Long-term metabolic and cardiovascular effects of antipsychotic drugs. A meta-analysis of randomized controlled trials

Most of the randomized controlled trials (RCTs) on antipsychotics (APs) have efficacy as their primary endpoint, leading to a lack of evidence on long-term metabolic effects of APs. The aim of the present meta-analysis is to compare different APs for the long-term modification of risk of major adverse cardiovascular events (MACE) and related mortality, in patients with schizophrenia and bipolar disorder. All RCTs found on Medline/Embase of at least 52 weeks up to 19 December 2017, enrolling patients with bipolar disorder or schizophrenia and comparing an AP with another AP or placebo were included. The primary outcome of this analysis was the association of APs with the incidence of cardiovascular death, myocardial infarction (MI), and stroke. 3013 studies were screened, 92 met the selection criteria. MI, stroke and cardiovascular death were reported in 11, 6 and 24 studies, respectively. No significant difference was observed with respect to MI and Stroke; a significantly higher cardiovascular mortality was observed for sertindole when compared to risperidone (Mantel-Haenszel Odds Ratio: 2.56, 95% CI: 1.33 - 5). Long-term cardiovascular effects of APs deserve to be studied more extensively. The request by regulatory authorities of cardiovascular safety data from specifically designed trials would be useful.