Advertisement

Hypertension Controversies

Part of the Contemporary Cardiology book series (CONCARD)

Abstract

This statement is printed on the front cover of The Lancet of October 29, 2005. It is surprising that this peer-reviewed journal would print such a misleading statement.
  • The quote was based on a metaanalysis by Lindholm et al., who concluded that beta-blockers should not remain first choice in the treatment of primary hypertension and should not be used as reference drugs in future randomized controlled trials (RCTs) of hypertension (1). Unfortunately, many experts in the field have endorsed the conclusions of this faulty metaanalysis. Beta-blockers have been used for more than 35 yr for the treatment of hypertension. The controversy regarding their continued use is of paramount importance, particularly because there are more than 1 billion hypertensive individuals who require treatment, and only four classes of antihypertensive agents are available: beta-blockers, diuretics, calcium antagonists, and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). The two other drug classes (alpha blockers [doxazosin] and centrally acting agents [methyldopa, clonidine]) have been rendered relatively obsolete for the management of primary hypertension (see later discussion and alpha-blocker section in Chapter 8). Methyl dopa remains useful mainly for hypertension in pregnancy.

  • In 14 studies analyzed by Lindholm et al., atenolol was the beta-blocker used; in four trials, mixtures of atenolol, metoprolol, and pindolol were used (see Table 9-1).

  • In a Lancet letter, Cruickshank stated that by lumping together all randomized hypertension trials involving beta-blockers, Lars Lindholm and colleagues have arrived at misleading conclusions (2), and I concur with this statement. This discussion reviews trials selected by Lindholm and colleagues and emphasizes that the metaanalysis suggests that atenolol is not an effective choice for the management of hypertension but does not indicate that other beta-blockers are ineffective in decreasing cardiovascular disease (CVD) morbidity and mortality associated with hypertension.

Keywords

Calcium Antagonist Coronary Heart Disease Event Primary Hypertension Achieve Goal Blood Pressure Conduit Artery Function Evaluation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lindholm LH, Carlberg B, Samuelsson O. Should P blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005;366:1545–1553.PubMedCrossRefGoogle Scholar
  2. 2.
    Cruickshank JM. β blockers for the treatment of primary hypertension. Lancet 2006;367:209.PubMedCrossRefGoogle Scholar
  3. 3.
    The IPPPSH Collaborative Group. Cardiovascular risk and risk factors in a randomised trial of treatment based on the beta-blocker oxprenolol. The International Prospective Primary Prevention Study in Hypertension (IPPPSH). J Hypertens 1985;3:379–392.CrossRefGoogle Scholar
  4. 4.
    Berglund G, Andersin O, Widgren B. Low-dose antihypertensive treatment with a thiazide diuretic is not diabetogenic. Acta Med Scand 1986;220:419–424.PubMedCrossRefGoogle Scholar
  5. 5.
    Yurenev AP, Dyakonova HG, Novikov ID, et al. Management of essential hypertension in patients with different degrees of left ventricular hypertrophy. Multicenter trial. Am J Hypertens 1992; (6 Pt 2): 182S–189S.Google Scholar
  6. 6.
    The Dutch TIA Trial Study Group. Trial of secondary prevention with atenolol after transient ischemic attack or nondisabling ischemic stroke. Stroke 1993;24:543–548.Google Scholar
  7. 7.
    Hansson L, Lindholm LH, Ekbom T, et al. Randomised trial of old and new antihypertensive drugs in elderly patients: Cardiovascular mortality and morbidity, the Swedish Trial in Old Patients with Hypertension-2 study. Lancet 1999;354:1751–1756.PubMedCrossRefGoogle Scholar
  8. 8.
    MRC Working Party. MRC trial of treatment of mild hypertension: Principal results. BMJ 1985;291: 97–104.Google Scholar
  9. 9.
    Treatment of hypertension: The 1985 results. Lancet 1985;2:645.Google Scholar
  10. 10.
    Norwegian Multicentre Group. Timolol induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med 1981;304:801–807.CrossRefGoogle Scholar
  11. 11.
    Khan M Gabriel. Hypertension. In: Cardiac Drug Therapy, 2nd ed. Philadelphia, WB Saunders, 1988, p. 62.Google Scholar
  12. 12.
    MRC Working Party. Medical Research Council Trial of treatment of hypertension in older adults: Principal results. BMJ 1992;304:405–412.CrossRefGoogle Scholar
  13. 13.
    Messerli FH, Grossman E, Goldbourt U. Are P-blockers efficacious as first-line therapy for hypertension in the elderly? JAMA 1998;279:1903–1907.PubMedCrossRefGoogle Scholar
  14. 14.
    CONVINCE: Black HR, Elliott WJ, Grandits G, et al. for the CONVINCE Research Group. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA 2003;289:2073–2082.PubMedCrossRefGoogle Scholar
  15. 15.
    Neutel JM, Smith DHG, Ram CVS. Application of ambulatory blood pressure monitoring in differentiating between antihypertensive agents. Am J Med 1993;94:181.PubMedCrossRefGoogle Scholar
  16. 16.
    Pitt B. The role of beta-adrenergic blocking agents in preventing sudden cardiac death. Circulation 1992; 85(1 Suppl):107.Google Scholar
  17. 17.
    Äblad B, Bjurö T, Björkman JA, Edström T, Olsson G. Role of central nervous beta-adrenoceptors in the prevention of ventricular fibrillation through augmentation of cardiac vagal tone. J Am Coll Cardiol 1991;17(Suppl):165.CrossRefGoogle Scholar
  18. 18.
    The CAPRICORN Investigators. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: The CAPRICORN randomised trial. Lancet 2001;357:1385–1390.CrossRefGoogle Scholar
  19. 19.
    CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): A randomised trial. Lancet 1999;353:9–13.CrossRefGoogle Scholar
  20. 20.
    BHAT: β blocker Heart Attack Trial Research Group. A randomised trial of propranolol in patients with acute myocardial infarction. I: Mortality results. JAMA 1982;247:1707–1714.CrossRefGoogle Scholar
  21. 21.
    Kokkinos P, Chrysohoou C, Panagiotakos D, et al. Beta-blockade mitigates exercise blood pressure in hypertensive male patients. J Am Coll Cardiol 2006;47:794–798.PubMedCrossRefGoogle Scholar
  22. 22.
    Morgan T, Lauri J, Anderson A. Effect of different antihypertensive drug classes on central aortic pressure. Am J Hypertens 2004;17:118–123.PubMedCrossRefGoogle Scholar
  23. 23.
    Dhakam Z, McEniery CM, Cockcroft JR, et al. Atenolol and eprosartan: differential effects on central blood pressure and aortic pulse wave velocity. Am J Hypertens 2006;19:214–219.PubMedCrossRefGoogle Scholar
  24. 24.
    CAFE investigators for the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) investigators. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: Principal results of the Conduit Artery Function Evaluation (CAFE) Study. Circulation 2006;113:1213–1225.CrossRefGoogle Scholar
  25. 25.
    ASCOT: Dahlof B, Sever PS, Poulter NR, et al. for the ASCOT investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): A multicentre randomised controlled trial. Lancet 2005;366: 895–906.PubMedCrossRefGoogle Scholar
  26. 25a.
    Poulter NR, Wedel H, Dahlof B, for the ASCOT investigators. Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). Lancet 2005;366:907–913.PubMedCrossRefGoogle Scholar
  27. 26.
    Safar ME, Blacher J, Pannier B, et al. Central pulse pressure and mortality in end-stage renal disease. Hypertension 2002;39:735–738.PubMedCrossRefGoogle Scholar
  28. 27.
    Wilkinson IB, MacCallum H, Flint L, et al. The influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol 2000;525:263–270.PubMedCrossRefGoogle Scholar
  29. 28.
    Kelly R, Daley J, Avolio A, O’Rourke M. Arterial dilation and reduced wave reflection: Benefit of dilevalol in hypertension. Hypertension 1989;14:14–21.PubMedGoogle Scholar
  30. 29.
    Wilkinson IB, McEniery CM, Cockcroft JR. Atenolol and cardiovascular risk: An issue close to the heart. Lancet 2006;367:627–629.PubMedCrossRefGoogle Scholar
  31. 30.
    Khan M Gabriel. Which beta blocker to choose. In: Heart Disease Diagnosis and Therapy, a Practical Approach, 2nd ed. Totowa, NJ, Humana Press, 2005, p. 55.Google Scholar
  32. 31.
    Cominacini L, Fratta Pasini A, Garbin U, et al. Nebivolol and its 4-keto derivative increase nitric oxide in endothelial cells by reducing its oxidative inactivation. J Am Coll Cardiol 2003;42:1838–1844.PubMedCrossRefGoogle Scholar
  33. 32.
    Beta-blocker Evaluation of Survival Trial Investigators. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med 2001;362:1659–1667.CrossRefGoogle Scholar
  34. 33.
    HOT: Hansson L, et al. for the HOT Study Group. Effects of intensive blood pressure lowering and lowdose aspirin in patients with hypertension: Principal results of the Hypertension Optimal Treatment (HOT) trial. Lancet 1998;351:1755–1762.PubMedCrossRefGoogle Scholar
  35. 34.
    Zanchetti A, et al. Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients in the Hypertension Optimal Treatment study. J Hypertens 2001; 19:1149–1159.PubMedCrossRefGoogle Scholar
  36. 35.
    Williams B, Poulter NR, Brown MJ, et al. Guidelines for management of hypertension: Report of the fourth working party of the British Hypertension Society, 2004-BHS IV. J Hum Hypertens 2004;18: 139–185.PubMedCrossRefGoogle Scholar
  37. 36.
    Loubatiere A, Mariani MM, Sorel G, et al. The action of beta adrenergic blocking drugs and stimulating agents on insulin secretion. Characteristic of the type of beta receptor. Diabetologica 1971;7:127–132.CrossRefGoogle Scholar
  38. 37.
    Murphy MB, Lewis PJ, Kohner E, Schumer B, Dollery CT. Glucose intolerance in hypertensive patients treated with diuretics: A fourteen-year follow-up. Lancet 1982;2:1293–1295.PubMedCrossRefGoogle Scholar
  39. 38.
    Padwal R, Laupacis A. Antihypertensive therapy and incidence of type 2 diabetes. A systematic review. Diabetes Care 2004;27:247–255.PubMedCrossRefGoogle Scholar
  40. 39.
    Mason JM, Dickinson HO, Nicolson DJ, et al. The diabetiogenic potential of thiazide-type diuretic and a beta blocker combinations in patients with hypertension. J Hypertens 2005;23:1777–1781.PubMedCrossRefGoogle Scholar
  41. 40.
    The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major out-comes 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;288:2981–2997.CrossRefGoogle Scholar
  42. 41.
    UKPDS: UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS. BMJ 1998;317:713–720.Google Scholar
  43. 42.
    Gress TW, Nieto FJ, Shahar E, et al. for The Atherosclerosis Risk in Communities Study. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. N Engl J Med 2000;342:905–912.PubMedCrossRefGoogle Scholar
  44. 43.
    LIFE: Dahlof B, Devereux RB, Kjeldsen SE, et al. for the 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.PubMedCrossRefGoogle Scholar
  45. 44.
    Lindholm LH, Ibsen H, Borch-Johnsen K, et al. Risk of new-onset diabetes in the Losartan Intervention for Endpoint Reduction in Hypertension Study. J Hypertens 2002;20:1879–1886.PubMedCrossRefGoogle Scholar
  46. 45.
    Julius S, Kjeldsen SE, Weber M, et al. for the VALUE trial group. Outcomes in hypertensive patients at high cardiovascular risk treated with regimes based on valsartan or amlodipine: The VALUE randomised trial. Lancet 2004;363:2002–2031.CrossRefGoogle Scholar
  47. 46.
    Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: The Captopril Prevention Project (CAPPP). Lancet 1999;353:611–616.PubMedCrossRefGoogle Scholar
  48. 47.
    Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network metaanalysis. The Lancet 2007;369:201–207.CrossRefGoogle Scholar
  49. 48.
    GEMINI: Bakris GL, Fonseca V, Katholi RE, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: A randomized controlled trial. JAMA 2004;292: 2227–2236.PubMedCrossRefGoogle Scholar
  50. 49.
    Khaw KT, Wareham N, Luben R, et al. Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk). BMJ 2001;322: 15–18.PubMedCrossRefGoogle Scholar
  51. 50.
    Wright JT, Bakris G, Greene T, et al. for the African American Study of Kidney Disease and Hypertension Study Group. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: Results from the AASK Trial. JAMA 2002;288:2421–2431.PubMedCrossRefGoogle Scholar
  52. 51.
    Yasunari K, Maeda K, Nakamura M, Yoshikawa J. Carvedilol inhibits pressure-induced increase in oxidative stress in coronary smooth muscle cells. Hypertens Res 2002;25:419–425.PubMedCrossRefGoogle Scholar
  53. 52.
    Yasunari K, Maeda K, Nakamura M, Watanabe T, Yoshikawa J, Asada A. Effects of carvedilol on oxidative stress in polymorphonuclear and mononuclear cells in patients with essential hypertension. Am J Med. 2004;116:460–465.PubMedCrossRefGoogle Scholar
  54. 53.
    Khan M Gabriel. Alpha-1 adrenergic blockers. In: Cardiac Drug Therapy, 4th ed. Philadelphia, WB Saunders, 1995, p. 103.Google Scholar
  55. 54.
    INSIGHT: Brown MJ, Palmer CR, Castaigne A, et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000;356: 366–372.PubMedCrossRefGoogle Scholar
  56. 55.
    Neal B, MacMahon S, Chapman N. Effects of ACE inhibitors, calcium antagonists, and other bloodpressure-lowering drugs: results of prospectively designed overviews of randomised trials: Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2000;356:1955–1964.PubMedCrossRefGoogle Scholar
  57. 56.
    Pahor M, Psaty BM, Alderman MH, et al. Health outcomes associated with calcium antagonists compared with other first-line antihypertensive therapies: A meta-analysis of randomised controlled trials. Lancet 2000;356:1949–1954.PubMedCrossRefGoogle Scholar
  58. 57.
    Khan M Gabriel. Recommendations for hypertension in young and older patients. In: Cardiac Drug Therapy, 6th ed. Philadelphia, WB Saunders, 2003, pp. 134–143.Google Scholar
  59. 58.
    The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JAMA 2003;289:2560–2572.Google Scholar
  60. 59.
    Materson B J, 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;328:914–921.PubMedCrossRefGoogle Scholar
  61. 59a.
    Materson BJ, Reda DJ. Correction: single-drug therapy for hypertension in men. N Engl J Med 1994; 330:1689.PubMedCrossRefGoogle Scholar
  62. 60.
    Deary A, Schumann AL, Murfet H. Double-blind placebo-controlled crossover comparison of five classes of antihypertensive drugs J Hypertens 2002;20:771–777.PubMedCrossRefGoogle Scholar
  63. 61.
    Dickerson JEC, Hingorani AD, Ashby MJ, et al. Randomisation of antihypertensive treatment by crossover rotation of four major classes. Lancet 1999;353:2008–2013.PubMedCrossRefGoogle Scholar
  64. 62.
    SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265:3255–3264.CrossRefGoogle Scholar
  65. 63.
    PROGRESS Collaborative Group. Randomized trial of a perindopril-based blood pressure lowering regimen among, individuals with previous stroke or transient ischaemic attack. Lancet 2001;358:1033–1041.CrossRefGoogle Scholar
  66. 64.
    Casas JP, Chau W, Loukogeorgakis S, et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: Systematic review and meta-analysis. Lancet 2005;366:2026–2033.PubMedCrossRefGoogle Scholar
  67. 65.
    Saunders E, Weir MR, Kong BW, et al. A comparison of the efficacy and safety of a beta-blocker, a calcium channel blocker, and a converting enzyme inhibitor in hypertensive blacks. Arch Intern Med 1990; 150:1707–1713.PubMedCrossRefGoogle Scholar
  68. 66.
    Cushman WC, Reda DJ, Perry HM, et al. Regional and racial differences in response to antihypertensive medication use in a randomized controlled trial of men with hypertension in the United States. Arch Intern Med 2000; 160:825–831.PubMedCrossRefGoogle Scholar
  69. 67.
    Kendall MJ, Cohen JD. β blockers as first-line agents for hypertension in the elderly. JAMA 1999;281: 131–133.PubMedCrossRefGoogle Scholar
  70. 68.
    Khan M Gabriel. Hypertension trials. In: Cardiac Drug Therapy, 6th ed. Philadelphia, WB Saunders, 2003, p. 505.Google Scholar
  71. 69.
    MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive heart failure (MERIT-HF). Lancet 1999;353:2001–2007.CrossRefGoogle Scholar
  72. 70.
    The National Heart, Lung and Blood Pressure Institute Working Group on Future Directions in Hypertension Treatment Trials. Major clinical trials of hypertension. What should be done next? Hypertension 2005;46:1–6.CrossRefGoogle Scholar
  73. 71.
    COPERNICUS: Packer M, Fowler MB, Roecker EB, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: Results of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study. Circulation 2002;106:2194–2199.PubMedCrossRefGoogle Scholar

Suggested Reading

  1. 72.
    Materson BJ, Reda DJ. Correction: single-drug therapy for hypertension in men. N Engl J Med 1994;330: 1689.PubMedCrossRefGoogle Scholar
  2. 73.
    Messerli FH, Re RN. Do we need yet another blocker of the renin-angiotensin system? J Am Coll Cardiol 2007;49:1164–1165.PubMedCrossRefGoogle Scholar
  3. 74.
    Oh Byung-Hee, Mitchell J, Herron JR, et al. Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-h blood pressure control in patients with hypertension. J Am Coll Cardiol 2007;49: 1157–1163.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2007

Personalised recommendations