Two-Year Clinical Outcomes of the REVELATION Study: Sustained Safety and Feasibility of Paclitaxel-Coated Balloon Angioplasty Versus Drug-Eluting Stent in Acute Myocardial Infarction

Objectives. The randomized REVELATION (REVascularization With PaclitaxEL-Coated Balloon Angioplasty Versus Drug-Eluting Stenting in Acute Myocardial InfarcTION) trial showed that in the setting of ST-segment elevation myocardial infarction (STEMI), a drug-coated balloon (DCB) strategy was non-inferior to a drug-eluting stent (DES) strategy in terms of fractional flow reserve assessed at 9 months. The aim of the present study is to evaluate the long-term clinical outcome of this treatment strategy. Methods. Between October 2014 and November 2017, a total of 120 patients with a non-severely calcified culprit lesion in a native coronary artery and a residual stenosis of <50% after predilation were randomized to treatment with DCB or DES. Primary clinical endpoint was the occurrence of major adverse cardiac events, defined as death, recurrent myocardial infarction, or target-lesion revascularization, the occurrence of definite ST, and non-coronary artery bypass grafting (CABG) major bleeding. Results. Complete clinical follow-up at 2 years was available for 109 patients (91%). A major adverse cardiac event occurred in 3 patients (5.4%) in the DCB group and 1 patient (1.9%) in the DES group (hazard ratio, 2.86; 95% confidence interval, 0.30-27.53; P=.34). Between 9 months and 2 years, only 1 additional event occurred (target-lesion revascularization in a patient randomized to DCB). Conclusion. In this randomized study of DCB vs DES in selected patients presenting with STEMI, 2-year clinical outcome was excellent and comparable between the DCB and DES groups.

J INVASIVE CARDIOL 2022;34(1):E39-E42. Epub 2021 November 18.

Key words: drug-coated balloon, drug-eluting stent, percutaneous coronary intervention, STEMI

In patients with ST-segment elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) using a drug-eluting stent (DES) is the preferred reperfusion strategy.^1,2 However, routine stenting has not been shown to reduce the incidence of cardiac death and recurrent myocardial infarction (MI) when compared with balloon angioplasty.^3,4 Additionally,  incomplete stent apposition and impaired stent coverage are more frequently observed than in elective patients and are associated with an increased risk of long-term stent-related events.^5-7

Therefore, alternative strategies aimed at not implanting a permanent vascular scaffold are of great interest. The use of a bioresorbable vascular scaffold (BVS), designed to provide transient mechanical support and drug delivery, failed as an alternative to DES as it was associated with a higher risk of stent thrombosis (ST) and recurrent MI.^8-10 A drug-coated balloon (DCB) strategy would succeed in the purpose of truly leaving nothing behind. DCB angioplasty has been shown to be an efficacious and safe treatment strategy for in-stent restenosis and small-vessel disease.^11-13 Only a few (mostly non-randomized) studies have evaluated the use of a DCB strategy in primary PCI, with limited clinical follow-up.^14-17

The REVELATION (REVascularization With PaclitaxEL-Coated Balloon Angioplasty Versus Drug-Eluting Stenting in Acute Myocardial InfarcTION) trial was the first prospective, randomized, controlled trial comparing DCB vs DES strategies in patients presenting with STEMI.¹⁸ At 9-month follow-up, the DCB strategy was non-inferior compared with DES regarding the primary endpoint of fractional flow reserve (FFR). In addition, there was no significant difference in late lumen loss.¹⁹ Long-term clinical follow-up is essential to further evaluate safety and efficacy. We therefore analyzed clinical outcomes at 2 years after enrollment in the REVELATION trial.

Study design and patients. The REVELATION trial’s design, methods, and 9-months results have been published elsewhere.^18,19 In summary, it was a prospective, 1:1 randomized controlled trial performed in the OLVG Hospital in Amsterdam, the Netherlands, in which we assessed the safety and efficacy of DCB angioplasty in STEMI. Patients presenting with a STEMI were found eligible for randomization if imaging indicated a de novo, non-severely calcified culprit lesion, with a residual stenosis <50% after thrombus aspiration (in case of visible thrombus) and mandatory predilation. In case of randomization to the DCB only strategy, the CE-marked Pantera Lux paclitaxel-coated balloon (Biotronik) was used. Bail-out stenting with a bare-metal stent was advised only in cases of >50% residual stenosis in the treated lesion or coronary artery dissection type C or higher leading to (threatening) vessel closure.²⁰ In case of randomization to the DES strategy, a third-generation DES was used, preferably the Orsiro sirolimus-eluting stent (Biotronik). All patients were treated according to current European guidelines and received dual-antiplatelet therapy for 1 year.¹

Angiographic and clinical follow-up were performed at 9 months (results previously published).¹⁹ Current clinical follow-up data were collected by telephone interview at 2 years after randomization. All patients gave written informed consent.

The study was conducted in accordance with the conditions stated by the Declaration of Helsinki, Good Clinical Practice guidelines, and applicable local requirements. The trial was approved by the medical ethics committee, “Verenigde commissies mensgebonden onderzoek” (Nieuwegein, The Netherlands) and the institutional review board of the OLVG, and is registered at www.ClinicalTrials.gov (identifier: NCT02219802).

Endpoints. The primary endpoint of the present study included major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent MI, and ischemia-driven target-lesion revascularization (TLR). Secondary endpoints were the occurrence of definite ST and non-coronary artery bypass grafting (CABG) major bleeding. All endpoint definitions were according to the Academic Research Consortium consensus; a full description was provided in the design article.^18-20 Clinical outcomes of interest were confirmed by source documentation and were adjudicated by an independent clinical events committee.

Patient and public involvement. This study was conducted without patient or public involvement. Patients were not involved in the design of this study and were not involved in the interpretation of the results. Patients were not invited to contribute to the writing or editing of this document.

Statistical analysis. Continuous variables are presented as mean ± standard deviation in case of normal distribution or as median (interquartile range) if not normally distributed. Categorical variables are presented as proportions and percentages. Categorical outcomes were compared with Chi-square or Fisher’s exact test. A 2-sided P-value of <.05 was considered to be statistically significant. Cumulative event rates were estimated using the Kaplan-Meier method and compared with the log-rank test. All analyses were performed according to the intention-to-treat principle. Data processing and statistical analysis were performed using the SPSS Statistics, version 26.0 (IBM Corporation).

Patient and procedural characteristics. Between October 2014 and November 2017, a total of 120 patients were included and randomized to receive either DCB or DES. The baseline clinical and procedural characteristics are depicted in Table 1. No significant differences were seen between the 2 groups. The mean age was 57.4 years and 87% of the patients were men. Bail-out stenting was required in 11 of the 60 DCB patients (18%), mainly due to coronary artery dissection ≥ type C.

Clinical follow-up at 2 years. At 2-year follow-up, vital status was available for all patients and no deaths were reported. Clinical follow-up regarding other endpoints was available for 109 out of 120 patients (91%) (Table 2). The occurrence of a clinical endpoint was observed in 3 patients in the DCB group and 1 patient in the DES group (hazard ratio, 2.86; 95% confidence interval, 0.30-27.53; P=.34) (Figure 1). Only 1 additional event was reported between 9-month and 2-year follow-up. This patient, allocated to DCB angioplasty, required bail-out stenting during the index procedure due to a spiral dissection after balloon inflations. TLR was indicated due to in-stent restenosis leading to an acute coronary syndrome at 561 days after implantation. No non-CABG major bleedings were reported.

The REVELATION trial is the first prospective, randomized, controlled trial comparing DCB angioplasty with stenting in patients presenting with STEMI. Previously, we presented non-inferiority of the DCB strategy with regard to the primary endpoint FFR at 9-month follow-up. The present study shows an excellent clinical outcome after DCB angioplasty without stenting up to 2 years. To our knowledge, this is the most extensive clinical follow-up of the use of DCB in primary PCI to date. Although the study population was relatively small and consisted of selected patients without extensive calcification and with a good response to proper predilation, there was no apparent risk of very late restenosis or recurrent MI in the treated segment.

Beyond the index hospitalization, only 3 clinical events were observed in both groups up to 2 years of follow-up, which included 2 cases of in-stent restenosis. These results correspond with the angiographic findings obtained at 9 months, by showing sustained safety and feasibility of both DCB angioplasty and DES in STEMI. The overall clinical event rate in this study is low compared with other studies evaluating the use of DCB during primary PCI.^14-17 This may be explained by the low risk profile of patients as they were relatively young and often had a preserved left ventricular function after their index event. Although the low event rate may hamper a proper comparison with DES in this study, the good long-term outcomes of these patients may serve as one of the primary reasons to consider a “leave nothing behind” strategy.

In recent years, several studies proved that DCB angioplasty is safe and efficacious when compared with stenting, varying from treatment of patients with high bleeding risk to patients presenting with acute coronary syndromes.^21,22 Our current findings support the use of DCB angioplasty without stenting in STEMI, as long as proper patient selection is applied. Meanwhile, DCB technology is evolving, demonstrated by improvements in balloon design and the recent addition of the antiproliferative drug sirolimus as an alternative to paclitaxel.²³ Theoretically, sirolimus has some advantages compared with paclitaxel and shows similar angiographic results, but so far evidence is limited.^24-28 Given these developments and the increasing evidence acquired from randomized trials, the “leave nothing behind” strategy should be considered as a valuable alternative to stenting in everyday practice, provided this is substantiated by properly sized randomized trials powered for clinical endpoints.   

Study limitations. There are some limitations to the present study. First, the sample size and power calculations were performed to evaluate the primary endpoint. The study was not powered to show differences in clinical outcomes. Therefore, no firm conclusions can be drawn based on the present results. Second, the study was performed in a selected group of patients in which culprit lesions were judged suitable for DCB based on the response to predilation and the absence of calcification.

Our current study provides insights into the long-term clinical outcomes of the use of DCB angioplasty in patients presenting with STEMI. A DCB strategy was feasible, with sustained safety comparable to DES up to 2 years of follow-up. The results of our study suggest the efficacy of a strategy of truly leaving nothing behind in selected STEMI patients, but this needs to be confirmed in an adequately powered randomized trial.

• Paclitaxel Drug-Coated Balloon for the Treatment of De Novo Small-Vessel and Restenotic Coronary Artery Lesions: 12-Month Results of the Prospective, Multicenter, Single-Arm PREVAIL Study
• Paclitaxel Drug-Coated Balloon After Bare-Metal Stent Implantation, an Alternative Treatment to Drug-Eluting Stent in High Bleeding Risk Patients (The Panelux Trial)
• Comparative Effectiveness Study of Drug Eluting and Bare Metal Peripheral Artery Stents in Endovascular Femoropopliteal Artery Revascularization