Cordis Cypher SES Studied in PRECOMBAT to Treat Unprotected Left Main Disease

April 4, 2011—Data from the PRECOMBAT study were presented at the American College of Cardiology's 60^th annual scientific session in New Orleans and concurrently published by Seung-Jung Park, MD, et al online ahead of print in The New England Journal of Medicine. 

The primary objective of the PRECOMBAT trial is to establish the safety and effectiveness of coronary stenting with the sirolimus-eluting balloon-expandable stent (Cypher, Cordis Corporation, Bridgewater, NJ) compared with bypass surgery for the treatment of an unprotected left main coronary artery (LMCA) stenosis. The investigators noted that although coronary artery bypass grafting (CABG) has been considered the treatment of choice, percutaneous coronary intervention (PCI) is increasingly used to treat unprotected LMCA stenosis.

As detailed in The New England Journal of Medicine, the investigators randomly assigned patients with unprotected LMCA stenosis to undergo CABG (300 patients) or PCI with sirolimus-eluting stents (300 patients). Using a wide margin for noninferiority, they compared the groups with respect to the primary composite endpoint of major adverse cardiac or cerebrovascular events (death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization) at 1 year. Event rates at 2 years were also compared between the two groups.

The investigators reported that the primary endpoint occurred in 26 patients assigned to PCI compared to 20 patients assigned to CABG (cumulative event rate, 8.7% vs 6.7%; absolute risk difference, two percentage points; 95% confidence interval [CI], –1.6 to 5.6; P = .01 for noninferiority). By 2 years, the primary endpoint had occurred in 36 patients in the PCI group compared to 24 in the CABG group (cumulative event rate, 12.2% vs 8.1%; hazard ratio (HR) with PCI, 1.5; 95% CI, 0.9–2.52; P = .12). The composite rate of death, myocardial infarction, or stroke at 2 years occurred in 13 and 14 patients in the two groups, respectively (cumulative event rate, 4.4% and 4.7%, respectively; HR, 0.92; 95% CI, 0.43–1.96; P = .83). Ischemia-driven target-vessel revascularization occurred in 26 patients in the PCI group compared to 12 patients in the CABG group (cumulative event rate, 9% vs 4.2%; HR, 2.18; 95% CI, 1.1–4.32; P = .02).

The investigators concluded that in this randomized trial involving patients with unprotected LMCA stenosis, PCI with sirolimus-eluting stents was shown to be noninferior to CABG with respect to major adverse cardiac or cerebrovascular events. However, the noninferiority margin was wide, and the results cannot be considered clinically directive.

“In spite of higher revascularization after angioplasty, it can be a potential alternative if the two treatments have a similar risk of hard endpoints, such as death, heart attack, or stroke,” commented Dr. Park. “At the time this study was initiated, there was great enthusiasm about the outcomes of angioplasty, and as a result, off-label use rapidly spread without enough evidence. Therefore, initiation of a randomized study was urgent.”

“Our study endpoints included safety and efficacy outcomes. The incidences of death, heart attack, and stroke—which are indicators of safety and have a significant impact on mortality – were comparable,” said Dr. Park. “Although angioplasty did have a higher risk of TVR, this efficacy endpoint does not have a direct association with mortality and thus has a less significant implication than the safety outcomes. Therefore, we can conclude that angioplasty can be a feasible alternative to CABG surgery.”