Importance: Cardiovascular disease (CVD) is a major global health concern, responsible for a significant proportion of deaths annually. Despite the widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs) in managing various conditions, their association with cardiovascular events poses a challenge, and existing guidelines lack a reliable risk prediction tool. This study addresses the critical need for an evidence-based instrument to assess the likelihood of NSAID-induced cardiovascular events, that provides clinicians with valuable decision support to improve safety in their use for pain management, especially in patients vulnerable to cardiovascular events. Objective: To develop a practical risk scoring tool, NSAID Induced Cardiovascular Events (NAÏVE), for estimating the risk of serious cardiovascular events associated with NSAID use. Design: Retrospective nested case-control study Setting: The study leveraged data from the DAVINCI database, integrating electronic health records, administrative data, and clinical data from both the Veterans Health Administration (VHA) and the Department of Defense (DoD). Participants: The study cohort consisted of individuals with at least one NSAID pharmacy claim, with cases defined as those experiencing non-fatal myocardial infarction, non-fatal stroke, or new heart failure. Interventions: Development of the NAÏVE risk scoring tool involved a comprehensive analysis of demographic, clinical, and prescription-related variables, including NSAID exposure, comorbidities, and medication history. Main Outcomes/Measures: The primary outcome was the first occurrence of a cardiovascular event. Results: The study cohort comprised 231,967 cases and 2,319,670 controls, identified from individuals with at least one NSAID pharmacy claim between October 1, 2016, and September 30, 2020. The risk index, NAÏVE, demonstrated strong discriminatory ability and calibration, with a C-statistic of 0.88. Variables such as age, NSAID exposure, comorbidities, and medication history were associated with increased odds of NSAID-induced cardiovascular events. Conclusions/Relevance: NAÏVE is the first evidence-based risk scoring tool providing clinicians with valuable decision support for assessing the potential risk of serious cardiovascular events associated with NSAID use. It fills a crucial gap in clinical practice, allowing for transparent discussions with patients and shared decision-making regarding NSAID prescriptions. Further validation and prospective testing are warranted for broader applicability.

The authors have declared no competing interest.

Retrospective nested case-control study using administrative data

All authors are federal government employees and received no funding for this study.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The study was determined to be exempt by the Defense Health Agency Institutional Review Board

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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Data from VAVINCI database integrating electronic health records, administrative data, and clinical data from both the Veterans Health Administration (VHA) and the Department of Defense (DoD). This is a permissioned dataset that can't be shared outside the VA but the methodology to repeat or confirm the data is provided