Improved diastolic function with the calcium antagonist nisoldipine (coat-core) in patients post myocardial infarction: Results of the DEFIANT study

A multicentre, randomized, double-blind, placebo-controlled, parallel-group trial was undertaken in 135 patients to determine whether 4 weeks of treatment with long-acting nisoldipine coat-core (20 mg once a day) could alter diastolic function in patients with a recent myocardial infarction and with mild left ventricular dysfunction as indicated by a left ventricular ejection fraction ≤50%. The primary endpoint was the change in diastolic filling parameters assessed by Doppler and two-dimensional echocardiography. The mean time of admission to the study was 20 days (range 7-35) after myocardial infarction. Mean left ventricular ejection fraction was 41%. The drug increased early diastolic peak velocity at the tips of the mitral leaflet by 0.06 m . s^-1 (95% confidence intervals (CI): 0.01, 0.11). The time velocity integral was increased by 1.2 cm (95% CI: 0.16, 2.27). These findings are indicative of increased early diastolic flow across the mitral valve. An important determinant appeared to be a reduced isovolumic relaxation time (by 14.7 ms, 95% CI: - 22.5, -6.9). As there was no change in heart rate, systolic and diastolic blood pressure or cardiac output, afterload reduction appeared unlikely as an explanation. Peak workload on exercise was 12 watts higher in the group on nisoldipine (95% CI: 0.8, 23.3). Thus, nisoldipine was shown to improve indices of diastolic ventricular function, as well as exercise capacity, in this group of patients. The observed effects of nisoldipine may reflect an anti-ischaemic effect or be due to improved relaxation of the myocardium.