Amlodipine+Benazepril is Superior to Hydrochlorothiazide+Benazepril Irrespective of Baseline Pulse Pressure: Subanalysis of the ACCOMPLISH Trial

Abstract

Pulse pressure (PP) is an independent risk factor for cardiovascular (CV) disease and death but few studies have investigated the effect of antihypertensive treatments in relation to PP levels before treatment. The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial showed that the combination of benazepril+amlodipine (B+A) is superior to benazepril+hydrochlorothiazide (B+H) in reducing CV events. We aimed to investigate whether the treatment effects in the ACCOMPLISH trial were dependent on baseline PP. High-risk hypertensive patients (n=11,499) were randomized to double-blinded treatment with singlepill combinations of either B+A or B+H and followed for 36 months. Patients were divided into tertiles according to their baseline PP and events (CV mortality/myocardial infarction or stroke) were compared. Hazard ratios (HRs) for the treatment effect (B+A over B+H) were calculated in a Cox regression model with age, coronary artery disease, and diabetes mellitus as covariates and were compared across the tertiles. The event rate was increased in the high tertile of PP compared with the low tertile (7.2% vs 4.4% P<.01). In the high and medium PP tertiles, HRs were 0.75 (95% confidence interval [CI], 0.60-0.95; P=.018) and 0.74 (CI, 0.56-0.98, P=.034), respectively, in favor of B+A. There was no significant difference between the treatments in the low tertile and no significant differences in treatment effect when comparing the HRs between tertiles of PP. B+A has superior CV protection over B+H in high-risk hypertensive patients independent of baseline PP although the absolute treatment effect is enhanced in the higher tertiles of PP where event rates are higher. J Clin Hypertens (Greenwich). 2015;17:141-146. ª 2014 Wiley Periodicals, Inc.Hypertension has been identified as the most important global risk factor for premature death. It causes 45% of deaths caused by heart disease and 51% of deaths caused by stroke.1 Rapsomaniki and colleagues recently highlighted the importance of blood pressure (BP) for various manifestations of cardiovascular (CV) disease in 1.25 million patients. Diastolic and systolic pressure associations were not concordant, and pulse pressure (PP), rather than systolic BP (SBP), was associated with some CV diseases.2 The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial investigated antihypertensive combination treatment with benazepril+amlodipine (B+A) or benazepril+hydrochlorothiazide (B+H) on CV outcomes in patients with systolic hypertension and with widely varying PPs.3,4 The overall study result was significantly lower for CV outcomes in the patients randomized to B+A compared with B+H despite no differences in the achieved BP between groups.PP is an indicator of arterial stiffness and is related to an increased risk for CV disease. [5][6][7][8][9][10][11] Results from the Framingham Heart Study show that for a given SBP, coronary heart disease ...

An Assessment of Oral Health in Hypertensive Patients Treated with HMG-CoA Reductase Inhibitors ( Statins )

“…Blood pressure levels of the present study showed the significant difference between Group II and III in the level of pulse pressure. This observation attributed to the variation in the nature of antihypertensives that used by the patients (13) . 3.…”

Formulations of Amlodipine: A Review

“…Not much information regarding the formulations is available as the studies are more clinically oriented and the combinations have been discussed with respect to their clinical outcomes only in majority of the cases. The drugs most commonly employed in combination with AD (i.e., single drug + AD combination) include aliskiren [39–41], atorvastatin [42–52], azilsartan [53], benazepril [54, 55], fimasartan [56], indapamide [57, 58], irbesartan [59], olmesartan (olmesartan medoxomil) [39, 60–67], perindopril [68–72], telmisartan [73–77], and valsartan [70, 71, 78–97]. …”

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