Effect of acetaminophen on the short-term mortality of hospitalized patients with hypertension: A retrospective cohort study

Hypertension represents a leading risk factor for morbidity and mortality worldwide. Acetaminophen (APAP), a widely used analgesic and antipyretic drug, exhibits a mechanism distinct from nonsteroidal anti-inflammatory drugs. APAP is widely considered a safe alternative to nonsteroidal anti-inflammatory drugs for patients with elevated cardiovascular risk. However, the safety of APAP has recently been questioned, particularly for hypertensive patients. Our study aims to further assess the safety of APAP in patients with hypertension. We utilized the Medical Information Mart for Intensive Care IV database in this study. The primary outcome of our study was in-hospital mortality, while secondary endpoints comprised 30-day and 60-day all-cause mortality. Adult hospitalized patients with hypertension were included in the analysis. Exposure refers to the use of APAP during hospitalization. Propensity score matching was conducted using a 1:1 ratio. Cox proportional hazards analyses were used to adjust for confounders. The Kaplan-Meier method APAP was utilized to compute the cumulative curve. Restricted cubic spline analysis was utilized to evaluate the nonlinear correlation between the dose and duration of APAP and in-hospital mortality. Multivariate analysis of 17,482 hypertensive patients demonstrated that APAP use was associated with significantly lower in-hospital mortality (hazard ratios [HR] = 0.56, 95% confidence interval [CI]:0.46-0.67, P < .001). Restricted cubic spline analyses revealed nonlinear relationships: for dosage, a threshold effect occurred at 2.64g with reduced mortality below this level (HR = 0.59, 95% CI:0.41-0.84, P < .001) but neutral effects above (HR = 1.01, 95% CI:0.83-1.24, P = .90); similarly, treatment duration showed benefit ≤ 4.6 days (HR = 0.62, 95% CI:0.53-0.72, P < .001) without additional advantage beyond this period. In hypertensive patients, the relationship between dose and duration of APAP and in hospital mortality was nonlinear. The optimal dose associated with the lowest risk of in-hospital death was 2.64 g, and the optimal course of treatment was 4.6 days.