Assessing short-term risk of ischemic stroke in relation to all prescribed medications

We examined the short-term risk of stroke associated with drugs prescribed in Norway or Sweden in a comprehensive, hypothesis-free manner using comprehensive nation-wide data. We identified 27,680 and 92,561 cases with a first ischemic stroke via the patient- and the cause-of-death registers in Norway (2004-2014) and Sweden (2005-2014), respectively, and linked these data to prescription databases. A case-crossover design was used that compares the drugs dispensed within 1 to 14 days before the date of ischemic stroke occurrence with those dispensed 29 to 42 days before the index event. A Bolasso approach, a version of the Lasso regression algorithm, was used to select drugs that acutely either increase or decrease the apparent risk of ischemic stroke. Application of the Bolasso regression algorithm selected 19 drugs which were associated with increased risk for ischemic stroke and 11 drugs with decreased risk in both countries. Morphine in combination with antispasmodics was associated with a particularly high risk of stroke (odds ratio 7.09, 95% confidence intervals 4.81-10.47). Several potentially intriguing associations, both within and across pharmacological classes, merit further investigation in focused, follow-up studies.