NSAIDs Plus Aspirin Associated With Development of Incident Heart Failure Risk

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used drugs worldwide.  These agents have been associated with higher risk of acute myocardial infarction, stroke, heart failure, and renal failure.^1-2 NSAID use appears to increase left ventricular end-diastolic and systolic dimensions, raises blood pressure, and attenuates the effect of diuretics and other antihypertensive drugs.^3-4 Aspirin is also a NSAID.  Although these agents are associated with decompensated heart failure in patients with diagnosed heart failure, it is not known whether these agents induce incident heart failure. 

A retrospective analysis of 6,769 participants enrolled in the Multi-Ethnic Study of Atherosclerosis found that the use of NSAIDs and aspirin together increased the risk of incident heart failure between 1.6 to 2-fold higher. Three models were analyzed based on adjustments for demographics, lifestyle, CVD risk factors, LV mass and NT pro-BNP determinations.⁵ Four groups were analyzed: no ASA or NSAID, ASA only, NSAID only, both ASA and NSAID.  Patients enrolled were between the ages of 45-84, free of baseline clinical cardiovascular disease, and with extensive data on risk factors, medication use, cardiac MRI and biomarker data over 10 years of follow-up.  The participants mean age was 62 years, 47% were male, and 61% were non-white.  Approximately 20% used ASA, 18.3% NSAIDs, and 5.2% used both.  This study was presented in abstract form at the American Heart Association Scientific Session in November, 2018.

This study adds to the growing literature of NSAID-induced cardiovascular agents, but adds that NSAIDs should be used with caution in patients taking aspirin or visa-versa.  In general, NSAID-induced adverse events usually occur early in treatment, are associated with higher doses, and increase with duration of treatment.⁴ Clinicians have no direct treatment options for these cardio-renal complications other than to advise against use, reduce the duration of use, or recommend an alternate pain management agent.^{4, 6}  There remains a critical need to develop a treatment to reduce the incidence of NSAID-induced cardiovascular adverse events, especially heart failure.

Mark A. Munger, PharmD, FCCP, FACC, is a professor of pharmacotherapy and adjunct professor of internal medicine, at the University of Utah, where he also serves as the associate dean of Academic Affairs for the College of Pharmacy. 

References:

1. Haag MD, Bos MJ, Hofman A, et al. Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs and risk of stroke. Arch Intern Med 2008;168:1219-24.
2. Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med November 13,2016 DOI: 10.1056/NEJMoz1611593.
3. van den Hondel KE, Ejgelsheim M, Ruiter R, et al. Effects of short-term NSAID use on echocardiographic parameters in elderly people: a population-based cohort study. Heart 2011;97:540-3.
4. https://www.fda.gov/Drugs/DrugSafety/ucm451800.htm  Accessed 06/03/2019
5. Mostertz WC, Chen J, Delaney JA, Shah SJ, Yeboah J, Bertoni AG. Association of nonsteroidal anti-inflammatory drug use with incident heart failure within the multi-ethnic study of atherosclerosis. Presented at: AHA 2018; November 10-12, 2018 Chicago, Illinois, Abstract Sa1113/1113.
6. Scarpignato C, Lanas A, Blandizzi C, Lems WF, Hermann M, Hunt RH, For the International NSAID Consensus Group. BMC Medicine 2015;13:55