Antipsychotic drug use and risk of stroke and myocardial infarction: a systematic review and meta-analysis

Abstract

Background: The effect of antipsychotic (AP) drugs on risk of stroke and myocardial infarction (MI) remains unclear due to methodological limitations of, and inconsistencies across, existing studies. We aimed to systematically review studies reporting on the associations between AP drug use and stroke or MI risk, and to investigate whether associations differed among different sub-populations.

Methods: We searched Medline, EMBASE, PsychINFO and Cochrane Library (from inception to May 28, 2017) for observational studies reporting on AP drug use and MI or stroke occurrence. We performed random-effects meta-analyses for each outcome, performing sub-groups analyses by study population - specifically general population (i.e. those not restricted to patients with a particular indication for AP drug use), people with dementia only and psychiatric illness only. Where feasible we performed subgroup analyses by AP drug class.

Results: From 7008 articles, we included 29 relevant observational studies, 19 on stroke and 10 on MI. Results of cohort studies that included a general population indicated a more than two-fold increased risk of stroke, albeit with substantial heterogeneity (pooled HR 2.31, 95% CI 1.13, 4.74, I² = 83.2%). However, the risk among patients with dementia was much lower, with no heterogeneity (pooled HR 1.16, 95% CI 1.00, 1.33, I² = 0%) and there was no clear association among studies of psychiatric populations (pooled HR 1.44, 95% CI 0.90, 2.30; substantial heterogeneity [I² = 78.8])). Associations generally persisted when stratifying by AP class, but few studies reported on first generation AP drugs. We found no association between AP drug use and MI risk (pooled HR for cohort studies: 1.29, 95% CI 0.88, 1.90 and case-control studies: 1.07, 95% CI 0.94, 1.23), but substantial methodological and statistical heterogeneity among a relatively small number of studies limits firm conclusions.

Conclusions: AP drug use may be associated with an increased risk of stroke, but there is no clear evidence that this risk is further elevated in patients with dementia. Further studies are need to clarify the effect of AP drug use on MI and stroke risk in different sub-populations and should control for confounding by indication and stratify by AP drug class.

Keywords: Antipsychotics; Dementia; Meta-analyses; Myocardial infarction; Stroke.

Fig. 1

Flow diagram of literature search and study selection

Fig. 2

Forest plots for the association between antipsychotics and stroke, by study population/antipsychotic class subgroups NB In plots a-c, n/N represents number of cerebrovascular events/total number in comparison group for those using antipsychotic medication and those not using antipsychotic medication. Chen (a) = haemorrhagic stroke; Chen (b) = ischaemic stroke. AP = antipsychotic; CI = confidence interval

Fig. 3

Forest plots for the association between APs and MI, by study design and AP class. *Number of MI events in the group prescribed antipsychotic drugs (exposed) and those not prescribed antipsychotic drugs (non-exposed). †Number of people prescribed antipsychotic drugs among cases (those with MI) and controls (those without MI). AP = antipsychotic; HR = hazard ratio; MI = myocardial infarction; NR = not reported