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Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations
  1. Cheuk-Chun Szeto1,2,
  2. Kentaro Sugano3,4,
  3. Ji-Guang Wang5,6,
  4. Kazuma Fujimoto7,8,
  5. Samuel Whittle9,10,
  6. Gopesh K Modi2,11,
  7. Chen-Huen Chen12,13,
  8. Jeong-Bae Park13,14,
  9. Lai-Shan Tam1,10,
  10. Kriengsak Vareesangthip2,15,
  11. Kelvin K F Tsoi16,
  12. Francis K L Chan16
  1. 1 Department of Medicine and Therapeutics, Chinese University of Hong Kong, New Territories, Hong Kong
  2. 2 Asian Pacific Society of Nephrology (APSN), Hong Kong, Hong Kong
  3. 3 Jichi Medical University, Shimotsuke, Tochigi, Japan
  4. 4 Asian Pacific Association of Gastroenterology (APAGE), Tochigi, Japan
  5. 5 Shanghai Institute of Hypertension, Shanghai, Shanghai, China
  6. 6 Asia Pacific Society of Hypertension (APSH), Shanghai, China
  7. 7 Saga University, Saga, Japan
  8. 8 Asia-Pacific Society for Digestive Endoscopy (APSDE), Saga, Japan
  9. 9 The University of Adelaide, Adelaide, South Australia, Australia
  10. 10 Asia Pacific League of Associations for Rheumatology (APLAR), Adelaide, South Australia, Australia
  11. 11 Samarpan Kidney Institute and Research Center, Bhopal, India
  12. 12 National Yang-Ming University, Taipei, Taiwan
  13. 13 Pulse of Asia (PoA), Taipei, Taiwan
  14. 14 JB Lab and Clinic and Sungkyunkwan University School of Medicine, Seoul, Korea
  15. 15 Mahidol University, Nakorn Pathom, Thailand
  16. 16 Chinese University of Hong Kong, New Territories, Hong Kong
  1. Correspondence to Professor Francis K L Chan, Chinese University of Hong Kong, New Territories, Hong Kong; fklchan{at}


Background Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed medications, but they are associated with a number of serious adverse effects, including hypertension, cardiovascular disease, kidney injury and GI complications.

Objective To develop a set of multidisciplinary recommendations for the safe prescription of NSAIDs.

Methods Randomised control trials and observational studies published before January 2018 were reviewed, with 329 papers included for the synthesis of evidence-based recommendations.

Results Whenever possible, a NSAID should be avoided in patients with treatment-resistant hypertension, high risk of cardiovascular disease and severe chronic kidney disease (CKD). Before treatment with a NSAID is started, blood pressure should be measured, unrecognised CKD should be screened in high risk cases, and unexplained iron-deficiency anaemia should be investigated. For patients with high cardiovascular risk, and if NSAID treatment cannot be avoided, naproxen or celecoxib are preferred. For patients with a moderate risk of peptic ulcer disease, monotherapy with a non-selective NSAID plus a proton pump inhibitor (PPI), or a selective cyclo-oxygenase-2 (COX-2) inhibitor should be used; for those with a high risk of peptic ulcer disease, a selective COX-2 inhibitor plus PPI are needed. For patients with pre-existing hypertension receiving renin-angiotensin system blockers, empirical addition (or increase in the dose) of an antihypertensive agent of a different class should be considered. Blood pressure and renal function should be monitored in most cases.

Conclusion NSAIDs are a valuable armamentarium in clinical medicine, but appropriate recognition of high-risk cases, selection of a specific agent, choice of ulcer prophylaxis and monitoring after therapy are necessary to minimise the risk of adverse events.

  • aspirin
  • bleeding peptic ulcer
  • cardiovascular disease
  • non-steroidal anti-inflammatory drugs
  • portal hypertension

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  • C-CS and KS contributed equally.

  • Correction notice This article has been corrected since it published Online First. The corresponding author details have been updated and affiliations 14 amended.

  • Contributors KS, KF and FKLC are responsible for the literature review and statement preparation of the gastroenterology section. JGW, CHC and JBP are responsible for the literature review and statement preparation of the cardiovascular and hypertension sections. CCS, GKM and KV are responsible for the literature review and statement preparation of the renal section. SW and LST are responsible for overall literature review and inter-disciplinary statements. KT is responsible for primary literature search and final proof of the manuscript. CCS, KS and FKLC are responsible for manuscript writing.

  • Funding This work was supported by unrestricted educational grants from Pfizer Inc. and the Faculty of Medicine, the Chinese University of Hong Kong. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

  • Competing interests C-CS is an adviser or consultant for Baxter Healthcare and Gilead Sciences; speaker for Baxter Healthcare, AstraZeneca, Pfizer Inc. KS reports conflict of interest with Takeda Pharmacol Inc. and Astra-Zeneca Pharma. J-GW was supported by grants from the National Natural Science Foundation of China (91639203) and State Ministry of Science and Technology (2018YFC1704902), Beijing, China and the Shanghai Commissions of Science and Technology (15XD1503200) and Health (15GWZK0802 and a special grant for 'leading academics'), Shanghai, China. J-GW also reports receiving lecture and consulting fees from Astra-Zeneca, Bayer, Daiichi-Sankyo, MSD, Novartis, Omron, Pfizer, Sanofi, Servier and Takeda. C-HC is an adviser or consultant for Novartis Pharmaceuticals Corporation; speaker or member of a speakers bureau for AstraZeneca, Pfizer Inc., Bayer AG, Bristol-Myers Squibb Company, Boehringer Ingelheim Pharmaceuticals Inc., Daiichi Sankyo Inc., Novartis Pharmaceuticals Corporation, SERVIER, Merck & Co. Inc., Sanofi, TAKEDA Pharmaceuticals International. FKLC reports speaker's honoraria from AstraZeneca, Pfizer, Eisai and Takeda.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.