Oral nitroglycerin as a prophylactic antianginal drug: clinical, physiologic, and statistical evidence of efficacy based on a three-phase experimental design

Abstract

With the use of a three-phase experimental design, the efficacy of oral nitroglycerin has been evaluated in a total of 53 patients with documented angina pectoris due to coronary artery disease. The study were a double-blind, randomized, and cross-over comparison of controlled-release nitroglycerin (2.6 mg. tablets administered three times daily) and an indistinguishable placebo. Sixteen patients recorded anginal symptoms by the diary method over a 6 month trial of randomly sequenced 1 month periods of drug or placebo. In 15 patients, ST segments were monitored with a Holter dynamic electrocardiograph for periods of 10 to 12 hours under normal life style and evaluated by matching activities during periods of drug and placebo. In 22 patients, a multistage treadmill exercise test was conducted to an endpoint of anginal pain. The three phases of the investigation were run in succession; each phase was completed before the next one was begun. Oral nitroglycerin reduced the incidence and severity of anginal attacks by 47.2 and 49.4 per cent, respectively, and decreased the number of sublingual nitroglycerin tablets used by 51.1 per cent in comparison to placebo (p less than 0.001). Eleven of 16 patients (69 per cent) decreased their need for sublingual nitroglycerin by over 50 per cent. Based on a polynomial trend analysis over a period of 8 weeks, no tolerance to the therapeutic effects of the drug was found. With DCG monitoring, drug decreased the ST segment depression from 1.76 mm. on placebo to 1.12 mm, with a significant difference of 0.64 mm. (p less than 0.001). ST segment depression was decreased more than 0.5 mm. by drug in comparison to placebo in 10 of 15 patients (66 per cent). Larger depressions of the ST segment noted with placebo at heart rates greater than 80 beats per minute were prevented by administration of the drug. During treadmill exercise, drug delayed the onset of pain by 83 seconds (64 per cent) over placebo (p less than 0.001) and decreased the duration of pain by 70 seconds (49 per cent) in comparison to placebo (p less than 0.001). Drug did not affect heart rate or systolic blood pressure at rest or after exercise, as well as rate-pressure product for production of angina following exercise (p less than 0.05). There was no side effects reported caused by the drug. The data demonstrate that oral nitroglycerin, given as controlled-release tablets, was absorbed from the gastrointestinal tract in quantities sufficient to provide statistically significant clinical improvement of angina pectoris.