A meta-analysis of cardiovascular events in intermittent androgen-deprivation therapy versus continuous androgen-deprivation therapy for prostate cancer patients.

BACKGROUND: Androgen-deprivation therapy (ADT) is the standard treatment for advanced and recurrent prostate cancer but it has been shown to cause adverse effects on the cardiovascular system. Intermittent androgen deprivation has been studied as an alternative therapy. To conduct a meta-analysis comparing the incidence of cardiovascular events in patients with prostate cancer receiving intermittent (IADT) versus continuous ADT (CADT).

METHODS: We searched Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, The National Cancer Institute Clinical Trials and The Clinical Trials Register of Trials Central, and Google Scholar from inception of each database through February 2016. References from published guidelines, reviews and other relevant articles were also considered. We selected randomized clinical trials comparing IADT versus CADT in patients with prostate cancer that reported data on cardiovascular events. Two reviewers performed the study selection, data abstraction and risk of bias assessment. We calculated risk ratios with the Mantel-Haenszel method, using random effect models. We assessed heterogeneity using I2 index. The primary outcome was incidence of cardiovascular events. Secondary outcomes were thromboembolic events and cardiovascular-related mortality.

RESULTS: Out of 106 references, we included seven articles from six trials (4810 patients) published between 2009 and 2015. We observed no significant difference between intermittent versus continuous androgen deprivation with respect to cardiovascular events (risk ratio (RR): 0.95; confidence interval (CI) 95%=0.83-1.08; seven trials, 4810 patients) and thromboembolic events (RR: 1.05; CI 95%=0.85-1.30; three trials, 1816 patients). There was marginally significant difference with respect to cardiovascular-related mortality (RR: 0.85; CI 95%=0.71-1.00; five trials, 4170 patients).

CONCLUSIONS: Compared with CADT, IADT shows no difference in terms of cardiovascular events and thromboembolic events. However, there was an association between lower cardiovascular-related mortality and intermittent androgen deprivation.