P1.24 DOSE-DEPENDENT INWARD ARTERIAL REMODELLING AND DE STIFFENING AFTER OLMESARTAN IN HYPERSENTSIVES WITH METABOLIC SYNDROME: THE VASCULAR MECHANISM STUDY

Abstract

Background: Whether angiotensin receptor blockers can dose-dependently remodel the arterial wall during long-term treatment has only been rarely studied. Olmesartan (OM) has previously shown a favourable pharmacodynamic profile for such an action. Methods: In this phase 3, multi-centre, double-blind, randomized, parallel-group study, 133 subjects with hypertension and metabolic syndrome were assigned to three treatment groups and received either OM 20 mg (n=44), OM 40 mg (n=42), or OM 80 mg (n=47) once a day according to a force-titration design during a 1 year period. Office blood pressure (BP), 24hABPM, aortic stiffness (carotid-femoral pulse wave velocity-PWV) and carotid parameters (diameter, intima-media thickness, and stiffness) were measured at baseline, 24 weeks (W24) and 52 weeks (W52). A mixed-model was used for statistical analysis. Results: PWV significantly decreased (P<0.001) with time in each group, with no significant time-dose interaction, despite a tendency for a smaller effect of 20 mg, compared to 40 and 80 mg at W52. When the 40 and 80 mg doses were combined (40/80 mg vs 20 mg), there was a tendency (p=0.0685) for a time-dose interaction in PWV reduction. After adjustment to changes in MBP, a significant BP-independent reduction in PWV was observed: PWV decreased by −0.61 m/s at W52 (p=0.0066) after 40/80 mg, whereas the non-adjusted reduction was −1.33 m/s (p<0.0001). Most carotid parameters were improved along with BP reduction, and at W52 significant reductions were observed for carotid PP (−7.15 mmHg) and internal diameter (−0.217 mm), indicating a chronic inward arterial remodeling. Patients receiving the highest dose of OM (40 and 80 mg) were shifted towards both a low elastic modulus and a low wall stress, indicating an improvement in the intrinsic elastic properties of the arterial wall material. Conclusion: These data suggest that 40 and 80 mg Olmesartan are able to significantly remodel and destiffen the arterial wall during long-term treatment, partly independently of MBP, compared to 20 mg