|Safety and efficacy outcomes of first and second generation durable polymer drug eluting stents and biodegradable polymer biolimus eluting stents in clinical practice: comprehensive network meta-analysis
|Navarese EP, Tandjung K, Claessen B, Andreotti F, Kowalewski M, Kandzari DE, Kereiakes DJ, Waksman R, Mauri L, Meredith IT, Finn AV, Kim HS, Kubica J, Suryapranata H, Aprami TM, Pasquale GD, von Birgelen C
This high quality review and network meta-analysis concluded that the newer durable polymer everolimus-ES and Resolute zotarolimus-ES and the biodegradable polymer biolimus-ES maintain the efficacy of sirolimus-ES; however, for safety endpoints, differences became apparent; everolimus-ES and Resolute zotarolimus-ES were the safest stents to date. This conclusion is likely to be reliable.
To assess the safety and effectiveness of durable polymer drug-eluting stents (DES) and biodegradable polymer biolimus-eluting stents (biolimus-ES).
MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, EMBASE and several websites (including ClinicalTrials.gov and fda.gov) were searched until 15 May 2013 using specified search terms without date or language restrictions.
Eligible for inclusion were randomised controlled trials (with at least 100 patients and a minimum follow-up of six months) that compared at least two of the durable polymer sirolimus eluting stents (sirolimus-ES) and paclitaxel eluting stents (paclitaxel-ES), newer durable polymer everolimus eluting stents (everolimus-ES), Endeavor and Resolute zotarolimus eluting stents (zotarolimus-ES), and biodegradable polymer biolimus-ES. Primary outcomes for safety were death, myocardial infarction, definite or probable stent thrombosis. Primary outcomes for effectiveness were target lesion and target vessel revascularisation assessed at up to one year and beyond.
The included populations were high-risk groups; most trials enrolled patients with stable coronary artery disease (54%) and acute coronary syndromes (46%). Nearly all included trials were multicentre. Most studies (46 for safety and 44 for effectiveness) had a follow-up of one year; four studies extending follow-up to five years.
Four investigators independently assessed eligibility. Divergences were resolved by consensus.
Assessment of study quality
The Cochrane Collaboration risk of bias tool was used to assess trial quality considering adequate sequence generation, allocation concealment, and blinded adjudication of events. Trials with high or unclear risk of bias for any of these components were regarded as trials with a high risk of bias.
Two investigators independently assessed the potential risk of bias. Discrepancies were resolved by discussion with a third investigator
Data were extracted to allow calculation of odds ratios and associated 95% credible intervals. All data were based on intention-to-treat.
Methods of synthesis
Bayesian network meta-analysis was used to derive posterior estimates of effect for all comparisons using a random-effects model. Heterogeneity was assessed using tau (Τ² greater than 0.4 indicated high heterogeneity) and inconsistency was assessed using node splitting. Sensitivity analyses were performed excluding trials at high risk of bias, using fixed-effect and outcomes beyond one year (using a Poisson regression model). Publication bias was assessed by visual inspection of funnel plots.
Results of the review
Sixty randomised controlled trials (predominantly at low risk of bias) were compared. Trials included 63,242 patients with stable coronary artery disease or acute coronary syndrome.
At one year, there were no clinically important differences in mortality among devices. Resolute and Endeavor zotarolimus-ES, everolimus-ES, and sirolimus-ES were associated with significantly reduced odds of myocardial infarction (by 29-34%) compared with paclitaxel-ES, but biodegradable polymer biolimus-ES was not significantly different. Compared with everolimus-ES, biodegradable polymer biolimus-ES were associated with significantly increased odds of myocardial infarction (by 29%), while Endeavor zotarolimus-ES and paclitaxel-ES were associated with significantly increased odds of stent thrombosis.
At one year, all investigated DES were similar with regards to efficacy endpoints, except for Endeavor zotarolimus-ES and paclitaxel-ES, which were associated with significantly increased odds of target lesion and target vessel revascularisation compared with other devices. Bayesian probability curves showed a gradient in the magnitude of effect, with everolimus-ES and Resolute zotarolimus-ES offering the highest safety profiles. Results were invariant to sensitivity analyses and there was no evidence of inconsistency despite the well-connected network structure. Heterogeneity was low to moderate for analyses and there was no apparent publication bias.
The newer durable polymer everolimus-ES and Resolute zotarolimus-ES and the biodegradable polymer biolimus-ES maintain the efficacy of sirolimus-ES; however, for safety end-points, differences became apparent; everolimus-ES and Resolute zotarolimus-ES were the safest stents to date.
This was a well-conducted systematic review, with appropriate methods used to minimise bias in the identification, selection, appraisal and synthesis of studies, but some components of risk of bias were not examined (random sequence generation, selective reporting). A large, well connected network was constructed and appropriate sensitivity and diagnostic analyses were undertaken indicating robust results. As with all meta-analysis, the clinical judgements on exchangeability may be the focus of criticism, but the authors' justifications for pooling were transparent. Similarly, the clinical interpretation of results was based on those presented. The paucity of data beyond one year of follow-up may limit generalisability.
Despite these caveats, the conclusions reflect the evidence and are likely to be reliable.
Implications of the review for practice and research
The authors did not state any implications for practice or research.
Navarese EP, Tandjung K, Claessen B, Andreotti F, Kowalewski M, Kandzari DE, Kereiakes DJ, Waksman R, Mauri L, Meredith IT, Finn AV, Kim HS, Kubica J, Suryapranata H, Aprami TM, Pasquale GD, von Birgelen C. Safety and efficacy outcomes of first and second generation durable polymer drug eluting stents and biodegradable polymer biolimus eluting stents in clinical practice: comprehensive network meta-analysis. BMJ 2013; 347: f6530
Subject indexing assigned by CRD
Acute Coronary Syndrome; Coronary Artery Disease; Drug-Eluting Stents; Humans; Paclitaxel; Sirolimus
Date bibliographic record published
Date abstract record published
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.