Renin-angiotensin system inhibition in the treatment of hypertension
- Johannes FE Mann, MD
Johannes FE Mann, MD
- Professor of Medicine
- Friedrich Alexander University of Erlangen-Nürnberg
- International Scholar, Population Health Research Institute, McMaster University, Canada
- Karl F Hilgers, MD
Karl F Hilgers, MD
- Professor of Internal Medicine and Hypertension Research
- Friedrich-Alexander University, Erlangen-Nuremberg
- Vice Chair, Department of Nephrology and Hypertension
- Erlangen University Hospital
- Section Editors
- George L Bakris, MD
George L Bakris, MD
- Editor-in-Chief — Nephrology
- Section Editor — Hypertension
- Professor of Medicine
- The University of Chicago
- Norman M Kaplan, MD
Norman M Kaplan, MD
- Editor-in-Chief — Nephrology
- Section Editor — Hypertension
- Clinical Professor of Internal Medicine
- University of Texas Southwestern Medical Center
Inhibitors of the renin-angiotensin system (RAS), including angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and direct renin inhibitors are commonly used in the treatment of hypertension. The role of the RAS in hypertension and the use of specific inhibitors of this system to treat hypertension will be reviewed here.
The use of RAS inhibitors in patients with kidney disease and diabetes are discussed separately. (See "Choice of drug therapy in primary (essential) hypertension" and "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults" and "Treatment of hypertension in patients with diabetes mellitus" and "Treatment of diabetic nephropathy".)
The importance of local (ie, tissue) RAS activity in low-renin hypertension and the effects of angiotensin II on the heart are presented elsewhere. (See "Low-renin primary (essential) hypertension" and "Actions of angiotensin II on the heart".)
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS
Since the introduction of captopril in 1977 , angiotensin-converting enzyme (ACE) inhibitors have become widely used for the treatment of hypertension and three of its major complications: acute myocardial infarction , congestive heart failure , and chronic kidney disease. Fifty to 60 percent of Caucasian patients have a good response to monotherapy with ACE inhibitors, a response rate similar to other first-line antihypertensive drugs . ACE inhibitors have the additional advantages of having a more favorable side effect profile than sympathetic blockers, beta blockers, and diuretics , and of producing more regression of left ventricular hypertrophy than beta blockers . (See "Clinical implications and treatment of left ventricular hypertrophy in hypertension", section on 'Choice of drugs'.)
Guidelines issued in 2009 by the European Society of Hypertension , and in 2011 by NICE (National Institute for Health and Clinical Excellence of Great Britain) , recommend the use of an ACE inhibitor or angiotensin II receptor blocker (ARB) in younger and non-black patients . However, this recommendation is based upon relatively small cross-over trials .
Subscribers log in hereLiterature review current through: Apr 2017. | This topic last updated: Jul 05, 2016.References
- Ondetti MA, Rubin B, Cushman DW. Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. Science 1977; 196:441.
- Pfeffer MA, Braunwald E, Moyé LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992; 327:669.
- SOLVD Investigators, Yusuf S, Pitt B, et al. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325:293.
- Neaton JD, Grimm RH Jr, Prineas RJ, et al. Treatment of Mild Hypertension Study. Final results. Treatment of Mild Hypertension Study Research Group. JAMA 1993; 270:713.
- Croog SH, Levine S, Testa MA, et al. The effects of antihypertensive therapy on the quality of life. N Engl J Med 1986; 314:1657.
- Klingbeil AU, Schneider M, Martus P, et al. A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med 2003; 115:41.
- Mancia G, Laurent S, Agabiti-Rosei E, et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. J Hypertens 2009; 27:2121.
- Krause T, Lovibond K, Caulfield M, et al. Management of hypertension: summary of NICE guidance. BMJ 2011; 343:d4891.
- Mancia G, De Backer G, Dominiczak A, et al. 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. J Hypertens 2007; 25:1751.
- Dickerson JE, Hingorani AD, Ashby MJ, et al. Optimisation of antihypertensive treatment by crossover rotation of four major classes. Lancet 1999; 353:2008.
- Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004; 43:S1.
- Linz W, Wiemer G, Gohlke P, et al. Contribution of kinins to the cardiovascular actions of angiotensin-converting enzyme inhibitors. Pharmacol Rev 1995; 47:25.
- Materson BJ, Reda DJ, Cushman WC, et al. Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. N Engl J Med 1993; 328:914.
- Townsend RR, Holland OB. Combination of converting enzyme inhibitor with diuretic for the treatment of hypertension. Arch Intern Med 1990; 150:1175.
- Vaughan ED Jr, Carey RM, Peach MJ, et al. The renin response to diuretic therapyl A limitation of antihypertensive potential. Circ Res 1978; 42:376.
- Slagman MC, Waanders F, Hemmelder MH, et al. Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial. BMJ 2011; 343:d4366.
- Pollare T, Lithell H, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med 1989; 321:868.
- Pickering TG. The use of angiotensin converting enzyme inhibitors in combination with other antihypertensive agents. Am J Hypertens 1991; 4:73S.
- Bangalore S, Kumar S, Messerli FH. Angiotensin-converting enzyme inhibitor associated cough: deceptive information from the Physicians' Desk Reference. Am J Med 2010; 123:1016.
- Beltrami L, Zanichelli A, Zingale L, et al. Long-term follow-up of 111 patients with angiotensin-converting enzyme inhibitor-related angioedema. J Hypertens 2011; 29:2273.
- Li DK, Yang C, Andrade S, et al. Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study. BMJ 2011; 343:d5931.
- Wald DS, Law M, Morris JK, et al. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med 2009; 122:290.
- Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet 2000; 355:637.
- Grossman E, Peleg E, Carroll J, et al. Hemodynamic and humoral effects of the angiotensin II antagonist losartan in essential hypertension. Am J Hypertens 1994; 7:1041.
- Huang XR, Chen WY, Truong LD, Lan HY. Chymase is upregulated in diabetic nephropathy: implications for an alternative pathway of angiotensin II-mediated diabetic renal and vascular disease. J Am Soc Nephrol 2003; 14:1738.
- Matchar DB, McCrory DC, Orlando LA, et al. Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension. Ann Intern Med 2008; 148:16.
- Kassler-Taub K, Littlejohn T, Elliott W, et al. Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan in mild-to-moderate hypertension. Irbesartan/Losartan Study Investigators. Am J Hypertens 1998; 11:445.
- Mallion J, Siche J, Lacourcière Y. ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension. J Hum Hypertens 1999; 13:657.
- Andersson OK, Neldam S. The antihypertensive effect and tolerability of candesartan cilexetil, a new generation angiotensin II antagonist, in comparison with losartan. Blood Press 1998; 7:53.
- Hedner T, Oparil S, Rasmussen K, et al. A comparison of the angiotensin II antagonists valsartan and losartan in the treatment of essential hypertension. Am J Hypertens 1999; 12:414.
- Tikkanen I, Omvik P, Jensen HA. Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension. J Hypertens 1995; 13:1343.
- Enomoto A, Kimura H, Chairoungdua A, et al. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature 2002; 417:447.
- ONTARGET Investigators, Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358:1547.
- Li EC, Heran BS, Wright JM. Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database Syst Rev 2014; :CD009096.
- Soffer BA, Wright JT Jr, Pratt JH, et al. Effects of losartan on a background of hydrochlorothiazide in patients with hypertension. Hypertension 1995; 26:112.
- Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 2008; 372:547.
- Oh BH, Mitchell J, Herron JR, et al. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension. J Am Coll Cardiol 2007; 49:1157.
- Pool JL, Schmieder RE, Azizi M, et al. Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan. Am J Hypertens 2007; 20:11.
- Villamil A, Chrysant SG, Calhoun D, et al. Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide. J Hypertens 2007; 25:217.
- Shafiq MM, Menon DV, Victor RG. Oral direct renin inhibition: premise, promise, and potential limitations of a new antihypertensive drug. Am J Med 2008; 121:265.
- Oparil S, Yarows SA, Patel S, et al. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet 2007; 370:221.
- Parving HH, Persson F, Lewis JB, et al. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008; 358:2433.
- Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012; 367:2204.
- Nicholls SJ, Bakris GL, Kastelein JJ, et al. Effect of aliskiren on progression of coronary disease in patients with prehypertension: the AQUARIUS randomized clinical trial. JAMA 2013; 310:1135.
- Tardif JC, Grégoire J. Renin-angiotensin system inhibition and secondary cardiovascular prevention. JAMA 2013; 310:1130.
- Harel Z, Gilbert C, Wald R, et al. The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis. BMJ 2012; 344:e42.
- Rajagopalan S, Bakris GL, Abraham WT, et al. Complete renin-angiotensin-aldosterone system (RAAS) blockade in high-risk patients: recent insights from renin blockade studies. Hypertension 2013; 62:444.