Abstract
Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) and ACE inhibitors are known to reduce proteinuria and, thus, progression towards renal and cardiovascular outcomes. Recent data from the ONTARGET study (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) have demonstrated a substantial equivalence between ACE inhibitors and ARBs in preventing major cardiovascular events in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes mellitus with end-organ damage, while their combination did not seem to confer additional cardiovascular benefits, in the presence of increased incidence of adverse effects and discontinuation. More recently, the results of a pre-specified analysis on the renal effects of ramipril, telmisartan and their combination have become available, confirming the equivalence between ACE inhibitors and ARBs in terms of renal outcomes. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.
This is a preview of subscription content, log in via an institution to check access.
References
Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008 Apr 10; 358(15): 1547–59
Yusuf S, Teo K, Anderson C, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet 2008 Sep 27; 372(9644): 1174–83
Gissi HFI, Tavazzi L, Maggioni AP, et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008 Oct 4; 372(9645): 1231–9
Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008 Dec 4; 359(23): 2456–67
Sjolie AK, Klein R, Porta M, et al. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial. Lancet 2008 Oct 18; 372(9647): 1385–93
Chaturvedi N, Porta M, Klein R, et al. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials. Lancet 2008 Oct 18; 372`(9647): 1394–402
Fox K, Ford I, Steg PG, et al. Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet 2008 Sep 6; 372(9641): 817–21
Fox K, Ford I, Steg PG, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet 2008 Sep 6; 372(9641): 807–16
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 Aug 16; 372(9638): 547–53
UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 1998 Sep 12; 317 (7160): 713–20
Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000 Jan 22; 355 (9200): 253–9
Parving HH, Lehnert H, Brochner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001 Sep 20; 345(12): 870–8
Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001 Sep 20; 345(12): 861–9
Olsen MH, Wachtell K, Ibsen H, et al. Reductions in albuminuria and in electrocardiographic left ventricular hypertrophy independently improve prognosis in hypertension: the LIFE study. J Hypertens 2006 Apr; 24(4): 775–81
Parving HH, Hommel E, Damkjaer Nielsen M, et al. Effect of captopril on blood pressure and kidney function in normotensive insulin dependent diabetics with nephropathy. BMJ 1989 Aug 26; 299(6698): 533–6
Parving HH, Hommel E, Smidt UM. Protection of kidney function and decrease in albuminuria by captopril in insulin dependent diabetics with nephropathy. BMJ 1988 Oct 29; 297(6656): 1086–91
Lewis EJ. Captopril and diabetic nephropathy [letter]. JAMA 1995 Jun 21; 273(23): 1831
Lewis EJ. Captopril and membranous glomerulopathy [letter]. JAMA 1984 Aug 17; 252(7): 900
Bauer JH, Reams GP, Hewett J, et al. A randomized, double-blind, placebo-controlled trial to evaluate the effect of enalapril in patients with clinical diabetic nephropathy. Am J Kidney Dis 1992 Nov; 20(5): 443–57
Marre M, Chatellier G, Leblanc H, et al. Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria. BMJ 1988 Oct 29; 297(6656): 1092–5
Acknowledgement
The author wishes to thank Giuliano Tocci, MD, for helping in preparing and revising the present manuscript.
The author is an ONTARGET Investigator. He has received research grants from Boehringer Ingelheim and Pfizer, has served in international advisory boards of Sanofi-aventis/Bristol Myers Squibb, Bayer Schering Pharma, Novartis Farma and Daichii Sankyo, and is speaker bureau of several drug companies producing ARBs and ACE inhibitors.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Volpe, M. The Myth of Janus. High Blood Press Cardiovasc Prev 16, 35–37 (2009). https://doi.org/10.2165/00151642-200916020-00001
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.2165/00151642-200916020-00001