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Indirect comparison meta-analysis of aspirin therapy after coronary surgery |
Lim E, Ali Z, Ali A, Routledge T, Edmonds L, Altman D G, Large S |
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CRD summary This review evaluated the efficacy of low and medium dose aspirin therapy after coronary surgery. Limited evidence showed that medium-dose aspirin may more successfully reduce graft occlusion than low-dose regimens in the first year after coronary surgery. No formal exploration of the differences between included studies is reported, and without this the results should be interpreted with caution.
Authors' objectives To evaluate the efficacy of low- and medium-dose aspirin therapy on graft patency after coronary surgery by using an indirect comparison meta-analysis.
Searching MEDLINE (from 1966 to April 2003) and EMBASE (from 1974 to week 17, 2003) were searched; the search terms were listed. In addition, the Cochrane Controlled Trials Register, the National Research Register, and trial sites on the Internet were searched for further articles. The reference lists of all relevant studies were checked, and experts in the area were contacted. There were no language restrictions, and abstracts and conference proceedings were included.
Study selection Study designs of evaluations included in the reviewRandomised controlled trials (RCTs) were eligible for inclusion.
Specific interventions included in the reviewStudies that compared medium- or low-dose aspirin with placebo were eligible for inclusion. Studies were excluded if they used a total daily dose of aspirin of less than 50 mg or more than 325 mg, or if they did not use aspirin as the sole therapy. The studies were grouped according to aspirin dose. Low dose was defined as 50 to 150 mg/day, and medium dose as 300 to 325 mg/day.
Participants included in the reviewStudies of patients who had undergone coronary artery surgery using vein grafts were eligible for inclusion. In the included studies, the mean age of the participants ranged from 55 to 60 years and the proportion of men ranged from 83 to 100%.
Outcomes assessed in the reviewThe studies had to assess the prevention of occlusion of vein grafts. The outcome was assessed by angiography and reported as graft occlusion and the event rate in patients. Grafts were considered occluded if the distal anastomosis could not be visualised by angiography. If the origin was occluded, all subsequent distal anastomoses were also considered to be occluded. The median time to angiography ranged from 10 to 363 days.
How were decisions on the relevance of primary studies made?Three reviewers independently assessed papers for inclusion and resolved any discrepancies by consensus.
Assessment of study quality Study quality was assessed on the basis of randomisation, blind assessment of the outcome, and the number lost to follow-up. The authors did not state how the papers were assessed for quality, or how many reviewers performed the quality assessment.
Data extraction The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.
Data were extracted on the number of occluded grafts. If angiography was performed on more than one occasion, the data closest to one year were analysed. As patients typically receive several grafts and these may not act independently, graft patency was also analysed in terms of rates of events in patients. An event in a patient was defined as one or more occlusions of a saphenous vein graft.
Methods of synthesis How were the studies combined?Since none of the studies included a head-to-head comparison, an indirect comparison using the common comparator (placebo) was performed. A meta-analysis was carried out combining trials that compared low-dose aspirin with placebo to obtain the estimated relative risk (RR).
a. Trials comparing medium-dose aspirin and placebo were pooled separately, also providing an estimated relative risk.
b. The logarithm of these two RRs (log a and log b) were calculated and combined to provide an estimate of the log RR for the difference in the effect of low- and medium-dose aspirin (log c), together with the 95% confidence interval (CI) for the log RR. The formula used to combine the RR was given.
How were differences between studies investigated?No formal tests for heterogeneity were reported. However, a forest plot of the individual study results was presented; this allows a visual qualitative assessment of heterogeneity.
Results of the review Five studies (n=1,354,231 in the medium-dose aspirin groups, 452 in the low-dose aspirin groups, and 671 in the placebo arms) were included. Two studies compared medium-dose aspirin with placebo, while three compared low-dose aspirin with placebo.
The pooled RR reduction for graft occlusion (per vein) was 45% in the medium-dose trials (RR 0.55, 95% CI: 0.41, 0.74) compared with placebo, and 26% in the low-dose trials (pooled RR 0.74, 95% CI: 0.60, 0.91) compared with placebo. The RR for low-dose aspirin compared with medium-dose aspirin was 0.74 (95% CI: 0.52, 1.06). The results for events per patient were similar, but with an RR of 0.81 (95% CI: 0.57, 1.16) for low- versus medium-dose aspirin.
Authors' conclusions Medium-dose aspirin may more successfully reduce graft occlusion than low-dose regimens in the first year after coronary surgery.
CRD commentary Two versions of this paper were available: an abridged one published in the paper version of the BMJ and a longer one published on the BMJ website. See Web Address at end of abstract. The review objective was clearly stated and was supported by well-defined inclusion criteria. A reasonable literature search was carried out, and it is unlikely that any important studies will have been missed. Appropriate methods to avoid bias when selecting the studies were reported. However, the authors did not report the number of reviewers involved in the data extraction or quality assessment processes. A formal quality assessment was carried out and the results were presented.
Appropriate methods, which included an indirect comparison meta-analysis, were used to pool the studies, although the authors did not state whether random-effects or fixed-effect methods were used. It should be noted that the results for indirect comparisons may not be as reliable as those from a direct comparison RCT. No formal tests for heterogeneity were reported and heterogeneity was not discussed in the 'Results' section. This limits the results of the review as the pooled estimate for the low-dose meta-analysis was driven by one large study that reported a higher RR than the other two studies of low-dose aspirin, which reported RRs very similar to those reported by the medium-dose studies. Without considering heterogeneity, and possible reasons for the differences between this larger study and the other two studies which could have accounted for the different estimates, it is difficult to draw firm conclusions from these results. One feature which did stand out about this larger trial was that the mean time to angiography was only around 10 days, compared with 130 and 180 days in the other two low-dose trials, and 363 and 367 days in the high-dose trials. The results of this review should, therefore, be interpreted with extreme caution. There were some minor discrepancies between the data tables in the published paper and those on the BMJ website.
Implications of the review for practice and research Practice: The authors did not state any implications for practice.
Research: The authors stated that further research, including direct comparison of medium- and low-dose aspirin in an RCT, is required.
Bibliographic details Lim E, Ali Z, Ali A, Routledge T, Edmonds L, Altman D G, Large S. Indirect comparison meta-analysis of aspirin therapy after coronary surgery. BMJ 2003; 327: 1309-1311 Indexing Status Subject indexing assigned by NLM MeSH Aspirin /administration & Blood Vessel Prosthesis Implantation; Coronary Disease /surgery; Graft Occlusion, Vascular /prevention & Humans; Platelet Aggregation Inhibitors /administration & Postoperative Care /methods; Randomized Controlled Trials as Topic; Risk Factors; control; dosage; dosage AccessionNumber 12004008065 Date bibliographic record published 30/11/2004 Date abstract record published 30/11/2004 Record Status 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. |
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