Review: Glycoprotein IIb/IIIa-receptor antagonists reduce combined death or MI in patients with ischemic heart disease
ACP J Club. 1999 July-Aug;131:4. doi:10.7326/ACPJC-1999-131-1-004
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• Correction: Glycoprotein IIb/IIIa-receptor antagonists reduce combined death or MI in patients with ischemic heart disease
Kong DF, Califf RM, Miller DP, et al. Clinical outcomes of therapeutic agents that block the platelet glycoprotein IIb/IIIa integrin in ischemic heart disease. Circulation. 1998 Dec 22/29;98:2829-35.
In patients with ischemic heart disease, do intravenous glycoprotein IIb/IIIa-receptor antagonists reduce death, myocardial infarction (MI), and the need for revascularization?
Randomized controlled trials were identified with MEDLINE (1980 to 1997) by using the terms platelet and random-, inhibi-, or block-, with various term endings. Unpublished studies from public presentations were also collected.
Blinded studies were selected if parenteral glycoprotein IIb/IIIa-receptor antagonists were studied and data on death, MI, or revascularization were provided.
Data were extracted on study duration, indication for treatment, infusion and dose, use of heparin, and primary end points (death; death or MI; and death, MI, or revascularization).
10 trials of percutaneous interventions (4 studied abciximab, 3 studied eptifibatide, and 2 studied tirofiban) and 6 trials of acute coronary syndromes were identified (2 each studied epitifibatide, tirofiban, and lamifiban). 32 135 patients were included. Overall, mortality was reduced at 48 to 96 hours (odds ratio 0.70, 95% CI 0.51 to 0.96, P < 0.03) but not at 30 days or at 6 months. Combined end points were reduced at all times (6-mo data are provided in the Table) (P < 0.01 for all comparisons). For percutaneous intervention and acute coronary syndrome studies, death was not reduced but combined end points were reduced at all times (Table) (P < 0.01 for all comparisons). Heterogeneity was detected in the percutaneous intervention trials.
Platelet glycoprotein IIb/IIIa-receptor antagonists reduce the combined end points of death or MI and death, MI, or revascularization in patients with ischemic heart disease.
Source of funding: Not stated.
For correspondence: Dr. R.M. Califf, Duke Clinical Research Institute, 2024 W. Main Street, Durham, NC 27705, USA. FAX 919-668-7000.
Table. Glycoprotein IIb/IIIa-receptor antagonists vs control for ischemic heart disease†
|Outcomes at 6 mo||Studies||Odds ratio (95% CI)||NNT (CI)|
|Death||All||0.97 (0.86 to 1.10)||Not significant|
|Death or MI||All||0.82 (0.74 to 0.91)||50 (36 to 91)|
|Death, MI or RV||All||0.89 (0.84 to 0.94)||44 (31 to 84)|
|Death||PI||0.90 (0.70 to 1.16)||Not significant|
|Death or MI||PI||0.76 (0.64 to 0.91)||44 (28 to 111)|
|Death, MI, or RV||PI||0.87 (0.80 to 0.95)||36 (23 to 84)|
|Death||ACS||1.00 (0.87 to 1.15)||Not significant|
|Death or MI||ACS||0.88 (0.79 to 0.97)||63 (38 to 250)|
|Death, MI, or RV||ACS||0.90 (0.83 to 0.97)||50 (28 to 250)|
†ACS = acute coronary syndrome; MI = myocardial infarction; PI = percutaneous intervention; RV = revascularization. Other abbreviations defined in Glossary; NNT and its CI calculated from data in articles.
The meta-analysis by Kong and colleagues confirms the results of randomized controlled trials that studied glycoprotein IIb/IIIa-receptor antagonists. First, it shows that a short intravenous infusion of these drugs reduces the combined outcome of death or MI for up to 6 months after patients have percutaneous interventions for ischemic heart disease or the acute coronary syndrome. Second, the benefit seems to be limited to the period of administration. This result is supported by the pharmacologic and pharmacokinetic properties of the drugs studied and by the pathophysiology of acute coronary events in ischemic heart disease.
This meta-analysis did not address 2 issues that are important for clinicians who may prescribe these drugs: The benefit of these agents might be greater in patients who have percutaneous coronary interventions and in men (1). The study of eptifibatide that provides these data was not included in the meta-analysis. The data with which to address these issues are available in the included studies or could have been obtained from the investigators.
To determine whether glycoprotein IIb/IIIa-receptor antagonists should be used routinely, we need to know more. We need to obtain a precise estimate of the bleeding rate. In addition, because the meta-analysis by Kong and colleagues does not distinguish between drug differences in the various diseases studied, physicians should be given data on other issues relevant to the decision-making process, such as cost and adverse effects.
Another, more general point deserves consideration. Is revascularization a relevant outcome? The decision to use revascularization is not standardized. For patients with acute or stable coronary syndrome, the rate of revascularization varies widely across geographic regions. Revascularization is more likely to occur in patients with previous percutaneous coronary interventions. Thus, the results of clinical trials that use the combined outcome of death, MI, or revascularization are less informative than they seem to be.
Jean-Pierre Boissel, MD
Université Claude BernardLyon, France
1. Boissel JP. Commentary on "Eptifibatide reduced mortality plus nonfatal myocardial infarctions in acute coronary syndromes." ACP J Club. 1999;130:1. Comment on: The PURSUIT Trial Investigators. Inhibition of platelet glcyoprotein IIB/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med. 1998 Aug 13;339:436-43.