ATTENUATION OF EXERCISE-INDUCED RISE IN SYSTOLIC BLOOD PRESSURE BY THE DIRECT RENIN INHIBITOR ALISKIREN: PP.24.472

Abstract

Objective: The exercise-induced rise in systolic BP (SBP) in hypertensive patients is an independent predictor of cardiovascular risk. However, few studies have evaluated the impact of BP-lowering therapies on exercise-related SBP changes. This study assessed the effects of aliskiren and valsartan on exercise-induced SBP rises after 8 weeks’ treatment, and whether these effects are maintained 48 h after the last dose of treatment. Design and Method: After a 2-week washout and 1–2-week placebo run-in, 68 patients who were able to exercise (mean age 59 ± 7 years; 68% male; 96% Caucasian) were randomized to once-daily aliskiren 300 mg (n = 33) or valsartan 320 mg (n = 35) for 8 weeks. At baseline, a treadmill exercise test was performed (Bruce protocol) to peak exercise (85% predicted maximum heart rate). Exercise tests were also performed at the end of the active treatment period (8 weeks) and 48 h after the last dose of medication (8 weeks + 2 days; ’missed dose’). Standing SBP was measured during each test at rest, at peak exercise and at 10-min intervals during a 30-min recovery period. Between-treatment differences in SBP rise (peak–rest) at week 8 and at week 8 + 2 days vs baseline were analyzed by ANCOVA, adjusting for baseline (peak–rest SBP). Results: Both treatments reduced peak SBP during exercise compared with pre-treatment baseline. At week 8, exercise-induced rises in mean SBP (peak–rest) were 49.1 mmHg for aliskiren and 53.8 mmHg for valsartan, with a between-treatment least-squares mean difference (aliskiren vs valsartan) of –2.0 mmHg (<i>p</i> = 0.654). After a missed dose (primary endpoint), the attenuation of exercise-induced SBP rises was more pronounced in favour of aliskiren (mean: 44.9 mmHg [aliskiren]; 53.2 mmHg [valsartan]); the between-treatment least-squares mean difference was –5.7 mmHg (<i>p</i> = 0.248). Both treatments were well tolerated, with no exercise-related adverse events. Conclusions: The direct renin inhibitor aliskiren reduces peak SBP during exercise. This effect was numerically greater than that observed with valsartan, especially after the missed dose, emphasizing the prolonged efficacy of aliskiren.