Clinical Evaluation of Anti-Anginal Drugs with Particular Reference to Benziodarone, a New Coronary Vasodilator

Abstract

ALTHOUGH many long-acting coronary vasodilators have been introduced for the prophylactic treatment of angina pectoris few have survived a controlled objective study in which the main criterion of effectiveness is an improvement in the degree of myocardial ischoemia and not solely an alteration in the frequency or severity of anginal attacks.A new coronary vasodilator, benziodarone (Cardivix), a benzfuran derivative, has been found experimentally to produce a marked increase in coronary blood flow in healthy dogs (Charlier, 1959), and has also been claimed to produce considerable improvement clinically in anginal patients (Gillott, I959). Gillott's study was based on an uncontrolled and subjective evaluation of the action of benziodarone. Assessment of any anti-anginal drug, however, must take into consideration the suggestibility of anginal patients, the limitations of subjective data provided by the patients themselves, and the lack of any direct relationship between the development and severity of anginal pain and the degree of coronary insufficiency (Russek, Zohman and Dorset, 1955).It is with these considerations in mind that it was decided to carry out a controlled doubleblind and objective evaluation of the use of benziodarone in the treatment of angina pectoris. Patients and MethodsTwelve patients, aged from 4I to 67 years, with typical angina pectoris on exertion were studied. All the patients were males but this was not due to sex selection as suitable patients were included in the trial as -they became available. The duration of angina ranged from 6 months to 4 years. The presumptive cause of the angina was coronary artery disease and 2 patients had electrocardiographic evidence of -previous myocardial infarction. All Exercise tolerance tests were carried out at the beginning of the study and at monthly intervals until its conclusion. The type of test used has been described in detail in an earlier publication (Sandler, I963) and briefly consists of exercise at the patient's own normal rate over 2 steps each 9 inches (23 cm.) high until he is stopped by anginal painthus keeping within the limits of his own capacity. The total amount of exercise, recorded as number of circuits, and the total time taken are noted. A tablet of glyceryl trinitrate sublingually is given at the onset of angina and the duration of the pain accurately timed with a stop-watch. Electrocardiograms are recorded fully before starting the exercise and then chest lead V5 is recorded immediately afterwards and at 30 second intervals until the electrocardiographic signs of ischxmia have disappeared (see Fig. I). The position of V5 is marked on the patient's chest before exercise so that it can be accurately replaced after exercise. Depression of the ST segment below the iso-electric line, either plane or sagging, of at least o.o8 second's duration is regarded as indicative of myocardial ischmmia (LloydThomas, I96I; Master and Rosenfeld, I96I); the degree and duration of depression are recorded for each patient. All 12 patients in th...