Drug-eluting stents versus bare metal stents for angina or acute coronary syndromes: Cochrane systematic review
Assessed as up to date: 2012/11/01
Coronary artery stents are tiny tubular devices used to 'scaffold' vessels open during percutaneous transluminal coronary angioplasty (PTCA). Restenosis (re-narrowing) of vessels treated with stents is a problem; in order to reduce restenosis, stents that elute drugs over time are available. An earlier review reported limited benefit for these more expensive devices. There is a need to assess their clinical benefits now that longer term data are available.Objectives
To update the previously published review which aimed to assess the clinical effectiveness of routine stenting with drug-eluting compared with non-eluting coronary artery stents in adults with stable angina or acute coronary syndrome (including acute myocardial infarction and unstable angina).Search methods
The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10, 2012 on The Cochrane Library), MEDLINE (OVID, 1946 to October week 4 2012) and EMBASE (OVID, 1980 to 2012 week 43) were searched. We carried out handsearching (electronic) up to May 2012. No language restrictions were applied.Selection criteria
We included RCTs comparing DES with BMS used in conjunction with PTCA techniques in the review. Participants were adults with stable angina or acute coronary syndrome (ACS). We considered published and unpublished sources and included them if they reported outcome data of interest.Data collection and analysis
Two review authors independently extracted data, assessed trial quality and checked decisions within the group. Data extraction included combined cardiovascular events (major adverse cardiac event, target vessel failure); mortality; acute myocardial infarction (AMI); target lesion revascularisation (TLR); target vessel revascularisation (TVR) and thrombosis. Data synthesis included meta-analysis of combined cardiovascular events, mortality, AMI and revascularisation rates, presented as odds ratios with 95% confidence intervals (CI) using a fixed-effect model. We assessed heterogeneity between trials.Main results
The update of the review included 24 new trials (13,391 participants) resulting in a total of 71 trials (28,713 participants). In the main there were no statistically significant differences in mortality, AMI or thrombosis between DES and BMS, (the exceptions were sirolimus reporting significant differences in AMI at two and three years and Everolimus DES thrombosis rates at one year. These benefits were not evident at four or five years). For composite events, TLR and TVR reductions were evident with use of sirolimus, paclitaxel, dexamethasone, zotarolimus and (to a limited extent) biolimus A9, everolimus and unspecified-eluting stents e.g. sirolimus composite events at five years (OR 0.49; 95% CI 0.40 to 0.61). These effects are demonstrated in the longer term follow up. Subgroup analyses (e.g. diabetics) largely mirrored these findings.Authors' conclusions
Drug-eluting stents releasing sirolimus, paclitaxel, dexamethasone and zotarolimus reduce composite cardiac events. However, this reduction is due largely to reductions in repeat revascularisation rates as there is no evidence of a significant effect on rates of mortality, AMI or thrombosis.
Hockenhull Juliet, Greenhalgh Janette, Dickson Rumona C, Ricciardi Mark, Patel Amisha
Drug-eluting stents versus bare metal stents for angina or acute coronary syndromes
Coronary artery disease generally results from the build-up of fatty material and other substances on the internal surface of the blood vessels which supply the heart, gradually reducing its supply of oxygen. There may or may not be associated pain (angina). The disease may cause sudden death and limit normal daily activity. One strategy used to control symptoms or restore blood supply is Percutaneous Transluminal Coronary Angioplasty (PTCA) in which a small elongated balloon is inflated at the site of the narrowing, compacting the deposited material against the vessel wall. This review explores the effects of one category of interventional device used with PTCA: coronary artery stents. These are expandable devices resembling a tubular wire mesh used to 'scaffold' vessels open during PTCA procedures to relieve coronary obstructions in patients. The success rates associated with implanting these devices are high, complication rates low and most patients experience improvement in symptoms. Nonetheless, rates of restenosis (re-narrowing of the treated vessel) which may require a repeat intervention, are a significant limitation of the use of stents. An adaption of stent technology involves stents which release (elute) drugs over time in order to reduce restenosis; however these stents are expensive in comparison to their bare metal equivalent. This updated review includes results from 71 studies (including more than 28,000 patients) and contains data up to five years following treatment. No statistically significant sustained differences in death, myocardial infarction or vessel blockage were reported between drug-eluting stents (DES) and bare metal stents (BMS). Use of DES did result in decrease in the number of times patients had to be re-treated due to blockage of the blood vessel and/or stent. Thus, DES are effective in reducing rates of restenosis but overall are not superior to standard BMS in terms of decreasing death, myocardial infarction or thrombosis.
Implications for practice
Stents eluting sirolimus, paclitaxel and zotarolimus represent better short-term outcomes in terms of preventing restenosis compared with BMS. However, they are expensive and long-term efficacy and safety data have not demonstrated an effect on rates of AMI or mortality. In light of this, a number of regulatory bodies have investigated the cost-effectiveness of the use of DES with a variety of outcomes. Some limit their use to specific patient populations (eg patients with small or long vessels), while others limit the number of DES that can be utilised. The National Institute for Health and Clinical Excellence have advised their use only if the price for DES over BMS can be reduced to £300.
Implications for research
Secondary research should involve continued systematic reviewing (to incorporate longer-term follow up, data on newer BMS and DES (although these may be less forthcoming in the future since the trend for evaluating new DES is likely to be in head-to-head trials).
Primary research should move towards standardisation of trial protocols, utilise clinically driven outcomes and measures relevant to patients such as the impact on quality of life of revascularisation. To this end, the ARC group recommendations for the type and definition of clinical endpoints in coronary stent trials, including the reporting of two composite endpoints, one that is device oriented and one that is patient oriented. The report further recommends the discontinuation of MACE (and other acronyms) given that historically MACE has been interpreted in a variety of different ways. Finally, ARC advise on the optimal basis for DES evaluation: "overall cardiovascular outcomes from the patient's perspective, including all mortality, MI, and repeat revascularization procedures. These outcomes reflect the complex interplay between device performance, revascularization strategy, and secondary prevention and key patient descriptors. Both the time course and the composite selected should characterize patient wellbeing related to the pathophysiology of the implanted DES device and its impact on underlying coronary artery disease outcome. For example, whether a device improves functional capacity and quality of life, but does not affect AMI rates or mortality--as is the case for percutaneous intervention in elective cases--should be clear so that regulatory authorities, clinicians and reimbursement agencies can carefully weigh the net benefit against possible safety concerns." ARC 2007Get full text at The Cochrane Library
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