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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.)

Objective: High blood pressure (BP) is commonly not diagnosed, and patients do not achieve target values when treated. Among 20,000 patients encompassing most races-ethnicities, we evaluated BP measurements and treatment response in a stroke prevention trial. Our goal was to identify BP measurement differences between clinical trial and patient determinations and among the racial-ethnic groups., Materials and Methods: A total of 20,332 patients with ischemic stroke were randomized to receive antiplatelet treatment and 80 mg of telmisartan versus placebo. BP measurements were obtained at the first clinic visit and then 1 and 3 months later and every 6 months thereafter. One week after the first clinic visit, patients were requested to report a BP measurement obtained elsewhere. Measurements at the trial clinics were obtained with the same electronic device. Statistical analysis was used to detect significant differences., Results: The mean patient age was 66 years; 36% were women, and race-ethnicity comprised 58% Whites, 33% Asian, 4.9% Hispanic, and 4% Black. Overall, 74% of patients were hypertensive. BP varied between the race-ethnicity groups, being highest in Hispanics (145/85) and lowest in Blacks (144/82). BP at visits clinic 1, nonclinic 1A, and clinic 2 were, respectively, 144/84, 137/80, and 139/81 mmHg, with the difference between visits 1-2 and visit 1A being significant. BPs were normal in 42% of the cases at visit 1A, and of these, only 44% were normal at visit 1 and 57.6% were normal on visit 2. Similar findings were noted for all race-ethnicity groups., Conclusion: BP values varied among race-ethnicities and showed differences between clinic and patient measurements. This finding questions the reliability of self-reported BP and has implications for BP management in daily clinical practice.

Combination therapy with benazepril 40 mg and amlodipine 10 mg (B+A) has been shown to be more effective than benazepril 40 mg and hydrochlorothiazide (HCTZ) 25 mg (B+H) in reducing cardiovascular (CV) events in high-risk patients with stage 2 hypertension with similar blood pressure reductions. In the present post hoc analysis, we evaluated whether B+A is more effective than B+H for reducing CV events in patients with known coronary artery disease (CAD) at baseline in a subgroup analysis of the Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) study. The main trial randomized 11,506 patients. Of those, 5,744 received B+A and 5,762 received B+H. Of the 11,506 patients, 5,314 (46%) were classified as having CAD at baseline. The mean patient follow-up period was 35.7 months for the B+A group and 35.6 months for the B+H group. The primary end point was the interval to the first event of composite CV morbidity and mortality. At baseline, significant differences were present between the 5,314 with CAD and the 6,192 without CAD. The patients with CAD had a lower systolic blood pressure and heart rate, a lower incidence of diabetes, and greater incidence of dyslipidemia. However, no baseline differences were found between the randomized B+A and B+H groups. In the patients with CAD, an 18% reduction occurred in the hazard ratio for CV events (primary end point) with B+A versus B+H (p = 0.0016). In a prespecified secondary analysis of the composite end point, including only CV death, myocardial infarction, and stroke, the hazard ratio in the patients with CAD was reduced by 25% (p = 0.0033) in the B+A group compared with the B+H group. B+A was more effective than B+H at comparable blood pressure reductions for reducing CV events in patients, regardless of the presence of CAD. In conclusion, our findings suggest that the combination of B+A should be preferentially used for older patients with high-risk, stage 2 hypertension., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Randomized controlled trials in hypertension demonstrate cardiovascular benefits when systolic blood pressures are reduced from higher values to<160 mm Hg. The value of lower targets has not been fully defined, although major guidelines recommend achieving systolic blood pressures of<140 mm Hg. This study was conducted to explore cardiovascular outcomes at differing on-treatment blood pressure levels., Methods: On the basis of a prespecified plan to explore relationships between clinical outcomes and systolic blood pressures, the pooled cohort of high-risk hypertensive patients (N=10,705) in the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension trial were divided into 4 strata of systolic blood pressure levels: >140 mm Hg, 130 to <140 mm Hg, 120 to <130 mm Hg, and 110 to <120 mm Hg. The primary end point was cardiovascular death or nonfatal myocardial infarction or stroke. Outcomes comparisons between the blood pressure groups were by Cox regression., Results: The mean patient age was 68 years, and the study duration was 35.7 months. The primary end point occurred in 171 of 3429 patients (5.0%) with systolic blood pressure in the 10 mm Hg range<140 and in 179 of 2354 patients (7.6%) with systolic blood pressure≥140 mm Hg (hazard ratio [HR], 0.62; 95% CI, 0.50-0.77; P=.0001). Likewise, cardiovascular death decreased by 36% (P=.0147), total myocardial infarction (fatal+nonfatal) decreased by 37% (P=.0028), and stroke decreased by 47% (P=.0002). Cardiovascular event rates in those with systolic blood pressure<130 mm Hg were not different from those with systolic blood pressure<140 mm Hg. However, compared with systolic blood pressure<130 mm Hg, stroke incidence in those with systolic blood pressure<120 mm Hg was lower (HR, 0.60; 95% CI, 0.35-1.01; P=.0529), but myocardial function was higher (HR, 1.52; 95% CI, 1.00-2.29; P=.0437), as were composite coronary events (myocardial infarction, hospitalized angina, or sudden death) (HR, 1.63; 95% CI, 1.18-2.24; P=.0023). The renal end point of a sustained>50% increase in serum creatinine was significantly lower in those with systolic blood pressure<140 mm Hg than in any of the other higher or lower blood pressure ranges., Conclusions: In high-risk hypertensive patients, major cardiovascular events are significantly lower in those with systolic blood pressures<140 mm Hg and<130 mm Hg than in those with levels>140 mm Hg. There are stroke benefits at levels<120 mm Hg, but they are offset by increased coronary events. Renal function is best protected in the 130 to 139 mm Hg range., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: In previous clinical trials in high-risk hypertensive patients, paradoxically higher cardiovascular event rates have been reported in patients of normal weight compared with obese individuals. As a prespecified analysis of the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, we aimed to investigate whether the type of hypertension treatment affects patients' cardiovascular outcomes according to their body size., Methods: On the basis of body-mass index (BMI), we divided the full ACCOMPLISH cohort into obese (BMI ≥30, n=5709), overweight (≥25 to <30, n=4157), or normal weight (<25, n=1616) categories. The ACCOMPLISH cohort had already been randomised to treatment with single-pill combinations of either benazepril and hydrochlorothiazide or benazepril and amlodipine. We compared event rates (adjusted for age, sex, diabetes, previous cardiovascular events, stroke, or chronic kidney disease) for the primary endpoint of cardiovascular death or non-fatal myocardial infarction or stroke. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00170950., Findings: In patients allocated benazepril and hydrochlorothiazide, the primary endpoint (per 1000 patient-years) was 30·7 in normal weight, 21·9 in overweight, and 18·2 in obese patients (overall p=0·0034). However, in those allocated benazepril and amlodipine, the primary endpoint did not differ between the three BMI groups (18·2, 16·9, and 16·5, respectively; overall p=0·9721). In obese individuals, primary event rates were similar with both benazepril and hydrochlorothiazide and benazepril and amlodipine, but rates were significantly lower with benazepril and amlodipine in overweight patients (hazard ratio 0·76, 95% CI 0·59-0·94; p=0·0369) and those of normal weight (0·57, 0·39-0·84; p=0·0037)., Interpretation: Hypertension in normal weight and obese patients might be mediated by different mechanisms. Thiazide-based treatment gives less cardiovascular protection in normal weight than obese patients, but amlodipine-based therapy is equally effective across BMI subgroups and thus offers superior cardiovascular protection in non-obese hypertension., Funding: Novartis Pharmaceuticals., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Unlabelled: HYPOTHESIS/ INTRODUCTION: We investigated whether diabetes modified the effectiveness of renin-angiotensin-aldosterone system (RAAS) inhibition on left ventricular hypertrophy (LVH) regression in hypertensive patients in the Aliskiren in Left Ventricular Hypertrophy (ALLAY) trial., Materials and Methods: Participants (n=465) with LVH and a BMI > 25 kg/m(2) were randomized to aliskiren 300mg, losartan 100mg or both daily for 36 weeks, and LVH regression was assessed by cardiac magnetic resonance imaging. Renin concentration, plasma renin activity and aldosterone were assessed in a subset of patients., Results: Patients with diabetes mellitus (DM) (n=111, 24%) were older (61±9 vs. 58±11 years, p=0.03), had higher BMI (32.2±4.2 vs. 30.7 ± 4 kg/m(2), p=0.004), higher systolic blood pressure (148±14 vs. 145±14mmHg, p=0.03) and lower eGFR (79±16 vs. 84±16ml/min, p=0.03) at baseline. Combination therapy with aliskiren plus losartan was associated with greater LVH reduction than losartan alone in patients with DM (p=0.01), but not in patients without DM (p=0.91; unadjusted interaction p=0.06; adjusted p = 0.038). In a subset of 138 participants, plasma aldosterone was reduced to a greater extent in patients with DM (p-interaction = 0.004)., Conclusions: Patients with DM and LVH may derive differential benefit with dual RAAS inhibition with a combination of aliskiren and losartan compared with losartan alone with respect to LVH reduction. Whether these findings will result in improved outcomes will be further explored in larger studies.

The ACCOMPLISH trial (Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension) was a 3-year multicenter, event-driven trial involving patients with high cardiovascular risk who were randomized in a double-blinded manner to benazepril plus either hydrochlorothiazide or amlodipine and titrated in parallel to reach recommended blood pressure goals. Of the 8125 participants in the United States, 1414 were of self-described Black ethnicity. The composite kidney disease end point, defined as a doubling in serum creatinine, end-stage renal disease, or death was not different between Black and non-Black patients, although the Blacks were significantly more likely to develop a greater than 50% increase in serum creatinine to a level above 2.6 mg/dl. We found important early differences in the estimated glomerular filtration rate (eGFR) due to acute hemodynamic effects, indicating that benazepril plus amlodipine was more effective in stabilizing eGFR compared to benazepril plus hydrochlorothiazide in non-Blacks. There was no difference in the mean eGFR loss in Blacks between therapies. Thus, benazepril coupled to amlodipine was a more effective antihypertensive treatment than when coupled to hydrochlorothiazide in non-Black patients to reduced kidney disease progression. Blacks have a modestly higher increased risk for more advanced increases in serum creatinine than non-Blacks.

Background: We have reported the benefits of atorvastatin and of an amlodipine-based regimen on coronary heart disease (CHD) events in hypertensive patients in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We report further analyses on the combined benefits of these interventions., Methods: 19,342 hypertensive patients were randomised to either an amlodipine or an atenolol-based regimen in the ASCOT Blood Pressure-Lowering Arm (BPLA). 10,305 subjects with total cholesterol

Objective: The purpose of this study was to determine the baseline predictors of new-onset diabetes (NOD) in hypertensive patients and to develop a risk score to identify those at high risk of NOD., Research Design and Methods: Among 19,257 hypertensive patients in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) who were randomly assigned to receive one of two antihypertensive regimens (atenolol +/- thiazide or amlodipine +/- perindopril), 14,120 were at risk of developing diabetes at baseline. Of these, 1,366 (9.7%) subsequently developed NOD during median follow-up of 5.5 years. A multivariate Cox model was developed to identify the independent predictors of NOD and individual risk scores., Results: NOD was significantly associated with an increase in baseline fasting plasma glucose (FPG), BMI, serum triglycerides, and systolic blood pressure. In contrast, amlodipine +/- perindopril in comparison with atenolol +/- thiazide treatment (hazard ratio 0.66 [95% CI 0.59-0.74]), high HDL cholesterol, alcohol use, and age >55 years were found to be significantly protective factors. FPG was the most powerful predictor with risk increasing by 5.8 times (95% CI 5.23-6.43) for each millimole per liter rise >5 mmol/l. The risk of NOD increased steadily with increasing quartile of risk score, with a 19-fold increase (95% CI 14.3-25.4) among those in the highest compared with those in the lowest quartile. The model showed excellent internal validity and discriminative ability., Conclusions: Baseline FPG >5 mmol/l, BMI, and use of an atenolol +/- diuretic regimen were among the major determinants of NOD in hypertensive patients. The model developed from these data allows accurate prediction of NOD among hypertensive subjects.

In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, a major reduction of all-cause mortality--especially cardiovascular mortality--in patients with diabetes with left ventricular hypertrophy was reported for treatment with losartan. We postulated post hoc that losartan might have a better effect on sudden cardiac death than atenolol, and we aimed to test this hypothesis. [ABSTRACT FROM AUTHOR]

SummaryBackgroundThe efficacy of new antihypertensive drugs has been questioned. We compared the effects of conventional and newer antihypertensive drugs on cardiovascular mortality and morbidity in elderly patients.MethodsWe did a prospective, randomised trial in 6614 patients aged 70-84 years with hypertension (blood pressure [> OR =]180 mm Hg systolic, [> OR =]105 mm Hg diastolic, or both). Patients were randomly assigned conventional antihypertensive drugs (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily) or newer drugs (enalapril 10 mg or lisinopril 10 mg, or felodipine 2.5 mg or isradipine 2-5 mg daily). We assessed fatal stroke, fatal myocardial infarction, and other fatal cardiovascular disease. Analysis was by intention to treat.FindingsBlood pressure was decreased similarly in all treatment groups. The primary combined endpoint of fatal stroke, fatal myocardial infarction, and other fatal cardiovascular disease occurred in 221 of 2213 patients in the conventional drugs group (19.8 events per 1000 patient-years) and in 438 of 4401 in the newer drugs group (19.8 per 1000; relative risk 0.99 [95% CI 0.84-1.16], p=0.89). The combined endpoint of fatal and non-fatal stroke, fatal and non-fatal myocardial infarction, and other cardiovascular mortality occurred in 460 patients taking conventional drugs and in 887 taking newer drugs (0.96 [0.86-1.08], p=0.49).InterpretationOld and new antihypertensive drugs were similar in prevention of cardiovascular mortality or major events. Decrease in blood pressure was of major importance for the prevention of cardiovascular events. [ABSTRACT FROM AUTHOR]