This review concluded that intravenous glycoprotein IIb/IIIa inhibitor drugs can significantly reduce the risk of heart attacks and need for bypass surgery in patients undergoing percutaneous coronary interventions, but can also increase the risk of minor bleeding. This was a well conducted systematic review and the conclusions are likely to be reliable.

To assess the efficacy and safety of intravenous glycoprotein IIb/IIIa inhibitor drugs in patients undergoing percutaneous coronary interventions for the treatment of acute myocardial infarction or acute coronary syndrome.

MEDLINE, EMBASE, BIOSIS Previews, Current Contents and HealthSTAR were searched in November 2001. The authors also used DIALOG alerts on MEDLINE, EMBASE and BIOSIS Previews until April 2004. The Cochrane Library was searched up to 2004. Search terms were reported. No date or language restrictions were applied. The authors also scanned websites of the HTA and related agencies and trial registers (for example NICE, AHRQ, CRD database, LILACS, National Research Register and CMA Infobase). Reference lists of selected studies were searched for additional relevant publications.

Randomised controlled trials (RCTs) comparing glycoprotein IIb/IIIa antagonists (eptifibatide, tirofiban and abciximab) with another glycoprotein IIb/IIIa antagonist or placebo in patients undergoing a percutaneous coronary interventions (PCI) were eligible for inclusion. The included trials had to report outcomes of at least one death, myocardial infarction or revascularisation (or a composite endpoint of at least two of these outcomes). Studies of patients with acute coronary syndromes who were not intended to undergo a PCI were excluded from the review.

Most of the included RCTs assessed abciximab and were placebo controlled. Some studies included concomitant treatments (percutaneous transluminal coronary angioplasty, stenting, balloon angioplasty and heparin). The average age of participants in any treatment arm ranged from 58 to 70 and the majority of patients were male (between 63% and 100%). Among the trials comparing a glycoprotein IIb/IIIa antagonist with placebo or other control (i.e. not head-to-head comparisons of different glycoprotein IIb/IIIa antagonists) 35% of participants had a history of myocardial infarction and 21% had diabetes.

Two reviewers independently selected studies for the review; disagreements were resolved by discussion.

Studies were assessed for validity using a form based on the 5-point Jadad scale, with higher values indicating superior quality.

The authors did not state how the validity assessment was performed.

Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for individual study outcomes. Where possible, data were extracted on an intention-to-treat basis. Data extraction was performed by two reviewers and verified for accuracy by the same reviewers.

The authors did not state how disagreements were resolved.

ORs were combined using a fixed-effect model (in the absence of heterogeneity) and a random-effects model. Results using the random-effects model were reported for all outcomes. Heterogeneity was assessed using the χ² and I² statistics. Numbers needed to treat and numbers needed to harm were calculated for statistically significant outcomes.

Twenty five RCTs were included in the review (n=29,323); 15 trials evaluated abciximab; four trials evaluated eptifibatide; two trials evaluated tirofiban; and four trials were head-to-head comparisons of different glycoprotein IIb/IIIa antagonists. The median quality score was 4 (range 2 to 5) out of a possible 5. Length of follow-up ranged from in-hospital stay to seven years.

Glycoprotein IIb/IIIa antagonists statistically significantly reduced death rates at 30 days after percutaneous coronary interventions (PCI) (OR 0.72, 95% CI: 0.56, 0.94, 16 RCTs) but there was no statistically significant difference at seven days, six months or one year after PCI. They also statistically significantly reduced myocardial infarction rates after PCI at seven days (OR 0.59, 95% CI: 0.46, 0.75, seven RCTs), 30 days (OR 0.63, 95% CI: 0.54, 0.74, 17 RCTs) and six months (OR 0.65, 95% CI: 0.55, 0.77, 12 RCTs).

Glycoprotein IIb/IIIa antagonists statistically significantly reduced the need for revascularisation after PCI at seven days (OR 0.43, 95% CI: 0.29, 0.84, six RCTs), 30 days (OR 0.66, 95% CI: 0.56, 0.77, 16 RCTs) and six months (OR 0.86, 95% CI: 0.78, 0.94, 12 RCTs). The risk of the composite end point after PCI was also statistically significantly reduced at seven days (OR 0.61, 95% CI: 0.50, 0.75, six RCTs), 30 days (OR 0.64, 95% CI: 0.56, 0.75, 15 RCTs) and six months (OR 0.73, 95% CI: 0.63, 0.86, 12 RCTs). The pooled estimates at 30 days and six months were associated with significant heterogeneity.

However, glycoprotein IIb/IIIa antagonists were also associated with a statistically significant increase in minor bleeding (OR 1.80, 95% CI: 1.47, 2.21, 13 RCTs) and thrombocytopenia (OR 1.41, 95% CI: 1.10, 1.81, 11 RCTs). There was no statistically significant increase in major bleeding.

The results of the head to head trials only included a small number of patients and were underpowered to show statistically significant differences between treatment groups.

Results were also presented for abciximab, eptifibatide and tirofiban separately. Results for numbers needed to treat and numbers needed to harm were presented in the report.

Glycoprotein IIb/IIIa inhibitor drugs significantly reduce myocardial infarction and the need for revascularisation at seven days, 30 days and six months after a percutaneous coronary intervention (PCI). The majority of evidence relates to abciximab treatment, which significantly reduces the death rate at 30 days after a PCI. Eptifibatide and tirofiban are not associated with a significant reduction in the risk of death. Small trials failed to show superiority of eptifibatide and tirofiban over abciximab. The benefits of glycoprotein IIb/IIIa inhibitor drugs must be weighed against the potential for a significant increase in minor bleeding.

The review addressed a clear question and was supported by appropriate inclusion criteria. A number of electronic databases and other sources were searched to identify relevant studies, with no language restrictions, reducing the potential for publication and language bias. Study validity was assessed using appropriate criteria and the median quality score was relatively high. Study selection and data extraction were performed in duplicate, reducing the potential for reviewer bias and error but the authors did not state how validity assessment was performed. Adequate study details were presented. Appropriate methods were used to combine studies and assess statistical heterogeneity. The authors acknowledged the variation in study inclusion and exclusion criteria and dosing regimens as limitations of the review. This was a well conducted systematic review and the authors' conclusions are likely to be reliable.

Practice: The authors stated that physicians should pay attention to the balance between the benefits of reduced cardiovascular events and the risk of increased complications when considering use of glycoprotein IIb/IIIa antagonists, owing to the significant increase in minor bleeding.

Research: The authors did not state any implications for further research.

Canadian Coordinating Office for Health Technology Assessment.

Labinaz M, Ho C, Banerjee S, et al. Meta-analysis of clinical efficacy and bleeding risk with intravenous glycoprotein IIb/IIIa antagonists for percutaneous coronary intervention. Can J Cardiol 2007;23:963-70.

This record is a structured abstract produced by CRD. The original has met a set of quality criteria. Since September 1996 abstracts have been sent to authors for comment. Additional factual information is incorporated into the record. Noted as [A:....].