Selective Heart Rate Reduction With Ivabradine Increases Central Blood Pressure in Stable Coronary Artery Disease.
Heart rate (HR) lowering by β-blockade was shown to be beneficial after myocardial infarction. In contrast, HR lowering with ivabradine was found to confer no benefits in 2 prospective randomized trials in patients with coronary artery disease. We hypothesized that this inefficacy could be in part related to ivabradine's effect on central (aortic) pressure. Our study included 46 patients with chronic stable coronary artery disease who were randomly allocated to placebo (n=23) or ivabradine (n=23) in a single-blinded fashion for 6 months. Concomitant baseline medication was continued unchanged throughout the study except for β-blockers, which were stopped during the study period. Central blood pressure and stroke volume were measured directly by left heart catheterization at baseline and after 6 months. For the determination of resting HR at baseline and at follow-up, 24-hour ECG monitoring was performed. Patients on ivabradine showed an increase of 11 mm Hg in central systolic pressure from 129±22 mm Hg to 140±26 mm Hg (P=0.02) and in stroke volume by 86±21.8 to 107.2±30.0 mL (P=0.002). In the placebo group, central systolic pressure and stroke volume remained unchanged. Estimates of myocardial oxygen consumption (HR×systolic pressure and time-tension index) remained unchanged with ivabradine.The decrease in HR from baseline to follow-up correlated with the concomitant increase in central systolic pressure (r=-0.41, P=0.009) and in stroke volume (r=-0.61, P<0.001). In conclusion, the decrease in HR with ivabradine was associated with an increase in central systolic pressure, which may have antagonized possible benefits of HR lowering in coronary artery disease patients. CLINICAL TRIALSURL: http://www.clinicaltrials.gov. Unique identifier NCT01039389.
From the Department of Cardiology and Clinical Research, Inselspital, University of Bern Hospital, Bern, Switzerland (S.F.R., F.H.M., D.C., S.G., T.T., C.S.); and Department of Pharmacology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Inserm UMR 970, University Paris Descartes, Paris, France (S.L.). Messerli.f@gmail.com stefano.rimoldi@insel.ch.
Stefano F
SF
Rimoldi
From the Department of Cardiology and Clinical Research, Inselspital, University of Bern Hospital, Bern, Switzerland (S.F.R., F.H.M., D.C., S.G., T.T., C.S.); and Department of Pharmacology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Inserm UMR 970, University Paris Descartes, Paris, France (S.L.). Messerli.f@gmail.com stefano.rimoldi@insel.ch.
Franz H
FH
Messerli
From the Department of Cardiology and Clinical Research, Inselspital, University of Bern Hospital, Bern, Switzerland (S.F.R., F.H.M., D.C., S.G., T.T., C.S.); and Department of Pharmacology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Inserm UMR 970, University Paris Descartes, Paris, France (S.L.).
David
D
Cerny
From the Department of Cardiology and Clinical Research, Inselspital, University of Bern Hospital, Bern, Switzerland (S.F.R., F.H.M., D.C., S.G., T.T., C.S.); and Department of Pharmacology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Inserm UMR 970, University Paris Descartes, Paris, France (S.L.).
Steffen
S
Gloekler
From the Department of Cardiology and Clinical Research, Inselspital, University of Bern Hospital, Bern, Switzerland (S.F.R., F.H.M., D.C., S.G., T.T., C.S.); and Department of Pharmacology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Inserm UMR 970, University Paris Descartes, Paris, France (S.L.).
Tobias
T
Traupe
From the Department of Cardiology and Clinical Research, Inselspital, University of Bern Hospital, Bern, Switzerland (S.F.R., F.H.M., D.C., S.G., T.T., C.S.); and Department of Pharmacology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Inserm UMR 970, University Paris Descartes, Paris, France (S.L.).
Stéphane
S
Laurent
From the Department of Cardiology and Clinical Research, Inselspital, University of Bern Hospital, Bern, Switzerland (S.F.R., F.H.M., D.C., S.G., T.T., C.S.); and Department of Pharmacology, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Inserm UMR 970, University Paris Descartes, Paris, France (S.L.).
Christian
C
Seiler
D000368:Aged; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001795:Blood Pressure Determination; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D000077550:Ivabradine; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013318:Stroke Volume / Q000187:drug effects*; D016896:Treatment Outcome
D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine
central blood pressure; coronary artery disease; heart rate; ivabradine; stroke volume; ventricular-vascular mismatch