Excessive reduction in peripheral resistance during exercise and risk of orthostatic symptoms with sustained-release nitroglycerin and diltiazem treatment of angina.
Acute effects of placebo, sustained-release nitroglycerin, diltiazem capsules, and the combination of both drugs were monitored in nine stable angina patients. They were randomized to receive either placebo or 13 mg of slow-release nitroglycerin orally (double-blind). This was followed in 1 hour by 120 mg of diltiazem orally, given to all patients (unblinded). Invasive hemodynamic measurements were made before and after each treatment at supine and sitting rest, two levels of submaximal, and at maximal exercise and twice in recovery. Compared to the control test at maximal exercise, sustained-release nitroglycerin increased aerobic capacity 24%, lowered peripheral resistance -32%, and lowered systemic pressure -23%, while the respective changes with placebo were -3%, 5%, and 2%. When diltiazem was added to placebo compared to the control test, there was a 4% increase in oxygen consumption and -9% and -4% reduction in systemic resistance and systemic pressure, respectively. The addition of diltiazem to nitroglycerin was associated with a 20% increase in oxygen consumption a -42% reduction in systemic resistance and a -32% reduction in systemic pressure. Two patients who received nitroglycerin plus diltiazem experienced symptomatic hypotension, while one patient who received placebo plus diltiazem experienced hypotension. These side effects caused the study to be terminated prematurely. Thus, although the combination of nitroglycerin and diltiazem had a greater effect on afterload than either drug alone, the combination did not provide greater improvement in cardiac performance.