Progression and regression of coronary atherosclerosis: data from a controlled clinical trial with nicardipine

Summary

Interventions that may influence the evolution of coronary atherosclerosis can be evaluated more rapidly and efficiently in clinical trials with angiographic endpoints as opposed to using coronary events as endpoints. Quantitative coronary arteriography provides precise and reproducible measurements of coronary artery dimensions. Variability of repeat measurement of minimum diameter, expressed as 1 standard deviation of the mean, increased from 0.088 mm (same frame) to 0.197 mm (films 1 to 6 months apart) as conditions decreased from optimal to those encountered in clinical studies. A change in minimum diameter ≥0.4mm is more than 2 standard deviations of the midterm variability and therefore represents a true change, either progression or regression, with greater than 95% probability.

To determine whether the calcium channel blocker nicardipine influences the progression of coronary atherosclerosis, 383 patients with stenoses≤75% in at least 4 coronary segments were randomized to 2 years of treatment with placebo or nicardipine 30 mg 3 times per day. Repeat coronary arteriography in 335 patients revealed progression of at least one lesion (using the ≥0.4 mm minimum diameter criterion) in 44% of nicardipine and 43% of placebo patients. Regression at one or more sites was seen in 23% of nicardipine and 19% of placebo patients. These differences were not statistically significant. However, minimal lesions, defined as those ≤20% at the first study, progressed in 15 of 99 nicardipine patients compared to 32 of 118 placebo patients (15% versus 27%, p = 0.046).

These results suggest that nicardipine has no effect on advanced coronary atherosclerosis but may retard the progression of early lesions. This type of study, with quantitative coronary measurements as endpoints, is an excellent tool to assess the effect of an intervention upon the evolution of coronary atherosclerosis.