COMFORTABLE AMI Data Support Biolimus-Eluting Stents With Biodegradable Polymer in STEMI Patients

August 22, 2012—In the COMFORTABLE AMI trial, investigators sought to compare stents that elute biolimus from a biodegradable polymer versus bare-metal stents for use in primary percutaneous coronary intervention (PCI). The investigators concluded that compared with a bare-metal stent, the use of biolimus-eluting stents with a biodegradable polymer resulted in a lower rate of composite major adverse cardiac events at 1 year among patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. Lorenz Räber, MD, et al published the study's findings in the Journal of the American Medical Association (JAMA) (2012;308:777–787). 

The background of the study, as stated in JAMA, is that the efficacy and safety of drug-eluting stents compared with bare-metal stents remains controversial in patients with STEMI who undergo primary PCI. COMFORTABLE AMI is a prospective, randomized, single-blinded, controlled trial of 1,161 patients presenting with STEMI at 11 sites in Europe and Israel between September 19, 2009, and January 25, 2011. Patients were randomized 1:1 to receive the biolimus-eluting stent (n = 575) or the bare-metal stent (n = 582). Clinical follow-up was performed at 1 and 12 months. The study's primary endpoint 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.

As summarized in JAMA, the investigators reported that 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% confidence interval [CI], 0.3–0.8; P = .004). The difference was driven by a lower risk of target vessel–related reinfarction (3 [0.5%] vs 15 [2.7%]; HR, 0.2; 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. The rates of cardiac death were not significantly different (16 [2.9%] vs 20 [3.5%]; P = .53). Definite stent thrombosis occurred in five patients (0.9%) treated with biolimus-eluting stents and 12 patients (2.1%) treated with bare-metal stents (HR, 0.42; 95% CI, 0.15–1.19; P = .1), reported the investigators.

In an audio interview available on the JAMA website, COMFORTABLE AMI study Chair Stephan Windecker, MD, of the Bern University Hospital in Bern, Switzerland, discussed the goals of continued investigation into these devices. He commented, “Future research will address several questions. First of all, it is interesting to observe that potentially drug-eluting stents with this biodegradable polymer offer a safety advantage in terms of reducing the incidence of target vessel myocardial infarction. Now, this is a hypothesis that needs to be proven in prospective, adequately designed, large-scale clinical trials. The second objective will be to provide longer-term follow-up all the way through 5 years to see whether these results in terms of benefits and risks bear out during long-term follow-up; and I am convinced we will obtain interesting data. And the third area of future research will actually address even further refined stent platforms, which will use polymers that biodegrade even faster than 6 to 9 months, and are thinner than the current polymer coatings and use drugs at maybe even lower dosages.”

In a JAMA editorial, Salvatore Cassese, MD, and Adnan Kastrati, MD, addressed some of the problems and the promise that have accompanied the increasing use of drug-eluting stents (2012;308:814–815), noting that, “Indeed, in no other setting has drug-eluting stent use elicited as much skepticism as in patients with STEMI,” but the new generation of drug-eluting stents may overcome these problems. They stated, “Two opposite, time-dependent effects have been described for polymers used in drug-eluting stent technology—an early protective effect and a late pro-inflammatory and prothrombotic effect. By their very nature, the biodegradable polymers used in newer-generation drug-eluting stents might offer the early advantages of polymers while avoiding the very late hazards, which may turn out to be especially useful in patients with STEMI.”