocardial infarction	6 (0.9%)	8 (1.2%)	8 (1.2%)
Definite/probable device thrombosis	5 (0.8%)	6 (0.9%)	6 (0.9%)
Revascularization	13 (2.0%)	22 (3.4%)	32 (5.0%)
Target lesion revascularization	6 (0.9%)	8 (1.2%)	9 (1.4%)
Target vessel revascularization	7 (1.1%)	11 (1.7%)	15 (2.3%)
Non-target vessel revascularization	6 (0.9%)	11 (1.7%)	17 (2.6%)
Target lesion failurea	13 (2.0%)	18 (2.8%)	22 (3.4%)
Target vessel failureb	14 (2.2%)	21 (3.3%)	28 (4.3%)
MACEc	25 (3.9%)	41 (6.3%)	62 (9.6%)
MACE, major adverse cardiovascular events. a Target lesion failure defined as cardiovascular death, target vessel myocardial infarction, and clinically indicated target lesion revascularization. b Target vessel failure defined as cardiovascular death, target vessel myocardial infarction, and target vessel revascularization. c MACE defined as all-cause mortality, any myocardial infarction, any revascularization.

Figure 2. 2-year cumulative incidence of events in the entire population (N = 646).

In the primary analysis population (patients treated with Angiolite stents only) at 2 years, the rates of TLF, target vessel failure, and MACE were 3.1%, 4.0%, and 8.0%, respectively. The rate of definite/probable stent thrombosis was 0.7%. No cases of stent thrombosis were found beyond the first 6 months. Table 5 and figure 3 summarize the individual event rate and timing.

Table 5. Outcomes in the primary analysis population: patients treated with the Angiolite stent only

Angiolite only population (N = 426)	6-month follow-up	1-year follow-up	2-year follow-up
Death	5 (1.2%)	10 (2.3%)	18 (4.2%)
Cardiovascular death	3 (0.7%)	5 (1.2%)	7 (1.6%)
Myocardial infarction	5 (1.2%)	5 (1.2%)	10 (2.3%)
Target vessel myocardial infarction	4 (0.9%)	4 (0.9%)	4 (0.9%)
Definite/probable device thrombosis	3 (0.7%)	3 (0.7%)	3 (0.7%)
Revascularization	7 (1.6%)	11 (2.7%)	18 (4.2%)
Target lesion revascularization	3 (0.7%)	4 (0.9%)	5 (1.2%)
Target vessel revascularization	4 (0.9%)	7 (1.6%)	9 (2.1%)
Non-target vessel revascularization	3 (0.7%)	4 (0.9%)	9 (2.1%)
Target lesion failurea	7 (1.6%)	10 (2.3%)	13 (3.1%)
Target vessel failureb	8 (1.9%)	13 (3.1%)	17 (4.0%)
MACEc	13 (3.2%)	22 (5.3%)	34 (8.0%)
MACE, major adverse cardiovascular events. a Target lesion failure defined as cardiovascular death, target vessel myocardial infarction, and clinically indicated target lesion revascularization. b Target vessel failure defined as cardiovascular death, target vessel myocardial infarction, and target vessel revascularization. c MACE defined as all-cause mortality, any myocardial infarction, any revascularization.

Figure 3. 2-year cumulative incidence of events in the primary analysis population of patients treated with the Angiolite stent only (N = 426).

The subgroup analysis rendered 2-year results that were slightly worse that those observed in the global population:

 

 

DISCUSSION

The results of the current real-world registry of the Angiolite coronary stent show an outstanding safety and efficacy profile as the ANCHOR5–first-in-human study–and the ANGIOLITE6 randomized clinical trial comparison with the XIENCE stent showed. The clinical profile shows a relatively high-risk population with a prevalence of diabetes mellitus of 30.8%, 17.6% on anticoagulation with oral drugs, 18.4% of patients diagnosed with previous myocardial infarction, and 23.4% with previous coronary revascularization. Also, a high rate of complex coronary artery disease was found in the recruited population: significant multivessel disease was diagnosed in 47.8%, compromised left main coronary artery in 4.5%, and diffuse coronary artery disease in 19.8% of the patients. Therefore, the mean number of significant lesions (1.98 ± 1.24), treated lesions (1.68 ± 0.95), and stents implanted per patient (1.8 ± 1.11) was relatively high. The ST-segment elevation myocardial infarction clinical setting of the PCI in around a quarter of the cases also shows the all-comer, real-world nature of the study.

The registry was designed to include all the patients in whom an Angiolite stent was intended to be used. Therefore, we may distinguish 2 different populations: those in whom ONLY the Angiolite stent was intended (primary analysis) and those who received different stents to treat other lesions on top of the Angiolite stent (secondary analysis). These populations have some significant differences: Angiolite ONLY-patients were more prone to have single vessel disease, few significant lesions, few treated lesions, and few stents implanted. Reasonably, this population with lower atherosclerotic burden showed less diffuse disease and fewer staged procedures. However, not all the characteristics of this group were so favorable since the presence of thrombus and the target lesion as the infarct-related artery were more common in the Angiolite ONLY stent group.

The primary endpoint, TLF at 1-year was consistently low both in the Angiolite ONLY population (primary analysis), 2.3%, and in the entire population (secondary analysis), 2.8%. Target vessel failure, a wider safety variable, was also noticeably low (3.1% and 3.3%, respectively). To confirm these results, MACE (including all-cause mortality too), a clinically oriented variable, was also very low (5.3% and 6.3%, respectively). An overview of the TLF results of different stents tested in registries and RCTs is shown on table 1 of the supplementary data. In these studies, the TLF mean value at 1-year is 5.4%, higher that the rate seen in this study.

The 2-year follow-up confirmed the very low rate of unfavorable cardiac events seen at the early 1-year period. The rate of new cardiac events, both device- and patient-oriented, within the second follow-up year was about half of the observed rate during the first year.

Both the ANCHOR FIH5 and the ANGIOLITE RCT6 pointed out an extraordinary antiproliferative efficacy of the Angiolite stent, with a mean late luminal loss < 0.05 mm. Consequently, we thought it was mandatory to assess the safety of this stent through the rate of stent thrombosis. The real-world use of the Angiolite stent is associated with a low rate of such a catastrophic complication (0.7% in primary analysis, 0.9% in secondary analysis), which guarantees the safe use of this powerful DES. The studies published showed a mean rate of stent thrombosis from 0.4% to 4.9% at the 2-year follow up (table 1 of the supplementary data). Also, the very low rate of definite/probable stent thrombosis beyond the first week (only 2 cases, 1 within the first month and the other 268 days later) restates this safety profile. We should mention that the use of dual antiplatelet therapy was high in this population (59.6% at the 1-year follow-up), which is indicative of the prevalence of acute coronary syndrome as the patients’ clinical presentation (68.3% of the patients).

The predefined subgroup analysis rendered interesting results. Diabetic patients showed TLF and stent thrombosis rates at 2 years, similar to the overall rate (3.0% vs 3.4%, and 1.0% vs 0.9%, respectively), while the rate of MACE was higher (14.1% vs 9.6%). This finding may show the worse clinical prognosis of diabetic patients, not necessarily associated with the lesion treated but with the remaining coronary artery disease. Our results are consistent with previous data published on the EVOLVE II substudy on diabetes13 that showed a 2-year TLF rate of 11.2% and a definite/probable stent thrombosis of 1.1%.

As expected, the subgroup of small vessel disease (≤ 2.5 mm) showed slightly higher rates of 2-year TLF and MACE (4.3% and 12.1%, respectively) than the global population (3.4% and 9.6%, respectively). The lack of definite/probable stent thrombosis cases could be indicative of detection bias as the thrombosis of these vessels may have a milder clinical expression. The results of this subgroup are usually hard to compare with other data as the definition of small vessel is highly arbitrary, from 2.25 mm to 3.0 mm. However, the results of our study are consistent with those reported in the Basket Small18 trial.

Limitations

The limitations of this study are the well-known issues of real-world observational registries: potential selection bias, reporting biases, and losses to follow-up (not in this case though, with a 98% of the follow-up period completed). However, the results are similar to previously reported data and are consistent with the results of previous studies with this stent. In the global population (patients who received other stents besides Angiolite stents), endpoints like probable stent thrombosis or cardiovascular death cannot be clearly attributed to a certain stent.

To minimize potential errors and reinforce the safety message, the steering committee has decided to extend the follow-up period up to 5 years.

CONCLUSIONS

In conclusion, the results of this observational registry on the use of the Angiolite DES in a real-world population confirm the excellent efficacy and safety profile seen in previous studies at the 2-year follow-up. An extended 5-year follow-up is planned to discard late events.

FUNDING

This study was conducted with financial support from Cardiva S.L. Data management and analysis were performed by an independent CRO. The final draft and the manuscript were wrote by investigators without any participation from the sponsors.

AUTHORS’ CONTRIBUTIONS

Idea and design: A. Pérez de Prado, F. Lozano Ruiz-Poveda, J. Moreu Burgos, B. García del Blanco, E. Pinar, V. Peral, J.R. Rumoroso, and R. Trillo Nouche. Data acquisition: A. Pérez de Prado, R. Ocaranza-Sánchez, F. Lozano Ruiz-Poveda, J. Moreu Burgos, R. Álvarez Ramos, A. Rodrigues, L. Fernández González, P. Aguar, B. García del Blanco, E. Pinar, V. Peral, F. Sainz Laso, J.R. Rumoroso, A. Torres, M. Sabaté, and R. Trillo Nouche. Statistical analysis and manuscript writing: A. Pérez de Prado, F. Lozano Ruiz-Poveda, J.R. Rumoroso, and R. Trillo Nouche. Provision of critical feedback to the manuscript and final content approval: A. Pérez de Prado, R. Ocaranza-Sánchez, F. Lozano Ruiz-Poveda, J. Moreu Burgos, R. Álvarez Ramos, A. Rodrigues, L. Fernández González, P. Aguar, B. García del Blanco, E. Pinar, V. Peral, F. Sainz Laso, J.R. Rumoroso, A. Torres, M. Sabaté, and R. Trillo Nouche.

CONFLICTS OF INTEREST

A. Pérez de Prado, and M. Sabaté received consulting honoraria and research grants from iVascular, and Cardiva S.L. F. Lozano Ruiz-Poveda received honoraria for his lectures from Abbott and Medtronic. All authors have declared payments to their centers from Cardiva S.L.

 

 

INTRODUCTION

Magnesium-based bioresorbable scaffolds (Magmaris) are safe devices with good results in the long run like the BIOSOLVE II1 and BIOSOLVE III2 clinical trials show where no device thrombosis was seen at the long-term 12- to 24-month follow-up. Despite this fact, the device own limitations (ill-advised in cases of calcified complex coronary anatomy or in long lesions) have reduced its use significantly in the routine clinical practice to the point that only 224 procedures with bioresorbable devices were performed in Spain in 2019 (0.2% of the total number of devices implanted).3

As already mentioned, the good results reported in long-term follow-ups have turned the Magmaris (Biotronik, Germany) into the only bioresorbable metal scaffold to receive the CE marking (Conformité Européenne).4

The role Magmaris plays in the acute coronary syndrome setting is not widely known and further studies will be needed before its safety profile can be assessed. The objective of this work was to analyze—through an observational study in the routine clinical practice—the long-term (> 12 months) clinical safety of Magmaris scaffolds implanted in patients with acute coronary syndrome in the cath lab of a single center.

METHODS

Consecutive observational registry of patients diagnosed with acute coronary syndrome implanted with magnesium-based bioresorbable scaffolds between November 2016 and November 2018. The study was approved by the hospital ethics committee and all patients gave their signed written informed consent to participate in the study. The study primary endpoint was a composite of target vessel myocardial infarction, target lesion failure, and cardiovascular death. The study secondary endpoint included the device thrombosis. The PSP strategy (predilation, sizing, and postdilation) derived from the GHOSTEU registry was used in all the cases.5 In 100% of the patients the optical coherence tomography was used for the right characterization of the lesion and size of the vessel.

RESULTS

A total of 36 patients (29 males, 80%) were included with a median age of 59.61 ± 9.74 years. The follow-up period was 1001 days with an interquartile range of 342 days. Table 1 summarizes the baseline clinical characteristics of the sample as well as the main angiographic characteristics.

Table 1. Baseline clinical characteristics and angiographic parameters of the patients

			N (%)
Family history of ischemic heart disease			11 (30.6)
Arterial hypertension			19 (52.8)
Diabetes mellitus			7 (19.4)
Dyslipidemia			23 (63.9)
Smoker			23 (63.9)
Type of acute coronary syndrome:
NSTEACS			23 (63.9)
STEACS			8 (22.2)
Unstable angina			5 (13.9)
Number of diseased vessels:
1 vessel			16 (44.4)
2 vessels			15 (41.7)
3 vessels			5 (13.9)
Location of the lesion treated with Magmaris:
LAD			27 (75%)
RCA			10 (27.8%)
LCX			4 (11.1%)
AHA classification of coronary lesions:
Type A			16 (44.5%)
Type B			12 (33.3%)
Type C			8 (22.2%)
Immediate success after device implantation			36 (100%)
Drug-eluting stent implantation			12 (36%)
Normal LVEF			26 (72.2%)
Antiplatelet therapy at discharge:
Acetylsalicylic acid			36 (100%)
Ticagrelor			29 (80.6%)
Clopidogrel			6 (16.7%)
Prasugrel			1 (2.8%)
Prolonged DAPT > 12 months			14 (38.9%)
Statins			36 (100%)
Beta-blockers			31 (86.1%)
Angiographic parameters	Length (mm)	Diameter (mm)	Peak inflation pressure (atm)
Target lesion	29.2 ± 13.4	3.4 ± 0.2
Predilation (noncompliant balloon)	16.8 ± 2.9	3.2 ± 0.4	20.2 ± 1.2
Magmaris	22.5 ± 3.05	3.4 ± 0.2	15.9 ± 0.9
Postdilation (noncompliant balloon)	21.4 ± 1.5	3.7 ± 0.3	21.4 ± 1.5
AHA, American Heart Association; DAPT, dual antiplatelet therapy; LAD, left anterior descending coronary artery; LCX, left circumflex artery; LVEF, left ventricular ejection fraction; NSTEACS, non-ST-segment elevation acute coronary syndrome; RCA, right coronary artery; STEACS, ST-segment elevation acute coronary syndrome.

A total of 100% of the patients received a Magmaris device in the target lesion causing the study acute coronary event. Drug-eluting stents were implanted at the discretion of the operator in 12 of the 36 patients (33.3%), and in 1 patient only (2.8%) the implantation of the stent and the Magmaris scaffold overlapped. However, in the remaining patients they were not implanted in the target vessel.

Only 1 Magmaris scaffold was used in 15 patients (41.7%), 2 in 12 cases (33.3%), 3 in 2 cases (5.6%), 4 in 3 cases (8.3%), 5 in 3 cases (8.3%), and a maximum of 6 Magmaris devices in 1 single patient (2.8%). In 20 patients (55.6%) the stent and the Magmaris device implantation overlapped.

Regarding the device-oriented composite endpoint, 0 cases of target vessel myocardial infarction occurred (0%). However, 2 cases of target lesion failure were confirmed (5.6%), and 1 noncardiovascular death (2.8%) was reported at the 36 months following Magmaris implantation. However, the cause remained elusive for the lack of an autopsy (figure 1). Regarding the secondary endpoints, no Magmaris thrombosis was reported at the follow-up (table 2).

Figure 1. Kaplan-Meier survival curve with respect to the study primary endpoint: a device-oriented composite endpoint of target vessel myocardial infarction, target lesion failure, and cardiovascular death. DOCE, device-oriented composite endpoint.

Table 2. Primary (device-oriented composite endpoint) and secondary clinical events of the patients at the follow-up (N = 36, 100%)

Event	Patients	Percentage
Target lesion failure	2	5.6 %
Target vessel myocardial infarction	0	0 %
Cardiovascular death*	1	2.8 %
Magmaris device thrombosis	0	0 %
* 1084 days after Magmaris implantation.

A total of 11 admissions were reported at the follow-up (30.6%). Among these, 8 were due to recurrent angina (22.2%), 2 to heart failure or de novo atrial fibrillation (5.6%), and 1 to atrioventricular block that required pacemaker implantation (2.8%).

The coronary angiography was repeated in 10 cases (27.8%), the absence of lesions was confirmed in 3 patients (8,3%), stent restenosis was reported in 1 patient 2.8%), Magmaris restenosis in 2 (5.6%), and de novo lesions in 4 patients (11.1%).

When the cases of Magmaris restenosis were studied across time it was found that all of these occurred after the 24-months follow-up (1 case after 737 days and the other after 1189 days). The cardiovascular death reported in 1 patient occurred 1084 days after implantation.

DISCUSSION

The magnesium-based bioresorbable scaffold (Magmaris) is a highly successful device when implanted following the recommendations made by the manufacturer6 including the right predilation and optimization of the lesions using intracoronary imaging modalities. A study proved that an optimal PSP technique was not associated with a lower rate of the device-oriented composite endpoint. However, patients with optimal PSP-3 had numerically fewer episodes compared to patients without optimal PSP-3 (0.5% vs 2.9%, P = .085, and 0.5% vs 1.8%, P = .248, respectively).7

The real-world 12-month follow-up results of a cohort registry with Magmaris have recently been published. These results have confirmed the Magmaris safety profile and its low rate of events (target lesion revascularization in 4.7%) and lack of thrombosis.8

Also, the use of magnesium-based bioresorbable scaffolds has been studied in a group of 50 patients with non-ST-segment elevation acute coronary syndrome. This device reached angiographic success in 100% of the cases. One case of failed target vessel revascularization was reported the day after the procedure that required the implantation of a bare-metal stent. No device-related events were reported at the 6-month follow-up.9

The Magmaris scaffold and the sirolimus-eluting stent were compared in a controlled, randomized, blinded, multicenter study of patients with ST-segment elevation acute coronary syndrome. This study proved that in 150 patients the primary endpoint of a greater vasomotor response to medication was better in the Magmaris group at the 1-year follow-up. However, the Magmaris scaffold was associated with a worse angiographic progression and a greater late luminal loss compared to the bare-metal stent. It was also associated with a higher rate of target lesion revascularization without a significantly higher number of thrombotic events being reported.10

In our registry, the immediate rate of successful device implantation was 100%. Device overlapping occurred in 55.6% of the cases with a high frequency of treatment of 2 and 3 vessels (55.4%). Despite the complexity of the lesions, device restenosis was only reported in 2 cases (5.6%) at the > 3-year follow-up. The rate of thrombosis at the follow-up was 0 cases and the rate of cardiovascular death—considering 1 case with the devices implanted 36 months beforehand (and without necropsy or previous clinical assessment)—was 2.8%. In our study of real-world clinical practice this confirms the device safety profile in the short and mid-term in the acute coronary syndrome setting. The results of the BIOSOLVE IV registry reported a target lesion failure rate of 4.3%,11 similar to the one seen in our registry—5.5%—despite our patients’ profile of higher ischemic risk (all of them with acute coronary syndrome and an average lesion length of 29.17 mm ± 13.39 mm with Magmaris overlapping in 55.6% of the cases).

Limitations

Our study main limitation is its small sample size, which shows the low penetration of resorbable scaffolds in our hospital setting. Another limitation is the registry observational nature with an inherent selection bias, without defined inclusion and exclusion criteria, and the use of second-generation drug-eluting stents in 33.3% of the patients outside de target vessel except for 1 case where the stent and the Magmaris device overlapped (2.8%).

Another limitation was the lack of an independent clinical event adjudication committee. However, 100% of the patients were followed-up (through electronic health records and phone calls) by the research working team.

CONCLUSIONS

In our registry of patients with acute coronary syndrome who received the Magmaris scaffold the primary endpoint of target lesion failure or target vessel myocardial infarction did not increase compared to registries previously published. No cases of scaffold definitive thrombosis were reported at the follow-up, and only 1 cardiovascular death was reported 36 months after implantation without knowing the definitive cause. Considering the aforementioned limitations, our results confirm that Magmaris scaffolds could have a favorable clinical profile in the complex setting of acute coronary syndrome.

FUNDING

No external funding has been received.

AUTHORS’ CONTRIBUTIONS

All authors contributed equally during the collection of clinical data and the performance of the interventional procedures including the follow-up of all of the patients.

CONFLICTS OF INTEREST

None reported.

 

 

REFERENCES

INTRODUCTION

The current estimates reveal the population gradual aging, which will be more evident in the coming years.1 Based on these estimates, by the year 2050, our country will become one of the oldest worldwide with more than 4 million people over 80 years of age. This means that the percentage of patients treated with primary angioplasty (PA) is on the rise in our setting.

Although old age is associated with worse prognoses, PA is still the best reperfusion strategy for these patients.2-5 This segment of the population has a high prevalence of comorbidities, is often recommended fewer treatments, and has a higher risk of complications during revascularization procedures. Also, these patients are often misrepresented in the clinical trials, meaning that there is little scientific evidence available on the clinical characteristics, results, and long-term prognosis after PA.6

The objectives of this study were to analyze the characteristics, results, mortality, and prognostic predictors of patients > 80 treated with PA in our center.

METHODS

Single-center, retrospective, and observational study. All patients > 80 treated with PA in our center from January 2013 through September 2019 were included. Different clinical and epidemiological variables like age, sex, cardiovascular risk factors, presence of comorbidities, and the total ischemic time were prospectively registered in the unit database. The Charlson Comorbidity was retrospectively obtained at admission to stratify the patients’ overall comorbidities.7,8 This study was approved by Hospital Universitario Fundación Alcorcón ethics committee and waiver of informed consent was accepted.

Catheterization and treatment

Most cases were treated with percutaneous coronary intervention using the standard technique via radial access. The contrast agents used in all the cases were iohexol (Omnipaque 350, and Omnipaque 300), and iodixanol (Visipaque 320). The number of main vessels damaged seen on the coronary angiography, the access route, the dose of contrast used, the x-ray image time, and the number and type of stent use were recorded. Angiographic success and the presence of complications during the procedure were recorded as well. The operator chose the type of stent he would use during the procedure, although the local protocol recommended the use of conventional stents preferably. Drug-eluting stents were spared for situations of high risk of restenosis.

Follow-up and endpoints

Follow-up data were obtained after reviewing our hospital electronic health records. Also, phone calls to the patient or his family were made followed by a standard survey when appropriate. The endpoints studied were in-hospital mortality and complications, cardiovascular events, and cardiac death at the long-term follow-up.

Definitions

Left ventricular systolic function was estimated on the echocardiogram. The presence of a left ventricular ejection fraction < 45% was considered moderate-to-severe left ventricular dysfunction. Cardiogenic shock was defined as systolic arterial pressure < 90 mmHg for, at least, 1 hour followed by tissue hypoperfusion that required inotropic support and/or intra-aortic balloon pump implantation. Cardiac deaths were due to acute coronary syndrome, heart failure or ventricular arrhythmia. Angiographic success was defined as the presence of TIMI grade ≥ 2 flow in the absence of residual stenosis > 50%. The glomerular filtration rate was estimated using the simplified modification of diet in renal disease (MDRD) equation.9 Chronic kidney disease was defined as a glomerular filtration rate < 60 mL/min/ 1.73 m2 at admission. Bleeding complications associated with vascular access were classified based on the Bleeding Academic Research Consortium (BARC) definitions.10 BARC type > 2 hemorrhages were considered major bleeding. Target lesion revascularization was defined as the need for a new revascularization procedure (whether percutaneous or surgical) of the coronary segment with stenting in the presence of angiographic restenosis (stenosis > 50%) and symptoms or signs of myocardial ischemia.

Statistical analysis

The statistical software package SPSS version 20 was used for the analysis of data. Quantitative variables were expressed as mean ± standard deviation. The categorical ones were expressed as absolute value and percentage.

Univariate and multivariate modified Poisson regression analyses were conducted to determine the independent prognostic factors of in-hospital mortality. The variables included in the multivariate analyses were those considered of the greatest clinical relevance: Killip Class > I at admission, age > 85, chronic kidney disease, Charlson Comorbidity index > 2, and presence of moderate-to-severe left ventricular dysfunction. Results were expressed as relative risks and their 95% confidence interval (95%CI).

Univariate and multivariate Cox regression analyses were conducted to determine the independent predictors of overall mortality at the long-term follow-up. The variables included in the multivariate analyses were those associated with a higher mortality rate in the univariate analysis and also those of the greatest clinical relevance: Killip Class > I at admission, age > 85, chronic kidney disease, Charlson Comorbidity index > 2, and presence of moderate-to-severe left ventricular dysfunction. Results were expressed as hazard ratios (HR) and their 95%CI. P values < .05 were considered statistically significant. The inter-group overall mortality-free survival rates based on the presence of chronic kidney disease and a Charlson comorbidity index > 2 were compared using the Kaplan-Meier Curves (log-rank test).

RESULTS

Clinical characteristics and of the interventional procedure

A total of 1269 PAs were performed in our center from January 2013 through September 2019. A total of 10.5% were ≥ 80 years old at admission. The study group included 133 patients (57 women [43%]) with a median age of 85.3 ± 3.8 years treated with PA. The study population had a high prevalence of cardiovascular risk factors. A total of 66.2% of the patients had chronic kidney disease. The anterior was the most common location of the infarction. A total of 16.6% of the patients were Killip Class III-IV. In 28.5% of the cases delays of more than 6 hours between the beginning of pain and reperfusion were reported. The mean Charlson Comorbidity index used to assess the comorbidities of the patients included in our series was 2.3 ± 1.6 (table 1).

Table 1. Clinical angiographic, and interventional procedure data

Patients	N = 133
Age (years)	85.3 ± 3.8
Sex (woman)	57 (43%)
Diabetes mellitus	46 (34.6%)
Dyslipidemia	77 (57.9%)
Arterial hypertension	110 (82.7%)
Active smoking	4 (3%)
Charlson Comorbidity index	2.3 ± 1.6
Body mass index	26.4 ± 3.3
Previous infarction	23 (17.3%)
Previous angioplasty	18 (13.5%)
Previous coronary artery bypass surgery	3 (2.3%)
Atrial fibrillation	31 (23.3%)
LVEF echocardiogram	47.1 ± 11
LVEF < 50%	61 (45.8%)
Creatinine levels at admission (mg/dL)	1.25 ± 0.44
GFR-MDRD (mL/min/1.73 m2)	52.2 ± 18.5
Chronic kidney disease*	88 (66.2%)
Location of the infarction
Anterior	62 (46.6%)
Inferior	48 (36.1%)
Lateral	11 (8.3%)
Undetermined	9 (6.8%)
Cardiac arrest	3 (2.3%)
Killip Class
I	100 (75.1%)
II	11 (8.3)
III	7 (5.3)
IV	15 (11.3)
Total ischemic time > 6h	37 (28.5%)
Median of total ischemic time (min)	268 [177-406]
Median of time from symptom onset until arrival at the PA-capable left (min)	203 [124-330]
Median of time from the arrival at the PA-capable leftuntil guidewire passage (min)	50 [37-77]
X-ray image time (min)	16.6 ± 13
Volume of contrast (mL)	173 ± 72
Radial access	107 (80.5%)
Number of diseased vessels
1	70 (52.6%)
2	39 (29.3%)
3	24 (18%)
Number of stents implanted	1.04 ± 0.2
Thrombus aspiration	34 (25.6%)
Glycoprotein IIb/IIIa inhibitors	17 (12.8%)
Drug-eluting stent	41 (30.8%)
PCI of NC lesions in the acute phase	4 (3%)
PCI of NC lesions in another procedure at admission	11 (8.3%)
Complete revascularization	69 (51.9%)
Angiographic success	127 (95.5%)
In-hospital mortality	24 (18%)
GFR-MDRD, glomerular filtration rate (Modification of Diet in Renal Disease); LVEF, left ventricular ejection fraction; NC, non-culprit; PA, primary angioplasty; PCI, percutaneous coronary intervention. Data are expressed as no. (%), mean ± standard deviation or median [interquartile range]. * Defined as a glomerular filtration rate < 60 mL/min/1.73 m2.

Regarding the angiographic and procedural data, the radial access was used in 80.5% of the patients of whom 47.4% had multivessel disease. Almost half of the patients were released from the hospital with incomplete angiographic revascularizations. Thrombus aspiration was performed in one fourth of the patients and drug-eluting stents were implanted in 30.8% of these patients (table 1).

Patient progression at the hospital setting

Regarding patient progression at the hospital setting, 63 patients (49%) developed heart failure and 24 patients (18%) died during admission. Two patients (1.5%) had stent thrombosis during their hospital stay. The cause of death of 21 of the dead patients (87.5%) was cardiovascular. There was a statistically significant higher in-hospital mortality rate in patients with Charlson comorbidity indices > 2 (28.9% vs 13.7%, P = .039), Killip Class > I (51.5% vs 7%; P < .001), and worse ventricular (26% vs 4.3%, P = .003) and renal functions (23.9% vs 6.7%; P = .031). The Killip Class-based mortality rate based was 7% for Killip Class I, 27.3% for Killip Class II, 57.1% for Killip Class III, and 66.7% for Killip Class IV (figure 1).

Figure 1. In-hospital mortality based on Killip Class.

In the multivariate modified Poisson regression analysis, the only independent prognostic factor of in-hospital mortality was the Killip Class at admission (relative risk, 6.5; 95%CI, 2.01-20.36; P = .001) (table 2).

Table 2. Factors associated with a higher in-hospital mortality rate. Univariate and multivariate modified Poisson regression analyses

	RR	95%CI	P
Univariate analysis
Age	1.06	0.8-1.15	.135
Sex (woman)	1.58	0.76-3.27	.221
Diabetes Mellitus	1.35	0.65-2.81	.42
Killip Class > I	7.36	3.34-16.22	< .001
Moderate-to-severe left ventricular dysfunction	6.07	1.81-20.28	.003
Total ischemic time (hours)	1.05	0.98-1.22	.163
Atrial fibrillation	1.65	0.78-3.48	.193
Charlson Comorbidity index > 2	2.12	1.04-4.31	.039
Chronic kidney disease	3.58	1.12-11.41	.031
Anterior location	1.60	0.77-3.36	.211
Multivessel disease	1.49	0.70-3.17	.297
Incomplete revascularization	1.38	0.67-2.86	.383
Drug-eluting stent	1.1	0.43-2.82	.846
Mulivariate analysis
Age	1.1	0.99-1.21	.074
Killip Class > I	6.5	2.01-20.36	.001
Chronic kidney disease	1.23	0.26-5.96	.793
Charlson Comorbidity index > 2	2.2	0.9-5.38	.083
Moderate-to-severe left ventricular dysfunction	3.05	0.95-9.81	.062
95%CI, 95% confidence interval; RR, relative risk.Statistically significant results are highlighted in bold.

Long-term follow-up

A long-term follow-up was conducted of the 109 survivors. The median clinical follow-up was 24.3 months (interquartile range, 6.9-49.4 months) with 3 patients (2.8%) lost to follow-up. The clin­ical events occurred at the follow-up are shown on table 3. The overall mortality rate at the long-term follow-up was 23% with 97.2% of deaths due to noncardiac deaths.

Table 3. Events at the long-term follow-up

Patients	N = 106
New acute coronary syndrome	10 (9.2%)
Target lesion revascularization	4 (3.7%)
Stent thrombosis	3 (2.8%)
BARC bleeding type > 2	19 (17.4%)
Stroke	9 (8.3%)
Overall mortality	25 (22.9%)
Cardiovascular mortality	3 (2.8%)
Infection	6 (5.5)
Neoplasm	6 (5.5)
Respiratory failure	5 (4.6)
Unknown	5 (4.6)
BARC, Bleeding Academic Research Consortium.

In the univariate Cox regression analysis, the variables associated with a higher overall mortality rate were Killip Class > I (HR, 4.26; 95%CI, 2.38-7.62; P = .001), chronic kidney disease (HR, 7.24; 95%CI, 1.7-30.8; P = .007), and a Charlson Comorbidity index > 2 (HR, 2.74; 95%CI, 1.18-6.36; P = .019) (table 4). Patients with chronic kidney disease had a higher percentage of cases with Charlson Comorbidity indices > 2, but this difference was not statistically significant (19% vs 28,4%; P = .27).

Table 4. Factors associated with a higher mortality rate at the long-term follow-up. Univariate and multivariate Cox regression analyses

	HR	95%CI	P
Univariate analysis
Age	1.1	0.99-1.23	.076
Sex (woman)	1.66	0.71-3.91	.244
Diabetes Mellitus	1.98	0.89-4.41	.094
Killip Class > I	4.26	2.38-7.62	.001
Moderate-to-severe left ventricular dysfunction	2.16	0.97-4.84	.06
Total ischemic time (hours)	1.05	0.98-1.12	.159
Atrial fibrillation	1.54	0.61-3.9	.361
Charlson Comorbidity index > 2	2.74	1.18-6.36	.019
Chronic kidney disease	7.24	1.7-30.81	.007
Anterior location	1.36	0.77-2.40	.287
Multivessel disease	1.43	0.81-2.53	.214
Incomplete revascularization	1.590	0.898-2.817	.112
Drug-eluting stent	0.949	0.46-1.957	.887
Multivariate analysis
Age	1.07	0.95-1.21	.258
Charlson Comorbidity index > 2	2.57	1.07-6.18	.035
Chronic kidney disease	5.7	1.29-25.5	.022
Killip Class > I	0.96	0.31-2.98	.943
Moderate-to-severe left ventricular dysfunction	1.77	0.77-4.04	.177
95%CI, 95% confidence interval; HR, hazard ratio. Statistically significant results are highlighted in bold.

In the multivariate Cox regression analysis, the only independent predictors of overall mortality were chronic kidney disease (HR, 5.7; 95%CI, 1.29-25.5; P = .022), and a Charlson Comorbidity index > 2 (HR, 2.57; 95%CI, 1.07-6.18; P = .035) (table 4).

Patients with chronic kidney disease had lower survival rates at the long-term follow-up (56 ± 4.4 months vs 75 ± 3 months; P = .002) (figure 2). Patients with Charlson comorbidity indices > 2 also had lower survival rates at the long-term follow-up (45.5 ± 5.9 months vs 65.8 ± 3.3 months; P = .015) (figure 3).

Figure 2. Survival curves at the long-term follow-up stratified based on the presence of chronic kidney disease (log rank test, P = .002). ERC, chronic kidney disease.

Figure 3. Survival curves at the long-term follow-up stratified based on the presence of Charlson comorbidity indices > 2 (log rank test, P = .015).

DISCUSSION

Information on the results of PA in elderly patients and its long-term prognosis is scarce because this group of patients is often misrepresented in clinical trials.6 Our study emphasizes these patients’ high mortality rate (mainly due to cardiac causes)—both in-hospital and at the long-term follow-up—with a significant contribution from noncardiac mortality and comorbidities as prognostic predictors.

This segment of the population has special characteristics that pose an added risk. These are patients with a high prevalence of comorbidities and worse renal function.5 Diagnosis is not always easy because of the atypical symptoms reported and possible presence of previous changes on the EKG, factors that contribute to delaying reperfusion therapy.11 Finally, these are patients with a higher risk of bleeding and other complications during PA.12

Regarding the clinical profile of patients > 80 treated with PA in our center we should mention the higher percentage of women (43%) compared to other series from the general population, and the high prevalence of chronic kidney disease (66%), delays of more than 6 hours (29%), and advanced Killip Class (17%). All these characteristics are consistent with what has already been described by former studies in this population.5,13

Regarding the procedural aspects, the radial access was used in 80.5% of the cases. Elderly patients, especially women, have higher rates of failure with this access, but at the same time, these patients have the highest risk of bleeding with the femoral access. Rodríguez-Leor et al.14 reported on the possibility of achieving radial access in 95.1% in a population of patients > 75 treated with PA.

The in-hospital mortality seen in our study (18) is obviously higher to that of the general population, but not significantly different from that reported by other registries of elderly patients.12-17 In a group of 34 80-year-old patients treated with PA Sim et al.5 reported an in-hospital mortality rate of 18%. However, it went up to 37% in patients with ST-segment elevation acute coronary syndrome not treated with PA. In their prospective registry of 496 patients > 80 who received invasive treatment, Kvakkestad et al.12 reported an in-hospital mortality rate of 13%. In our series the main prognostic factor during admission was the patient’s hemodynamic situation measured using Killip Class. It is a well-known prognostic factor that has been widely described in PA studies.18

The mortality rate at the long-term follow-up was 23% with a striking contribution from noncardiac mortality, which is a differential factor with respect to series from the general population. This lower rate of adverse cardiovascular events in elderly patients who survive a myocardial infarction was found in other registries and may be due to the high early selection during the acute phase.13,17 In the aforementioned registry of Kvakkestad et al.12 the mortality rate at the 3-year follow-up was 29%. In the Swedish registry of 80-year-old patients treated with PA from 2001 to 2010, the annual mortality rate reported was 25%.17 In our series, the fact that mortality at the long-term follow-up was mostly noncardiac contributed to the fact that the main prognostic predictors at the long-term follow-up are extracardiac factors like renal function and the Charlson Comorbidity index. These factors may be understudied at the follow-up after PA.

The effect of comorbidities in the prognosis of patients is often quantified using the Charlson Comorbidity index.7,8 This index assigns a given score to a series of comorbidities based on the risk of mortality of every comorbidity. The overall score is associated with a given mortality risk. Over the last few years, interest has been growing on the analysis of comorbidities and other variables associated with age. However, data are still scarce on their prognostic influence on patients with infarction treated invasively. The existing growing heterogeneity among 80-year-old patients with infarction requires prognostic indices to stratify these patients into risk groups based on uniform criteria. Using a tool to guide us in the long-term prognosis of these patients may help us decide what the most suitable follow-up is. Several studies have proven the utility of the Charlson Comorbidity index in the acute coronary syndrome as a predictor of mortality. Núñez et al. determined the prognostic predictive value of this index in patients with myocardial infarction mostly treated conservatively.19 They found that the comorbidities present at admission were associated with higher rates of mortality or reinfarction at the 30-day and 1-year follow-up. In our series of invasive management, we found that a Charlson Comorbidity index > 2 was an independent predictor of mortality at the long-term follow-up. However, it is not a predictor of patient progression at the hospital setting where the most important thing is the patient’s hemodynamic situation. Therefore, in this population the Charlson Comorbidity index can help us plan their long-term follow-up.

Glomerular filtration rate impairment is a powerful predictor of mortality in different conditions including myocardial infarction.20 Same as it happens with the Charlson Comorbidity index, in our series of patients, renal function impairment was also an independent predictor of long-term mortality. This confirms that a more comprehensive assessment of 80-year-old survivors of a PA including an accurate assessment of comorbidities and renal function can optimize the management of this population after hospital discharge.

Risk stratification and decision-making are especially complex in 80-year-old patients with myocardial infarction because these a highly heterogeneous patients in whom chronological age may not reflect their actual biological situation. In view of our study findings we believe that in elderly patients it is important to include the measurement of the glomerular filtration rate and, above all, the assessment of comorbidities in the decision-making process at the long-term follow-up after PA. The close follow-up of these patients with several comorbidities can help diagnose potential decompensations (both cardiac and noncardiac) to prevent new hospitalizations. On the other hand, comorbidities determine a high use of drugs which favors the appearance of adverse events, interactions, and therapeutic compliance mistakes. The best thing to do would be to maximize compliance in this population, specify the benefits expected, and minimize the risks associated with the therapy used. Also, optimizing the management of noncardiac diseases can be the key to stabilize coronary artery disease. For all this, keeping a close collaboration with geriatric units after the hospital discharge of 80-year-old patients treated with PA improves their prognosis.

Limitations and strengths

Although the demographic, clinical, and angiographic data were collected prospectively, this was a retrospective analysis with the corresponding limitations of this type of studies. The size of the sample may have limited the statistical power of our study to detect the statistical significance of some associations. Also, the low number of events may have limited the reliability of the multivariate analysis regarding in-hospital mortality and mortality at the long-term follow-up since it included 5 variables in each of these 2 analyses. Since this was a single-center study, results may not be generalizable to other settings.

One of the strengths of the study is that results are based on a thorough and consecutive registry of patients from our setting who were hospitalized after a PA. Also, that a great deal of clinical, analytical, and angiographic information was obtained during their hospital stay and several evolutionary variables were registered at the very long follow-up.

CONCLUSIONS

Patients over 80 treated with PA have a high in-hospital mortality rate (18% in our series). The only independent predictor of in-hospital mortality was Killip Class. Over the next 2 years, mortality is still very high (23%), but is basically associated with noncardiac problems. The independent predictors of overall mortality at the long-term follow-up were chronic kidney disease and a Charlson Comorbidity index > 2

FUNDING

None.

AUTHORS’ CONTRIBUTIONS

L. Hernando Marrupe and J. Botas Rodríguez had the study idea. L. Hernando Marrupe, J. Botas Rodríguez, C. Marco Quirós, and R. Gayoso Gayo designed the study. L. Hernando Marrupe, C. Marco Quirós, R. Gayoso Gayo, V. Espejo Bares, V. Artiaga de la Barrera, C. Jiménez Martínez, R. Del Castillo Medina, and A. Núñez García collaborated in the study data mining. L. Hernando Marrupe, and E. Pérez Fernández conducted the statistical analysis. L. Hernando Marrupe, C. Marco Quirós, and R. Gayoso Gayo interpreted the results and wrote the manuscript first draft. L. Hernando wrote the manuscript final version, and J. Botas conducted the manuscript critical review.

CONFLICTS OF INTEREST

None reported.

 

 

REFERENCES