Stenting with Platelet IIb/IIIa Inhibitors
ABSTRACT & COMMENTARY
Synopsis: Abciximab substantially improves the safety of angioplasty with stenting.
Source: The EPISTENT Investigators. Lancet 1998; 352:87-92.
Because of reduced repeat revascularization rates, coronary stents have become the main approach to coronary revascularization. Prevention of stent thrombosis usually involves the administration of heparin followed by aspirin and ticlopidine for several days. Platelet IIb/IIIa receptor inhibitors have been shown to improve outcomes in balloon angioplasty, but their role with stenting is unclear. Thus, the report of the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial is of interest. The investigators in 63 U.S. and Canadian hospitals randomized 2399 patients undergoing coronary artery revascularization to stenting plus placebo, stenting plus abciximab, or balloon angioplasty plus abciximab. The primary end point was death, myocardial infarction, or urgent re-revascularization within 30 days. All patients received heparin and aspirin, and many received ticlopidine before abciximab administration. The primary end point was lowest in the stent plus abciximab group (5.3%) and the balloon angioplasty plus abciximab (6.9%) vs. the stent plus placebo group (10.8%). Also, death or large myocardial infarction (MI) occurred less frequently in the abciximab groups. In addition, abciximab significantly reduced side branch occlusion compared to placebo. Interestingly, women had better results with angioplasty plus abciximab vs. stenting plus abciximab, which was opposite the results in men. There was no difference in major bleeding complications between the three groups. The investigators conclude that abciximab substantially improves the safety of angioplasty with stenting.
COMMENT BY MICHAEL H. CRAWFORD, MD
Previously published reports from three trials (EPIC, EPILOG, and CAPTURE) have established that better outcomes are obtained with coronary angioplasty of complex lesions or high-risk patients if abciximab is used. Thus, because of the cost of this agent (approximately $1500 per dose), most laboratories have limited its use to such cases. Not surprisingly, this trial of abciximab with routine stenting of all cases shows markedly better 30-day outcomes with the use of the IIb/IIIa inhibitor. Whether the gain will be maintained after 30 days remains to be proven, but it likely will since the major benefit was a 50% reduction in large MI; such an outcome is likely to be of prognostic value for outcomes after 30 days. Consequently, the authors state that "our trial provides strong evidence that the armamentarium of heparin, aspirin, and ticlopidine is insufficient and that a decrease of more than 50% in major events can be achieved with abciximab," and "a new standard of care for prevention of major adverse ischaemic outcomes with percutaneous coronary revascularization procedures has emerged." Strong words to show your hospital administrator. Since about two-thirds of percutaneous coronary procedures involve at least one stent placement, adopting a policy of abciximab for all stent palcements will result in higher procedure costs. Whether the gains in preventing future events will offset these costs has not been shown. My guess is that many health plans will await such data before adopting this "new standard of care."
The fact that the stent placebo group had a slightly higher subsequent event rate than prior balloon angioplasty alone trials makes sense, since the metal stent and side branch occlusions probably increase the incidence of coronary thrombosis. Interestingly, inhibiting this response with abciximab plus aspirin and ticlopidine did not increase major bleeding episodes, although minor episodes did occur more frequently (2.9% vs l.7%). The investigators attributed this to tight control of heparin during the procedure and its discontinuation before sheaths were pulled.
A limitation of this study was the lack of a balloon angioplasty placebo group. Thus, confirmation of the superiority of abciximab in balloon angioplasty could not be assessed in this cohort of patients, which was more inclusive than prior balloon angioplasty trials with abciximab. This deficiency makes it more difficult to understand the better results in women with balloon angioplasty plus abciximab vs. stenting with abciximab. Hospital administrators may argue that women may not need stents if abciximab is used-a nice cost trade-off.