|Clinical efficacy of drug-eluting stents in diabetic patients: a meta-analysis
|Mahmud E, Bromberg-Marin G, Palakodeti V, Ang L, Creanga D, Demaria A N
This review investigated revascularisation and major adverse cardiac event rates in diabetic patients treated with paclitaxel-eluting and sirolimus-eluting stents. The authors found that drug-eluting stents had single-digit revascularisation rates; revascularisation and major adverse cardiac event estimates were similar for both stents. Potential error and bias, and possible inappropriate pooling of studies, suggests the conclusions should be viewed with caution.
To investigate rates of revascularisation and major adverse cardiac events in diabetic patients treated with paclitaxel and sirolimus drug-eluting stents.
MEDLINE and EMBASE were searched (January 2002 to February 2007) for English language articles. Search terms were reported. Abstracts and presentations from five international cardiology conferences from this time period were also searched.
Randomised, controlled trials (RCTs) and registries (data collected prospectively) that evaluated diabetic patients with de novo coronary lesions treated with paclitaxel-eluting stent or sirolimus-eluting stent were eligible for inclusion. Included studies were required to address at least one of the clinical endpoints of interest: target lesion revascularisation or major adverse cardiac events for RCTs; target vessel revascularisation or major adverse cardiac events for registries. Target lesion revascularisation was defined as any procedure (percutaneous coronary intervention or coronary artery bypass graft surgery) performed to revascularise the index lesion. Target vessel revascularisation was defined as any procedure to revascularise the index vessel.
Most of the included studies were conducted in the USA and Europe; participants were mostly male and had a mean age ranging from 59.3 to 68.3 years. The included RCTs compared sirolimus-eluting stents with paclitaxel-eluting stents, sirolimus-eluting/paclitaxel-eluting stents with bare-metal stents, and paclitaxel-eluting stents with sirolimus-coated stents. Registry studies evaluated sirolimus-eluting stents compared with paclitaxel-eluting stents, and the sirolimus-eluting/paclitaxel-eluting stent experience. Follow-up ranged from six to 12 months. Major adverse cardiac event definition consisted of cardiac death, myocardial infarction and repeat revascularisation in most of the included studies. In the RCTs, dual antiplatelet therapy was generally recommended for at least six months after paclitaxel-eluting stents and at least two to three months after sirolimus-eluting stents
At least two reviewers performed study selection.
Assessment of study quality
Methodological quality of the RCTs was evaluated using the Silber score, which assesses trials in terms of factors such as trial power, presence of an independent events committee and a clinical end point. High scores (closer to the total of 10 points) indicated better quality.
The authors did not state how the validity assessment was performed and did not state that they assessed validity of the registry studies.
Target lesion revascularisation, target vessel revascularisation, major adverse cardiac events and stent thrombosis rates were extracted and point estimates, with associated 95% confidence intervals (CIs), were computed for each outcome. Stent thrombosis rates and 95% confidence intervals were based on the observed data and represented the percentage of stent thromboses out of the total diabetic cohort. Authors were contacted if data were not available for the diabetic cohort. Registry data not published in complete form were analysed separately.
The authors did not state how data were extracted for the review, or how many reviewers performed the data extraction.
Methods of synthesis
Data from RCTs and registries were analysed separately. For studies of each design, pooled event rates with 95% confidence intervals were calculated separately for sirolimus-eluting and paclitaxel-eluting stents. Data from studies that directly compared sirolimus-eluting and paclitaxel-eluting stents were also pooled for RCTs and for registries that reported outcomes with both stents in similar populations. Analyses of RCTs were repeated for studies with a Silber score greater than 5. Statistical heterogeneity was assessed using Cochran Q statistic and, if present, the results of the random-effects model presented; otherwise a fixed-effect model was used. Random-effects models were used for all analyses, except for target lesion revascularisation and major adverse cardiac event for each type of stent from the RCTs. All analyses were intention to treat.
Results of the review
Thirteen RCTs (n=2,422 patients) with Silber scores ranging from 4 to 10, and 16 registries (n=10,156) were included in the review.
RCTs: Results of the pooled analyses for rates of target lesion revascularisation (paclitaxel-eluting stent 8.6%, 95% CI 6.5 to 11.3; sirolimus-eluting stent 7.6%, 95% CI 5.8 to 9.9), major adverse cardiac event (paclitaxel-eluting stent 15.4%, 95% CI 12.4 to 19.1; sirolimus-eluting stent 12.9%, 95% CI 8.5 to 19.2) and stent thrombosis (paclitaxel-eluting stent 1.48%, 95% CI 0.74 to 2.63; sirolimus-eluting stent 0.55%, 95% CI 0.11 to 1.59) were similar for both stents. Rates of stent thrombosis were low for both stents (1.4% for paclitaxel-eluting stents and 0.5% sirolimus-eluting stents). Results of subgroup analysis of RCTs with Silber scores greater than 5 were similar. For studies that directly compared paclitaxel-eluting with sirolimus-eluting stents, there was no statistically significant difference in target lesion revascularisation between stents (OR 1.37, 95% CI 0.64 to 2.9; four RCTs).
Registries: Point estimates for target vessel revascularisation (paclitaxel-eluting stent 5.8%, 95% CI 3.9 to 8.5; sirolimus-eluting stent 7.2%, 95% CI 4.6 to 11.2) and major adverse cardiac event (paclitaxel-eluting stent 10.1%, 95% CI 7.3 to 13.8; sirolimus-eluting stent 11.9%, 95% CI 8.6 to 16.4) were similar and low for both paclitaxel-eluting and sirolimus-eluting stents. This was similar for the subgroup of studies that had been published. Target vessel revascularisation (OR 0.77, 95% C: 0.54 to 1.10; eight studies) and major adverse cardiac events (OR 0.83, 95% CI 0.68 to 1.01; seven studies) were non-significantly lower for paclitaxel-eluting stents than sirolimus-eluting stents .
Single-digit revascularisation rates were found with drug-eluting stents; revascularisation and major adverse cardiac event estimates were similar for paclitaxel-eluting and sirolimus-eluting stents.
The study question was supported by inclusion criteria for study design, participants, intervention and outcomes. Published and unpublished literature was searched, reducing the risk of publication bias. Only English language articles were sought, increasing the possibility of language bias. Validity of the RCTs was assessed, but the authors did not assess the quality of the registry studies, so the reliability of their results and their pooled results could not be ascertained. Study selection was performed by two reviewers, reducing possible error and bias, but it was not clear whether similar steps were taken for validity assessment and data extraction. Results of the assessment of heterogeneity were not reported, but the use of random-effects models for some analyses indicated significant heterogeneity, so it may have not been appropriate to pool statistically heterogeneous studies. The baseline characteristics and length of follow-up varied, so the studies also appeared to be clinically heterogeneous. Although the authors' conclusions reflected the results, there was potential for error and bias in the review and studies may have been inappropriately pooled, so the conclusions should be viewed with caution.
Implications of the review for practice and research
The authors did not state any implications for practice or further research.
Boston Scientific and Cordis Corporation; Boston Scientific.
Mahmud E, Bromberg-Marin G, Palakodeti V, Ang L, Creanga D, Demaria A N. Clinical efficacy of drug-eluting stents in diabetic patients: a meta-analysis. Journal of the American College of Cardiology 2008; 51(25): 2385-2395
Subject indexing assigned by NLM
Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease /drug therapy /therapy; Coronary Restenosis /prevention & control; Coronary Thrombosis /prevention & control; Diabetes Mellitus /physiopathology; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents /therapeutic use; Male; Middle Aged; Odds Ratio; Paclitaxel /therapeutic use; Randomized Controlled Trials as Topic; Registries; Risk Assessment; Risk Factors; Sirolimus /therapeutic use; Treatment Outcome
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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.