Mortality Risk and NSAIDs
By Michael M. Ward, MD
Gislason GH, Rasmussen JN, Abildstrom SZ, et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med. 2009;169:141-149.
Background: Accumulating evidence indicates increased cardiovascular risk associated with nonsteroidal anti-inflammatory drug (NSAID) use, in particular in patients with established cardiovascular disease. We studied the risk of death and hospitalization because of acute myocardial infarction and heart failure (HF) associated with use of NSAIDs in an unselected cohort of patients with HF.
Methods: We identified 107,092 patients surviving their first hospitalization because of HF between January 1, 1995, and December 31, 2004, and their subsequent use of NSAIDs from individual-level linkage of nationwide registries of hospitalization and drug dispensing by pharmacies in Denmark. Data analysis was performed using Cox proportional hazard models adjusted for age, sex, calendar year, comorbidity, medical treatment, and severity of disease; and propensity-based risk-stratified models and case-crossover models.
Results: A total of 36,354 patients (33.9%) claimed at least one prescription of an NSAID after discharge; 60,974 (56.9%) died, and 8,970 (8.4%) and 39,984 (37.5%) were hospitalized with myocardial infarction or HF, respectively. The hazard ratio (95% confidence interval) for death was 1.70 (1.58–1.82), 1.75 (1.63–1.88), 1.31 (1.25–1.37), 2.08 (1.95–2.21), 1.22 (1.07–1.39), and 1.28 (1.21–1.35) for rofecoxib, celecoxib, ibuprofen, diclofenac, naproxen, and other NSAIDs, respectively. Furthermore, there was a dose-dependent increase in risk of death and increased risk of hospitalization because of myocardial infarction and HF. Propensity-based risk-stratified analysis and case-crossover models yielded similar results.
Conclusions: NSAIDs are frequently used in patients with HF and are associated with increased risk of death and cardiovascular morbidity. Inasmuch as even commonly used NSAIDs exerted increased risk, the balance between risk and benefit requires careful consideration when any NSAID is given to patients with HF.
Among their serious complications, NSAIDs can cause exacerbations of congestive heart failure (CHF). This effect has been attributed to the ability of NSAIDs to cause systemic vasoconstriction, hypertension, reduced renal blood flow, and fluid retention, all leading to an increase in cardiac afterload. This study documented an increased risk of hospitalization for treatment of CHF among patients using NSAIDs but also—and most importantly—found an increased risk of mortality among users of NSAIDs.
This nationwide population-based study examined all patients discharged alive from hospitals in Denmark from 1995 to 2004 who had a diagnosis of congestive HF. Data on NSAID use were obtained by linking the patients’ records with a national prescription registry, which in the Danish universal health care system captures all NSAID prescriptions except those for low-dose ibuprofen (which can be obtained without prescription). The outcomes of these patients were tracked using national hospitalization and mortality registries, which allowed the investigators to know the timing of death or subsequent hospitalizations for CHF or myocardial infarction. Patients were elderly, with a mean age 74.8 years, and 33.9% received a prescription for an NSAID after their hospital discharge for CHF. NSAID use was generally short-term, with median durations of treatment ranging from 40 to 97 days among different medications.