Effect of biolimus-eluting stents with biodegradable polymer vs bare-metal stents on cardiovascular events among patients with acute myocardial infarction: the COMFORTABLE AMI randomized trial.

CONTEXT: The efficacy and safety of drug-eluting stents compared with bare-metal stents remains controversial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). OBJECTIVE: To compare stents eluting biolimus from a biodegradable polymer with bare-metal stents in primary PCI. DESIGN, SETTING, AND PATIENTS: A prospective, randomized, single-blinded, controlled trial of 1161 patients presenting with STEMI at 11 sites in Europe and Israel between September 19, 2009, and January 25, 2011. Clinical follow-up was performed at 1 and 12 months. INTERVENTION: Patients were randomized 1:1 to receive the biolimus-eluting stent (n = 575) or the bare-metal stent (n = 582). MAIN OUTCOME MEASURES: Primary end point was the rate of major adverse cardiac events, a composite of cardiac death, target vessel-related reinfarction, and ischemia-driven target-lesion revascularization at 1 year. RESULTS: Major adverse cardiac events at 1 year occurred in 24 patients (4.3%) receiving biolimus-eluting stents with biodegradable polymer and 49 patients (8.7%) receiving bare-metal stents (hazard ratio [HR], 0.49; 95% CI, 0.30-0.80; P = .004). The difference was driven by a lower risk of target vessel-related reinfarction (3 [0.5%] vs 15 [2.7%]; HR, 0.20; 95% CI, 0.06-0.69; P = .01) and ischemia-driven target-lesion revascularization (9 [1.6%] vs 32 [5.7%]; HR, 0.28; 95% CI, 0.13-0.59; P < .001) in patients receiving biolimus-eluting stents compared with those receiving bare-metal stents. Rates of cardiac death were not significantly different (16 [2.9%] vs 20 [3.5%], P = .53). Definite stent thrombosis occurred in 5 patients (0.9%) treated with biolimus-eluting stents and 12 patients (2.1%; HR, 0.42; 95% CI, 0.15-1.19; P = .10) treated with bare-metal stents. CONCLUSION: Compared with a bare-metal stent, the use of biolimus-eluting stents with a biodegradable polymer resulted in a lower rate of the composite of major adverse cardiac events at 1 year among patients with STEMI undergoing primary PCI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00962416.

Selective use of contemporary drug-eluting stents in primary angioplasty for ST-elevation myocardial infarction: pooled analysis of COMFORTABLE AMI and EXAMINATION.

AIMS: Selective use of DES only in patients at higher risk of MACE is common practice, particularly in healthcare systems with a large premium payable for DES. We aimed to identify subgroups of patients in which the use of BMS in primary percutaneous coronary intervention (PPCI) for STEMI can still be justified. METHODS AND RESULTS: We performed a patient-level pooled analysis of COMFORTABLE AMI and EXAMINATION comparing contemporary DES with BMS in PPCI. A risk score was applied using three parameters: lesion length >15 mm, vessel size <3 mm, and diabetes mellitus. Individual data were available for 2,655 patients. The incidence of MACE at one year was incrementally higher in patients with risk scores of 1 or 2/3. MACE rates were lower in patients with a risk score 0 or 1 who were treated with DES (p=0.0073 and p=0.008). No difference in death or reinfarction was seen between DES and BMS in any group. There was a significant reduction in TLR with DES in all three groups. CONCLUSIONS: A score comprising vessel size, lesion length, and diabetes did not identify patients at low risk with equivalent or better results from BMS use. The results suggest that the practice of only selective use of DES in primary PCI should be discouraged.

Comparison of biolimus eluted from an erodible stent coating with bare metal stents in acute ST-elevation myocardial infarction (COMFORTABLE AMI trial): rationale and design.

AIMS: Compared with bare metal stents (BMS), early generation drug-eluting stents (DES) reduce the risk of revascularisation in patients with ST-elevation myocardial infarction (STEMI) at the expense of an increased risk of very late stent thrombosis (ST). Durable polymer coatings for controlled drug release have been identified as a potential trigger for these late adverse events and this has led to the development of newer generation DES with durable and biodegradable polymer surface coatings with improved biocompatibility. In a recent all-comers trial, biolimus-eluting stents with a biodegradable polymer surface coating were found to reduce the risk of very late ST by 80% compared with sirolimus-eluting stents with durable polymer, which also translated into a lower risk of cardiac death and myocardial infarction (MI) beyond one year. METHODS AND RESULTS: The multicentre COMFORTABLE AMI trial (NCT00962416) randomly assigned 1,161 patients to treatment with biolimus-eluting stents with biodegrable polymer and bare metal stents of otherwise identical design at 11 international sites. The primary endpoint is a composite of cardiac death, target-vessel MI and target lesion revascularisation at one year. Assuming a relative risk reduction of 40% in event rates of the primary endpoint in favour of biolimus-eluting stents with biodegradable polymer, 1,064 patients will provide 80% power to demonstrate superiority. Clinical follow-up will be continued through five years. CONCLUSIONS: The COMFORTABLE AMI trial will determine whether biolimus-eluting stents with biodegradable polymer are superior to bare metal stents of otherwise identical design. This is the first randomised controlled trial (RCT) investigating DES with a biodegradable polymer surface coating for drug release in the treatment of patients with STEMI.