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The Hypertension Optimal Treatment (HOT) Study investigated the relationship between target office diastolic blood pressure (BP) ≤80, ≤85 or ≤90 mmHg and cardiovascular morbidity and mortality in 18,790 patients aged 50–80 years. The home BP sub-study enrolled 926 patients and the aim was to clarify whether the separation into the BP target groups in the office prevailed in the out-of-office setting. The present study aimed to identify variables that characterised masked uncontrolled hypertension (MUCH) and white coat uncontrolled hypertension (WUCH). The sub-study participants took their home BP when office BP had been up titrated. The cut-off for normal or high BP was set to ≥135/85 mmHg at home and ≥140/90 mmHg in the office. We analysed data by using multivariate and stepwise multivariate logistic regression with home and office BP combinations as the dependent variables. WUCH was associated with lower body mass index (BMI) (odds ratio (OR) 0.92, 95% confident intervals (CIs) 0.88–0.96, p < 0.001). MUCH was associated with smoking (OR 1.89, 95% CIs 1.25–2.86, p = 0.0025) and with lower baseline heart rate (OR 0.98, 95% CIs 0.97–0.99, p = 0.03) and higher BMI (OR 1.03, CIs 1.00–1.06, p = 0.04). MUCH remained associated with smoking (OR 2.76, 95% CIs 1.76–4.35, p < 0.0001) also when using ≥140/90 mmHg as the cut-off for both home and office BP. MUCH was also associated with higher BMI (OR 1.05, 95% CIs 1.01–1.09, p = 0.009) while WUCH was associated with lower BMI (OR 0.93, 95% CIs 0.90–0.97, p = 0.0005) when using ≥140/90 mmHg as a cut-off. Our data support that 'reversed or masked' treated but uncontrolled hypertension (MUCH) is common and constitutes about 25% of treated hypertensive patients. This entity (MUCH) is rather strongly associated with current smoking and overweight while uncontrolled white coat (office) hypertension (WUCH) is associated with lower BMI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/m2. 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 140/90mmHg. 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. [ABSTRACT FROM AUTHOR]