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drug adverse effects of ACE inhibitors

Adverse effects: 1) cough [4] a) may occur after several weeks to 1 year b) dose reduction may alleviate cough c) switching ACE inhibitor is generally of little benefit 2) hyperkalemia & hyponatremia via inhibition of aldosterone secretion* 3) hypotension & renal insufficiency with reduced preload - may decrease GFR & increase serum creatinine in patients with renal perfusion maintained by increased angiotensin-2 [4] 4) acute renal insufficiency may develop in patients with bilateral renal artery stenosis* 5) rash 6) angioedema (1%) [6,8] a) generally occurs within 1st week b) may occur years later c) more common in blacks than whites; 1% vs 0.3% [11] d) probably via inhibiting breakdown of bradykinin [5] e) small intestine angioedema presenting as acute abdominal pain [12] f) 2% of patients with angioedema on an ACE inhibitor also get angioedema on an ARB [11] g) standard therapy consists of intravenous prednisolone 500 mg plus clemastine 2 mg [13] h) icatibant 30 mg SQ is an alternative [13] i) may not respond to epinephrine [4,8] f) wait at least 4 weeks after stopping an ACE inhibitor to start an ARB [11] 7) dysgeusia 8) increased serum creatinine a) 15-20% initial increase is acceptable [4]; up to 30% acceptable [16] b) decline in creatinine within 1 month [4] (2 months [16]), otherwise discontinue c) increases in serum creatinine after the start of ACE inhibitor or ARB is associated with adverse cardiorenal outcomes, even below the guideline recommended threshold of a 30% increase for stopping treatment [14] d) <2% with serum creatinine increases of >=30% - these patients with increased risk for - end-stage renal disease (RR=3.4) - myocardial infarction (RR=1.5) - heart failure (RR=1.4) - all-cause mortality (RR=1.8) [14] 9) proteinuria may or may not [2] be present 10) contrast nephropathy [7] 11) leukopenia 12) vasomotor rhinitis 13) may exacerbate psoriasis [4] 14) congenital malformations when used during 1st trimester of pregnancy [9] 15) exposure during the 2nd & 3rd trimesters of pregnancy are associated with neonatal renal failure & death [4] 16) associated with increased risk of hospitalization with acute renal failure [10] 17) increased risk of lung cancer relative to ARB (1.6 vs 1.2 per 1000 person-years) [15] 18) increased risk of stroke 11% & stroke mortality 19% vs diuretic [17] * Serum creatinine & K+ should be checked within 1 week of starting an ACE inhibitor.

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DRUGS: ACE inhibitor FORM: drug adverse effects angiotensin converting enzyme inhibitor

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 117
  2. contribution from Peter Baylor, M.D. VAMC, UCSF Fresno
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, American College of Physicians, Philadelphia 1998, 2012 - Dicpinigaitis PV. Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan;129(1 Suppl):169S-173S. PMID: 16428706
  5. Prescriber's Letter 11(7):31 2004
  6. Prescriber's Letter 9(4):19 2002 - Prescriber's Letter 9(11):62 2002
  7. Rim MY et al. The effect of renin-angiotensin-aldosterone system blockade on contrast-induced acute kidney injury: A propensity-matched study. Am J Kidney Dis 2012 Oct; 60:576. PMID: 22658321
  8. Malde B, Regalado J, Greenberger PA. Investigation of angioedema associated with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Ann Allergy Asthma Immunol. 2007 Jan;98(1):57-63. PMID: 17225721
  9. Cooper WO, Hernandez-Diaz S, Arbogast PG et al Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006 Jun 8;354(23):2443-51. PMID: 16760444
  10. Tomlinson LA et al ACE Inhibitor and Angiotensin Receptor-II Antagonist Prescribing and Hospital Admissions with Acute Kidney Injury: A Longitudinal Ecological Study. PLoS ONE. 2013 8(11): e78465 PMID: 24223154 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0078465
  11. Prescriber's Letter 21(7): 2014 Safe Use of ARBs in Patients with ACE Inhibitor-Associated Angioedema. Detail-Document#: 300722 (subscription needed) http://www.prescribersletter.com
  12. Scheirey CD et al. Angiotensin-converting enzyme inhibitor-induced small-bowel angioedema: Clinical and imaging findings in 20 patients. AJR Am J Roentgenol 2011 Aug; 197:393. PMID: 21785085
  13. Bas M et al A Randomized Trial of Icatibant in ACE-Inhibitor-Induced Angioedema. N Engl J Med 2015; 372:418-425. January 29, 2015 PMID: 25629740 http://www.nejm.org/doi/full/10.1056/NEJMoa1312524
  14. Schmidt M et al Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study. BMJ 2017;356:j791 PMID: 28279964 Free full text http://www.bmj.com/content/356/bmj.j791
  15. Hicks BM, Filion KB, Yin H et al Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study. BMJ 2018;363:k4209 PMID: 30355745 Free PMC Article https://www.bmj.com/content/363/bmj.k4209 - Cronin-Fenton D Angiotensin converting enzyme inhibitors and lung cancer. BMJ 2018;363:k4337 PMID: 30355573 https://www.bmj.com/content/363/bmj.k4337
  16. NEJM Knowledge+ Complex Medical Care
  17. Yamal JM, Martinez J, Osani MC et al Mortality and Morbidity Among Individuals With Hypertension Receiving a Diuretic, ACE Inhibitor, or Calcium Channel Blocker. A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023;6(12):e2344998. PMID: 38048133 PMCID: PMC10696481 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2812523