Acute cardiovascular effects associated with the use of prescription medications: A Danish nationwide screening study

This study aims to conduct a hypothesis-generating screening for acute cardiovascular effects of prescription medications.

This Danish nationwide screening study was conducted among incident cases of cardiovascular diseases, including myocardial infarction (MI), ischemic stroke (IS), heart failure (HF), venous thromboembolism (VTE), myocarditis, and atrial fibrillation (AF), between January 2000 and December 2022. Using a case-crossover study design, we examined exposure to individual drugs on the date of the cardiovascular event (focal date) and three reference dates corresponding to days -180, -270 and -360 prior to index date. We calculated odds ratios (ORs) with 95% credible intervals (CIs) for associations between exposure drug and cardiovascular outcomes using the conditional logistic regression with a weak Bayesian shrinkage.

After applying exclusion criteria, we identified 191,979 cases of AF, 145,148 cases of MI, 132,271 cases of IS, 71,821 cases of HF, 16,127 cases of VTE and 10,045 cases of myocarditis. Based on the threshold for the strength of associations (OR ≥ 1.5; lower limit of CI ≥ 1), we identified 222 associations for 104 individual drugs across all six outcomes. Some major drug classes, such as antibiotics, analgesics and corticosteroids, consistently demonstrated associations for most cardiovascular outcomes. Use of pantoprazole, in contrast to other PPIs, was associated with AF (OR 1.83; 95% CI 1.68-2.00) along with MI, HF, myocarditis and VTE. Similarly, oxazepam stood out among other benzodiazepines and demonstrated increased risk of VTE (OR 2.53; 95% CI 1.55-4.13) as well as MI, HF and AF.

The results highlight several potentially important associations across various pharmacological drug classes that warrant further investigation in tailored pharmacoepidemiological analyses.