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Abstract-Diastolic dysfunction may precede development of heart failure in hypertensive patients. We randomized 228 patients with uncontrolled hypertension, preserved ejection fraction, and diastolic dysfunction to 2 targeted treatment strategies: intensive, with a systolic blood pressure target of Ͻ130 mm Hg, or standard, with a systolic blood pressure target of Ͻ140 mm Hg, using a combination of valsartan, either 160 or 320 mg, plus amlodipine, either 5 or 10 mg, with other antihypertensive medications as needed. any of the adverse sequelae of hypertension are the direct result of target-organ damage to the vasculature, the kidneys, and the heart. In the heart, long-standing hypertension serves as a stimulus for progressive fibrosis, ventricular hypertrophy, 1-3 and diastolic dysfunction, which may be one of the earliest manifestations of cardiac target-organ damage. 4 These changes may be accelerated by age and hypertension-related changes in central aortic stiffness, which may contribute to abnormal pulse wave reflection and enhanced pulsatile arterial load. Present in Յ50% of hypertensive patients, diastolic dysfunction likely represents an important intermediate in the development of heart failure, particularly in patients with preserved systolic function. 5,6 We have demonstrated previously that blood pressure lowering in patients with stage 1 hypertension is associated with improvement in diastolic function, whether a renin-angiotensin-aldosterone system inhibitor or non-renin-angiotensin-aldosterone system blood pressure lowering was used. 7 Because the degree of improvement in diastolic function appears to be closely tied to the degree of blood pressure lowering, we hypothesized that a strategy of aggressive blood pressure control (beyond the established Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure targets 8 ) would be more effective than a less intensive strategy in attenuating cardiac dysfunction. More aggressive targets have already been recommended in certain subgroups of patients, including those with diabetes mellitus, chronic kidney disease, and coronary artery disease. 9 The Exforge Intensive Control of Hypertension to Evaluate Efficacy in Diastolic Dysfunction (EXCEED) Trial was designed to prospectively test the hypothesis that, among patients with uncontrolledContinuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz. The principal investigator and steering committee wrote the article, made the decision to submit for publication, and take responsibility for its contents. This trial has been registered at www.clinicaltrials.gov (identifier NCT00523549).

The strategy of initiating hypertension treatment with combination versus single-drug therapy was formally tested in a prospective, double-blind, parallel-group trial in blacks with stage 2 hypertension (mean sitting systolic BP (MSSBP) X160 and o200 mm Hg). Participants were randomized equally to amlodipine/valsartan (A/V) (n ¼ 286) or amlodipine (A) monotherapy (n ¼ 286). After 2 weeks, there was forced titration of A/V 5/160 mg to A/V 10/160 mg and of A 5 to A 10 mg followed by 10 additional weeks of treatment. If SBP was X130 mm Hg at week 4, the protocol allowed optional titration of A/V to the 10/320 mg dose and, at week 8, hydrochlorothiazide 12.5 mg was optionally added to both A/V and A if SBP X130 mm Hg. Amlodipine/ valsartan at week 8 lowered MSSBP last observation carried forward significantly4A (33.3 vs 26.6 mm Hg, Po0.0001). Lowering of MSSBP with A/V significantly exceeded that of A in several specified subgroups-the elderly (X65 years), isolated systolic hypertension, and those with body mass index (BMI) X30 kg/m 2 . More patients treated with A/V than A achieved BP control (o140/90 mm Hg) both at weeks 8 (49.8 vs 30.2%; Po0.0001) and 12 (57.2 vs 35.9%; Po0.0001). Both treatment regimens were well tolerated. In conclusion, the strategy of initiating combination antihypertensive drug therapy in blacks with stage 2 hypertension with amlodipine /valsartan achieves greater and quicker reductions in BP as well as significantly higher BP control rates than starting treatment with amlodipine monotherapy.