The authors concluded that abciximab reduces death and reinfarction rates in patients undergoing primary stenting for acute ST-elevation myocardial infarction. The evidence presented appears to support the authors’ conclusion, but poor reporting of review methods means it is difficult to confirm their reliability.

To evaluate the long-term effects of glycoprotein (GP) IIb/IIIa inhibition in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary interventions and stenting.

MEDLINE and the Cochrane CENTRAL Register were searched. In addition, the reference lists of studies and reviews were screened and proceedings of meetings checked for studies published in the last 10 years.

Study designs of evaluations included in the review

The review included individual patient data (IPD) from randomised controlled trials (RCTs) with at least 1 year’s follow-up. Trial investigators had to be willing to share IPD. The duration of follow-up in the included studies was 1 or 3 years.

Specific interventions included in the review

Studies that compared GP IIb/IIIa inhibitors with no GP IIb/IIIa inhibitors were eligible for inclusion. All of the included studies evaluated abciximab (0.25 mg/kg bolus followed by a 0.125 microg/kg per minute infusion, up to a maximum of 10 microg/minute, over 12 hours).

Participants included in the review

Studies of patients with clinically defined STEMI treated with reperfusion therapy without fibrinolytic agents and with primary stenting were eligible for inclusion; studies had to use no angiographic selection criteria. The included studies enrolled patients within 6, 12 or 48 hours of chest pain. The patients in the included studies had moderate- to high-risk characteristics (acute anterior myocardial infarction 41%, cardiogenic shock 8.4% and previous coronary artery bypass grafting 3.1%), and most were male (78%). Between 53% and 70% of patients were diabetics. All patients in the included studies received aspirin and unfractionated heparin in addition to thienopyridine after stenting. Bare stents were used in all patients.

Outcomes assessed in the review

Studies that assessed death (from any cause) and reinfarction were eligible for inclusion. The primary review outcome was a composite of death or reinfarction. The review also assessed individual outcomes (death, reinfarction and major bleeding). The trial investigators’ definitions of reinfarction were accepted.

How were decisions on the relevance of primary studies made?

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

For each study, consistency and completeness checks of data were performed. Any discrepancies were resolved through direct contact with the trial investigators. The authors did not state how many reviewers performed the checks.

The trial investigators were asked for the following IPD: baseline characteristics; allocated treatment; and date of randomisation, last follow-up and outcome events of interest. Results from preliminary analyses were compared with published results. Any discrepancies were resolved through direct contact with the trial investigators. The authors did not state how many reviewers were involved in comparing the results. Intention-to-treat data were used in the analyses.

How were the studies combined?

For each outcome, cumulative hazard rates (RRs) with 95% confidence intervals (CIs) were calculated using a frailty Cox regression model with a random treatment/study interaction. Pooled analyses were censored at 3 years’ follow-up. Where there was a significant difference between treatments, the number-needed-to-treat (NNT) to avoid one event over 3 years was calculated with its 95% CI. Differences in bleeding rates between treatments were compared using Fisher’s exact test.

How were differences between studies investigated?

The statistical significance of the study/treatment interaction was tested. Analyses were repeated using a fixed-effect model. The influence of the following factors was examined using a priori subgroup analysis: gender, risk factors, type of myocardial infarction, and shock.

Three RCTs (n=1,101) were included.

All of the studies were placebo-controlled and one was double-blinded.

Abciximab was associated with a statistically significant reduction in the cumulative hazard rate for death or reinfarction compared with placebo: 12.9% versus 19.0%; (RR 0.633, 95% CI: 0.452, 0.887, p=0.008); no significant study/treatment interaction was found. The NNT to prevent one death or reinfarction was 19 (95% CI: 11, 135).

Abciximab was associated with a reduction in the cumulative hazard rate for death at the limit of statistical significance (10.8% versus 14.3%; RR 0.695, 95% CI: 0.482, 1.003, p=0.052) and a statistically significant reduction in the cumulative hazard rate for reinfarction (2.25% versus 5.5%; RR 0.41. 95% CI: 0.203, 0.831. p=0.013; NNT to prevent one re-infarction was 31, 95% CI: 18, 133).

There was no statistically significant difference between abciximab and placebo in the rate of major bleeding: 14 patients in the abciximab group versus 11 in the placebo group (p>0.5).

In control treatment arms, death or cumulative MI rates and death rates were four times higher among diabetics compared with nondiabetics: 54% versus 13.5% and 39.7% versus 10.1%, respectively.

The subgroup analysis showed that, in diabetics, abciximab was associated with a significant reduction in death or reinfarction compared with placebo (RR 0.525, 95% CI: 0.303, 0.911, p=0.022); the NNT was 6 (95% CI: 4, 64). In hypertensive patients, abciximab was associated with a significant reduction in reinfarction (RR 0.210, 95% CI: 0.06, 0.738, p=0.015) and death or reinfarction (RR 0.562, 95% CI: 0.358, 0.882, p=0.012) compared with placebo.

Abciximab reduces death and reinfarction rates in patients undergoing primary stenting for acute STEMI.

The review addressed a clear question that was defined in terms of the participants, intervention, outcomes and study design. Several relevant sources were searched but, since no specific attempts to minimise either publication or language bias were reported, relevant studies might have been missed. The methods used to select studies were not described, so it is not known whether any efforts were made to reduce reviewer error and bias. The validity of the eligible studies was assessed by checking IPD from each study and resolving discrepancies with the trial investigators; however, the number of reviewers involved in this process was not reported. The data were pooled using appropriate methods and relevant subgroup analyses were conducted. The evidence presented appears to support the authors’ conclusion, but incomplete reporting of review methods means it is difficult to confirm their reliability.

Practice: The authors stated that the 0.6% absolute increase in major bleeding associated with abciximab could be reduced by more cautious heparin dosing, taking increased care with sheath management or using a transradial approach.

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

Not stated.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.