Effects of a fixed-dose ace inhibitor-diuretic combination on ambulatory blood pressure and arterial properties in isolated systolic hypertension: comparison with calcium channel blocker and diuretic therapy

Abstract

The ideal therapy for patients with isolated systolic hypertension (ISH) is unclear; diuretics, calcium channel blockers (CCB’s) and ACE inhibitors are all used in clinical practice. Ambulatory blood pressures (ABP) are superior to clinic BP in ISH as predictors of cardiovascular risk. ISH is characterized by increased arterial stiffness, also a predictor of cardiovascular events. We hypothesized that a fixed-dose ACE-inhibitor/diuretic combination would reduce ABP and arterial stiffness in ISH more than monotherapies. Using a double-blind, randomized, cross-over design, the effects of 8 wks of Fosinopril/Hydrochlorothiazide combination (FOS-HCT, 10/12.5mg, titrated up to 20/12.5mg) were compared with CCB (AMLO, Amlodipine, 5mg titrated up to 10mg) and diuretic (INDA, Indapamide, 2.5mg) monotherapy in 28 patients with ISH (mean BP 165/86±2/1). Each patient received all 3 therapies with a 2 wk washout period in between; treatment order was randomly selected. Effects of therapy were assessed on 24h ABP, clinic BP, and applanation tonometry-derived augmentation index, a measure of wave reflection and an indirect marker of vascular stiffness. At 8 wks, the fall in average 24h systolic BP (SBP) and night-time SBP were greater in the FOS-HCT group, compared to AMLO and INDA (Table). The decrease in augmentation index was also greater in the FOS-HCT group, compared to AMLO (Table). There was no difference between therapies in their effects on clinic systolic (p=0.23) or diastolic BP (p=0.22), a.m. measurements made 2-3 hrs after dosing of antihypertensive therapy, nor on diastolic ABP, (24h, diurnal or nocturnal). Thus, compared with either CCB or diuretic therapy a fixed-dose ACE-inhibitor/diuretic combination induces greater reductions in systolic ABP, particularly at night, favorable effects that may be related to a decrease in the intensity of, or delay in, arterial wave reflections. ACE-inhibitor/diuretic combination therapy is thus a useful approach to cardiovascular risk reduction in ISH. Reduction in 24h, Day, and Night Systolic ABP (mmHg) and Augmentation Index (%) Reduction in 24h, Day, and Night Systolic ABP (mmHg) and Augmentation Index (%)