Risk profile and benefits from Gp IIb-IIIa inhibitors among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-regression analysis of randomized trials

Abstract

AimsSeveral randomized trials and a previous meta-analysis have shown significant benefits from Gp IIb-IIIa inhibitors, especially abciximab. Recent randomized trials (BRAVE-3 and HORIZON trials) have shown no benefits from adjunctive Gp IIb-IIIa inhibitors on the top of clopidogrel administration. However, the relatively low mortality may have hampered the conclusion of these recent trials. Thus, the aim of the current study was to perform an update meta-analysis of randomized trials on adjunctive Gp IIb-IIIa inhibitors in primary angioplasty, and to evaluate by meta-regression analysis, whether the results may be related to risk profile.Methods and resultsWe obtained results from all randomized trials evaluating the benefits of adjunctive Gp IIb-IIIa inhibitors among STEMI patients undergoing primary angioplasty. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL) from January 1990 to September 2008. The following key words were used: randomized trial, myocardial infarction, reperfusion, primary angioplasty, Gp IIb-IIIa inhibitors, abciximab, tirofiban, and eptifibatide. Clinical endpoint was mortality at 30 days. Major bleeding complications were assessed as safety endpoint. No language restriction was applied. A total of 16 randomized trials were finally included in the meta-analysis, involving 10 085 patients (5094 or 50.5% in the Gp IIb-IIIa inhibitors group and 4991 or 49.5% in the control group. Gp IIb-IIIa inhibitors did not reduce 30 day mortality (2.8 vs. 2.9%, P = 0.75) or re-infarction (1.5 vs. 1.9%, P = 0.22), but were associated with higher risk of major bleeding complications (4.1 vs. 2.7%, P = 0.0004). However, we observed a significant relationship between patient's risk profile and benefits from adjunctive Gp IIb-IIIa inhibitors in terms of death (P = 0.008) but not re-infarction (P = 0.25).ConclusionThis meta-analysis shows a significant relationship between benefits in mortality from Gp IIb-IIIa inhibitors and patient's risk profile. Thus, Gp IIb-IIIa inhibitors should be strongly considered among high-risk patients.

Glycoprotein IIb/IIIa Antagonists in Acute Coronary Syndromes Undergoing PCI: A Long Way to Select Optimal Agent and Route

“…Upstream GP IIb/IIIa inhibitors did not decrease 30-day mortality (primary endpoint: 2.0% versus 2.0%, P = 0.84) or recurrence of myocardial infarction (secondary endpoint: 7.0% versus 7.6%, P = 0.11) but were associated with higher risk of major bleeding complications (1.8% versus 1.3%, P = 0.0002). It seems therefore ( Table 1) that a strategy of upstream GP IIb/IIIa inhibitors (overall considered) cannot be recommended [2] thus confirming, at least related to the downstream arm of the GP IIb/IIIa inhibitors, previous results obtained by the same authors who meta-analysed 16 randomized trials involving 10085 patients (5094 enrolled in the GP IIb/IIIa inhibitors group versus 4991 patients in the control group) [3]. GP IIb/IIIa inhibitors did not reduce 30-day mortality (2.8 versus 2.9%, P = 0.75) or reinfarction (1.5 versus 1.9%, P = 0.22) but were associated with higher risk of major bleeding complications (4.1 versus 2.7%, P = 0.0004).…”

“…GP IIb/IIIa inhibitors did not reduce 30-day mortality (2.8 versus 2.9%, P = 0.75) or reinfarction (1.5 versus 1.9%, P = 0.22) but were associated with higher risk of major bleeding complications (4.1 versus 2.7%, P = 0.0004). Interestingly, a significant relationship was observed between patient's risk profile and benefits from adjunctive GP IIb/IIIa inhibitors in terms of death (P = 0.008) but not reinfarction (P = 0.25), pointing to the need to consider GP IIb/IIIa inhibitors especially among high-risk patients [2,3].…”

“…There might be elements to justify the decline of GP IIb/IIIa inhibitors use during PCI in recent years, mostly based on the incremental use of clopidogrel (also at high dosage, as discussed above) and aspirin but also on the appearance of new potent and relatively safer antiplatelet agents [1,3,25]. However, 1 of the 3 approved GP IIb/IIIa inhibitors was used in about 39% of PCI procedures during 2008, as reported in June 2010, and the market is still a "big business" with more than $475 million in the US alone in 2008 and definitely much more worldwide [26].…”

Efficacy and Safety of Unfractionated Heparin Plus Glycoprotein IIb/IIIa Inhibitors During Revascularization for an Acute Coronary Syndrome: A Meta‐Analysis of Randomized Trials Performed With Stents and Thienopyridines

“…This is consistent with a recent meta-analysis of GPIs in ST-elevation myocardial infarction did not demonstrate a reduction in myocardial infarction. 7 By including studies of both non-ST-elevation myocardial infarction and ST-elevation myocardial infarction, which are both processes of plaque rupture, our analysis had more than twice as many patients to analyze. Our results largely apply to patients pretreated with a thienopyridine.…”

Mortality Reduction with Administration of Abciximab during Primary PCI is Confined to STEMI Patients with Complex Lesions

“…Still, some centres routinely use abciximab in high-risk ACS patients scheduled for coronary angiography (CAG), hence before the coronary anatomy and nature of the lesion is known. However, the most marked benefits of abciximab are observed among patients with high-risk ACS, such as STEMI, and even more among those with high-risk coronary lesions [8,9].…”