Relative risks of cardiovascular disease in people prescribed olanzapine, risperidone and quetiapine

Antipsychotics may confer long term benefits and risks, including cardiovascular disease (CVD) risk. Several studies using routine clinical data have reported associations between antipsychotics and CVD but potential confounding factors and unclear classification of drug exposure limits their interpretation.

We used data from The Health Improvement Network, a large UK primary care database to determine relative risks of (CVD) comparing similar groups of people only prescribed olanzapine versus either risperidone or quetiapine. We included participants over 18 between 1995 and 2011. To assess confounding factors we created propensity scores for being prescribed each antipsychotic. We used propensity score matching and Poisson regression to calculate the CVD incidence rate ratios for olanzapine versus the other two drugs.

We identified 18,319 people who received a single antipsychotic during follow-up (n=5090 risperidone, 7797 olanzapine and 4613 quetiapine). In unmatched analyses, the CVD incidence rate ratio (IRR) for olanzapine versus risperidone was 0.63 (0.51-0.77) but the propensity score matched IRR was 0.78 (0.61-1.02). In the unmatched olanzapine versus quetiapine analysis the IRR adjusted for age and sex for olanzapine was 1.52 (1.16-1.98) but the propensity score matched analysis gave an IRR of 1.08 (0.79-1.46).

After propensity score matching, we found no statistical differences in CVD incidence between olanzapine and either risperidone or quetiapine. Analyses which did not account for confounding factors produced very different results. Researchers must address confounding factors when designing observational studies to assess adverse outcomes of drugs, including antipsychotics.