Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise.
Author(s): Joannides R, Moore N, Iacob M, Compagnon P, Lerebours G, Menard JF, Thuillez C
Affiliation(s): Department of Pharmacology, Rouen University Hospital, INSERM U644, Rouen, France.
Publication date & source: 2006-02, Br J Clin Pharmacol., 61(2):127-37.
Aim To compare in humans the effects of ivabradine and propranolol on cardiac and systemic haemodynamics at rest, during tilt and exercise. Methods Nine healthy volunteers randomly received single oral doses of ivabradine (Iva, 30 mg), propranolol (Propra, 40 mg) or placebo (Plac) during a double-blind cross-over study. Doses were selected to be equipotent in heart rate (HR) reduction. HR, systolic and diastolic blood pressure (SBP, DBP), cardiac index (CI, bioimpedance), rate pressure product (RPP), plasma epinephrine (E) and norepinephrine (NE), were measured at rest at baseline, before and after two tilt and exercise tests, started 2 and 5 h after drug intake. Heart rate variability (low to high frequency ratio LF/HF) was evaluated at rest and at 5th minute of tilt. Results At rest, HR and RPP decreased similarly with Iva and Propra (both P < 0.01). During tilt, HR increased less with Iva than Propra (P < 0.01), LF/HF decreased after Iva (P < 0.03), SBP and mean blood pressure decreased after Propra (both P < 0.01), RPP decreased similarly after Iva and Propra (both P < 0.01) and CI decreased to a greater exent with Propra than with Iva or Plac (both P < 0.04). During exercise, Iva and Propra similarly decreased HR (both P < 0.01) and RPP (P < 0.01). Conclusions These results demonstrate that for a similar decrease in HR at rest and during sympathetic stimulation, acute administration of ivabradine, a selective heart rate-lowering agent, decreased myocardial oxygen demand to the same extent as a reference beta-blocker, propranolol, but without evidence of depressant effect on cardiac function.