BackgroundEffectiveness estimates from observational studies on ticagrelor use in routine clinical care are conflicting, with some contrary to the results of the pivotal randomized controlled trial of ticagrelor in acute coronary syndrome. The aim of this study was to estimate the effect of implementing and using ticagrelor in routine clinical care in patients with myocardial infarction using a natural experimental approach. Methods and ResultsThis is a retrospective cohort study including patients hospitalized for myocardial infarction in Sweden between 2009 and 2015. The study exploited differences in the timing and speed of ticagrelor implementation between treatment centers as a source of random treatment assignment. The effect of implementing and using ticagrelor was estimated based on the admitting centers likelihood of treating patients with ticagrelor, measured as the proportion of patients treated in the 90 days before patient admission. The main outcome was 12-month mortality. The study included 109 955 patients, of whom 30 773 were treated with ticagrelor. Being admitted to a treatment center with higher past ticagrelor use was associated with a reduction in 12-month mortality (2.5 percentage points for 100% versus 0% past use [95% CI, 0.2-4.8]). The results are in line with the findings from the ticagrelor pivotal trial. ConclusionsUsing a natural experiment, this study finds that the implementation and use of ticagrelor in routine clinical care has reduced 12-month mortality in patients admitted to the hospital with myocardial infarction in Sweden and supports the external validity of randomized evidence on ticagrelor effectiveness.