The design of the Mortality Assessment in Congestive Heart Failure Trial (MACH-1, mibefradil).

Background: Despite the advances in therapy for heart failure with the use of angiotensin-converting enzyme inhibitors, heart failure remains a major medical problem, impacting on well-being and survival.

Hypothesis: Mibefradil is a member of new class of agents that, due to its unique mechanism of action and pharmacologic and physiologic profile, may offer a significant advance in the treatment of heart failure. Mibefradil is a nonvoltage-regulated T-channel calcium blocker that differs from all the other currently available L-channel calcium blockers. The drug is a potent peripheral and coronary vasodilator, with no clinical negative inotropic activity. Furthermore, because of its long half-life, it can be given once a day and appears to be free of the common side effects seen with other calcium-channel blockers. The trial was designed to investigate whether the addition of mibefradil to standard therapy for heart failure will reduce mortality in patients with symptomatic heart failure.

Methods: This manuscript describes the design, organization, and status of MACH-1 (Mortality Assessment in Congestive Heart Failure), a double-blind, placebo-controlled study. It is to be a 2,400-patient international trial assessing the ability of mibefradil to impact upon survival and symptoms of heart failure in patients who are in NYHA classes II-IV and who were already treated with standard therapy.