The authors concluded that vascular brachytherapy improved long-term outcomes compared with bare-metal stents alone for coronary artery in-stent restenosis; drug-eluting stents appeared similar to vascular brachytherapy in the short-term. Overall the authors’ conclusions appeared to be supported by the evidence presented but, given the limited data available, findings about long-term outcomes should be interpreted with caution.

To evaluate outcomes following vascular brachytherapy and drug-eluting stents for the treatment of coronary artery in-stent restenosis.

PubMed, EMBASE, the Cochrane Library and ProQuest were searched from August 2005 to April 2006 for studies published in English. Search terms for PubMed were reported. Additional studies were sought using the Google search engine and by contacting principal authors of studies. All searching details were available in a separate 'add on' document online (see URL for Additional Information field).

Randomised controlled trials (RCTs) that evaluated the effects of vascular brachytherapy or drug-eluting stents in patients with native coronary artery in-stent restenosis on clinical and angiographic outcomes after a minimum of six months were eligible for inclusion. Included trials could also contain only a subset of patients with in-stent restenosis. Eligible trials could refer to intravascular or intracoronary instead of 'vascular' and radiotherapy or radiation instead of ‘brachytherapy’. Eligible outcomes included binary restenosis, late lumen loss, major adverse cardiac events (defined as death, myocardial infarction, target vessel revascularisation or target lesion revascularisation) and the individual components of major adverse cardiac events; the authors' definitions of these outcomes were accepted. Short-term (in-hospital or 30 days), intermediate (six to 24 months) and long-term (three years or more) clinical outcomes were assessed.

Most of the included trials compared vascular brachytherapy with control; other trials compared drug-eluting stents with control and drug-eluting stents with vascular brachytherapy. In most trials, vascular brachytherapy followed balloon angioplasty plus selective placement of bare-metal stents and/or atherectomy and controls were ‘comparable interventions’. In most trials, all patients had in-stent restenosis. Most patients were male (range 60 to 82%), the mean age ranged from 58 to 70 years and overall approximately one third of patients had diabetes mellitus (range 18 to 45%). In most trials the target lesion length was over 15mm and the minimum luminal diameter was less than 9 mm.

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

Two reviewers independently assessed validity using the Jadad scale (scores from 0 to 5). Scores from each reviewer were summed. Inter-reviewer agreement was assessed.

Two reviewers independently extracted data and resolved disagreements by discussion. Authors were contacted if required for missing data. Categorical data were expressed as relative risks (RR) and continuous data as mean differences.

Studies evaluating drug-eluting stents and vascular brachytherapy were analysed separately. Measures of treatment effect were combined using a random-effects model and 95% confidence intervals (CI) were calculated. Standardised mean differences were calculated for continuous data. Heterogeneity was assessed using the Q statistic. Sensitivity analysis was undertaken by analysing studies grouped by percentage of patients with in-stent restenosis (100% or less than 100%), type of radiation (gamma or beta), length of follow-up (one year or one year and more) and study quality (lower quality or other). Publication bias was assessed using a funnel plot and the fail-safe N test.

Fourteen RCTs were included (n=3,103 patients). Two RCTs compared vascular brachytherapy with drug-eluting stents, one RCT compared drug-eluting stents with control and eleven RCTs compared vascular brachytherapy with control. Two trials were judged to be low quality.

Vascular brachytherapy versus control treatments: Compared to all control treatments, vascular brachytherapy was associated with a statistically significant reduction in major adverse cardiac events (RR 0.68, 95% CI 0.52 to 0.87), target lesion revascularisation (RR 0.54, 95% CI 0.34 to 0.85), target vessel revascularisation (RR 0.72, 95% CI 0.53 to 0.99), restenosis (RR 0.57, 95% CI 0.42 to 0.78) and late loss (standardised difference in means -0.63, 95% CI -0.84 to -0.41) at intermediate follow-up and major adverse cardiac events (RR 0.72, 95% CI 0.61 to 0.85) at long-term follow-up. Significant heterogeneity was found for target vessel revascularisation, target lesion revascularisation, major adverse cardiac events after one year and late loss (p<0.001).

Drug-eluting stents versus control treatments: Compared to all control treatments, drug-eluting stents was associated with a statistically significant reduction in restenosis (RR 0.50, 95% CI 0.37 to 0.68) and target vessel revascularisation (RR 0.47, 95% CI 0.36 to 0.62) and major adverse cardiac events (RR 0.51 to 95% CI 0.39 to 0.67) after one year of follow-up.

Vascular brachytherapy versus drug-eluting stents: Compared to vascular brachytherapy, drug-eluting stents were also associated with a statistically significant reduction in target vessel revascularisation, target lesion revascularisation, restenosis and major adverse cardiac events in the intermediate term. No significant heterogeneity was found for these analyses.

Results of sensitivity analyses were also reported.

Funnel plots showed no evidence of publication bias.

Vascular brachytherapy improved long-term outcomes compared with bare-metal stents alone for the treatment of coronary artery in-stent restenosis. Drug-eluting stents appeared similar to vascular brachytherapy in the short-term.

The review question was clearly stated and inclusion criteria were defined for interventions, participants, outcomes and study design. Several relevant sources were searched but no attempts were made to minimise publication or language bias. The potential for publication bias was assessed and no evidence was found. Methods were used to minimise reviewer errors and bias in the assessment of validity and extraction of data, but it was not clear whether similar steps were taken in study selection. Only RCTs were included and validity was assessed, Although the authors reported that only two trials were judged to be of low quality, the lack of full reporting of trial quality made it difficult to judge the reliability of the results, Appropriate methods were used for the meta-analyses. Heterogeneity was assessed and various predefined sensitivity analyses were conducted. There was a lack of long-term data on outcomes. There were limitations to the review, in particular the absence of adequate reporting of trial quality. Overall the authors’ conclusions appeared to be supported by the evidence presented, but findings about long-term outcomes should be interpreted with caution given the limited data available.

Practice: The authors did not state any implications for practice.

Research: The authors stated that larger studies with longer-term follow-up are required to determine if the benefits of drug-eluting stents are maintained longer-term.

National Institute of Health, USA, grant number R01 HL080010-01; National, Health and Medical Research Council, Australia, grant number 279408/379600. One author holds a Practitioner’s Fellowship from the NHMRC, Australia, 431503.

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.