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Meta-analysis of large outcome trials of angiotensin receptor blockers in hypertension

Abstract

Angiotensin receptor blockers (ARBs), also known as sartans, block the activation of angiotensin type 1 receptors and have a recognised role in the treatment of heart failure and nephropathy. Since 2002, there have been three major outcome trials of ARBs in hypertension. We performed a meta-analysis to evaluate the impact of ARB on major outcomes. Randomised controlled trials of ARBs in hypertensive subjects with an average follow-up of at least 2 years and at least 100 major cardiovascular events were included. For each trial, the ARB used, number and characteristics of subjects, baseline and change in blood pressure, cardiovascular and noncardiovascular outcomes were recorded. Three trials involving 29 375 subjects were included in the meta-analysis. In Losartan Intervention For Endpoint (LIFE) and Study on Cognition and Prognosis in the Elderly (SCOPE) but not in Valsartan Antihypertensive Long-term Use Evaluation trial (VALUE), an ARB reduced the occurrence of the primary end point and stroke compared to control. Compared to other antihypertensive drugs, ARB treatment was associated with no significant change in all-cause mortality (relative risk ratio (RRR) 0.96, 95% CI: 0.88–1.06, P=0.45). There was an increase in myocardial infarction (RRR, 1.12, 95% CI: 1.01–1.26, P=0.041), but a decrease in new-onset diabetes mellitus (RRR, 0.80, 95% CI: 0.74–0.86, P<0.0000001). In conclusion, the reduction in new-onset diabetes partly offsets any increase in the risk of myocardial infarction. Most hypertensive patients require more than one class of drugs. Small differences in treatment outcome should not over-ride the importance of good blood pressure control.

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References

  1. Pitt B, Segal R, Martinez FA, Meurers G, Cowley AJ, Thomas I et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997; 349 (9054): 747–752.

    Article  CAS  Google Scholar 

  2. Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial—the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355: 1582–1587.

    Article  CAS  Google Scholar 

  3. Cohn JN, Tognoni G, for the Valsartan Heart Failure Trial Investigators. A randomised trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345: 1667–1675.

    Article  CAS  Google Scholar 

  4. Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL et al CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM–Overall programme. Lancet 2003; 362: 759–766.

    Article  CAS  Google Scholar 

  5. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH et al RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with Type 2 diabetes and nephropathy. J Engl J Med 2001; 345: 861–869.

    Article  CAS  Google Scholar 

  6. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB et al Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–860.

    Article  CAS  Google Scholar 

  7. Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P, Irbesartan in patients with type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345 (12): 870–878.

    Article  CAS  Google Scholar 

  8. Hansson L, Lindholm LH, Ekbom T, Dahlöf B, Lanke J, Scherstén B et al for the STOP-Hypertension-2 study group. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity in the Swedish Trial in Old Patients with Hypertension-2 study. Lancet 1999; 354: 1751–1756.

    Article  CAS  Google Scholar 

  9. Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999; 353 (9153): 611–616.

    Article  CAS  Google Scholar 

  10. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288 (23): 2981–2997.

  11. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U et al LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995–1003.

    Article  CAS  Google Scholar 

  12. Carlberg B, Samuelsson O, Lindholm LH . Atenolol in hypertension: is it a wise choice? Lancet. 2004; 364 (9446): 1684–1689.

    Article  CAS  Google Scholar 

  13. Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A, Olofsson B et al for the SCOPE Study Group. The study on cognition and prognosis in the elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003; 21: 875–886.

    Article  CAS  Google Scholar 

  14. Julius S, Kjelsen SE, Weber M, Brunner HR, Ekman S, Hansson L et al for the VALUE trial group. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363: 2022–2031.

    Article  CAS  Google Scholar 

  15. Kjeldsen SE, Julius S, Brunner H, Hansson L, Henis M, Ekman S et al. Characteristics of 15,314 hypertensive patients at high coronary risk. The VALUE trial. The Valsartan Antihypertensive Long-term Use Evaluation. Blood Press 2001; 10 (2): 83–91.

    Article  CAS  Google Scholar 

  16. Fleiss JL . Measure of effect size for categorical data. In: Cooper H, Hedges LV (eds) The Handbook of Research Synthesis. New York, NY: Russell Sage Foundation, 1994 pp 245–260.

    Google Scholar 

  17. Dickstein K, Kjekshus J, OPTIMAAL Steering Committee of the OPTIMAAL Study Group. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 2002; 360: 752–760.

    Article  CAS  Google Scholar 

  18. Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Kober L, Maggioni AP et al Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349: 1893–1906.

    Article  CAS  Google Scholar 

  19. Berl T, Hunsicker LG, Lewis JB, Pfeffer MA, Porush JG, Rouleau JL et al Irbesartan Diabetic Nephropathy Trial. Collaborative Study Group. Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med 2003; 138: 542–549.

    Article  CAS  Google Scholar 

  20. Strippoli GF, Craig M, Deeks JJ, Schena FP, Craig JC . Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review. BMJ 2004; 329 (7470): 828.

    Article  CAS  Google Scholar 

  21. Turnbull F, Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003; 362: 1527–1535.

    Article  CAS  Google Scholar 

  22. Staessen JA, Wang JG, Thijs L . Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1st March 2003. J Hypertens 2003; 21: 1055–1076.

    Article  CAS  Google Scholar 

  23. Weber MA, Julius S, Kjeldsen SE, Brunner HR, Ekman S, Hansson L et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet 2004; 363 (9426): 2049–2051.

    Article  CAS  Google Scholar 

  24. Staessen JA, Wang JG, Birkenhager WH . Outcome beyond blood pressure control? Eur Heart J 2003; 24 (6): 504–514.

    Article  Google Scholar 

  25. Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J et al Diabetics Exposed to Telmisartan and Enalapril Study Group. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 2004; 351 (19): 1952–1961.

    Article  CAS  Google Scholar 

  26. Williams B . Recent hypertension trials. Implications and controversies. J Am Coll Cardiol 2005; 45 (6): 813–827.

    Article  Google Scholar 

  27. Scheen AJ . VALUE: analysis of results (letter). Lancet 2004; 364 (9438): 932–933.

    Article  Google Scholar 

  28. Scheen AJ . Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials. Diabetes Metab 2004; 30 (6): 487–496.

    Article  CAS  Google Scholar 

  29. Lindholm LH, Persson M, Alaupovic P, Carlberg B, Svensson A, Samuelsson O . Metabolic outcome during 1 year in newly detected hypertensives: results of the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation (ALPINE study). J Hypertens 2003; 21 (8): 1563–1574.

    Article  CAS  Google Scholar 

  30. Verma S, Strauss M . Angiotensin receptor blockers and myocardial infarction. BMJ 2004; 329: 1248–1249.

    Article  Google Scholar 

  31. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289 (19): 2560–2572.

    Article  CAS  Google Scholar 

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Acknowledgements

BMY Cheung, CR Kumana and CP Lau are members of the Institute of Cardiovascular Science and Medicine, University of Hong Kong. BMY Cheung and CP Lau are investigators of the Research Centre of Heart, Brain, Hormone and Healthy Ageing, Faculty of Medicine, University of Hong Kong.Funding: None.Competing interests: The authors have, at various times in the past 5 years, been reimbursed by MSD, Takeda, Novartis, Pfizer and Sanofi for organising, attending or speaking in scientific meetings.

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Correspondence to B M Y Cheung.

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Cheung, B., Cheung, G., Lauder, I. et al. Meta-analysis of large outcome trials of angiotensin receptor blockers in hypertension. J Hum Hypertens 20, 37–43 (2006). https://doi.org/10.1038/sj.jhh.1001931

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