Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and the risk of developing rheumatoid arthritis in antihypertensive drug users

Hilda J. I. de Jong, Rob J. Vandebriel, Siti R. F. Saldi, Liset van Dijk, Henk van Loveren, Jan Willem Cohen Tervaert, Olaf H. Klungel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Purpose Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective in the treatment of cardiovascular disease. Next to effects on hypertension and cardiac function, these drugs have anti-inflammatory and immunomodulating properties which may either facilitate or protect against the development of autoimmunity, potentially resulting in autoimmune diseases. Therefore, we determined in the current study the association between ACE inhibitor and ARB use and incident rheumatoid arthritis (RA). Methods A matched casecontrol study was conducted among patients treated with antihypertensive drugs using the Netherlands Information Network of General Practice (LINH) database in 20012006. Cases were patients with a first-time diagnosis of RA. Each case was matched to five controls for age, sex, and index date, which was selected 1 year before the first diagnosis of RA. ACE inhibitor and ARB exposure was considered to be any prescription issued in the period before index date. Logistic regression analysis was used to estimate odds ratios (ORs) and their 95% confidence intervals (CI). Results Our study included 211 cases and 667 matched controls. After controlling for potential confounders, ever use of ACE inhibitors or ARBs was not associated with incident RA (adjusted ORs [95%CI], 0.99 [0.551.79] and 1.02 [0.671.56], respectively). The adjusted ORs (95%CI) for current and past use of ACE inhibitors were 1.18 (0.751.85) and 0.61 (0.281.35). For current and past use of ARBs, these adjusted ORs (95%CI) were 1.40 (0.802.45) and 0.29 (0.051.67), respectively. No duration and doseeffect relationship was observed. Conclusions ACE inhibitor or ARB use is not associated with incident RA.
Original languageEnglish
Pages (from-to)835-843
JournalPharmacoepidemiology and Drug Safety
Issue number8
Publication statusPublished - Aug 2012


  • angiotensin-converting enzyme inhibitor
  • angiotensin II receptor blocker
  • rheumatoid arthritis
  • autoimmune
  • immunomodulation
  • case-control study
  • pharmacoepidemiology

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