The Myth of Janus

The Two Faces of Renal Outcomes in the ONTARGET Study
Editorial
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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.

Key words

angiotensin II receptor blockers ACE inhibitors cardiovascular risk cardiovascular mortality clinical trials 

References

  1. 1.
    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): 1547–59PubMedCrossRefGoogle Scholar
  2. 2.
    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): 1174–83PubMedCrossRefGoogle Scholar
  3. 3.
    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): 1231–9CrossRefGoogle Scholar
  4. 4.
    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): 2456–67PubMedCrossRefGoogle Scholar
  5. 5.
    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): 1385–93PubMedCrossRefGoogle Scholar
  6. 6.
    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): 1394–402CrossRefGoogle Scholar
  7. 7.
    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): 817–21PubMedCrossRefGoogle Scholar
  8. 8.
    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): 807–16PubMedCrossRefGoogle Scholar
  9. 9.
    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): 547–53PubMedCrossRefGoogle Scholar
  10. 10.
    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): 713–20Google Scholar
  11. 11.
    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): 253–9Google Scholar
  12. 12.
    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): 870–8PubMedCrossRefGoogle Scholar
  13. 13.
    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): 861–9PubMedCrossRefGoogle Scholar
  14. 14.
    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): 775–81PubMedCrossRefGoogle Scholar
  15. 15.
    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): 533–6PubMedCrossRefGoogle Scholar
  16. 16.
    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): 1086–91PubMedCrossRefGoogle Scholar
  17. 17.
    Lewis EJ. Captopril and diabetic nephropathy [letter]. JAMA 1995 Jun 21; 273(23): 1831PubMedCrossRefGoogle Scholar
  18. 18.
    Lewis EJ. Captopril and membranous glomerulopathy [letter]. JAMA 1984 Aug 17; 252(7): 900PubMedCrossRefGoogle Scholar
  19. 19.
    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): 443–57PubMedGoogle Scholar
  20. 20.
    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): 1092–5PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Division of Cardiology, II Faculty of MedicineUniversity of Rome “La Sapienza”, Sant’Andrea HospitalRomeItaly
  2. 2.IRCCS NeuromedPozzilli, IserniaItaly

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