Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise.
OBJECTIVE
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 5 th 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 extent 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.
Joannides
Robinson
R
Department of Pharmacology, Rouen University Hospital, INSERM U644, Rouen, France.
Moore
Nicholas
N
Iacob
Michaela
M
Compagnon
Patricia
P
Lerebours
Guy
G
Menard
Jean-François
JF
Thuillez
Christian
C
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D000328:Adult; D001552:Benzazepines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D018592:Cross-Over Studies; D003864:Depression, Chemical; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D015444:Exercise / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D000077550:Ivabradine; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011433:Propranolol / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D012146:Rest / Q000502:physiology; D018667:Tilt-Table Test
D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine; D011433:Propranolol; D009638:Norepinephrine; D004837:Epinephrine