Dispensed prescription medications and short-term risk of pulmonary embolism in Norway and Sweden

Abstract

Scandinavian electronic health-care registers provide a unique setting to investigate potential unidentified side effects of drugs. We analysed the association between prescription drugs dispensed in Norway and Sweden and the short-term risk of developing pulmonary embolism. A total of 12,104 pulmonary embolism cases were identified from patient- and cause-of-death registries in Norway (2004-2014) and 36,088 in Sweden (2005-2014). A case-crossover design was used to compare individual drugs dispensed 1-30 days before the date of pulmonary embolism diagnosis with dispensation in a 61-90 day time-window, while controlling for the receipt of other drugs. A BOLASSO approach was used to select drugs that were associated with short-term risk of pulmonary embolism. Thirty-eight drugs were associated with pulmonary embolism in the combined analysis of the Norwegian and Swedish data. Drugs associated with increased risk of pulmonary embolism included certain proton-pump inhibitors, antibiotics, antithrombotics, vasodilators, furosemide, anti-varicose medications, corticosteroids, immunostimulants (pegfilgrastim), opioids, analgesics, anxiolytics, antidepressants, antiprotozoals, and drugs for cough and colds. Mineral supplements, hydrochlorothiazide and potassium-sparing agents, beta-blockers, angiotensin 2 receptor blockers, statins, and methotrexate were associated with lower risk. Most associations persisted, and several additional drugs were associated, with pulmonary embolism when using a longer time window of 90 days instead of 30 days. These results provide exploratory, pharmacopeia-wide evidence of medications that may increase or decrease the risk of pulmonary embolism. Some of these findings were expected based on the drugs' indications, while others are novel and require further study as potentially modifiable precipitants of pulmonary embolism.

Keywords: Drugs; Medications; Pulmonary embolism.

Figure 1

Case-crossover analysis of dispensed prescription medication use and risk of pulmonary embolism. The above plot illustrates (A) unique drug types which were selected in Norway, (B) unique drug types which were selected in Sweden, and (C) 59 drugs which were common hits from both the countries. Y-axis displays relative risk on the log scale, X-axis displays all the prescribed drugs studied grouped by the anatomical therapeutic chemical (ATC) classification.