DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20213114

Pleiotropic benefits and utility of angiotensin converting enzyme inhibitors in current practice

Vishal Madanlal Chaudhari, Dnyanoba Kishanrao Bhaskar, Medha Ajit Oak

Abstract


The renin-angiotensin-aldosterone system (RAAS) is responsible for maintaining hemodynamic stability and thereby impacts multiple organ systems, such as the central nervous system, heart, and kidneys. Angiotensin II (ang II) is the main effector of the RAAS. However, overactivity of the RAAS can give rise to cardiovascular disorders, stroke, and nephrosclerosis. Unfavorable effects on cardiovascular system are attributed to ang II. RAAS activation also results in release and increased activity of several hormonal and inflammatory mediators, trigger formation of a number of secondary messengers and/or activate pathways, which negatively affects blood vessels and tissue. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and calcium channel blockers can protect various organs from damage by blocking the protean manifestation of RAAS activity, either in its circulating or its locally tissue-active form. This review explains on the pleiotropic effects and benefits that go beyond mere blood pressure control. ACEIs in terms of mortality reduction, long‑term survival benefits, cardioprotective and vasculo-protective effects as well as improve fibrinolytic balance. Ramipril has been clinically proven to reduce rates of mortality, myocardial infarction, and stroke. ACEIs and ARBs were associated with lesser risks of COVID-19 infection.


Keywords


ACE inhibitors, Renin-angiotensin system, Pleiotropic benefits, COVID-19

Full Text:

PDF

References


Jankowski P, Safar ME, Benetos A. Pleiotropic Effects of Drugs Inhibiting the Renin-Angiotensin-Aldosterone System. Curr Pharmaceutical Design. 2009;15,571-84.

Ismail H, Mitchell R, McFarlane SI, Makaryus AN. Pleiotropic Effects of Inhibitors of the RAAS in the Diabetic Population: Above and Beyond Blood Pressure Lowering. Curr Diab Rep. 2010;10:32-6.

Sica D. Are there pleiotropic effects of antihypertensive medications or is it all about the blood pressure in the patient with diabetes and hypertension? J Clin Hypertens (Greenwich). 2011;13:301-4.

Bahit MC, Kochar A, Granger CB. Post-Myocardial Infarction Heart Failure. JACC Heart Fail. 2018;6:179-86

Verma S, Strauss M. Angiotensin receptor blockers and myocardial infarction. BMJ. 2004;329:1248-9.

McDonald MA, Simpson SH, Ezekowitz JA, Gyenes G, Suyuki RT. Angiotensin receptor blockers and risk of myocardial infarction: systematic review. BMJ. 2005;331:873.

Volpe M, Tocci G, Sciarretta S, Verdecchia P, Trimarco B, Mancia G. Angiotensin II receptor blockers and myocardial infarction: an updated analysis of randomized clinical trials. J Hypertens. 2009;27:941-6.

Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100,000 patients in randomized trials. ACE Inhibitor Myocardial Infarction Collaborative Group. Circulation. 1998;97:2202-12.

Choi IS, Park IB, Lee K, Ahn TH, Kim JH, Ahn Y, et al. Angiotensin-Converting Enzyme Inhibitors Provide Better Long-Term Survival Benefits to Patients With AMI Than Angiotensin II Receptor Blockers After Survival Hospital Discharge. J Cardiovasc Pharmacol Ther. 2019;24:120-29.

Lv X, Zhang Y, Niu Y, Song Qi, Zhao Q. Comparison of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on cardiovascular outcomes in hypertensive patients with type 2 diabetes mellitus: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2018;97:e0256.

Lonn EM, Yusuf S, Jha P, Montague TJ, Teo KK, Benedict CR et al. Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection. Circulation. 1994;90:2056-69.

Matsumoto T, Horie M. Angiotensin-converting enzyme inhibition and fibrinolytic balance. Hypertens Res. 2011;34:448-9.

Warner GT, Perry CM. Ramipril: a review of its use in the prevention of cardiovascular outcomes. Drugs. 2002;62:1381-05.

Anderson VR, Perry CM, Robinson DM. Ramipril: a review of its use in preventing cardiovascular outcomes in high-risk patients. Am J Cardiovasc Drugs. 2006;6:417-32.

The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet. 1993;342:821-8

Hall AS, Murray GD, Ball SG. Follow-up study of patients randomly allocated ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) Study. Acute Infarction Ramipril Efficacy. Lancet. 1997;349:1493-7.

Heart Outcomes Prevention Evaluation Study Investigators, Yusuf S, Sleight P, Pogue J. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342:145-53.

Lonn E, Shaikholeslami R, Yi Q, Bosch J, Sullivan B, Tanser P et al. Effects of ramipril on left ventricular mass and function in cardiovascular patients with controlled blood pressure and with preserved left ventricular ejection fraction: a substudy of the Heart Outcomes Prevention Evaluation (HOPE) Trial. J Am Coll Cardiol. 2004;43:2200-6.

Wienbergen H, Schiele R, Gitt AK, Juenger C, Heer T, Meisenzahl C et al. MITRA PLUS Study Group. Impact of ramipril versus other angiotensin-converting enzyme inhibitors on outcome of unselected patients with ST-elevation acute myocardial infarction. Am J Cardiol. 2002;90:1045-9.

Pilote L, Abrahamowicz M, Rodrigues E, Eisenberg MJ, Rahme E. Mortality rates in elderly patients who take different angiotensin-converting enzyme inhibitors after acute myocardial infarction: a class effect? Ann Intern Med. 2004;141:102-12.

Wagner A, Herkner H, Schreiber W, Bur A, Woisetschläger C, Stix G et al. Ramipril prior to thrombolysis attenuates the early increase of PAI-1 in patients with acute myocardial infarction. Thromb Haemost. 2002;88:180-5.

Patel AB, Verma A. COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: What Is the Evidence? JAMA. 2020;323:1769-70.

Hippisley-Cox J, Young D, Coupland C, Channon KM, Tan PS, Harrison DA et al. Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people. Heart. 2020;106:1503-11.

Düsing R. Pharmacological interventions into the renin-angiotensin system with ACE inhibitors and angiotensin II receptor antagonists: effects beyond blood pressure lowering. Ther Adv Cardiovasc Dis. 2016;10(3):151-61.

Leong DP, Leong DP, McMurray JV, Joseph PG, Yusuf S. From ACE Inhibitors/ARBs to ARNIs in Coronary Artery Disease and Heart Failure (Part 2/5). J Am Coll Cardiol. 2019;74(5):683-98.