title: Impact of Ivabradine on Central Aortic Blood Pressure and Myocardial Perfusion in Patients With Stable Coronary Artery Disease.
abstract: Treatment of hypertensive patients with β-blockers reduces heart rate and decreases central blood pressure less than other antihypertensive drugs, implying that reducing heart rate without altering brachial blood pressure could increase central blood pressure, explaining the increased cardiovascular risk reported with β-blocker. We describe a randomized, double-blind study to explore whether heart rate reduction with the If inhibitor ivabradine had an impact on central blood pressure. We included 12 normotensive patients with stable coronary artery disease, heart rate ≥70 bpm (sinus rhythm), and stable background β-blocker therapy. Patients received ivabradine 7.5 mg BID or matched placebo for two 3-week periods with a crossover design and evaluation by aplanation tonometry. Treatment with ivabradine was associated with a significant reduction in resting heart rate after 3 weeks versus no change with placebo (-15.8±7.7 versus +0.3±5.8 bpm; P=0.0010). There was no relevant between-group difference in change in central aortic systolic blood pressure (-4.0±9.6 versus +2.4±12.0 mm Hg; P=0.13) or augmentation index (-0.8±10.0% versus +0.3±7.6%; P=0.87). Treatment with ivabradine was associated with a modest increase in left ventricular ejection time (+18.5±17.8 versus +2.8±19.3 ms; P=0.074) and a prolongation of diastolic perfusion time (+215.6±105.3 versus -3.0±55.8 ms with placebo; P=0.0005). Consequently, ivabradine induced a pronounced increase in Buckberg index, an index of myocardial viability (+39.3±27.6% versus -2.5±13.5% with placebo; P=0.0015). In conclusion, heart rate reduction with ivabradine does not increase central aortic blood pressure and is associated with a marked prolongation of diastolic perfusion time and an improvement in myocardial perfusion index.
  
  
  BACKGROUND
  URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2011-004779-35.
authors.affiliation: From the Service de Cardiologie, Hôpital Lariboisière, Paris, France (J.-G.D., P.H., D.L., S.M.S.); Adipose Vascular Research Unit, Adelaide and Meath Hospital, Dublin, Ireland (V.M.); Department of Medical Science, IRCCS San Raffaele Pisana, Rome, Italy (C.V.); Institut de Recherches Internationales Servier, Cardiovascular Therapeutic Innovation Pole, Suresnes, France (G.A.); and Physiologie Clinique, Explorations Fonctionnelles, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France (B.I.L.); Inserm U970, PARRC HEGP, Paris, France (B.I.L.).
authors.forename: Jean-Guillaume
authors.initials: JG
authors.lastname: Dillinger
authors.affiliation: From the Service de Cardiologie, Hôpital Lariboisière, Paris, France (J.-G.D., P.H., D.L., S.M.S.); Adipose Vascular Research Unit, Adelaide and Meath Hospital, Dublin, Ireland (V.M.); Department of Medical Science, IRCCS San Raffaele Pisana, Rome, Italy (C.V.); Institut de Recherches Internationales Servier, Cardiovascular Therapeutic Innovation Pole, Suresnes, France (G.A.); and Physiologie Clinique, Explorations Fonctionnelles, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France (B.I.L.); Inserm U970, PARRC HEGP, Paris, France (B.I.L.).
authors.forename: Vincent
authors.initials: V
authors.lastname: Maher
authors.affiliation: From the Service de Cardiologie, Hôpital Lariboisière, Paris, France (J.-G.D., P.H., D.L., S.M.S.); Adipose Vascular Research Unit, Adelaide and Meath Hospital, Dublin, Ireland (V.M.); Department of Medical Science, IRCCS San Raffaele Pisana, Rome, Italy (C.V.); Institut de Recherches Internationales Servier, Cardiovascular Therapeutic Innovation Pole, Suresnes, France (G.A.); and Physiologie Clinique, Explorations Fonctionnelles, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France (B.I.L.); Inserm U970, PARRC HEGP, Paris, France (B.I.L.).
authors.forename: Cristiana
authors.initials: C
authors.lastname: Vitale
authors.affiliation: From the Service de Cardiologie, Hôpital Lariboisière, Paris, France (J.-G.D., P.H., D.L., S.M.S.); Adipose Vascular Research Unit, Adelaide and Meath Hospital, Dublin, Ireland (V.M.); Department of Medical Science, IRCCS San Raffaele Pisana, Rome, Italy (C.V.); Institut de Recherches Internationales Servier, Cardiovascular Therapeutic Innovation Pole, Suresnes, France (G.A.); and Physiologie Clinique, Explorations Fonctionnelles, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France (B.I.L.); Inserm U970, PARRC HEGP, Paris, France (B.I.L.).
authors.forename: Patrick
authors.initials: P
authors.lastname: Henry
authors.affiliation: From the Service de Cardiologie, Hôpital Lariboisière, Paris, France (J.-G.D., P.H., D.L., S.M.S.); Adipose Vascular Research Unit, Adelaide and Meath Hospital, Dublin, Ireland (V.M.); Department of Medical Science, IRCCS San Raffaele Pisana, Rome, Italy (C.V.); Institut de Recherches Internationales Servier, Cardiovascular Therapeutic Innovation Pole, Suresnes, France (G.A.); and Physiologie Clinique, Explorations Fonctionnelles, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France (B.I.L.); Inserm U970, PARRC HEGP, Paris, France (B.I.L.).
authors.forename: Damien
authors.initials: D
authors.lastname: Logeart
authors.affiliation: From the Service de Cardiologie, Hôpital Lariboisière, Paris, France (J.-G.D., P.H., D.L., S.M.S.); Adipose Vascular Research Unit, Adelaide and Meath Hospital, Dublin, Ireland (V.M.); Department of Medical Science, IRCCS San Raffaele Pisana, Rome, Italy (C.V.); Institut de Recherches Internationales Servier, Cardiovascular Therapeutic Innovation Pole, Suresnes, France (G.A.); and Physiologie Clinique, Explorations Fonctionnelles, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France (B.I.L.); Inserm U970, PARRC HEGP, Paris, France (B.I.L.).
authors.forename: Stephane
authors.initials: S
authors.lastname: Manzo Silberman
authors.affiliation: From the Service de Cardiologie, Hôpital Lariboisière, Paris, France (J.-G.D., P.H., D.L., S.M.S.); Adipose Vascular Research Unit, Adelaide and Meath Hospital, Dublin, Ireland (V.M.); Department of Medical Science, IRCCS San Raffaele Pisana, Rome, Italy (C.V.); Institut de Recherches Internationales Servier, Cardiovascular Therapeutic Innovation Pole, Suresnes, France (G.A.); and Physiologie Clinique, Explorations Fonctionnelles, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France (B.I.L.); Inserm U970, PARRC HEGP, Paris, France (B.I.L.).
authors.forename: Guillaume
authors.initials: G
authors.lastname: Allée
authors.affiliation: From the Service de Cardiologie, Hôpital Lariboisière, Paris, France (J.-G.D., P.H., D.L., S.M.S.); Adipose Vascular Research Unit, Adelaide and Meath Hospital, Dublin, Ireland (V.M.); Department of Medical Science, IRCCS San Raffaele Pisana, Rome, Italy (C.V.); Institut de Recherches Internationales Servier, Cardiovascular Therapeutic Innovation Pole, Suresnes, France (G.A.); and Physiologie Clinique, Explorations Fonctionnelles, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France (B.I.L.); Inserm U970, PARRC HEGP, Paris, France (B.I.L.). bernard.levy@inserm.fr.
authors.forename: Bernard I
authors.initials: BI
authors.lastname: Levy
mesh_terms: D000368:Aged; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002317:Cardiovascular Agents / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000503:physiopathology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine
keywords: blood pressure; cardiovascular diseases; coronary artery disease; heart rate; ivabradine