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Background: Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin-converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin-converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear., Methods and Results: We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow-up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus <15%) were associated with a 26% higher hazard of cardiovascular outcomes (95% CI, 1.07-1.48). In spline-based analysis, risk for cardiovascular outcomes was higher in the hydrochlorothiazide arm at every level of decline in eGFR compared with the same magnitude of eGFR decline in the amlodipine arm., Conclusion: Combined use of benazepril and amlodipine remains superior to benazepril and hydrochlorothiazide for cardiovascular outcomes, regardless of the magnitude of the decline in eGFR that occurred with initiation of therapy.

The greater antihypertensive responses to initial therapy with calcium channel blockers (CCBs) or thiazide-type diuretics than renin-angiotensin system blockers as initial therapy in non-Hispanic Black (NHB) adults was recognized in the US High BP guidelines from 1988 to 2003. The 2014 Report from Panel Members Appointed to the Eighth Joint National Committee (2014 aJNC8 Report) and the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline were the first to recommend CCBs or thiazide-type diuretics rather than renin-angiotensin system blockers as initial therapy in NHB. We assessed the temporal relationship of these recommendations on self-reported CCB or thiazide-type diuretics monotherapy by NHB and NHW adults with hypertension absent compelling indications for β-blockers or renin-angiotensin system blockers in National Health and Nutrition Examination Surveys 2015 to 2018 versus 2007 to 2012 (after versus before 2014 aJNC8 Report). CCB or thiazide-type diuretics monotherapy was unchanged in NHW adults (17.1% versus 18.1%, P =0.711) and insignificantly higher after 2014 among NHB adults (43.7% versus 38.2%, P =0.204), although CCB monotherapy increased (29.5% versus 21.0%, P =0.021) and renin-angiotensin system blocker monotherapy fell (44.5% versus 31.0%, P =0.008). Although evidence-based CCB monotherapy increased among NHB adults in 2015 to 2018, hypertension control declined as untreated hypertension and monotherapy increased. While a gap between recommended and actual monotherapy persists, evidence-based monotherapy appears insufficient to improve hypertension control in NHB adults, especially given evidence for worsening therapeutic inertia. Initiating treatment with single-pill combinations and timely therapeutic intensification when required to control hypertension are evidence-based, race-neutral options for improving hypertension control among NHB adults.

Background: During intensive BP lowering, acute declines in renal function are common, thought to be hemodynamic, and potentially reversible. We previously showed that acute declines in renal function ≥20% during intensive BP lowering were associated with higher risk of ESRD. Here, we determined whether acute declines in renal function during intensive BP lowering were associated with mortality risk among 1660 participants of the African American Study of Kidney Disease and Hypertension and the Modification of Diet in Renal Disease Trial., Methods: We used Cox models to examine the association between percentage decline in eGFR (<5%, 5% to <20%, or ≥20%) between randomization and months 3-4 of the trials (period of therapy intensification) and death., Results: In adjusted analyses, compared with a <5% eGFR decline in the usual BP arm (reference), a 5% to <20% eGFR decline in the intensive BP arm was associated with a survival benefit (hazard ratio [HR], 0.77; 95% confidence interval [95% CI], 0.62 to 0.96), but a 5% to <20% eGFR decline in the usual BP arm was not (HR, 1.01; 95% CI, 0.81 to 1.26; P <0.05 for the interaction between intensive and usual BP arms for mortality risk). A ≥20% eGFR decline was not associated with risk of death in the intensive BP arm (HR, 1.18; 95% CI, 0.86 to 1.62), but it was associated with a higher risk of death in the usual BP arm (HR, 1.40; 95% CI, 1.04 to 1.89) compared with the reference group., Conclusions: Intensive BP lowering was associated with a mortality benefit only if declines in eGFR were <20%., (Copyright © 2018 by the American Society of Nephrology.)

Background: The ACCOMPLISH (Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension) trial demonstrated that combination therapy using amlodipine, rather than hydrochlorothiazide, in conjunction with benazepril provided greater cardiovascular risk reduction among high-risk hypertensive patients. Few trials have evaluated the effect of prior antihypertensive therapy used among participants on the study outcomes., Methods and Results: In a post hoc observational analysis, we examined the characteristics of the drug regimens taken before trial enrollment in the context of the primary composite outcome (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac death, and coronary revascularization). In the "primary subgroup" (n=4475), patients previously taking any renin-angiotensin system blockade plus either a diuretic or a calcium channel blocker alone or as part of their antihypertensive regimen, there were 206 of 2193 (9.4%) versus 281 of 2282 (12.3%) primary composite events among those randomized to combination therapy involving amlodipine versus hydrochlorothiazide, respectively (adjusted Cox proportional hazard ratio, 0.74; 95% confidence interval, 0.62-0.89; P =0.0015). All other participants (n=6975) previously taking any antihypertensive regimen not included in the primary subgroup also benefited from randomization to amlodipine plus benazepril (adjusted hazard ratio, 0.84; 95% confidence interval, 0.72-0.98; P =0.024). Outcomes among most other subgroups, including patients previously taking lipid-lowering medications or dichotomized by prior blood pressure control status, showed similar results., Conclusions: When combined with an angiotensin-converting enzyme inhibitor, amlodipine provides cardiovascular risk reduction superior to hydrochlorothiazide, largely regardless of prior medication use. These findings add further support for the initial use of this combination regimen among high-risk hypertensive patients., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

The magnitude of decline in renal function that should be tolerated during intensive BP lowering and its association with risk of ESRD are unclear. To determine whether the acute declines in kidney function in the intensive BP lowering arm of two trials in CKD associated with higher risk of ESRD, we performed a retrospective study of 899 African American Study of Kidney Disease and Hypertension (AASK) and 761 Modification of Diet in Renal Disease (MDRD) Trial participants previously randomized to strict versus usual BP control. The predictor was the percentage decline in eGFR (<5%, 5% to <20%, or ≥20%) between randomization and months 3 and 4 of the trial (time to achieve BP goals). ESRD was the outcome of interest. Compared with a <5% eGFR decline in the usual BP arm, a 5% to <20% eGFR decline during intensive BP lowering did not associate with a higher risk of ESRD in the AASK (adjusted hazard ratio [aHR], 1.19; 95% confidence interval [95% CI], 0.84 to 1.68) or the MDRD Trial (aHR, 1.08; 95% CI, 0.84 to 1.40). However, a 5% to <20% eGFR decline in the usual BP arm associated with higher risk of ESRD in AASK (aHR, 1.83; 95% CI, 1.30 to 2.57) and MDRD Trial (aHR, 1.62; 95% CI, 1.25 to 2.11). A ≥20% eGFR decline associated with higher risk of ESRD in both strict and usual BP arms. Thus, acute eGFR declines ≥20% during intensive BP lowering identified a subset of patients at higher risk for adverse outcomes., (Copyright © 2017 by the American Society of Nephrology.)

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.)

For people enrolled in Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL), we sought to examine whether variation exists in the baseline medical therapy of different geographic regions and if any variations in prescribing patterns were associated with physician specialty. Patients were grouped by location within the United States (US) and outside the US (OUS), which includes Canada, South America, Europe, South Africa, New Zealand, and Australia. When comparing US to OUS, participants in the US took fewer anti-hypertensive medications (1.9 ± 1.5 vs. 2.4 ± 1.4; P < .001) and were less likely to be treated with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (46% vs. 62%; P < .001), calcium channel antagonist (37% vs. 58%; P < .001), and statin (64% vs. 75%; P < .05). In CORAL, the identification of variations in baseline medical therapy suggests that substantial opportunities exist to improve the medical management of patients with atherosclerotic renal-artery stenosis., (Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

A 2014 hypertension guideline raised goal systolic blood pressure (SBP) from <140 mm Hg to <150 mm Hg for adults 60 years and older without diabetes mellitus (DM) or chronic kidney disease (CKD). The authors aimed to define the status of hypertension in black adults 60 to 79 years from the National Health and Nutrition Examination Survey 2005-2012 and provide practical guidance. Black patients were more often aware and treated (P≤.005) for hypertension than whites and had higher rates of DM/CKD (P<.001), similar control to <140/<90 mm Hg with DM/CKD (P=.59), and lower control without DM/CKD (<140/<90 mm Hg and <150/<90 mm Hg, P≤.01). Limited awareness (<30%) and infrequent health care (>30% 0-1 health-care visits per year) occurred in untreated black and white hypertensive patients without DM/CKD and BP ≥140/<90 mm Hg. The literature suggests benefits of treated SBP <140 mm Hg in adults 60 to 79 years without DM/CKD. The International Society of Hypertension in Blacks recommends: (1) continuing efforts to achieve BP <140/<90 mm Hg in those with DM/CK, and (2) identifying hypertensive patients without DM/CKD and BP ≥140/<90 mm Hg and treat to an SBP <140 mm Hg in black adults 60-79 years., (© 2015 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.)

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommended a thiazide-like diuretic, alone or in combination with other antihypertensive drug classes, as initial therapy for hypertension. JNC 7, however, did not specify preferred combinations. The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial was completed five years after the JNC 7 and demonstrated a 20 % advantage in cardiovascular risk reduction when blood pressure was lowered using the single-pill combination of benazepril-amlodipine compared to benazepril-hydrochlorothiazide (Jamerson et al. 359(23):2417-28 [1]). This new and significant finding provided compelling evidence that the long-standing preference for diuretics as initial therapy could be refuted, but it may also be relevant to the lower-than-expected reduction in coronary disease related events (compared to stroke) observed for decades prior to the ACCOMPLISH approach to therapy. The JNC 8 panel members recently published their recommendations, and while the group did not recommend benazepril-hydrochlorothiazide over other combinations, they did highlight the findings of ACCOMPLISH, rating the primary ACCOMPLISH paper as "good." The American Society of Hypertension position paper and the European Hypertension Society guidelines endorse such combinations as a first-line agent for patients with stage 2 hypertension. We review the current position of ACCOMPLISH in the guidelines regarding treatment of stage 2 hypertension.

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.)

The objective of our study was to determine the effects of 2 antihypertensive drug dose schedules (PM dose and add-on dose) on nocturnal blood pressure (BP) in comparison with usual therapy (AM dose) in blacks with hypertensive chronic kidney disease and controlled office BP. In a 3-period, crossover trial, former participants of the African American Study of Kidney Disease were assigned to receive the following 3 regimens, each lasting 6 weeks, presented in random order: AM dose (once-daily antihypertensive medications taken in the morning), PM dose (once-daily antihypertensives taken at bedtime), and add-on dose (once-daily antihypertensives taken in the morning and an additional antihypertensive medication before bedtime [diltiazem 60-120 mg, hydralazine 25 mg, or additional ramipril 5 mg]). Ambulatory BP monitoring was performed at the end of each period. The primary outcome was nocturnal systolic BP. Mean age of the study population (n=147) was 65.4 years, 64% were men, and mean estimated glomerular filtration rate was 44.9 mL/min per 1.73 m(2). At the end of each period, mean (SE) nocturnal systolic BP was 125.6 (1.2) mm Hg in the AM dose, 123.9 (1.2) mm Hg in the PM dose, and 123.5 (1.2) mm Hg in the add-on dose. None of the pairwise differences in nocturnal, 24-hour, and daytime systolic BP was statistically significant. Among blacks with hypertensive chronic kidney disease, neither PM (bedtime) dosing of once-daily antihypertensive nor the addition of drugs taken at bedtime significantly reduced nocturnal BP compared with morning dosing of antihypertensive medications.

Background: The ACCOMPLISH Trial investigated intensive antihypertensive combination treatment with benazepril + amlodipine (B+A) or benazepril + hydrochlorothiazide (B+H) on cardiovascular outcomes in patients with systolic hypertension. We analyzed the baseline predictors of achieving a systolic blood pressure (SBP) <140 mmHg and achieved SBP level by the end of 12 months in both treatment groups., Methods: Baseline and 12-month SBP was available in 10,506 patients, of whom 6250 had diabetes. Univariate and multivariate logistic regression models were used for SBP control at 12 months and multivariable regression models were used for the prediction of SBP at 12 months. A stepwise procedure was used to select significant (p < 0.001) predictors in multivariate analyses., Results: Mean (± SD) BP fell from 145.4/80.1 (± 18.3/10.7) mmHg at randomization to 132.8/74.7 (± 16.0/9.6) mmHg at 12 months. The main baseline predictors of SBP control <140 mmHg were region (USA >Nordic region) and Caucasian ethnicity in both randomization arms. A higher diastolic BP and the use of lipid lowering agents indicated favorable effects in the B+H arm only. The predictors of uncontrolled SBP were: (i) higher baseline SBP values, (ii) higher number of previous antihypertensive medications in both arms, (iii) the previous use of insulin in the B+A arm, and (iv) pre-trial calcium channel blocker (CCB) use in the B+H arm. Additionally, pre-trial use of thiazides and electrocardiogram (ECG)-left ventricular hypertrophy (LVH) at baseline predicted higher, and smoking lower absolute SBP in the B+A arm and the use of thiazides and proteinuria a higher SBP in the B+H arm., Conclusion: Irrespective of treatment, patients in the USA and Caucasians achieved better SBP control, whereas higher baseline SBP and more previous antihypertensive medications indicated less control. Concomitant use of lipid lowering treatment indicated a better SBP control in the benazepril + hydrochlorothiazide arm. Lastly, insulin use and ECG-LVH in the benazepril + amlodipine arm and proteinuria in the benazepril + hydrochlorothiazide arm indicated poor control.

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.

Objectives: Added-risk hypertensive patients with co-morbidities such as diabetes and metabolic syndrome often require two or more antihypertensives to achieve blood pressure (BP) targets. The aim of this sub-analysis was to determine the efficacy and safety of telmisartan 40 or 80 mg plus amlodipine 5 or 10 mg in patients with hypertension, stratified according to certain criteria such as type 2 diabetes mellitus and metabolic syndrome., Methods: Patients were treated for 8 weeks with telmisartan 20-80 mg plus amlodipine 2.5-10 mg. This post-hoc analysis included patients treated with higher doses, and stratified according to a number of sub-populations (age, race, diabetes, obesity, metabolic syndrome, elevated baseline systolic BP (SBP), renal impairment)., Results: Eight weeks' treatment with telmisartan plus amlodipine combinations provided consistent reductions in mean SBP/diastolic BP (DBP) across the different sub-populations, similar to the overall population. SBP/DBP reductions ranged from -13.5 to -34.7/-12.6 to -26.1 mmHg and BP goal rates (<140/90 mmHg) ranged from 29.8-100% for the four key dose combinations of telmisartan plus amlodipine. For the highest dose combination of telmisartan 80 mg plus amlodipine 10 mg, SBP/DBP reduction ranged from -19.1 to -34.7/-16.4 to -22.8 mmHg and goal attainment rate from 66.7% to 87.0%. Across the sub-populations, high SBP and DBP response rates were seen with combination treatment (83.3-97.7% and 75.0-95.7%, respectively, with telmisartan 80 mg plus amlodipine 10 mg). The combination was safe and well tolerated across all sub-populations and the incidence of peripheral oedema with telmisartan 40-80 mg plus amlodipine 10 mg was generally lower than with A10 monotherapy., Conclusions: Despite small patient numbers in some sub-populations and the post-hoc nature of the analysis, this does show that the combination of telmisartan plus amlodipine provides an effective, safe and well-tolerated antihypertensive treatment for added-risk hypertensive patients.

Background: In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients., Methods: We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years., Results: During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P=0.27). However, the effects differed according to the baseline level of proteinuria (P=0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P=0.01)., Conclusions: In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.)

Objectives: The aim of this study was to determine which combination therapy in patients with hypertension and diabetes most effectively decreases cardiovascular events., Background: The ACCOMPLISH (Avoiding Cardiovascular Events Through COMbination Therapy in Patients Living With Systolic Hypertension) trial compared the outcomes effects of a renin-angiotensin system blocker, benazepril, combined with amlodipine (B+A) or hydrochlorothiazide (B+H). A separate analysis in diabetic patients was pre-specified., Methods: A total of 6,946 patients with diabetes were randomized to treatment with B+A or B+H. A subgroup of 2,842 diabetic patients at very high risk (previous cardiovascular or stroke events) was also analyzed, as were 4,559 patients without diabetes. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for angina, resuscitated arrest, and coronary revascularization., Results: In the full diabetes group, the mean achieved blood pressures in the B+A and B+H groups were 131.5/72.6 and 132.7/73.7 mm Hg; during 30 months, there were 307 (8.8%) and 383 (11.0%) primary events (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.68 to 0.92, p = 0.003). For the diabetic patients at very high risk, there were 195 (13.6%) and 244 (17.3%) primary events (HR: 0.77, 95% CI: 0.64 to 0.93, p = 0.007). In the nondiabetic patients, there were 245 (10.8%) and 296 (12.9%) primary events (HR: 0.82, 95% CI: 0.69 to 0.97, p = 0.020). In the diabetic patients, there were clear coronary benefits with B+A, including both acute clinical events (p = 0.013) and revascularizations (p = 0.024). There were no unexpected adverse events., Conclusions: In patients with diabetes and hypertension, combining a renin-angiotensin system blocker with amlodipine, compared with hydrochlorothiazide, was superior in reducing cardiovascular events and could influence future management of hypertension in patients with diabetes. (Avoiding Cardiovascular Events Through COMbination Therapy in Patients Living With Systolic Hypertension [ACCOMPLISH]; NCT00170950)., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality. We assessed the effects of these drug combinations on progression of chronic kidney disease., Methods: ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1.73 m(2) or need for dialysis). Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00170950., Findings: The trial was terminated early (mean follow-up 2.9 years [SD 0.4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. At trial completion, vital status was not known for 143 (1%) patients who were lost to follow-up (benazepril plus amlodipine, n=70; benazepril plus hydrochlorothiazide, n=73). All randomised patients were included in the ITT analysis. There were 113 (2.0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3.7%) in the benazepril plus hydrochlorothiazide group (HR 0.52, 0.41-0.65, p<0.0001). The most frequent adverse event in patients with chronic kidney disease was peripheral oedema (benazepril plus amlodipine, 189 of 561, 33.7%; benazepril plus hydrochlorothiazide, 85 of 532, 16.0%). In patients with chronic kidney disease, angio-oedema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without chronic kidney disease, dizziness, hypokalaemia, and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group., Interpretation: Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent., Funding: Novartis., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) is an outcome study investigating aggressive antihypertensive combination treatment. It has achieved a larger fraction of overall patients with blood pressure (BP) <140/90 mmHg (73.3%) and diabetic patients <130/80 mmHg (43.3%) at 12 months of follow-up than any other large outcomes trial. We have analyzed baseline predictors of BPs and BP control at 12 months., Methods: Blinded baseline and 12-month BP was available in 10,173 patients of whom 6132 had diabetes. Univariate and multivariate logistic regression models were used for BP control at 12 months; simple and multiple regression models were used for absolute BP value at 12 months. A stepwise procedure was used to select significant predictors in multivariate analyses., Results: Mean (SD) BP fell from 145.5/80.2 mmHg (18.2/10.7 mmHg) at randomization to 132.7/74.7 mmHg (16/9.6 mmHg) at 12 months. The main baseline predictors of achieving BP control were region (USA), Caucasian race and taking lipid-lowering drugs. The predictors of uncontrolled BP were higher baseline systolic BP values, more previous antihypertensive medications, proteinuria and previous thiazide use., Conclusion: Patients in the USA, Caucasians and patients taking lipid-lowering therapy were most likely to reach BP targets with combination therapy. Strong predictors of uncontrolled hypertension were more severe hypertension, an established need for more antihypertensive drugs and target organ damage.

Various populations with hypertension have been singled out by current treatment guidelines as requiring more specific treatment. These include patients with stage 2 hypertension, black patients, and patients with coexistent diabetes mellitus and coronary heart disease. Hypertension in these groups is often associated with higher risk of cardiovascular morbidity and mortality. This article reviews current knowledge regarding hypertension in high-risk patient populations, with a particular focus on the importance of prompt, aggressive treatment to lower blood pressure and prevent cardiovascular disease progression. Such treatment includes the early use of multiple-drug therapy with agents that have complementary blood pressure-lowering mechanisms and provide protection from target organ damage. While 2- or 3-drug antihypertensive therapy in these high-risk groups has typically included a diuretic, other combinations of agents may be indicated. Evidence suggests that therapy with a calcium channel blocker and an inhibitor of the renin-angiotensin system is one effective strategy for lowering blood pressure and improving outcomes in these populations.

The Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) trial was the first trial to compare the cardiovascular outcomes of initial fixed-dose combination angiotensin-converting enzyme inhibitor (ACEI)/calcium channel blocker (CCB) and ACEI/diuretic therapy in patients with hypertension and high risk of cardiovascular events. The initial combination therapy was effective in this population, with ACEI/CCB therapy providing the greatest benefit (reduction in risk of cardiovascular events). Whether or not the findings of ACCOMPLISH can be applied to other renin-angiotensin-aldosterone system (RAAS) inhibitor/CCB combinations, such as angiotensin receptor blocker (ARB)/CCB combinations, has yet to be investigated. The present report reviews the results of ACCOMPLISH, data from trials comparing ARB and ACEI therapies, and findings from studies of ARB/CCB combination therapy that support the use and further study of combination therapy with RAAS inhibitors and CCBs.

We have previously shown that the angiotensin receptor blocker valsartan is associated with a lower incidence of new-onset type 2 diabetes than that with the calcium-channel antagonist amlodipine in the treatment of hypertensive patients at high cardiovascular risk. We have now investigated the benefits of valsartan vs amlodipine in patients of different categories of diabetogenic risk. Some 9995 patients without diabetes at onset participated in VALUE, with average follow-up of 4.2 years. Predictors of new diabetes were analyzed by stepwise logistic regression. A diabetes risk score for each patient was calculated based on a multivariate model. The risk of developing new diabetes in quartiles of risk for the disease was calculated as an odds ratio (OR) with 95% confidence intervals (CI). New diabetes was reported in 580 (11.5%) patients on valsartan and in 718 (14.5%) patients on amlodipine (p<0.0001). There was a more than sevenfold rise in the development of new diabetes from the lowest to the highest quartile of risk. When study treatment was included in the risk model, the odds in favor of valsartan in preventing new diabetes progressively increased with higher risk. Fifty-two (4.03%) patients developed diabetes on valsartan and 50 (4.14%) patients on amlodipine in the lowest quartile of risk, 73 (5.70%) patients on valsartan and 83 (6.81%) patients on amlodipine in the second quartile, and 126 (10.27%) patients on valsartan and 160 (12.58%) patients on amlodipine in the third quartile. The difference between treatments was highly significant in quartile 4 with 329 (26.68%) patients developing new diabetes on valsartan vs 425 (33.57%) patients on amlodipine (OR = 0.72, 95% CI 0.61-0.86, p = 0.0002). The number of patients needed for treatment for the duration of the trial in order to gain the benefit of valsartan over amlodipine in preventing one new case of diabetes was 43 in the third quartile and 15 in the fourth quartile of risk categories. We conclude that valsartan compared with amlodipine reduces the risk of developing diabetes mellitus, particularly in hypertensive patients with the highest susceptibility for development of diabetes.

A panel was convened to discuss the topic of the management of hypertension in the African American patient. Jackson T. Wright, MD, PhD, Professor of Medicine, Case Western Reserve University, Cleveland, OH, moderated the panel. Kenneth A. Jamerson, MD, Professor of Medicine, University of Michigan, Ann Arbor, MI, and Keith C. Ferdinand, MD, Association of Black Cardiologists, Inc, and Emory University, Atlanta, GA, participated in the discussion. This expert panel discussion was supported by Novartis and each author received an honorarium from Novartis for time and effort spent participating in the discussion and reviewing the transcript for important intellectual content prior to publication. The authors maintained full control of the discussion and the resulting content of this article; Novartis had no input in the choice of topic, speakers, or content.

Background: ACCOMPLISH is a "new-generation" hypertension trial assessing single-tablet combination therapy for initial treatment of high-risk hypertension. At baseline, 97% of subjects were treated with anti-hypertensive medication at entry, but only 37% of participants had blood pressure (BP) control (<140/90 mmHg). Single-tablet combination therapy may improve control rates., Methods: The mean BP change from baseline at the end of 6 months (the time point when subjects should have had all of the drug titrations to achieve BP control) was examined for 10,704 randomized patients. Within-group changes were examined using t-tests. Comparisons between subgroups were made using analysis of variance (ANOVA) and covariance (ANCOVA)., Results: Mean (+/-SD) BP fell from 145+/-18/80+/-11 mmHg at randomization to 132+/-16/74+/-10 mmHg. The 6-month BP control rate was 73% in the overall trial (78% in the US), 43% in diabetics and 40% in patients with renal disease. Of the patients uncontrolled, 61% were not on maximal medications, suggesting potential increases in control rates. Serious hypotensive events occurred in 1.8% of participants., Conclusion: ACCOMPLISH BP control rates are the highest of any multi-national trial to date. Whereas current guidelines recommend combination therapy only for stage 2 hypertension, in this trial it is expedient and safe for both stage 1 and 2 hypertension.

ACCOMPLISH is the first trial designed to compare the effects on major fatal and non-fatal cardiovascular endpoints of two forms of antihypertensive combination therapy: benazepril plus hydrochlorothiazide and amlodipine plus benazepril in hypertensive patients at high cardiovascular risk. Enrollment for this trial is now complete and this report describes the clinical characteristics of the study cohort. Patients with hypertension and a previous history of cardiovascular events, strokes or diabetes mellitus were randomized to double-blind treatment with either of the two combination regimens. The data in this report detail the clinical history and demographic characteristics in patients immediately prior to randomization to study drugs. A total of 11,454 patients were randomized. Mean age (+/-SD) was 68.4+/-6.9 years, 60% were men, and 1360 (12%) were African American. Mean body mass index (BMI) was 31.0+/-6.3 kg/m(2). At study entry, 46% of patients had a history of acute coronary syndromes, coronary artery bypass grafts or percutaneous coronary interventions; 13% had a history of stroke. A history of diabetes mellitus was reported in 6928 (60%) of patients. Mean blood pressure at baseline (on prior hypertension therapy) was 145.4/80.0 mmHg; only 38% of patients had a BP less than 140/90 mmHg. Overall, 97% of patients had received previous antihypertensive treatment (74% on at least two drugs); 53% were on oral diabetes therapy or insulin, 68% on anti-lipid therapy and 63% on anti-platelet agents. In summary, the ACCOMPLISH trial has recruited hypertensive patients at high risk of cardiovascular morbidity and mortality. It is noteworthy that the mean BMI of 31 in this cohort is clearly above the accepted diagnostic criterion of obesity and that 60% of patients are diabetic, possibly reflecting secular trends in clinical disease.

Context: Type 2 diabetes is emerging as a major health problem, which tends to cluster with hypertension in individuals at high risk of cardiovascular disease., Objective: To test for the first time the hypothesis that treatment of hypertensive patients at high cardiovascular risk with the angiotensin-receptor blocker (ARB) valsartan prevents new-onset type 2 diabetes compared with the metabolically neutral calcium-channel antagonist (CCA) amlodipine., Design: Pre-specified analysis in the VALUE trial. Follow-up averaged 4.2 years. The risk of developing new diabetes was calculated as an odds ratio (OR) with 95% confidence intervals (CI) for different definitions of diabetes., Patients: A sample of 9995 high-risk, non-diabetic hypertensive patients., Interventions: Valsartan or amlodipine with or without add-on medication [hydrochlorothiazide (HCTZ) and other add-ons, excluding other ARBs, angiotensin-converting enzyme (ACE) inhibitors, CCAs]., Main Outcome Measure: New diabetes defined as an adverse event, new blood-glucose-lowering drugs and/or fasting glucose > 7.0 mmol/l., Results: New diabetes was reported in 580 (11.5%) patients on valsartan and in 718 (14.5%) patients on amlodipine (OR 0.77, 95% CI 0.69-0.87, P < 0.0001). Using stricter criteria (without adverse event reports) new diabetes was detected in 495 (9.8%) patients on valsartan and in 586 (11.8%) on amlodipine (OR 0.82, 95% CI 0.72-0.93, P = 0.0015)., Conclusion: Compared with amlodipine, valsartan reduces the risk of developing diabetes mellitus in high-risk hypertensive patients.

Reducing blood pressure (BP) to target levels is a major priority in preventing clinical events in hypertension. Typically this requires more than one drug, and recent guidelines on hypertension management therefore recommend starting with combination treatment in many patients. Diuretics have often been part of such therapy, usually paired with angiotensin converting enzyme (ACE) inhibitors or similar agents; but calcium channel blockers are also highly efficacious in reducing BP when combined with ACE inhibitors. In addition, these drug classes, separately and in combination, appear to have vasculoprotective properties. Because the primary goal of treating hypertension is to enhance survival and reduce cardiovascular outcomes, the Rationale and Design of Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) trial is designed as the first blinded and randomized study to prospectively compare the effects on these endpoints of two antihypertensive combinations, benazapril/hydrochlorothiazide (force titrated to 40/12.5 mg) and amlodipine besylate/benazapril (force titrated to 5/40 mg). The doses can be further titrated to 40/25 mg or 10/40 mg, and other classes of drugs can be added as needed for optimal BP control. The primary study endpoint is a composite of cardiovascular mortality and morbidity. The study will be performed in hypertensive patients (systolic BP > or = 160 mm Hg or currently on antihypertensive therapy) with risk factors for cardiovascular events (prior events, target organ damage, kidney disease, or diabetes). A total of 6300 subjects will be randomized to each group with the expectation that a total of 1642 primary endpoints will occur during a 5-year period, providing 90% power to detect the 15% relative reduction in events (alpha = 0.05) hypothesized to favor the amlodipine besylate/benazapril group. The ACCOMPLISH study will be performed in the United States and Europe. The first patient was randomizedduring 2003, and the trial should conclude in 2008., (Copyright 2004 American Journal of Hypertension, Ltd.)

Background: The Seventh Report of the Joint National Committee (JNC 7) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends initial combination therapy for patients whose blood pressure (BP) is >20/10 mm Hg above goal. This study evaluated the efficacy and safety of initial combination therapy versus that of monotherapy in patients with stage 2 hypertension, who by definition meet the JNC 7 recommendation for initial combination antihypertensive therapy., Methods: This multicenter, double-blind, 12-week study randomized 364 patients with stage 2 hypertension to fixed-dose combination therapy with amlodipine besylate/benazepril HCl (5/20 mg/d titrated to 10/20 mg/d) or amlodipine besylate monotherapy (5 mg/d titrated to 10 mg/d)., Results: Significantly more patients randomized to combination therapy (74.2%) compared with those randomized to monotherapy (53.9%; P <.0001) achieved the primary end point (reductions in systolic BP > or =25 mm Hg, if baseline systolic BP was <180 mm Hg, or > or =32 mm Hg, if baseline systolic BP was > or =180 mm Hg). Significantly more patients randomized to combination therapy compared with monotherapy attained BP goals of <140/90 mm Hg (61.0% v 43.3%; P =.0007) and < or =130/85 mm Hg (35.7% v 19.1%; P =.0004). Among patients with baseline systolic BP > or =180 mm Hg, combination therapy resulted in significantly greater reductions in systolic BP compared with monotherapy (-42.3 v -30.4 mm Hg; P =.001). More than 90% of patients in each group were titrated to the higher dose. Both treatments were well tolerated., Conclusions: Combination therapy was well tolerated and resulted in significantly greater BP reductions and attainment of BP goals compared with monotherapy in patients with stage 2 hypertension. This evidence supports the recommendation of combination therapy as first-line treatment in stage 2 hypertension.

Current recommendations for the treatment of hypertension clarify the need to achieve lower blood pressure levels in the general population (<140/90 mm Hg) and in specific high-risk patient groups such as patients with diabetes or chronic renal disease (<130/80 mm Hg). Further, it is evident that to reach appropriate blood pressure control, most patients with high blood pressure will require two or more antihypertensive agents. There is scarce clinical trial outcome evidence to guide clinicians in the selection of optimal combinations of antihypertensive classes for high-risk hypertensive patients. A new clinical trial, Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH), is the first large clinical trial to directly compare cardiovascular mortality and morbidity rates for two fixed-dose combination therapies. Results from ACCOMPLISH should provide much-needed guidance for selecting optimal combination therapy for high-risk hypertensive patients.

Context: Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD., Objective: To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension., Design: Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998., Setting and Participants: A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years., Interventions: Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals., Main Outcome Measures: Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol., Results: Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups., Conclusions: No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.

BACKGROUND The 2017 hypertension guidelines lowered systolic blood pressure (BP) goals to <130 mm Hg and redefined resistant hypertension. We investigated if these changes alter the cardiovascular benefits demonstrated by combining a calcium channel blocker (CCB), rather than hydrochlorothiazide (HCTZ), with an angiotensin-converting enzyme inhibitor (ACEI). METHODS In this post hoc analysis of the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension trial (n = 11,506), we compared the primary composite outcome (cardiovascular death, myocardial infarction, stroke, hospitalization for angina, resuscitation after sudden cardiac death, and coronary revascularization) between the 2 combination-treatment limbs in patients achieving a systolic BP ≤130 mm Hg and those with "apparent resistant hypertension" (prescribed ≥4 antihypertensive medications). RESULTS Among study patients, 5,221 (45.4%) achieved a systolic BP ≤130 mm Hg. There were fewer primary endpoints in the amlodipine/benazepril (9.2%) vs. the HCTZ/benazepril (10.9%) limb (adjusted hazard ratio [HR] 0.83, 95% confidence interval [CI], 0.70–0.99). There were also fewer primary endpoints in the amlodipine/benazepril (12.8%) vs. the HCTZ/benazepril (15.2%) limb (n = 4,451, 38.7%) among patients with apparent resistant hypertension (HR 0.81, 95% CI, 0.70–0.95). CONCLUSIONS Combination therapy adding a CCB, rather than HCTZ, to an ACEI was more effective in preventing composite cardiovascular events even in hypertensive patients achieving aggressive systolic BP targets as well as in those with apparent resistant hypertension. Our findings add support that most patients, including those following contemporary clinical guidelines, will benefit from this combination. CLINICAL TRIALS REGISTRATION Trial Number NCT00170950. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

It is interesting to note that there is evidence to suggest that controlling blood pressure (BP) will reduce more cardiovascular disease (CVD) events than glycemic control alone.[1],[2] The ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) assessed the effects of optimal glycemic and BP targets, and lipid management in 10 000 patients with DM. Instead, the 6-month SBP reduction was correlated with the increase in urinary sodium excretion, suggesting that the BP-lowering effect of SGLT-2 inhibitors at 6 months derives mainly from plasma volume reduction because of a natriuretic effect. Editorials, blood pressure, cardiovascular diseases, diabetes mellitus, empagliflozin, sodium-glucose cotransporter 2 inhibitors. [Extracted from the article]

Assesses the prevalence of complication and responses to various antihypertensive therapies in ethnic minority groups in the United States. Comparison between the biologic and social concept of race; Effects of access to health care in African Americans; Outcomes to treatment of blood pressure in African Americans versus European Americans.