Original contributionsRationale and design of the avoiding cardiovascular events through combination therapy in patients living with systolic hypertension (ACCOMPLISH) trial: The first randomized controlled trial to compare the clinical outcome effects of first-line combination therapies in hypertension
Section snippets
Considerations regarding BP
There is strong evidence for a relationship between BP and the probability of cardiovascular events.1, 2 Even differences in systolic BP as small as 2 mm Hg have meaningful effects on such outcomes as fatal strokes or coronary events.3 Recently cited data, however, indicate that only about one third of hypertensive individuals in the United States have their BP adequately controlled,4 despite evidence that aggressive BP treatment is associated with more effective prevention of major events.5, 6
Effects of different drug types
Early clinical trials showed that active antihypertensive therapy was superior to placebo in reducing major clinical events. In general, more recent studies have shown similar outcomes when differing drug classes, both older and newer, are compared with each other.7, 12, 13, 14, 15 Meta-analysis of the large trials in general has not demonstrated major overall differences among the antihypertensive drug classes in their outcomes effects,16 although there might be differences when individual
Experience with combinations
Few if any of the major hypertension trials have depended on a single drug. Rather, to achieve adequate BP control in the treatment groups, additional drugs generally have been used, making it difficult to determine whether the original drugs being tested, as opposed to the regimens built around them, were responsible for the clinical effects. The most common combinations tested have used diuretics. Diuretics work well in combination with such agents as angiotensin-converting enzyme (ACE)
First combination comparison
For these reasons, there is considerable interest in comparing the clinical endpoint effects of this ACE inhibitor/calcium channel blocker combination (benazapril/amlodipine) with an ACE inhibitor/diuretic combination. If the newer combination produces greater cardiovascular benefits, it would obviously become a powerful tool for improving clinical outcomes in patients with hypertension. This is the critical question that underlies the rationale and design of the Avoiding Cardiovascular events
Power of the study
Sample size is calculated with 90% power to detect a treatment difference of 15% risk reduction for the primary efficacy endpoint for the benazepril/amlodipine combination group compared with the benazepril/hydrochlorothiazide combination group at a two-sided overall significance level of 5%. An annual event rate of 3.5% for the primary efficacy endpoint is assumed for patients in the benazepril/hydrochlorothiazide combination group. Considerations for the performance of four equally spaced
Discussion
The ACCOMPLISH trial is unique in being the first clinical outcomes trial in hypertension to compare two established forms of fixed-dosed combination therapy. This study is particularly timely, as the most recent clinical guidelines by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7),4 International Society on Hypertension in Blacks(ISHIB),10 and the European Society of Hypertension11 all now recommend starting treatment with drug
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2013, The LancetCitation Excerpt :The ACCOMPLISH trial was designed, supervised, analysed and interpreted by an executive committee (members were KJ, MAW, GLB, BD, EJV, and BP). The roles of key supporting committees for the trial, and the role of the original sponsor (Novartis), have been described previously.15–17 The institutional review board of every participating institution approved the study protocol.
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