Acetaminophen Use and Risk of Myocardial Infarction and Stroke in a Hypertensive Cohort

Abstract

Abstract-Recent data suggest that self-reported acetaminophen use is associated with increased risk of cardiovascular events and that acetaminophen causes a modest blood pressure rise. There are no randomized trials or studies using verified prescription data of this relationship. We aimed to assess the relationship between verified acetaminophen prescription data and risk of myocardial infarction or stroke in patients with hypertension. We performed a retrospective data analysis using information contained within the UK Clinical Research Practice Datalink. Multivariable Cox proportional hazard models were used to estimate hazard ratios for myocardial infarction (primary end point), stroke, and any cardiovascular event (secondary end points) associated with acetaminophen use during a 10-year period. Acetaminophen exposure was a time-dependent variable. A propensity-matched design was also used to reduce potential for confounding. We included 24 496 hypertensive individuals aged ≥65 years. Of these, 10 878 were acetaminophen-exposed and 13 618 were not. There was no relationship between risk of myocardial infarction, stroke, or any cardiovascular event and acetaminophen exposure on adjusted analysis (hazard ratio, 0.98; 95% confidence interval, 0.76-1.27; hazard ratio, 1.09; 95% confidence interval, 0.86-1.38; and hazard ratio, 1.17; 95% confidence interval, 0.99-1.37; respectively). Results in the propensity-matched sample (n=4000 per group) and when men and women were analyzed separately were similar. High-frequency users (defined as receiving a prescription for >75% of months) were also not at increased risk. After allowance for potentially confounding variables, the use of acetaminophen was not associated with an increased risk of myocardial infarction or stroke in a large cohort of hypertensive patients.

Should Acetaminophen Be Added to the List of Anti-Inflammatory Agents That Are Associated With Cardiovascular Events?

“…In this issue, Fulton et al 7 used the UK Clinical Practice Research Database (GPRD) to assess the association of acet-aminophen with adverse cardiovascular events. The past decade has seen a surge in the use of computerized healthcare data for pharmacoepidemiologic study.…”

“…One of the strengths of the study by Fulton et al 7 is that they supplemented their main analyses with the acetaminophen use propensity estimation and conducted analyses on the matched subsample. The study group used the neighbor nearest propensity matching that is a robust approach to the one-to-one matching.…”

“…The study group used the neighbor nearest propensity matching that is a robust approach to the one-to-one matching. Fulton et al 7 have also attempted to provide both graphic and numeric diagnostics of the quality of the matching technique. The authors listed the following variables used in the calculation of the propensity score: age, sex, diabetes mellitus, statins, aspirin, and NSAID exposure without aspirin.…”

Where are we now with paracetamol?

“…11 Nevertheless, a recent study of over 24 000 patients from the UK did not show any association between paracetamol and myocardial infarction or stroke. 12 While observational data such as these may be confounded, they provide some reassurance, and the study should be repeated across international datasets.…”

Risk of Acute Cerebrovascular and Cardiovascular Events Among Users of Acetaminophen or an Acetaminophen-Codeine Combination in a Cohort of Patients with Osteoarthritis: A Nested Case-Control Study

“…Evidence suggests a possible association between the use of acetaminophen and elevation in blood pressure, and a cohort study showed an increased risk of acute cardiovascular events in women exposed to acetaminophen . Although these findings might be supported by a mechanism of acetaminophen‐induced inhibition of the cyclooxygenase‐2 enzyme in the vascular endothelium, the overall available evidence on the cerebrovascular and cardiovascular safety of acetaminophen is conflicting . In fact, observational studies have reported relative risks of ACCEs for acetaminophen users, compared with nonusers, ranging from 0.84 (95% confidence interval [CI] 0.74–0.95) to 1.68 (95% CI 1.10‐2.58), suggesting both protective and harmful effects.…”