Regular Acetaminophen Use and Blood Pressure in People With Hypertension: The PATH-BP Trial
Open accessAbstract
Background: Acetaminophen is widely used as first-line therapy for chronic pain because of its perceived safety and the assumption that, unlike nonsteroidal anti-inflammatory drugs, it has little or no effect on blood pressure (BP). Although observational studies suggest that acetaminophen may increase BP, clinical trials are lacking. We, therefore, studied the effects of regular acetaminophen dosing on BP in individuals with hypertension. Methods: In this double-blind, placebo-controlled, crossover study, 110 individuals were randomized to receive 1 g acetaminophen 4× daily or matched placebo for 2 weeks followed by a 2-week washout period before crossing over to the alternate treatment. At the beginning and end of each treatment period, 24-hour ambulatory BPs were measured. The primary outcome was a comparison of the change in mean daytime systolic BP from baseline to end of treatment between the placebo and acetaminophen arms. Results: One-hundred three patients completed both arms of the study. Regular acetaminophen, compared with placebo, resulted in a significant increase in mean daytime systolic BP (132.8±10.5 to 136.5±10.1 mm Hg [acetaminophen] vs 133.9±10.3 to 132.5±9.9 mm Hg [placebo]; P <0.0001) with a placebo-corrected increase of 4.7 mm Hg (95% CI, 2.9–6.6) and mean daytime diastolic BP (81.2±8.0 to 82.1±7.8 mm Hg [acetaminophen] vs 81.7±7.9 to 80.9±7.8 mm Hg [placebo]; P =0.005) with a placebo-corrected increase of 1.6 mm Hg (95% CI, 0.5–2.7). Similar findings were seen for 24-hour ambulatory and clinic BPs. Conclusions: Regular daily intake of 4 g acetaminophen increases systolic BP in individuals with hypertension by ≈5 mm Hg when compared with placebo; this increases cardiovascular risk and calls into question the safety of regular acetaminophen use in this situation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01997112. URL: https://www.clinicaltrialsregister.eu ; Unique identifier: 2013-003204-40.
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Some observational studies show an increase in blood pressure among chronic paracetamol users.
“On the other hand, the risk of worsening hypertension should be considered, with some observational studies showing an increase in blood pressure among chronic paracetamol users.97,98”
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Ettehad, D., Emdin, C. A., Kiran, A., Anderson, S. G., Callender, T., Emberson, J., Chalmers, J., Rodgers, A., & Rahimi, K. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01225-8 · Cited by 3,755 · see citing works
Oliveira, C. B., Maher, C. G., Pinto, R. Z., Traeger, A. C., Lin, C.-W. C., Chenot, J.-F., van Tulder, M., & Koes, B. W. (2018) · European Spine Journal · doi:10.1007/s00586-018-5673-2 · Cited by 1,584 · see citing works
Do Nonsteroidal Anti-inflammatory Drugs Affect Blood Pressure? A Meta-Analysis
Johnson, A. G., Nguyen, T. V., & Day, R. O. (1994) · Annals of Internal Medicine · doi:10.7326/0003-4819-121-4-199408150-00011 · Cited by 717 · see citing works
A Meta-analysis of the Effects of Nonsteroidal Anti-inflammatory Drugs on Blood Pressure
Pope, J. E. (1993) · Archives of Internal Medicine · doi:10.1001/archinte.1993.00410040045007 · Cited by 527 · see citing works
Long‐term adverse effects of paracetamol – a review
McCrae, J. C., Morrison, E. E., MacIntyre, I. M., Dear, J. W., & Webb, D. J. (2018) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13656 · Cited by 308 · see citing works
Self-citationNon-Narcotic Analgesic Dose and Risk of Incident Hypertension in US Women
Forman, J. P., Stampfer, M. J., & Curhan, G. C. (2005) · Hypertension · doi:10.1161/01.hyp.0000177437.07240.70 · Cited by 196 · see citing works
Acetaminophen use and change in blood pressure in a hypertensive population
Dawson, J., Fulton, R., McInnes, G. T., Morton, R., Morrison, D., Padmanabhan, S., Hewitt, J., Meredith, P., Muir, S., Dominiczak, A. F., et al. (2013) · Journal of Hypertension · doi:10.1097/hjh.0b013e328360f6f8 · Cited by 27 · see citing works
Flagged first, then by citations
Research works printed but not linked: 16
- [2]Saragiotto BT Machado GC Ferreira ML Pinheiro MB Abdel Shaheed C Maher CG Paracetamol for low back pain Cochrane Database Syst Rev 2016 CD012230 27271789 PMC6353046
- [3]da Costa BR Reichenbach S Keller N Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis Lancet 2017 390 e21 e33 28699595
- [5]Williams CM Maher CG Latimer J Efficacy of paracetamol for acute low-back pain: a double-blind, randomised controlled trial Lancet 2014 384 1586 96 25064594
- [6]Pettie JM Caparrotta TM Hunter RW Safety and efficacy of the SNAP 12-hour acetylcysteine regimen for the treatment of paracetamol overdose EClinicalMedicine 2019 11 11 7 31317129 PMC6610779
- [7]Turtle EJ Dear JW Webb DJ A systematic review of the effect of paracetamol on blood pressure in hypertensive and non-hypertensive subjects Br J Clin Pharmacol 2013 75 1396 405 23145789 PMC3690099
- [8]What dose of paracetamol for older people? Drug Ther Bull 2018 56 69 72 29903753
- [9]Stergiou GS Giovas PP Gkinos CP Patouras JD Validation of the Microlife WatchBP Home device for self home blood pressure measurement according to the International Protocol Blood Press Monit 2007 12 185 8 17496469
- [10]National Institute for Health and Care Excellence Hypertension in adults: diagnosis and management last accessed 01 Oct 2021 [online]. Available at https://www.nice.org.uk/guidance/ng136 31577399
- [11]Sudano I Flammer AJ Periat D Acetaminophen increases blood pressure in patients with coronary artery disease Circulation 2010 122 1789 96 20956208
- [12]Lewington S Clarke R Qizilbash N Peto R Collins R Prospective Studies C Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies Lancet 2002 360 1903 13 12493255
- [14]Paulose-Ram R Hirsch R Dillon C Gu Q Frequent monthly use of selected non-prescription and prescription non-narcotic analgesics among U.S. adults Pharmacoepidemiol Drug Saf 2005 14 257 66 15386703
- [15]Hwang AY Dave CV Smith SM Use of prescription medications that potentially interfere with blood pressure control in new-onset hypertension and treatment-resistant hypertension Am J Hypertens 2018 31 1324 31 30052747 PMC6233674
- [16]Curhan GC Willett WC Rosner B Stampfer MJ Frequency of analgesic use and risk of hypertension in younger women Arch Intern Med 2002 162 2204 8 12390063
- [21]Aw TJ Haas SJ Liew D Krum H Meta-analysis of cyclooxygenase-2 inhibitors and their effects on blood pressure Arch Intern Med 2005 165 490 6 15710786
- [22]Ruschitzka F Borer JS Krum H 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 3282 92 29020251 PMC8139400
- [23]Chan AT Manson JE Albert CM Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events Circulation 2006 113 1578 87 16534006
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Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association
Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Anderson, C. A. M., Arora, P., Avery, C. L., Baker-Smith, C. M., Beaton, A. Z., Boehme, A. K., Buxton, A. E., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001123 · Cited by 8,300 · see citing works
Jones, D. W., Ferdinand, K. C., Taler, S. J., Johnson, H. M., Shimbo, D., Abdalla, M., Altieri, M. M., Bansal, N., Bello, N. A., Bress, A. P., et al. (2025) · JACC · doi:10.1016/j.jacc.2025.05.007 · Cited by 280 · see citing works
Lewey, J., Beckie, T. M., Brown, H. L., Brown, S. D., Garovic, V. D., Khan, S. S., Miller, E. C., Sharma, G., Mehta, L. S., & on behalf of the American Heart Association Cardiovascular Disease and Stroke in Women and Underrepresented Populations Committee of the Council on Clinical Cardiology; Council on Cardiopulmonary, C. C. (2024) · Circulation · doi:10.1161/cir.0000000000001212 · Cited by 229 · see citing works
Mallet, C., Desmeules, J., Pegahi, R., & Eschalier, A. (2023) · Journal of Pain Research · doi:10.2147/jpr.s393809 · Cited by 83 · see citing works
“On the other hand, the risk of worsening hypertension should be considered, with some observational studies showing an increase in blood pressure among chronic paracetamol users.(97,98) Still, published studies failed to show an association between elevated blood pressure and the risk of serious cardiovascular events…”
BackgroundAlchin, J., Dhar, A., Siddiqui, K., & Christo, P. J. (2022) · Current Medical Research and Opinion · doi:10.1080/03007995.2022.2049551 · Cited by 65 · see citing works
- Authors
- MacIntyre, I. M., Turtle, E. J., Farrah, T. E., Graham, C., Dear, J. W., Webb, D. J., McCallum, M., Melville, V., Fok, H., McCrae, J. C., Sule, A., Caparrotta, T. M., Kirkby, N. S., & Mitchell, J. A.
- Affiliations
- National Health Service (GB)
- British Heart Foundation (GB)
- University of Edinburgh (GB)
- Corresponding author
- Webb, David J.
- ORCID
- Venue
- Circulation
- Published
- 2022-02-08
- Volume
- 145
- Issue
- 6
- Pages
- 416-423
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC7612370
- OpenAlex
- W4210386945
- Cited by
- 80
- References
- 7
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 14 · 2023: 24 · 2022: 18
- FWCI
- 12.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Circulation (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc)
- Funders
- Scottish Government
- British Heart Foundation (RG/18/4/33541, FS/16/1/31699, PG/13/26/30128)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- paracetamol, hypertension, blood pressure, ambulatory blood pressure, systolic blood pressure, drug safety, cardiovascular risk, placebo-controlled crossover trial
- MeSH terms
- Acetaminophen, Blood Pressure, Double-Blind Method, Female, Humans, Hypertension, Male, Middle Aged, Cross-Over Studies
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