Long-term trandolapril treatment is associated with reduced aortic stiffness: the prevention of events with angiotensin-converting enzyme inhibition hemodynamic substudy

Abstract

The Prevention of Events with Angiotensin Converting Enzyme inhibition (PEACE) trial evaluated angiotensin-converting enzyme inhibition with trandolapril versus placebo added to conventional therapy in patients with stable coronary disease and preserved left ventricular function. The PEACE hemodynamic substudy evaluated effects of trandolapril on pulsatile hemodynamics. Hemodynamic studies were performed in 300 participants from 5 PEACE centers a median of 52 months (range, 25 to 80 months) after random assignment to trandolapril at a target dose of 4 mg per day or placebo. Central pulsatile hemodynamics and carotid-femoral pulse wave velocity were assessed by using echocardiography, tonometry of the carotid and femoral arteries, and body surface transit distances. Patients randomly assigned to trandolapril tended to be older (mean+/-SD: 64.2+/-7.9 versus 62.9+/-7.7 years; P=0.14), with a higher body mass index (28.5+/-4.0 versus 27.8+/-3.9 kg/m(2); P=0.09) and lower ejection fraction (57.1+/-8.1% versus 58.7+/-8.4%; P<0.01). At the time of the hemodynamic substudy, the trandolapril group had lower mean arterial pressure (93.1+/-10.2 versus 96.3+/-11.3 mm Hg; P<0.01) and lower carotid-femoral pulse wave velocity (geometric mean [95% CI]: 10.4 m/s [10.0 to 10.9 m/s] versus 11.2 m/s [10.7 to 11.8 m/s]; P=0.02). The difference in carotid-femoral pulse wave velocity persisted (P<0.01) in an analysis that adjusted for baseline characteristics and follow-up mean pressure. In contrast, there was no difference in aortic compliance, characteristic impedance, augmentation index, or total arterial compliance. Angiotensin-converting enzyme inhibition with trandolapril produced a modest reduction in carotid-femoral pulse wave velocity, a measure of aortic wall stiffness, beyond what would be expected from blood pressure lowering or differences in baseline characteristics alone.

Carotid–femoral PWV plotted separately by treatment group according to quintile of on-treatment MAP. Treatment with trandolapril was associated with a downward shift in the relation between mean pressure and carotid–femoral PWV (P=0.003), indicating a pressure-independent reduction in aortic stiffness. A test for an interaction between treatment group and quintile of MAP was not significant (P=0.45). MAP minimum and maximum values (mm Hg) in the groups were as follows: I (68.5 to 86.0), II (86.1 to 91.0), III (91.1 to 96.0), IV (96.1 to 102.5), and V (102.6 to 133.0).