Abstract
Prospective comparisons of different drug classes have shown that differences in blood pressure control, rather than differences between drug classes, have the over-riding influence on overall outcome. The same studies have also reinforced the need, in the majority of patients, to use combinations of drugs in order to achieve the target of <140/85 mmHg. By contrast, most patients in routine practice receive single agents and consequently fail to achieve target blood pressure. This failure reflects in part the emphasis in individual studies and subsequent guidelines on comparison of individual drugs. In this article we show how the consistency of both theory and a broad range of evidence permits a didactic approach to combination therapy. Our advice is based on the growing recognition that essential hypertension and its treatment fall into two main categories. Younger Caucasians usually have renin-dependent hypertension that responds well to angiotensin-converting-enzyme inhibition or angiotensin receptor blockade (A) or ß blockade (B). Most other patients have low-renin hypertension that responds better to calcium channel blockade (C) or diuretics (D). These latter drugs activate the renin system rendering patients responsive to the addition of renin suppressive therapy. Coincidence of the initials of these main drug classes with the first four letters of the alphabet permits an AB/CD rule, according to which recommended combinations are one drug from each of the ‘AB’ and ‘CD’ categories of drugs. However, the diabetogenic potential of the older ‘B’ and ‘D’ classes leads us to advise against combining ‘B’ and ‘D’ in older patients, and to recommend ‘A’ + ‘C’ + ‘D’ as standard triple therapy for resistant hypertension.
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References
Murray CJL, Lopez AD . Evidence-based health policy—lessons from the global burden of disease study. Science 1998; 274: 740–743.
MacMahon S et al. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990; 335: 765–774.
Neal B, MacMahon S, Chapman N . Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists' Collaboration. Lancet 2000; 356: 1955–1964.
Ramsay LE et al. British Hypertension Society guidelines for hypertension management 1999. BMJ 1999; 319: 630–635.
Chalmers JP et al. World Health Organization—International Society of Hypertension Guidelines for the management of hypertension. J Hypertens 1999; 17: 151–185.
The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157: 2413–2446.
Primatesta P, Brookes M, Poulter NK . Improved hypertension management and control: results from the health survey for England 1998. Hypertension 2001; 38: 827–832.
Colhoun HM, Dong W, Poulter NR . Blood pressure screening, management and control in England: results from the health survey for England 1994. J Hypertens 1998; 16: 747–752.
Du X et al. Case–control study of stroke and the quality of hypertension control in north west England. BMJ 1997; 314: 272–276.
Hansson L, Zanchetti A . Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998; 351: 1755–1762.
UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317: 703–713.
Dahlof B et al. The Losartan intervention for endpoint reduction in hypertension study. Lancet 2002; 359: 995–1003.
Brown MJ et al. Morbidity and mortality in patients randomised to double-blind treatment with once-daily calcium channel blockade or diuretic in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000; 356: 366–342.
Chalmers J et al. 1999 World Health Organization—International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee. Clin Exp Hypertens 1999; 21: 1009–1060.
Buhler FR et al. Antihypertensive beta blocking action as related to renin and age: a pharmacologic tool to identify pathogenetic mechanisms in essential hypertension. Am J Cardiol 1975; 36: 653–669.
Dickerson JE et al. Optimisation of antihypertensive treatment by crossover rotation of four major classes. Lancet 1999; 353: 2008–2013.
Deary A et al. Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs. Hyperten 2002; 20: 771–777.
Materson BJ 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.
Guthrie Jr GP et al. Dissociation of plasma renin activity and aldosterone in essential hypertension. J Clin Endocrinol Metab 1976; 43: 446–448.
Philipp T et al. Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitren-dipine, and enalapril in antihypertensive treatment: results of the HANE study. BMJ 1997; 315: 154–159.
MacGregor G . The St George's ‘Star’ and Imploding Diamond'. J Hum Hypertens 1999; 13: 353–354.
Lip GY, Beevers M, Beevers DG . The ‘Birmingham Hypertension Square’ for the optimum choice of add-in drugs in the management of resistant hypertension. J Hum Hypertens 1998; 12: 761–763.
Sever PS et al. Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators. J Hypertens 2001; 19: 1139–1147.
Lind L, Pollare T, Berne C, Lithell H . Long-term metabolic effects of antihypertensive drugs. Am Heart J 1994; 128: 1177–1183.
Gordon RD et al. High incidence of primary aldosteronism in 199 patients referred with hypertension. Clin Exp Pharmacol Physiol. 1994; 21: 315–318.
Lim PO et al. Potentially high prevalence of primary aldosteronism in a primary-care population. Lancet 1999; 353: 40.
Marques-Vidal P Tuomilehto J . Hypertension awareness, treatment and control in the community: is the ‘rule of halves’ still valid? J Hum Hypertens 1997; 11: 213–220.
Epstein M, Bakris G . Newer approaches to antihypertensive therapy. Use of fixed-dose combination therapy. Arch Intern Med 1996; 156: 1969–1978.
Yusuf S et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 145–153.
Williams B . The renin angiotensin system and cardiovascular disease: hope or hype? J Renin Angiotensin Aldosterone Syst 2000; 1: 142–146.
Sleight P et al. Blood-pressure reduction and cardiovascular risk in HOPE study. Lancet 2001; 358: 2130–2131.
Svensson P et al. Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE substudy. Hypertension 2001; 38: 28e–32.
Progress Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033–1041.
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Brown, M., Cruickshank, J., Dominiczak, A. et al. Better blood pressure control: how to combine drugs. J Hum Hypertens 17, 81–86 (2003). https://doi.org/10.1038/sj.jhh.1001511
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DOI: https://doi.org/10.1038/sj.jhh.1001511
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