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The effects of race and age on 24-hour mean ambulatory systolic blood pressure (maSBP) responses to sequential 4-week periods of angiotensin receptor blocker therapy (valsartan [VAL] 160 mg/d then 320 mg/d and combination VAL/hydrochlorothiazide [HCTZ] 320/12.5 mg/d) were compared in 304 patients with stage 1 or 2 hypertension. There were lesser blood pressure (BP) responses from baseline with VAL monotherapy in black than Caucasian patients (-2.9 and -4.0 mm Hg vs -8.2 and -9.3 mm Hg, respectively; P<.001 each) but VAL/HCTZ BP responses were similar in both groups (-12 vs -15 mm Hg). Participants 65 years and older had lower BP responses with VAL 160 mg/d and 320 mg/d than those younger than 65 years (-2.8 and -4.5 mm Hg vs -6.5 and -7.5 mm Hg, respectively; P<.001) but similar responses to VAL/HCTZ (-14 vs -17 mm Hg). No BP response differences were found between those older than and those younger than 55 years. The authors conclude that: (1) adding low-dose HCTZ (12.5 mg daily) to VAL is more effective than VAL titration, irrespective of age or race, (2) VAL BP efficacy is lower in blacks than Caucasians, and (3) ARB responses are diminished in patients older than 65 years. Guidelines for stage 1 or 2 hypertension that suggest age 55 should determine initial monotherapy choice (eg, ARB vs thiazide diuretic) or that fail to recommend initial ARB-thiazide combination therapy should be reconsidered., (©2016 Wiley Periodicals, Inc.)

To evaluate the effects of achieved systolic blood pressure (SBP) during treatment on cardiovascular (CV) outcomes, the authors measured event rates of a composite primary endpoint (CV death or nonfatal myocardial infarction or stroke) at on-treatment SBPs of ≥140 mm Hg and the 10 mm Hg intervals of <140 mm Hg, <130 mm Hg, and <120 mm Hg in 6459 patients with diabetes (mean age, 67) and 4246 patients without diabetes (mean age, 69) from the Avoiding Cardiovascular Events in Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial. In the diabetic cohort, the primary endpoint was 49% lower (P<.001) at <140 mm Hg than at ≥140 mm Hg, and the separate components of this endpoint were also significantly reduced. Further SBP reductions did not improve outcomes, and at <120 mm Hg they were no longer different (except for stroke) from ≥140 mm Hg. In contrast, in the nondiabetic cohort, the primary endpoint event rate fell steadily (although not significantly) through the decreasing SBP categories until it was reduced by 45% (P=.0413) at <120 mm Hg. Total stroke rates for both the diabetic (-56%, P=.0120) and nondiabetic (-68%, P=.0067) cohorts were lowest at <120 mm Hg, and adverse renal events (serum creatinine increase ≥50%) were significantly lowest in the range of 130 mm Hg to 139 mm Hg for both cohorts. Diabetic patients (<140 mm Hg or <130 mm Hg) and nondiabetic patients (<120 mm Hg) may require different SBP targets for optimal CV protection, although stroke and renal considerations should also influence the selection of blood pressure targets., (© 2016 Wiley Periodicals, Inc.)

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 single-pill 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., (© 2014 Wiley Periodicals, Inc.)

Postmenopausal women are at greater risk for hypertension-related cardiovascular disease. Antihypertensive therapy may help alleviate arterial stiffness that represents a potential modifiable risk factor of hypertension. This randomized controlled study investigated the difference between an angiotensin receptor blocker and a calcium channel blocker in reducing arterial stiffness. Overall, 125 postmenopausal hypertensive women (age, 61.4 ± 6 years; systolic blood pressure/diastolic blood pressure [SBP/DBP], 158 ± 11/92 ± 9 mm Hg) were randomized to valsartan 320 mg ± hydrochlorothiazide (HCTZ) (n = 63) or amlodipine 10 mg ± HCTZ (n = 62). The primary outcome was carotid-to-femoral pulse wave velocity (PWV) changes after 38 weeks of treatment. Both treatments lowered peripheral blood pressure (BP) (-22.9/-10.9 mm Hg for valsartan and -25.2/-11.7 mm Hg for amlodipine, P = not significant) and central BP (-15.7/-7.6 mm Hg for valsartan and -19.2/-10.3 mm Hg for amlodipine, P<.05 for central DBP). Both treatments similarly reduced the carotid-femoral PWV (-1.9 vs -1.7 m/s; P = not significant). Amlodipine was associated with a higher incidence of peripheral edema compared with the valsartan group (77% vs 14%, P<.001). BP lowering in postmenopausal women led to a reduction in arterial stiffness as assessed by PWV measurement. Both regimens reduced PWV to a similar degree after 38 weeks of treatment despite differences in central BP lowering, suggesting that the effect of valsartan on PWV is mediated through nonhemodynamic effects., (© 2012 Wiley Periodicals, Inc.)

The authors previously reported that addition of valsartan ameliorated the negative metabolic effects of hydrochlorothiazide in obese hypertensive patients through an enhanced postprandial insulin response. In this secondary analysis, the authors tested whether this enhanced insulin response to valsartan/hydrochlorothiazide was influenced by serum potassium levels, which were reduced to a lesser extent, when compared with amlodipine/hydrochlorothiazide. Results showed that the early insulin response with valsartan plus hydrochlorothiazide occurred regardless of serum potassium levels. Heightened insulin response was, however, not significantly different when patients with normal potassium (>3.9 mEq/L) at baseline and low potassium (≤3.9 mEq/L) at the end of the study were compared with the amlodipine/hydrochlorothiazide group. Despite the influence of serum potassium on insulin secretory response to a glucose challenge, the addition of valsartan maintained normoglycemia in patients given hydrochlorothiazide. Thus, the metabolic response to hydrochlorothiazide was improved with addition of valsartan through an enhanced insulin response that was not greatly affected by changes in potassium levels., (© 2012 Wiley Periodicals, Inc.)

This pooled analysis of ambulatory blood pressure (BP) monitoring data from two 8-week randomized controlled trials compared the antihypertensive efficacy and safety of combination aliskiren/valsartan vs valsartan alone in hypertensive patients (nocturnal dippers or nondippers). At study end, patients were taking aliskiren/valsartan 300/320 mg or valsartan 320 mg. In dippers (n=138) and nondippers (n=132), aliskiren/valsartan provided significantly (P<.05) greater reductions from baseline to week 8 than valsartan in 24-hour, daytime, and last-4-hour mean ambulatory systolic BP (maSBP). Treatment differences were more pronounced in nondippers. Nighttime maSBP reductions with aliskiren/valsartan were significantly greater vs valsartan in nondippers (-17.0 mm Hg vs -8.9 mm Hg; P<.05) but not dippers (-7.6 mm Hg vs -4.5 mm Hg; P=.16). In all time periods, combination therapy was generally associated with BP reductions that were greater in nondippers than dippers. Conversion from nondipper to dipper status was 32% vs 22% for aliskiren/valsartan vs valsartan (P=.48). Both treatments were similarly well tolerated. Although the addition of aliskiren to valsartan did not significantly alter dipper status, our data suggest an increased contribution of the renin-angiotensin-aldosterone system to the nondipper status of hypertensive patients., (© 2012 Wiley Periodicals, Inc.)

The authors evaluated the blood pressure (BP)-lowering effects of combination valsartan/hydrochlorothiazide (HCTZ) vs. amlodipine/HCTZ in a 16-week, double-blind, randomized, forced-titration study and ambulatory BP monitoring (ABPM) substudy involving centrally obese hypertensive patients 40 years and older. Patients were started on valsartan/HCTZ 160/12.5 mg or HCTZ 12.5 mg monotherapy, force-titrated at week 4 to valsartan/HCTZ 320/25 mg and HCTZ 25 mg, respectively. The HCTZ group initiated amlodipine 5 mg at week 8 and 10 mg at week 12. A subset of patients had 24-hour ABPM at baseline and weeks 8 and 16. At week 16 in the intent-to-treat population (n=401), valsartan/HCTZ and amlodipine/HCTZ lowered office systolic BP (-30.6 vs. -28.3 mm Hg; P=.14). In the ABPM subgroup (n=111), valsartan/HCTZ was more effective than amlodipine/HCTZ in reducing 24-hour systolic BP (-20.6 vs. -14.5 mm Hg; P=.011). In obese hypertensive patients, valsartan/HCTZ reduced office BP similar to amlodipine/HCTZ but lowered 24-hour systolic BP more., (© 2011 Wiley Periodicals, Inc.)

This 16-week trial investigated the efficacy and safety of single-pill valsartan/hydrochlorothiazide (HCTZ) vs. the individual components in patients 70 years and older with systolic hypertension. Patients were randomized to valsartan/HCTZ 160/12.5 mg (n=128), HCTZ 12.5 mg (n=128), or valsartan 160 mg (n=128) for 4 weeks. Patients whose blood pressure (BP) was ≥140/90 mm Hg at weeks 4, 8, or 12 were up-titrated to a maximum of valsartan/HCTZ 320/25 mg. Week 4 systolic BP reduction (primary efficacy outcome) was greater with valsartan/HCTZ than valsartan (-17.3 mm Hg vs. -8.6 mm Hg, P <.0001) but only marginally greater than HCTZ (-13.6 mm Hg, P =.096). Median time to BP control was shorter with valsartan/HCTZ (4 weeks) vs HCTZ (8 weeks, P<.05) or valsartan (12 weeks, P<.0001). Thiazide monotherapy was more effective than angiotensin receptor blocker monotherapy (by about 5 mm Hg), but greater antihypertensive efficacy was achieved by initiating treatment with combination valsartan/HCTZ in the elderly., (© 2011 Wiley Periodicals, Inc.)

Several studies reported racial/ethnic differences in blood pressure (BP) response to antihypertensive monotherapy. In a 10-week study of stage 2 hypertension, 320/25 mg valsartan/hydrochlorothiazide (HCTZ) reduced ambulatory BP (ABP) significantly more effectively than 10/25 mg amlodipine/HCTZ. Results (post hoc analysis) are described in Caucasians (n=256), African Americans (n=79), and Hispanics (n=86). Compared with clinic-measured BP (no significant treatment-group differences in ethnic subgroups), least-squares mean reductions from baseline to week 10 in mean ambulatory systolic BP (MASBP) and mean ambulatory diastolic BP (MADBP) favored valsartan/HCTZ over amlodipine/HCTZ in Caucasians (-21.9/-12.7 mm Hg vs -17.6/-9.5 mm Hg; P=.0004/P<.0001). No treatment-group differences in MASBP/MADBP were observed in African Americans (-17.3/-10.6 vs -17.9/-9.5; P=.76/P=.40) or Hispanics (-17.9/-9.7 vs -14.2/-7.2; P=.20/P=.17). Based on ABP monitoring, valsartan/HCTZ is more effective than amlodipine/HCTZ in lowering ABP in Caucasians. In African Americans and Hispanics, both regimens are similarly effective., (© 2010 Wiley Periodicals, Inc.)

Hypertensive patients with the cardiometabolic syndrome (CMS) are at increased risk for type 2 diabetes and cardiovascular disease. The authors examined effects of valsartan and hydrochlorothiazide (HCTZ) combined and alone on insulin sensitivity (using homeostasis model assessment-insulin resistance [HOMA-IR]), and inflammatory/metabolic biomarkers in prediabetic hypertensive persons with CMS. Eligible patients entered 16-week therapy with valsartan 320 mg/d (n=189), HCTZ 25 mg/d (n=190), or valsartan/HCTZ 320/25 mg/d (n=187). At the end point, there were no statistically significant differences in HOMA-IR among the 3 groups. HCTZ significantly increased hemoglobin A(1c) and triglyceride concentrations and lowered serum potassium levels vs valsartan. HCTZ also increased plasma aldosterone and C-reactive protein levels. Blood pressure reduction and blood pressure control rates were highest with valsartan/HCTZ. There were no differences between combination valsartan/HCTZ or monotherapies on a measure of insulin sensitivity; however, the negative metabolic effects of HCTZ (increase in triglyceride and hemoglobin A(1c) values) were absent with valsartan/HCTZ, indicating an ameliorating effect of valsartan on these measures.

To assess the strategy of increasing the dose of a diuretic compared with using an angiotensin receptor blocker in combination with a diuretic, the authors performed a multicenter, randomized, parallel group trial in hypertensive patients (baseline blood pressure [BP], 153/97 mm Hg) whose BP remained uncontrolled on initial low-dose diuretic monotherapy (hydrochlorothiazide [HCTZ] 12.5 mg Hg). Patients with stage 1 and 2 hypertension were randomized to treatment with valsartan/HCTZ (160/12.5 mg) or to doubling of the HCTZ dose (25 mg). The primary end point was the percentage of patients whose clinic BP values were <140/90 mm Hg following 4 weeks of double-blind therapy. A significantly higher proportion (P<.001) of hypertensive patients met BP control levels in the valsartan/HCTZ (160/12.5 mg) group compared with the HCTZ 25 mg group (37% vs 16%). Changes from baseline in BP were significantly greater (P<.001) for both systolic BP and diastolic BP in the combination therapy arm compared with the diuretic monotherapy arm (-12. 4/-7.5 mm Hg in valsartan/HCTZ 160/12.5 mg group vs -5.6/-2.1 mm Hg in HCTZ 25 mg group). Tolerability and adverse events were similar in the 2 treatment groups. This study suggests that in the management of hypertension, utilizing an angiotensin receptor blocker/diuretic combination was more effective in lowering BP and achieving BP goals when compared with increasing the dose of the diuretic.