Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study)

OBJECTIVES To determine the effect of angiotensin-converting enzyme (ACE) inhibition on brachial flow-mediated vasodilation. BACKGROUND Quinapril, an ACE inhibitor with high affinity, has been shown to improve coronary endothelial dysfunction in patients with coronary artery disease. The effectiveness of different vasoactive agents to improve human endothelial function is unknown. METHODS High resolution ultrasound was used to assess endothelium-dependent brachial artery flow-mediated vasodilation (FMD) in patients with coronary disease. We studied 80 patients (mean age 58 +/- 0.9 years) in a partial-block, cross-over design trial. Patients were randomized to one of four different drug sequences to receive quinapril 20 mg, enalapril 10 mg, losartan 50 mg or amlodipine 5 mg daily. Each patient received three drugs with a two-week washout period between treatments. The primary end point was the absolute difference in FMD after eight weeks of each study drug compared with their respective baselines analyzed in a blinded fashion. RESULTS There was mild impairment of FMD at baseline (7.3 +/- 0.6%). The change in FMD from baseline was significant only for quinapril (1.8 +/- 1%, p < 0.02). No change was seen with losartan (0.8 +/- 1.1%, p = 0.57), amlodipine (0.3 +/- 0.9%, p = 0.97) or enalapril (-0.2 +/- 0.8%, p = 0.84). No significant change in nitroglycerin-induced dilation occurred with drug therapy. The improvement in quinapril response was not seen in those with the DD ACE genotype (0.5 +/- 2.1%) but was seen in those with the ID and II genotype (3.3 +/- 1.2 and 3.2 +/- 1.9%, respectively, p = 0.03). CONCLUSION Only quinapril was associated with significant improvement in FMD, and this response is related to the presence of the insertion allele of the ACE genotype.