Long-term dual antiplatelet therapy does not increase mortality risk

1. Extended duration dual antiplatelet therapy was not found to be linked to an increased all-cause, cardiovascular, or non-cardiovascular mortality risk.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Recent studies have shown conflicting evidence as to the safety of long term dual antiplatelet therapy for patients at risk of thrombotic events. The Dual Antiplatelet Therapy (DAPT) study is the most recent large-scale multicenter study which found that long-term dual antiplatelet therapy led to an increased risk of non-cardiovascular mortality. The DAPT finding is; however, at odds with other previous studies which showed no difference in all-cause mortality in patients with dual therapy as compared with aspirin alone. The authors set out to undertake a meta-analysis of the current randomized control trial data that exist on dual antiplatelet therapy with the aim of settling the current controversy that exists regarding long-term dual antiplatelet use. This study gains credence from its robust and heterogeneous pool of included studies, allowing for a diverse selection of trial methods, patients populations, and study endpoints enhancing the generalizability of the study. The study is; however, limited by the fact that the heterogeneity of the studies may obscure effects due to differences in definitions or study design.

Click to read the study in The Lancet

Relevant Reading: Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events

In-Depth [meta-analysis]: This study included 69,644 patients from 14 different randomized controlled trials. Results from the 14 studies were pooled utilizing a hierarchical Bayesian random-effects model. In sensitivity analyses, sequential exclusion of each trial from the meta-analysis showed results consistent with the full analysis for all-cause, cardiovascular, or non-cardiovascular mortality.

All 14 studies reported all-cause mortality. There was no significant evidence of heterogeneity in trials with respect to all-cause mortality, as assessed by Cochran’s Q (Q=17.7, p=0.17). The authors found that extended duration anti-platelet therapy was not associated with increased all-cause mortality (hazard ratio [HR], 1.05; 95% credible interval [Cr], 0.96-1.19; p=0.33). 12 studies (n=66,269) reported cardiovascular mortality. Baysian random-effects meta-analysis showed that dual antiplatelet therapy was not associated with increased such mortality (HR 1.01; 95% CrI, 0.93-1.12; p=0.81). Funnel plots suggested no evidence of publication bias.

11 studies (n=65,418) reported non-cardiovascular mortality. Baysian random-effects meta-analysis showed that dual antiplatelet therapy was not associated with increased such mortality (HR 1.04; 95% CrI, 0.90-1.26; p=0.66). Funnel plots suggested no evidence of publication bias.

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