News:A meta-analysis of over 180,000 patients suggests that drug eluting stents are safe for both on-label and off-label use

March 28, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP [mailto:vkunadian@perfuse.org]

Concerns were raised regarding the safety of DES during the European Society of Cardiology Congress meeting in 2006. Subsequent to this a number of patient level analyses from on-label use in the randomized controlled trials (RCTs) suggested that DESs are safe and effective in reducing target vessel revascularization (TVR) with no additional risk of an increase in mortality and myocardial infarction.

The researchers from the CRF performed a meta-analysis to determine if the same effect is seen among the “real world” population with off-label use and estimated the all-cause mortality, myocardial infarction (MI) and target vessel revascularization (TVR) in studies with ≥ 1 year follow-up. This study consisted of randomized controlled trials (RCTs) comparing DES and bare metal stents (BMS) and registry studies utilizing sirolimus eluting stents and paclitaxel eluting stents consisting of ≥100 patients in a study with follow-up information up to one year. Fixed effects (Inverse-Variance weighted) and random effects (DerSimonian and Laird) models were used to analyze the data.

Among patients in the RCTs (n=8867, 21 RCTs), there was no significant difference in all-cause mortality [fixed effect estimate 0.97 (0.81-1.15) p=0.72] for both on-label (p=0.69) and off-label use (p=0.24) between DES and BMS. On the other hand, among patients in the registries (161,232 patients, 28 registries), there was a significant reduction in all-cause mortality (random effect estimate 0.80 (0.72-0.88) p<0.001) with DES compared to BMS.

There was no difference [fixed effect estimate 0.94 (0.79, 1.13), p=0.54] in the occurrence of MI between the DES group and BMS group in the RCTs (n=8,850, 20 RCTs) including on-label [fixed effect estimate 1.03 (0.81, 1.30), p=0.82] and off-label use [fixed effect estimate 0.83 (0.62, 1.10), p=0.19]. In the registry studies (n=129,955, 24 registries), there was a significant reduction in MI [random effect estimate 0.89 (0.80, 0.98), p=0.023]. There was a highly significant reduction in the occurrence of TVR among patients both in the RCTs which consisted of an analysis of 7291 patients from 16 RCTs [random treatment effect estimate 0.45 (a value <1.0 indicates DES is better)] and in the registry studies which consisted of 73,819 patients from 17 studies (random treatment effect estimate 0.53).

This analysis therefore demonstrates that in the RCTs, there was a non-significant reduction in mortality (3%) and myocardial infarction (6%) and a significant reduction in TVR (55%) with DES and in the registry studies, there was a significant reduction in mortality (20%), myocardial infarction (11%) and a significant reduction in TVR (47%) with DES.

The investigators concluded that DES is safe and effective for both on-label and off-label use in the RCTs and in the “real world” population.

Source
Presented by Dr Ajay Kirtane at the CRF-DES evening symposium, March 28 Chicago.