This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent evidence from the Antihypertensive and Lipid-Lowering to Prevent Heart Attack Trial (ALLHAT) suggests initial therapy with a thiazide-type diuretic confers significantly higher reductions in stroke and coronary heart disease events compared to newer antihypertensive agents such as angiotensin-converting enzyme inhibitors and calcium channel blockers. Chlorthalidone, the thiazide-type diuretic utilized in ALLHAT, has traditionally been the diuretic utilized in many of the landmark clinical trials in hypertension. However, hydrochlorothiazide (HCTZ) is the thiazide diuretic typically used in clinical practice in the United States. Although most clinicians assume HCTZ and chlorthalidone are clinically interchangeable, there is a lack of data comparing these agents directly to one another. This is an 8-week, open-label, crossover trial comparing the antihypertensive effects of HCTZ versus chlorthalidone on both office-based and ambulatory blood pressures. Men and women with essential hypertension and meeting inclusion criteria will be recruited from two primary care practices at the University of Iowa Family Care Center. After a 2-4 week washout period during which time patients will return for weekly office blood pressure measurements, patients will then undergo a baseline ambulatory blood pressure monitoring session and be randomized to either HCTZ 25 mg/d or chlorthalidone 12.5 mg/d. Patients will return biweekly for office blood pressure measurements, and/or laboratory measurements, and/or dosage titration (to a max dose of 25 mg for chlorthalidone and 50 mg of HCTZ). Ambulatory blood pressure monitoring will be repeated at week 8. Following completion of the first arm of the study, patients will again undergo a second 2-4 week washout period and proceed into the opposite arm of the study which is identical to the first arm but with the opposite medication.
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