Predictors of blood pressure response to intensified and fixed combination treatment of hypertension: The ACCOMPLISH Study

University of Michigan Health System, Ann Arbor, Michigan, USA.
Blood Pressure (Impact Factor: 1.81). 02/2008; 17(1):7-17. DOI: 10.1080/08037050801972857
Source: PubMed


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.
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.
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.
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.

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    • "Aggressive antihypertensive treatment using a combination therapy that includes drugs with different mechanisms of action has been recommended as a means of achieving better blood pressure control [1-3]. Reflecting the clinical evidence, including the findings of the ACCOMPLISH study [4], an angiotensin-receptor blocker (ARB) together with a calcium-channel blocker (CCB) is the combination most frequently prescribed to Japanese hypertensive patients [5,6]. For patients who have comorbidities such as hyperlipidemia, diabetes, and chronic renal disease, more aggressive treatment, with the addition of thiazide diuretics (i.e., hydrochlorothiazide or HCTZ) is provided to achieve therapeutic goals [7]. "
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    ABSTRACT: Background: The prescription of fixed-dose combinations (FDC) of antihypertensive drugs has increased rapidly since the relaxation of the prescription-term restriction. In this study, we used the opportunity of this policy change in Japan as an instrument to assess the causal impact of switching to FDC on hypertensive treatment costs. Methods: Claims data from 64 community pharmacies located in Tokyo were used to identify hypertensive patients under continuous treatment with angiotensin-receptor blockers (ARBs). Patients switching to FDC between December 2010 and April 2011 were compared to patients who did not receive FDC (control group). Changes in annual antihypertensive drug costs were compared using a difference-in-differences approach to adjust for patient characteristics and use of concomitant medication. Subpopulation analyses were also performed, taking into account pre-index treatment patterns and prescribers' characteristics. Results: There were 542 patients who switched to FDC and 9664 patients in the control group. No significant differences were observed between the 2 groups, except for antihypertensive drug use patterns before the policy change and prescribers' characteristics. The switch to FDC was associated with an annual saving of 10,420 yen (US$112.0) in antihypertensive drug costs. Approximately 20% of the FDC patients, however, switched from ARB alone, and their drug costs increased by 2376 yen (US$25.5). Conclusions: For hypertensive patients who required ARB-based combination therapy, switching to FDC drugs had a significant cost-saving effect. However, the policy change of relaxing the prescription-term restriction could encourage aggressive treatment, i.e., switching to a combination therapy from monotherapy, regardless of medical conditions. Further research is required to evaluate the possible negative aspects of FDC drugs.
    Full-text · Article · Apr 2013 · BMC Health Services Research
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    • "Hypertension currently affects more than 1 billion adults worldwide, and by 2025, the projected estimate is 1.5 billion [1]. Calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs), angiotensin converting enzyme (ACE) inhibitors , and diuretics are generally used for hypertension therapy [2] [3] [4]. Amlodipine besilate (AML), chemically, 3- ethyl-5-methyl(4RS)-2-[(2-aminoethoxy)methyl]-4-(2-chlo- rophenyl)-methyl-1-dihydropyridine-3,5-dicarboxylate benzenesulfonate , is a long acting CCB [5]. "
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    ABSTRACT: A simple, rapid, and selective HPLC-UV method was developed for the determination of antihypertensive drug substances: amlodipine besilat (AML), olmesartan medoxomil (OLM), valsartan (VAL), and hydrochlorothiazide (HCT) in pharmaceuticals and plasma. These substances are mostly used as combinations. The combinations are found in various forms, especially in current pharmaceuticals as threesome components: OLM, AML, and HCT (combination I) and AML, VAL, and HCT (combination II). The separation was achieved by using an RP-CN column, and acetonitrile-methanol-10 mmol orthophosphoric acid pH 2.5 (7 : 13 : 80, v/v/v) was used as a mobile phase; the detector wavelength was set at 235 nm. The linear ranges were found as 0.1-18.5 μ g/mL, 0.4-25.6 μ g/mL, 0.3-15.5 μ g/mL, and 0.3-22 μ g/mL for AML, OLM, VAL, and HCT, respectively. In order to check the selectivity of the method for pharmaceutical preparations, forced degradation studies were carried out. According to the validation studies, the developed method was found to be reproducible and accurate as shown by RSD ≤6.1%, 5.7%, 6.9%, and 4.6% and relative mean error (RME) ≤10.6%, 5.8%, 6.5%, and 6.8% for AML, OLM, VAL, and HCT, respectively. Consequently, the method was applied to the analysis of tablets and plasma of the patients using drugs including those substances.
    Full-text · Article · Mar 2013 · Journal of Analytical Methods in Chemistry
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    • "If one assumes that one drug results in a given reduction in blood pressure, independent of level, a combination of drugs will result in a multiplicative relationship. Even though some combination trials have been undertaken [2,54], these are too few to represent a basis for evaluating all clinical relevant combination therapies. Hence, the results with respect to combination therapy are more uncertain than those based with single drug comparisons. "
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    ABSTRACT: Hypertension is one of the leading causes of cardiovascular disease (CVD). A range of antihypertensive drugs exists, and their prices vary widely mainly due to patent rights. The objective of this study was to explore the cost-effectiveness of different generic antihypertensive drugs as first, second and third choice for primary prevention of cardiovascular disease. We used the Norwegian Cardiovascular Disease model (NorCaD) to simulate the cardiovascular life of patients from hypertension without symptoms until they were all dead or 100 years old. The risk of CVD events and costs were based on recent Norwegian sources. In single-drug treatment, all antihypertensives are cost-effective compared to no drug treatment. In the base-case analysis, the first, second and third choice of antihypertensive were calcium channel blocker, thiazide and angiotensin-converting enzyme inhibitor. However the sensitivity and scenario analyses indicated considerable uncertainty in that angiotensin receptor blockers as well as, angiotensin-converting enzyme inhibitors, beta blockers and thiazides could be the most cost-effective antihypertensive drugs. Generic antihypertensives are cost-effective in a wide range of risk groups. There is considerable uncertainty, however, regarding which drug is the most cost-effective.
    Full-text · Article · Apr 2012 · BMC Cardiovascular Disorders
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