Ivabradine in Combination with Metoprolol Improves Symptoms and Quality of Life in Patients with Stable Angina Pectoris: A post hoc Analysis from the ADDITIONS Trial.
OBJECTIVE
Elevated heart rate can increase myocardial oxygen demand and reduce myocardial perfusion, provoking myocardial ischemia and angina symptoms. We evaluated adding ivabradine to the therapy of patients on metoprolol.


METHODS
ADDITIONS (prActical Daily efficacy anD safety of Procoralan® In combinaTION with betablockerS) was a multicenter, 4-month, noninterventional, prospective, open-label trial that involved stable-angina patients. Along with metoprolol, patients received ivabradine (5 or 7.5 mg, b.i.d.). We investigated the effect of ivabradine on heart rate, angina attacks, nitrate consumption, quality of life (QoL) and tolerability as well as the influence of baseline heart rate.


RESULTS
Heart rate fell by 19.7 ± 11.2 bpm, with an 8-fold decrease in weekly angina attacks (1.7 ± 2.2 to 0.2 ± 0.7) and nitrate consumption (2.4 ± 3.4 to 0.3 ± 0.9). Patient numbers in Canadian Cardiovascular Society class I more than doubled (i.e. from 29 to 65%) and QoL improved (the EQ-5D index and visual analog scale scores rose from 0.68 ± 0.27 to 0.84 ± 0.20 and 58.1 ± 18.4 to 72.2 ± 15.5 mm, respectively). The effect of ivabradine was greater in patients with a baseline heart rate ≥70 bpm (mean reduction in heart rate -21.2 ± 10.4 bpm, with a relative reduction in angina attacks and short-acting nitrate consumption of 87.1 and 87.2%, respectively).


CONCLUSIONS
Ivabradine combined with metoprolol safely and effectively reduces heart rate, angina attacks and nitrate use, and improves QoL in stable-angina patients.
Department of Medicine and Heart Centre, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.
Karl
K
Werdan
Henning
H
Ebelt
Sebastian
S
Nuding
Florian
F
Höpfner
Georg
G
Stöckl
Ursula
U
Müller-Werdan
D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D060050:Angina, Stable / Q000188:drug therapy* / Q000523:psychology; D001552:Benzazepines / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D005858:Germany; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D008875:Middle Aged; D009566:Nitrates; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires
D058671:Adrenergic beta-1 Receptor Antagonists; D001552:Benzazepines; D002317:Cardiovascular Agents; D009566:Nitrates; D000077550:Ivabradine; D008790:Metoprolol