Impact of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular outcomes in patients with stable atherothrombosis or multiple risk factors

Background: We aimed to assess whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of cardiovascular (CV) events in stable patients with established atherothrombosis or multiple risk factors. Methods: We analysed the 23,728 European patients of the REACH Registry; 20,588 (86.8%) had established atherothrombotic disease and 3140 (13.2%) had multiple risk factors only. Aspirin (ASA) and/or NSAIDs use was determined at enrolment and ischemic events were recorded over two years of follow-up. cMACCE was defined as the composite of CV death, MI or stroke. Bleeding was defined as any bleeding leading to both hospitalisation and transfusion. Results: The mean age of population was 67.2 ± 9.8 years. At baseline, 1573 patients (6.6%) received NSAIDs and 15,395 (64.9%) received ASA. Four groups were defined: 1) no ASA/no NSAIDs, 2) ASA only, 3) NSAIDs only, 4) NSAIDs + ASA, with 7722 (32.5%), 14,433 (60.8%), 611 (2.6%) and 962 (4.1%) patients in these groups, respectively. Among the 22,028 (92.8%) with complete 2-year follow-up, 683 (3.2%) died from CV causes, while 395 (1.9%) had MI, 665 (3.1%) stroke, 1651 (7.6%) cMACCE and 199 (1.0%) bleeding. After adjustment, NSAID use was independently associated with an increased risk of stroke (OR 1.635; 95% CI 1.239-2.159, p < 0.001), and a trend towards an increased bleeding rate (OR 1.554; CI 95% 0.960-2.51, p = 0.07). No association was found between NSAID use and MI or MACCE. Conclusions: In stable atherothrombosis patients, the use of NSAIDs appears to be independently associated with an increased cerebrovascular event risk.