All Thiazide‐Like Diuretics Are Not Chlorthalidone: Putting the ACCOMPLISH Study Into Perspective

In the 31 years since the first Joint National Committee (JNC) report, remarkable advances have occurred in our understanding of hypertension treatment, yet our successes in improving overall population control rates have come at a slower pace. Only an estimated 38% of patients with hypertension had blood pressure (BP) that was controlled to their goal in a study from 1999 to 2004, although a recent national survey suggests that this number may be as high as 50%. With control rates falling short of Healthy People 2010 targets, one could surmise that ineffective drugs might be part of the problem. However, each of the conventional classes of antihypertensives—diuretics, b-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, and calcium channel blockers—have consistently demonstrated overall reductions in cardiovascular (CV) outcomes in large active and placebo-controlled clinical trials, owing primarily to their ability to effectively lower BP. Research on the pharmacotherapy of hypertension has evolved progressively from the initial question of whether pharmacologic treatment is beneficial to which agents are effective in reducing CV outcomes, which is the most effective drug, and more recently, what is the ‘‘best’’ combination regimen. On the surface, the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial appears to address the latter question. But in attempting to answer the question, an equally intriguing question has reemerged: ‘‘Is a thiazide diuretic a thiazide diuretic? ’’ The traditional approach to hypertension management (recommended by JNC 7) is to initiate monotherapy, typically with a thiazide-type diuretic unless compelling indications for other medications are present, and add medications sequentially to achieve goal BP. In the case of patients with Stage 2 hypertension (ie, BP >160 ⁄100 mm Hg), a 2-drug regimen (which may be a fixed-dose combination agent) is recommended initially since most patients with this degree of BP elevation will require multidrug therapy to control BP. Thiazide diuretics have been recommended as the foundation of any multidrug regimen, either as initial monotherapy or as part of an initial 2-drug combination, due to their ability to enhance the antihypertensive effects of virtually all other classes of antihypertensives. The ACCOMPLISH hypertension treatment trial, sponsored by Novartis Pharmaceuticals, compared initial therapy with 2 different fixeddose combinations, a diuretic-based combination From the Division of Clinical and Administrative Pharmacy, College of Pharmacy; Department of Family Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA; the Primary Care Service Line, Ralph H. Johnson VA Medical Center, Charleston, SC; and the Division of General Internal Medicine ⁄ Geriatrics, Medical University of South Carolina, Charleston, SC Address for correspondence: Michael E. Ernst, PharmD, Department of Family Medicine, 01291-A PFP, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242 E-mail: michael-ernst@uiowa.edu