Commentary

Is Acetaminophen Safe for Patients With Hypertension?

AUTHOR:
Michael J Bloch, MD
Associate Professor, University of Nevada School of Medicine
Medical Director, Renown Vascular Care, Renown Institute for Heart and Vascular Health
President, Blue Spruce Medical Consultants, PLLC

CITATION:
Bloch MJ. Is acetaminophen safe for patients with hypertension? Consultant360. Published online March 17, 2022.

 

Health care providers who treat hypertension are increasingly aware that non-steroidal anti-inflammatory (NSAID) use can increase blood pressure (BP), contribute to renal dysfunction, and increase the risk of cardiovascular (CV) events. This is true for traditional NSAIDs like ibuprofen and naproxen but also appears to be true for COX-2 inhibitors, such as celecoxib, although perhaps to a lesser extent.5

The 2017 American Heart Association/American College of Cardiology (AHA/ACC) guidelines on management of BP suggested that clinicians avoid use of systemic NSAIDs whenever possible in patients with elevated blood pressure.1 In addition, a scientific statement from the AHA advised that use of NSAIDs for pain relief should be “limited to patients for [whom] there are no appropriate alternatives and then [used] only in the lowest dose and for the shortest duration necessary,” particularly in patients with higher CV risk.2 Both these and other clinical recommendations suggest that acetaminophen be considered as a safer alternative for pain control in patients with hypertension and/or high CV risk.

While some might say these recommendations imply that acetaminophen must be safe for patients with hypertension, emerging evidence suggests that we should not necessarily assume this as incontrovertible fact. When clinicians prescribe acetaminophen for chronic pain, we are usually concerned most about the potential for hepatotoxicity, but there have been previous reports suggesting that perhaps chronic acetaminophen use may increase BP.3 Since these previous reports have largely been purely observational and subject to the bias induced by chronic pain, most clinicians are either unaware of these reports or have not given them much credence.

Now, however, we have a new randomized controlled clinical trial that suggests that the association between chronic acetaminophen use and increased BP may be real and clinically meaningful. In this trial by MacIntyre and colleagues,4 110 individuals with hypertension were randomized to receive 1 g of acetaminophen 4 times daily or matched placebo for 2 weeks and then to cross-over to the alternative treatment for an additional 2 weeks. The primary outcome measure was change in daytime ambulatory systolic BP on ambulatory BP monitoring from baseline to the end of treatment between the placebo and acetaminophen treatment. Since each patient served as their own control and was free of chronic pain at baseline, the chance of confounding variables was minimized.

The results were somewhat striking. The use of acetaminophen was associated with a placebo-corrected increase in mean daytime BP of 4.7 mmHg (132.8 vs 136.5 mmHg). Statistically significant increases in BP were also seen for diastolic daytime BP, mean 24-hour systolic and diastolic BP, and clinic systolic and diastolic BP. The results were similar for participants with treated and untreated hypertension. As the authors point out, based on longitudinal studies of patients with treated hypertension, a change in BP of this magnitude, if sustained, would be expected to result in an approximately 20% increase in CV events.

The exact mechanism by which acetaminophen might lead to increased BP remains unclear and whether the association lasts beyond a couple of weeks also remains unknown. Importantly, the dose of acetaminophen used in this study (4 g per day) was considerably higher than commonly prescribed in the United States. But, despite these limitations, the study by MacIntyre and colleagues4 calls into question the recommendation that acetaminophen is a “safer alternative” to NSAIDs. Given the widespread availability of over-the-counter acetaminophen, the increasing prevalence of hypertension, and the prevailing notion among both patients and providers that acetaminophen is “safe” for patients with hypertension, it seems that a larger and longer randomized controlled study with lower doses of acetaminophen is clearly needed. In the meantime, clinicians should temper their enthusiasm for choosing acetaminophen as a “safe” alternative to NSAIDs in patients with hypertension.

References:

  1. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J am Coll Cardiol. 2018;71(19):e127-e248. doi:10.1016/j.jacc.2017.11.006
  2. Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA; American Heart Association. Use of nonsteroidal anti-inflammatory drugs: an update for clinicians: a scientific statement from the American heart association. Circulation. 2007;115(12):1634-42. doi:10.1161/CIRCULATIONAHA.106.181424
  3. Turtle EJ, Dear JW, Web DJ. A systemic review of the effect of paracetamol on blood pressure in hypertensive and non-hypertensive subjects. Br J Clin Pharmacol. 2013;75(6):1396-1405. doi:10.1111/bcp.12032
  4. MacIntyre IM, Turtle EJ, Farrah TE, GRAHAM C, Dear JW, Webb DJ; PATH-BP (Paracetamol in Hypertension-Blood Pressure) Investigators. Regular acetaminophen use and blood pressure in people with hypertension: the PATH-BP trial. Circulation. 2022;145(6):416-423. doi:10.1161/CIRCULATIONAHA.121.056015
  5. Ruschitzka F, Borer JS, Krum H, et al. Differential blood pressure effects of ibuprofen, naproxen, and celecoxib in patients with arthritis: the PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement) Trial. Eur Heart J. 2017;38(44):3282-3292. doi:10.1093/eurheartj/ehx508