Purpose: To evaluate time trends in the prevalence of antithrombotic and statin use in four European countries. Methods: Using population-based data from the United Kingdom, Denmark, Spain and Italy between 2010 and 2018, we calculated standardized annual prevalence proportions of antithrombotics and statin use, and changes in prevalence proportions (2018 vs. 2010). Results: Prevalence proportion of statins increased from 24.8% to 24.6% (UK), 21.0% to 22.3% (Region of Southern Denmark [RSD]), 12.9% to 14.3% (Udine, Italy), and 20.3% to 23.2% (Spain). Prevalence proportions of antithrombotics declined in all four countries: 18.7% to 15.9% (UK; − 2.8% points), 18.9% to 18.1% (RSD; − 0.8% points), 17.7% to 16.6% (Udine; − 1.1% points) and 15.0% to 13.6% (Spain; − 1.4% points). These declines were driven by reductions in low-dose aspirin use: 15.3% to 8.9% (UK; − 6.4% points), 16.3% to 9.5% (RSD; − 6.8% points), 13.5% to 11.6% (Udine; − 1.9% points), and 10.2% to 8.8% (Spain; − 1.4% points). In the UK, low-dose aspirin use declined from 9.1% to 4.3% (− 4.8% points) for primary CVD prevention, and from 49.6% to 36.9% (− 12.7% points) for secondary prevention. Oral anticoagulant use gradually increased but did not fully account for the decrease in low-dose aspirin use. Conclusions: Antithrombotic use in the UK, RSD, Udine and Spain declined between 2010 and 2018, driven by a reduction in use of low-dose aspirin that is not completely explained by a gradual increase in OAC use. Use of statins remained constant in the UK, and increased gradually in the RSD, Udine and Spain.