Topol EJ for the Epistent Evaluation of Platelet IIbIIIa Inhibitor for Stenting Investigators

Reference

Lancet 1998; 352: 87-92 Abstract

BACKGROUND: Coronary stenting with the use of heparin, aspirin, and ticopidine for thromboprophylaxis is performed in more than 500,000 patients per year worldwide. We did a randomized controlled trial to assess the role of platelet glycoprotein IIb/IIIa blockade for use in elective stenting. METHODS: At 63 hospitals in the USA and Canada, 2399 patients with ischemic heart disease and suitable coronary artery lesions were randomly assigned stenting plus placebo (n = 809), stenting plus abciximab, a IIb/IIIa inhibitor (n = 794), or balloon angioplasty plus abciximab (n = 796). The primary endpoint was a combination of death, myocardial infarction, or need for urgent revascularization in the first 30 days. All patients received heparin, aspirin, and standard pharmacological therapy. FINDINGS: The primary endpoint occurred in 87 (10.8%) of 809 patients in the stent plus placebo group, 42 (5.3%) of 794 in the stent plus abciximab group (hazard ratio 0.48 [95% CI 0.33-0.69] p < 0.001), and 55 (6.9%) of 796 in the balloon plus abciximab group (0.63 [0.45-0.88] p = 0.007). The main outcomes that occurred less with abciximab were death and large myocardial infarction -7.8% in the placebo group, 3.0% for stent plus abciximab (p < 0.001), and 4.7% for balloon angioplasty plus abciximab (p = 0.01). Major bleeding complications occurred in 2.2% of patients assigned stent plus placebo, 1.5% assigned stent plus abciximab, and 1.4% assigned balloon angioplasty plus abciximab (p = 0.38). INTERPRETATION: Platelet glycoprotein IIb/IIIa blockade with abciximab substantially improves the safety of coronary-stenting procedures. Balloon angioplasty with abciximab is safer than stenting without abciximab.

Summary

By 1996, coronary stenting had been adopted as the desired technique for percutaneous intervention. Standard pharmacological prevention of stent thrombosis included heparin, aspirin, and the thienopyridine ticlopidine. The investigators hypothesized that a platelet glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor, superimposed on standard pharmacological prevention, would further improve outcomes in coronary stenting.

In a multicentre, randomized, double-blind, controlled, parallel group trial, 2399 patients were assigned to stenting plus placebo, stenting plus abciximab, or balloon angioplasty plus abciximab. The composite primary endpoint of death, myocardial infarction, or urgent revascularization was tabulated at 30 days.

The primary endpoint was lowest in the stent plus abciximab group (5.3%, hazard ratio 0.48, p < 0.001) and was also reduced in the balloon angioplasty plus abciximab group (6.9%, hazard ratio 0.63, p = 0.007), compared with the stent plus placebo group (10.8%).

Citation Count 838

Related References

1. Serruys PW, de Jaegere P, Kiemeneij F, et al. A comparison of balloon-expandable stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994;331: 489-495.

2. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994; 331: 496-501.

3. Lincoff MA, Califf RM, Moliterno DJ, for the EPISTENT Investigators. Complementary clinical benefits of coronary-artery stenting and blockade of platelet glycoprotein Ilb/IIIa receptors. N Engl J Med 1999; 341: 319-327.

4. Topol EJ, Lincoff AM, Kereiakes DJ, for the EPISTENT Investigators. Multi-year follow-up of abciximab therapy in three randomized, placebo-controlled trials of percutaneous coronary revascularization. Am J Med 2002; 113: 1-6.

Key message

Even with stent implantation and aggressive anti-platelet therapy including aspirin and a thienopyri-dine, blockade of the platelet GP IIb/IIIa receptor with abciximab further reduces adverse cardiac events in patients undergoing placement of an intracoronary stent. This is accomplished primarily by reducing rates of death or large myocardial infarction (MI) (defined as new Q waves or creatinine kinase MB fraction greater than five times the upper limit of normal). Furthermore, balloon angioplasty plus abciximab is safer than the strategy of coronary stenting without the use of abciximab.

Why it's important

The BENESTENT and related studies had demonstrated the superiority of coronary stenting over balloon angioplasty primarily due to a reduction in the need for repeat revascularization. However, this benefit had come with a price tag, namely the problem of subacute stent thrombosis, occurring in 1-3% of patients. Furthermore, some in the interventional community did not believe platelet GP IIb/IIIa blockade to be relevant in the setting of stent implantation. EPISTENT (Evaluation of Platelet IIb/IIIa Inhibitor for Stenting) was the first to evaluate a GP IIb/IIIa receptor blocker, superimposed on the standard anti-thrombotic therapy, in patients undergoing elective coronary stenting, and demonstrated that abciximab reduced major events by more than 50% without an increase in bleeding complications. Furthermore, among 794 patients who received abciximab with stenting, there were no cases of sub-acute thrombosis. Lastly, the benefits of abciximab persisted at 6 months and at 1 year. A mortality benefit was also demonstrated at 1 year.

Strengths

EPISTENT was a well-designed, large, randomized, prospective trial with clearly defined and relevant clinical endpoints. The study addressed an issue of high clinical relevance, namely the utility of GP IIb/IIIa blockade following the paradigm shift from balloon to stent technologies during percutaneous coronary intervention (PCI).

Weaknesses

The number of patients undergoing vein graft angioplasty (n = 51) was too small for definitive evaluation of this subgroup. Relevance of the MI component of the primary endpoint continues to be debated.

Relevance

Simply put, EPISTENT ushered in a new standard of care for prevention of major adverse cardiovascular events with PCI. Potent anti-platelet therapy with abciximab during coronary stent-ing or angioplasty reduces the likelihood of patient death or large MI, without causing an excess in bleeding complications.

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