Abstract
Beta‐adrenergic receptor blockers (beta‐blockers) are effective and safe antihypertensive drugs, and have been recommended as first‐line therapy for hypertension by all Joint National Committees (JNCs) for the prevention, detection, evaluation, and treatment of high blood pressure (BP) from the first to the last (JNC‐7) in 2003. However, recently questions have been raised by several investigators regarding the antihypertensive effectiveness and safety of these drugs. The Medline literature on this subject was searched and pertinent studies were retrieved. Other pertinent references from existing publications were retrieved and analyzed up to 2007. Additionally, a historical perspective on the discovery of beta‐blockers and their mechanism of action is given. Most of the reviewed short‐term and long‐term clinical trials demonstrate an effective and safe antihypertensive pattern for the beta‐blockers. The weaknesses identified include the adverse effect of older beta‐blockers on glucose control and stroke protection, especially in older persons. These adverse effects are attributed to their mechanism of action and BP effectiveness. On the basis of the evidence presented, beta‐blockers are effective and safe antihypertensive drugs and should still be recommended as first‐line therapy in most uncomplicated hypertensive patients, either alone or in combination with other drugs. There are reservations regarding their administration to diabetic and older hypertensive patients. However, when compelling indications for their use exist, they should not be withheld. Copyright © 2008 Wiley Periodicals, Inc.
Keywords: hypertension, blood pressure, treatment, beta‐blockers, review
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References
- 1. Ahlquist RP: A study of the adrenotropic receptors. Am J Physiol 1948; 153: 586–600. [DOI] [PubMed] [Google Scholar]
- 2. Stapleton MP: Sir James Black and propranolol: the role of the basic sciences in the history of cardiovascular pharmacology. Tex Heart Inst J 1997; 24: 336–342. [PMC free article] [PubMed] [Google Scholar]
- 3. Chobanian AV, Bakris GL, Black HR, Cusman WC, Green LA, et al.: Seventh report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure (JNC‐7). Hypertension 2003; 42: 1206–1252. [DOI] [PubMed] [Google Scholar]
- 4.Guidelines Committee: European Society of Hypertension European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–1053. [DOI] [PubMed] [Google Scholar]
- 5.Medical Research Council Working Party: MRC trial of treatment of mild hypertension: principal results. Br Med J 1985; 291: 97–104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.MRC Working Party: Medical Research Council trial of treatment of hypertension in older adults: principal results. Br Med J 1992; 304: 405–412. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.The IPPPSH Collaborative Group: Cardiovascular risk factors in a randomized trial of treatment based on the beta‐blocker oxprenolol. The International Prospective Primary Prevention Study in Hypertension (IPPPSH). J Hypertens 1985; 3: 379–392. [DOI] [PubMed] [Google Scholar]
- 8. Wikstrand J, Warnold I, Olsson G, Tuomilehto J, Elmfeld D, et al.: Primary prevention with metoprolol in patients with hypertension: mortality results from the MAPHY study. JAMA 1988; 259: 1976–1982. [PubMed] [Google Scholar]
- 9. Coope J, Warrender TS: Randomized trial of treatment of Hypertension in Elderly Patients in primary care (HEP). Br Med J 1986; 293: 1145–1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers DG, et al., LIFE Study Group: Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet 2002; 359: 995–1003. [DOI] [PubMed] [Google Scholar]
- 11. Black HR, Elliott WJ, Grandits G, Grambsch P, Lucente T, et al: The Convince Research Group. Principal results of the Control Onset Verapamil Investigation of Cardiovascular Endpoints (CONVINCE) trial. JAMA 2003; 289: 2073–2082. [DOI] [PubMed] [Google Scholar]
- 12. Wright JT, Bakris G, Greene T, Agodoa LY, Appel LJ, et al. 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. [DOI] [PubMed] [Google Scholar]
- 13. Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, et al: ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive of amlodipine added perindopril, as required, versus atenolol adding bendroflumethiazide, as required, in the Anglo‐Scandinavian Cardiac Outcomes Trial‐Blood Pressure Lowering Arm (ASCOT‐BPLA), a multicenter randomized trial. Lancet 2005; 366: 895–906. [DOI] [PubMed] [Google Scholar]
- 14. Messerli FH, Grossman E, Goldbourt U. Are beta‐blockers efficacious as first‐line therapy for hypertension in the elderly? A systematic review. JAMA 1998; 279: 1903–1907. [DOI] [PubMed] [Google Scholar]
- 15. Lindholm LH, Carlberg B, Samuelsson O. Should b‐blockers remain first choice in the treatment of primary hypertension? A meta‐analysis. Lancet 2005; 366: 1545–1553. [DOI] [PubMed] [Google Scholar]
- 16.National Institute for Health and Clinical Excellence. Hypertension: management of hypertension in adults in primary care (NICE clinical guideline update). Available at http://www.nice.org.uk. Accessed March 1, 2007.
- 17. Frishman W. Silverman R. Clinical pharmacology of the new beta‐adrenergeric blocking drugs part 2: physiologic and metabolic effects. Am Heart J 1979; 97: 797–807. [DOI] [PubMed] [Google Scholar]
- 18. Neutel JM, Schnaper H, Cheung DC, Graettinger WF, Weber MA. Antihypertensive effects of beta‐blockers administered once daily: 24 hour measurements. Am Heart J 1990; 120: 166–171. [DOI] [PubMed] [Google Scholar]
- 19. Garrett BN, Kaplan NM. Plasma renin activity suppression: duration after withdrawal from beta‐adrenergic blockade. Arch Intern Med 1980; 140: 1316–1318. [DOI] [PubMed] [Google Scholar]
- 20. Manin't Veld AJ, Vanden Meiracker AH, Schalekamp MA. Do beta‐blockers really increase peripheral vascular resistance? Review of the literature and new observations under basal conditions. Am J Hypertens 1988; 1: 91–96. [DOI] [PubMed] [Google Scholar]
- 21. Pierce CJ, Wallin JD. Labetolol and other agents that block both alpha‐ and beta‐adrenergic receptors. Cleve Clin J Med 1994; 61: 59–69. [DOI] [PubMed] [Google Scholar]
- 22. McTavish D, Campoli‐Richards D, Sorkin EM. Carvedilol. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy. Drugs 1993; 45: 232–258. [DOI] [PubMed] [Google Scholar]
- 23. Tzemos N, Lim PO, MacDonald TM. Nebivolol reverses endothelial dysfunction in essential hypertension. A randomized, double‐blind, crossover study. Circulation 2001; 104: 511–514. [DOI] [PubMed] [Google Scholar]
- 24. Zachariah PK, Bonnet G, Chrysant SG, DeBacker G, Goldstein R, et al. Evaluation of the antihypertensive efficacy of lisinopril compared to metoprolol in moderate to severe hypertension. J Cardiovasc Pharmacol 1987; 9(3): S53–S58. [DOI] [PubMed] [Google Scholar]
- 25. Chrysant SG, Chrysant C, Bal IS, Trus J, Hitchcock A. Treatment of severe hypertension with atenolol and betaxalol with once daily regimens: Hemodynamic aspects. Chest 1989; 96: 499–504. [DOI] [PubMed] [Google Scholar]
- 26. Chrysant SG, Chappel C, Farnham DJ, Levin B, Lueg M, et al. Antihypertensive and metabolic effects of single and combined atenolol regimens. J Clin Pharmacol 1992; 32: 61–65. [DOI] [PubMed] [Google Scholar]
- 27.Veterans Administration Cooperative Study Group on Antihypertensive Agents. Efficacy of nadolol alone and combined with bendroflumethiazide and hydrolazine for systemic hypertension. Am J Cardiol 1983; 52: 1230–1237. [DOI] [PubMed] [Google Scholar]
- 28.Veterans Administration Cooperative Study Group on Antihypertensive Agents. Comparison of propranolol and hydrochlorothiazide for the initial treatment of hypertension II: results of long‐term therapy. JAMA 1982; 248: 2004–2011. [PubMed] [Google Scholar]
- 29. Green RG. Brittish MRC trial of treatment for mild hypertension–a more favorable interpretation. Am J Hypertens 1996; 4: 723–724. [DOI] [PubMed] [Google Scholar]
- 30.UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes (UKPDS38). Brit Med J 1998; 317: 703–713. [PMC free article] [PubMed] [Google Scholar]
- 31. Palatini P, Benetos A, Grassi G, Julius S, Kjeldsen SE, et al. Identification and management of the hypertensive patient with elevated heart rate: statement of a European Society of Hypertension consensus meeting. J Hypertens 2006; 24: 603–610. [DOI] [PubMed] [Google Scholar]
- 32.Norwegian Multicenter Study Group: Timolol‐induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med 1981; 304: 801–807. [DOI] [PubMed] [Google Scholar]
- 33.b‐Blocker Heart Attack Trial (BHAT) Research Group. A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality Results. JAMA 1982; 247: 1707–1714. [DOI] [PubMed] [Google Scholar]
- 34. Yancy CW. Heart failure and its management with beta‐blockade: potential applications for once daily therapy. J Clin Hypertens 2007; 9(11): 28–35. [Google Scholar]
- 35. Fogari R, Zoppi A. Beta‐blockers and primary cardioprotection in hypertension. Drugs Expt Clin Res 1990; 16: 113–122. [PubMed] [Google Scholar]
- 36.Blood Pressure Lowering Treatment Trialists Collaboration. Effects of different blood pressure‐lowering regimens on major cardiovascular events: results of prospectively‐designed overviews of randomized trials. Lancet 2003; 362: 1527–1535. [DOI] [PubMed] [Google Scholar]
- 37. Psaty BM, Smith NL, Siscovick DS, Koepsell TD, Weiss NS, et al. Health outcomes associated with antihypertensive therapies used as first‐line agents. A systematic review and meta‐analysis. JAMA 1997; 277: 739–745. [PubMed] [Google Scholar]
- 38. Kjekshus J. Heart rate reduction–a mechanism of benefit? Eur Heart J 1987; 8(L) 115–122. [DOI] [PubMed] [Google Scholar]
- 39. Kokkinos P, Chrysohoou C, Panagiotakos D, Narayan P, Greenberg M, et al.: Beta‐blockade mitigates exercise blood pressure in hypertensive male patients. J Am Coll Cardiol 2006; 47: 794–798. [DOI] [PubMed] [Google Scholar]
- 40. Van de Pol MA, van Houdenhoven M, Hans EW, Boersma E, Bax JJ, et al. Influence of cardiac risk factors and medication on length of hospitalization in patients undergoing major vascular surgery. Am J Cardiol 2006; 97: 1423–1426. [DOI] [PubMed] [Google Scholar]
- 41. Bakris GL, Fonseca V, Katholi RE, McGill JB, Messerli FH, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension. JAMA 2004; 292: 2227–2236. [DOI] [PubMed] [Google Scholar]
- 42. Chrysant SG. The pathophysiologic role of the brain renin‐angiotensin system in stroke protection: clinical implications. J Clin Hypertens 2007; 9: 454–459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43. Chrysant SG, Chrysant GS, Desai A. Current status of angiotensin receptor blockers for the treatment of cardiovascular diseases: Focus on telmisartan. J Hum Hypertens 2005; 19: 173–183. [DOI] [PubMed] [Google Scholar]
- 44. Moser M. Hypertension treatment guidelines: Is it time for an update? J Clin Hypertens 2007; 9: 9–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45. Nguyen G, Delarue F, Burkle C, Bouzhir L, Giller T, et al.: Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular response to renin. J Clin Invest 2002; 190: 1417–1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
