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Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system.

Publication ,  Journal Article
Toh, S; Reichman, ME; Houstoun, M; Ross Southworth, M; Ding, X; Hernandez, AF; Levenson, M; Li, L; McCloskey, C; Shoaibi, A; Wu, E ...
Published in: Arch Intern Med
November 12, 2012

BACKGROUND: Although certain drugs that target the renin- angiotensin-aldosterone system are linked to an increased risk for angioedema, data on their absolute and comparative risks are limited. We assessed the risk for angioedema associated with the use of angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and the direct renin inhibitor aliskiren. METHODS: We conducted a retrospective, observational, inception cohort study of patients 18 years or older from 17 health plans participating in the Mini-Sentinel program who had initiated the use of an ACEI (n = 1 845 138), an ARB (n = 467 313), aliskiren (n = 4867), or a β-blocker (n = 1 592 278) between January 1, 2001, and December 31, 2010. We calculated the cumulative incidence and incidence rate of angioedema during a maximal 365-day follow-up period. Using β-blockers as a reference and a propensity score approach, we estimated the hazard ratios of angioedema separately for ACEIs, ARBs, and aliskiren, adjusting for age, sex, history of allergic reactions, diabetes mellitus, heart failure, or ischemic heart disease, and the use of prescription nonsteroidal anti-inflammatory drugs. RESULTS: A total of 4511 angioedema events (3301 for ACEIs, 288 for ARBs, 7 for aliskiren, and 915 for β-blockers) were observed during the follow-up period. The cumulative incidences per 1000 persons were 1.79 (95% CI, 1.73-1.85) cases for ACEIs, 0.62 (95% CI, 0.55-0.69) cases for ARBs, 1.44 (95% CI, 0.58-2.96) cases for aliskiren, and 0.58 (95% CI, 0.54-0.61) cases for β-blockers. The incidence rates per 1000 person-years were 4.38 (95% CI, 4.24-4.54) cases for ACEIs, 1.66 (95% CI, 1.47-1.86) cases for ARBs, 4.67 (95% CI, 1.88-9.63) cases for aliskiren, and 1.67 (95% CI, 1.56-1.78) cases for β-blockers. Compared with the use of β-blockers, the adjusted hazard ratios were 3.04 (95% CI, 2.81-3.27) for ACEIs, 1.16 (95% CI, 1.00-1.34) for ARBs, and 2.85 (95% CI, 1.34-6.04) for aliskiren. CONCLUSIONS: Compared with β-blockers, ACEIs or aliskiren was associated with an approximately 3-fold higher risk for angioedema, although the number of exposed events for aliskiren was small. The risk for angioedema was lower with ARBs than with ACEIs or aliskiren.

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Published In

Arch Intern Med

DOI

EISSN

1538-3679

Publication Date

November 12, 2012

Volume

172

Issue

20

Start / End Page

1582 / 1589

Location

United States

Related Subject Headings

  • Young Adult
  • United States
  • Time Factors
  • Risk Factors
  • Retrospective Studies
  • Renin-Angiotensin System
  • Middle Aged
  • Male
  • Incidence
  • Humans
 

Citation

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Toh, S., Reichman, M. E., Houstoun, M., Ross Southworth, M., Ding, X., Hernandez, A. F., … Hennessy, S. (2012). Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system. Arch Intern Med, 172(20), 1582–1589. https://doi.org/10.1001/2013.jamainternmed.34
Toh, Sengwee, Marsha E. Reichman, Monika Houstoun, Mary Ross Southworth, Xiao Ding, Adrian F. Hernandez, Mark Levenson, et al. “Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system.Arch Intern Med 172, no. 20 (November 12, 2012): 1582–89. https://doi.org/10.1001/2013.jamainternmed.34.
Toh S, Reichman ME, Houstoun M, Ross Southworth M, Ding X, Hernandez AF, et al. Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system. Arch Intern Med. 2012 Nov 12;172(20):1582–9.
Toh, Sengwee, et al. “Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system.Arch Intern Med, vol. 172, no. 20, Nov. 2012, pp. 1582–89. Pubmed, doi:10.1001/2013.jamainternmed.34.
Toh S, Reichman ME, Houstoun M, Ross Southworth M, Ding X, Hernandez AF, Levenson M, Li L, McCloskey C, Shoaibi A, Wu E, Zornberg G, Hennessy S. Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system. Arch Intern Med. 2012 Nov 12;172(20):1582–1589.

Published In

Arch Intern Med

DOI

EISSN

1538-3679

Publication Date

November 12, 2012

Volume

172

Issue

20

Start / End Page

1582 / 1589

Location

United States

Related Subject Headings

  • Young Adult
  • United States
  • Time Factors
  • Risk Factors
  • Retrospective Studies
  • Renin-Angiotensin System
  • Middle Aged
  • Male
  • Incidence
  • Humans