Optimization of antihypertensive therapy with a novel, extended-release formulation of diltiazem: results of a practice-based clinical study

Abstract

Although the effectiveness of diltiazem for the treatment of patients with hypertension has been well demonstrated in numerous placebo-controlled and comparative clinical trials, most physicians have had some concern about its efficacy and have used it predominantly in patients with mild hypertension. Few large-scale studies have evaluated the efficacy and safety of higher dosages of diltiazem for the treatment of patients with hypertension, and few have evaluated the use of diltiazem in patients with more severe hypertension. Tiazac™ (Forest Pharmaceuticals, Inc., St. Louis, Missouri), a new, extended-release formulation of diltiazem, provides 24-hour blood pressure control with a single daily dose of up to 360 mg. The Study of Titration and Response to Tiazac (START) is an ongoing practice-based, open-label, multicenter study designed to evaluate the efficacy and safety profiles of Tiazac at greater-than-traditional doses in hypertensive patients and to assess the ability of Tiazac to decrease the rate-pressure product, a surrogate marker for cardiac workload. Patients were eligible for study entry whether their hypertension was newly diagnosed or previously treated with a different formulation of diltiazem or any other antihypertensive agent. Normotensive (sitting diastolic blood pressure [SDBP] <90 mm Hg) subjects and those with mild (SDBP 90 to 99 mm Hg), moderate (SDBP 100 to 109 mm Hg), severe (SDBP 110 to 119 mm Hg), and very severe (SDBP ≥120 mm Hg) hypertension were assessed at baseline (visit 1), visit 2 (10 to 14 days after visit 1), and visit 3 (25 to 28 days after visit 1). A total of 3082 patients were enrolled, and data from 2802 assessable patients (ie, those who completed visits 1, 2, and 3) were analyzed. No subjects were lost to follow-up as a result of adverse effects. All subjects received a starting dose of Tiazac 180 mg or 240 mg once daily, and doses were titrated upward to 360 mg once daily as clinically indicated. Blood pressure reduction matched the severity of hypertension in all patients. Subjects who were switched from another diltiazem formulation demonstrated further decreases in SDBP. Antihypertensive monotherapy with Tiazac was well tolerated. This interim START report demonstrates that a daily dose of up to 360 mg of diltiazem is optimal in terms of both control of hypertension and patient compliance. It also provides the practice-based physician with useful clinical information on dose titration and response to a new formulation of an approved drug and supports the efficacy and safety profiles of diltiazem documented in previous well-controlled clinical trials.