Physicians' Academy for Cardiovascular Education

Majority of patients require multiple antihypertensive drugs to achieve target BP

Literature - Bakris et al., J Am Soc Hypertens. 2013 - J Am Soc Hypertens. 2013 Dec 2

Review of blood pressure control rates and outcomes

Bakris G, Sarafidis P, Agarwal R, Ruilope L.
J Am Soc Hypertens. 2013 Dec 2. doi: 10.1016/j.jash.2013.07.009. [Epub ahead of print]


Data from the National Health and Nutritional Examination Survey (NHANES) 2007 through 2010 showed that 77.9 million adults in the United States (33.0%) have hypertension. 81.5% of these individuals were aware of their condition. While 74.9% of those were receiving treatment, 52.5% had hypertension under control, and 47.5% did not [1]. Prevalence of hypertension is estimated to rise.
Effective reduction of blood pressure (BP) is associated with cardiovascular (CV) risk reduction and fewer cerebrovascular events and related morbidity and mortality [2]
Most patients (~75%) require combination therapy, and some (~25%) need three antihypertensive agents to sufficiently lower BP [3,4]. NHANES data suggest that 12.8% of the American antihypertensive-treated population meets criteria for resistant hypertension (BP> 140/90 mmHg despite use of three antihypertensive agents from three different classes, or four or more antihypertensive drug classes irrespective of BP) [5].
Previous studies, including the Cardiac Arrhythmia Suppression Trial (CAST), have raised doubts regarding the strength of the concept of use of surrogate biomarker end points to substitute for clinical CV end points in phase III trials [6,7]. This review aimed to perform a literature search of outcome studies published since CAST to examine the percentage of patients treated for hypertension who achieved office BP goal/target in CV outcome trials. 28 studies were included in this review, encompassing data on 226877 patients.

Main results

  • Twelve active comparator studies reported the proportion of patients who achieved a prespecified office BP goal (in ten studies this was <140/90 mmHg). BP target achievement ranged from 45% to 75.4% (see publication for details of the different studies examined).
  • In many studies, multiple antihypertensive therapies were required to achieve BP control.
  • The placebo-controlled studies showed significant benefits of antihypertensive treatment as compared with placebo in decreasing the risk of primary CV outcome endpoints, including fatal and non-fatal stroke, myocardial infarction, CV death, and other CV events.
    In the active comparator studies different classes of antihypertensive medications were tested, and showed CV benefits, including with respect to risk reduction of fatal/non-fatal stroke, fatal/non-fatal myocardial infarction, heart failure, CV death, coronary heart disease, and total CVD morbidity/mortality.
  • No significantly greater incidence of adverse events was identified for either monotherapy or combination therapy. However, trials with lower target BP required more medications to achieve the goals, and more adverse events were reported in those trials, as compared to trials with higher BP goals and less intensive therapy. However, none of the studies reported adverse effects that would discourage the use of combination therapy to improve BP control.


This literature review shows that the majority of patients require more than one, and even up to three, antihypertensive agent to achieve BP control. Guidelines have evolved over time to recommend combination therapy, rather than single-agent antihypertensive treatment. Indeed, the combination therapy approach improves the potential for timely BP control, without an increased incidence of adverse effects.
Please find this article on Pubmed


1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics - 2013 update - a report from the American Heart Association. Circulation 2013;127:143–52.
2. Mancia G, Laurent S, Agabiti-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ, et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. Blood Press 2009;18:308–47.
3. Gradman AH, Basile JN, Carter BL, Bakris GL. Combination therapy in hypertension. J Am Soc Hyper- tens 2010;4:42–50.
4 Gradman AH. Strategies for combination therapy in hypertension. Curr Opin Nephrol Hypertens 2012;21: 486–91.
5. Persell SD. Prevalence of resistant hypertension in the United States, 2003-2008. Hypertension 2011;57: 1076–80.
6. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias- Manno D, Barker AH, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991;324:781–8.
7. Tardif JC, Heinonen T, Orloff D, Libby P. Vascular biomarkers and surrogates in cardiovascular disease. Circulation 2006;113:2936–42.

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