Clinical effectiveness of the angiotensin converting enzyme inhibitor, Ramipril, in patients with intermittent claudication : randomised, double-blind, placebo-controlled trial

• Main Author: Shahin, Yousef
• Published: Cardiff University 2015
• Subjects: 616.1; R Medicine (General)
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.667910

Background: The HOPE trial showed that ramipril reduced cardiovascular morbidity and mortality in patients with peripheral arterial disease (PAD). However, evidence regarding the effect of angiotensin converting enzyme (ACE) inhibitors on walking distance, ankle brachial pressure index (ABPI), arterial stiffness and quality of life (QoL) in this group of patients is limited. Objective: The aim of this study is to investigate ACE inhibitors effect on clinical parameters of PAD, arterial stiffness and QoL in patients with intermittent claudication (IC). Methods: 33 patients (25 males, mean age: 65+/-7.8) with IC (Fontaine stage II or higher) were randomised to receive ramipril (5 mg once daily for 2 weeks increased to 10 mg once daily for 22 weeks, n=14) or placebo (n=19) for 24 weeks in a double-blind study. Walking distance was assessed using a standard laboratory treadmill test (2.5 km/hr at 10% incline). ABPI was assessed pre (r-ABPI) and post-exercise (t-ABPI). Arterial stiffness indices were measured using the SphygmoCor device. Results: After 24 weeks, ramipril improved maximum treadmill walking distance; adjusted mean change difference (95% confidence interval); by 130.5 (61.8 to 199.2) m longer than placebo (P=0.001), improved treadmill intermittent claudication distance by 121.9 (55.9 to 187.8) m longer than placebo (P=0.001) and improved patient reported walking distance by 159 (5.5 to 313) m compared to placebo (P=0.040). Ramipril reduced carotid femoral pulse wave velocity (a measure of arterial stiffness) by -1.47 (-2.4 to -0.57) m/s compared to placebo (P=0.002). However, r-ABPI and t-ABPI minimally changed in both groups (Ramipril 0.02 (-0.08 to 0.11)) vs. placebo 0.03 (-0.05 to 0.10, P=0.830) and (Ramipril 0.04 (-0.04 to 0.12)) vs. placebo 0.02 (-0.04 to 0.09, P=0.720), respectively. Ramipril had a slight insignificant effect on QoL physical domains compared to placebo. Conclusion: Ramipril improves walking distance in patients with IC; however, this improvement is not related to improvement in ABPI but might be due to ramipril ability to reduce arterial stiffness. ACE inhibitors effect on QoL needs to be validated in a larger randomised controlled trial.