Official reprint from UpToDate®
www.uptodate.com ©2015 UpToDate®

NSAIDs and acetaminophen: Effects on blood pressure and hypertension

Norman M Kaplan, MD
Raymond R Townsend, MD
Section Editors
Richard H Sterns, MD
George L Bakris, MD
Deputy Editor
John P Forman, MD, MSc


Nonsteroidal anti-inflammatory drugs (NSAIDs) have a variety of adverse effects. From a cardiovascular viewpoint, they can both raise the blood pressure and affect overall cardiovascular risk.

The effect of NSAIDs and acetaminophen on blood pressure and the development of hypertension will be reviewed here. The cardiovascular effects of NSAIDs as well as their adverse effects in patients with chronic kidney disease are discussed separately. (See "Nonselective NSAIDs: Adverse cardiovascular effects" and "COX-2 selective inhibitors: Adverse cardiovascular effects" and "NSAIDs: Acute kidney injury (acute renal failure)".)


All NSAIDs in doses adequate to reduce inflammation and pain can increase blood pressure in both normotensive and hypertensive individuals [1]. The average rise in blood pressure is 3/2 mmHg but varies considerably [2-4]. In addition, NSAID use may reduce the effect of all antihypertensive drugs except calcium channel blockers [5]. These effects may contribute to the increase in cardiovascular risk associated with the selective cyclooxygenase-2 (COX-2) inhibitors [6]. (See "COX-2 selective inhibitors: Adverse cardiovascular effects".)

The prohypertensive effect is dose dependent and probably involves inhibition of COX-2 in the kidneys, which reduces sodium excretion and increases intravascular volume [5]. Low-dose aspirin has no COX-2-inhibiting or prohypertensive effects. As an example, 75 mg/day of aspirin did not interfere with antihypertensive therapy, as compared with placebo, in 18,790 patients in the Hypertension Optimal Treatment (HOT) Study [7]. However, these conclusions cannot be extended to larger doses of aspirin.


Acetaminophen produces its analgesic effect by inhibiting the same cyclooxygenase, prostaglandin H2 synthase, that is the target of NSAID and aspirin [8]. However, acetaminophen blocks this enzyme at its peroxidase catalytic rather than at the cyclooxygenase catalytic site. Therefore, the acetaminophen-mediated inhibition is sensitive to changes in the tissue peroxide levels; higher concentrations of peroxide in activated leukocytes and platelets block the effect of acetaminophen on inflammation and platelet thrombosis. However, acetaminophen is able to inhibit prostaglandins in the central nervous system, thus providing relief of pain and fever. Therefore, acetaminophen is not an NSAID or antithrombotic agent.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Oct 2015. | This topic last updated: Sep 8, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2015 UpToDate, Inc.
  1. Warner TD, Mitchell JA. COX-2 selectivity alone does not define the cardiovascular risks associated with non-steroidal anti-inflammatory drugs. Lancet 2008; 371:270.
  2. Grover SA, Coupal L, Zowall H. Treating osteoarthritis with cyclooxygenase-2-specific inhibitors: what are the benefits of avoiding blood pressure destabilization? Hypertension 2005; 45:92.
  3. Pope JE, Anderson JJ, Felson DT. A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure. Arch Intern Med 1993; 153:477.
  4. Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med 1994; 121:289.
  5. White WB. Cardiovascular effects of the cyclooxygenase inhibitors. Hypertension 2007; 49:408.
  6. Messerli FH, Sichrovsky T. Does the pro-hypertensive effect of cyclooxygenase-2 inhibitors account for the increased risk in cardiovascular disease? Am J Cardiol 2005; 96:872.
  7. Zanchetti A, Hansson L, Leonetti G, et al. Low-dose aspirin does not interfere with the blood pressure-lowering effects of antihypertensive therapy. J Hypertens 2002; 20:1015.
  8. Aronoff DM, Oates JA, Boutaud O. New insights into the mechanism of action of acetaminophen: Its clinical pharmacologic characteristics reflect its inhibition of the two prostaglandin H2 synthases. Clin Pharmacol Ther 2006; 79:9.
  9. Chan AT, Manson JE, Albert CM, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation 2006; 113:1578.
  10. Forman JP, Rimm EB, Curhan GC. Frequency of analgesic use and risk of hypertension among men. Arch Intern Med 2007; 167:394.
  11. Chalmers JP, West MJ, Wing LM, et al. Effects of indomethacin, sulindac, naproxen, aspirin, and paracetamol in treated hypertensive patients. Clin Exp Hypertens A 1984; 6:1077.
  12. Dedier J, Stampfer MJ, Hankinson SE, et al. Nonnarcotic analgesic use and the risk of hypertension in US women. Hypertension 2002; 40:604.
  13. Sudano I, Flammer AJ, Périat D, et al. Acetaminophen increases blood pressure in patients with coronary artery disease. Circulation 2010; 122:1789.
  14. Radack KL, Deck CC, Bloomfield SS. Ibuprofen interferes with the efficacy of antihypertensive drugs. A randomized, double-blind, placebo-controlled trial of ibuprofen compared with acetaminophen. Ann Intern Med 1987; 107:628.
  15. Dawson J, Fulton R, McInnes GT, et al. Acetaminophen use and change in blood pressure in a hypertensive population. J Hypertens 2013; 31:1485.