This review assessed the effects of pioglitazone and rosiglitazone on restenosis in people undergoing coronary stent implantation. The authors concluded that whilst these drugs may be effective, more research is needed before recommendations can be made. Whilst the review had some limitations, these conclusions are suitably conservative.

To assess the effects of thiazolidinedione therapy on in-stent restenosis after percutaneous coronary intervention (PCI).

PubMed was searched in May 2006; the search terms were reported. The reference lists of relevant papers were checked. Only studies published in the English language were included.

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) with at least 6 months’ follow-up were eligible for inclusion.

Specific interventions included in the review

Studies were eligible for inclusion if they compared pioglitazone or rosiglitazone, added to standard therapy, with other antidiabetic drugs in people with diabetes, or with no antidiabetic therapy in people without diabetes. Studies assessing troglitazone were excluded. In the included studies, treatment was started either prior to PCI or up to 2 weeks post-PCI. The dose for pioglitazone was 30 mg daily, and for rosiglitazone 4 mg daily. Bare metal and drug-eluting stents from nine different manufacturers were used.

Participants included in the review

Studies on people undergoing PCI were eligible for inclusion. Four of the 5 included studies were on people with diabetes; the remaining study was on people without diabetes. In addition, where stated, people also had acute coronary syndrome, acute myocardial infarction (MI), unstable angina or exercise-induced ischaemia.

Outcomes assessed in the review

Studies had to have assessed outcomes using quantitative coronary angiography at 6 months or longer. The primary outcomes were rate of restenosis (defined as more than 50% of target lesion), percentage diameter stenosis and in-stent minimum lumen diameter. The secondary outcomes included rates of target lesion revascularisation, MI, mortality and drug side-effects.

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.

Quality was assessed by awarding scores according to the reporting of items related to randomisation methods, double-blinding, withdrawals and allocation concealment. The maximum score was 5 and a study scoring more than 2 was classified as a good-quality study. The authors did not state how the validity assessment was performed.

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction. Results for MI, side-effects and mortality were calculated on an intention-to-treat basis. Other results were reported on an available data basis.

How were the studies combined?

The results were pooled using a random-effects model. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were presented for dichotomous data, and weighted difference in means (WDM) for continuous data.

How were differences between studies investigated?

Statistical heterogeneity was assessed using the chi-squared test. The authors also discussed differences between the studies in the narrative.

Five RCTs (259 participants, of whom 235 were evaluable) were included.

The mean study quality score was 2.4 (range: 2 to 3). Variations in treatment regimens meant that there was clinical heterogeneity between the studies.

In 3 RCTs pioglitazone or rosiglitazone reduced restenosis compared with control. Studies showed a reduction in restenosis rates (OR 0.29, 95% CI: 0.15, 0.56), lower percentage diameter stenosis (WDM 14.35, 95% CI: 19.99, 8.72) and higher minimal lumen diameter (WDM 0.43, 95% CI: 0.21, 0.65).

People in the pioglitazone or rosiglitazone group were less likely to undergo target lesion revascularisation (OR 0.24, 95% CI: 0.09, 0.61; 4 RCTs).

Amongst all 259 participants there was one death (in the treatment group) and one MI (in the control group). No drug-related side-effects were reported.

The results suggest that thiazolidinedione therapy may be associated with lower rates of restenosis and repeat revascularisation in people undergoing coronary stent implantation.

The aims of this review were stated clearly. The search was limited to one database and to English language studies; data from one eligible Japanese study were not included in the review. It is also possible that other studies were missed; this could affect the results of the review, particularly as so few studies were found and included. The methods of the review were not described, thus it is not possible to comment on the likelihood of reviewer bias or the possible introduction of errors into the review process. The scoring method used in the quality assessment is considered to be problematic, and the cut-off score for defining a good-quality study was rather low. The data were pooled despite clinical heterogeneity. In view of these comments the results should be treated with some caution. However, the authors acknowledged the limitations of the available data and drew suitably conservative conclusions.

Practice: The authors stated that decisions on clinical use must wait for further results from larger double-blind RCTs.

Research: The authors stated that a large multicentre trial is needed to define the role of thiazolidinedione therapy in preventing restenosis.

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.