Coronary artery diseaseEfficacy of Ivabradine, a Selective If Inhibitor, in Patients With Chronic Stable Angina Pectoris and Diabetes Mellitus
Section snippets
Methods
Data were drawn from the 8 multicenter, randomized, double-blind, controlled trials designed to assess the efficacy and safety of ivabradine during its clinical development before regulatory approval in Europe (Table 1). In the large efficacy and safety studies (studies 1 to 6), male or female outpatients with chronic stable angina pectoris and documented CAD were treated for ≥3 months. The exclusion criteria included important heart disease other than CAD, Prinzmetal's or microvascular angina,
Results
Patients with DM were approximately 18% of the total patient sample. Thus, the analyses of efficacy and heart rate changes were done using data from 535 patients with and 2,372 patients without DM treated with ivabradine. However, the number of patients varied for the different analyses, depending on data availability. For example, the pharmacokinetic analysis, for which only a subset of patients was tested, involved 788 patients treated with ivabradine (146 with DM). The baseline demographic
Discussion
These analyses have indicated, first, that DM does not affect plasma exposure to ivabradine and its active metabolite as measured by the pharmacokinetic parameters maximum drug concentration. and area under the curve, although it should be noted that patients with severe hepatic and renal failure were excluded in these studies. Second, our data have suggested that DM does not affect the heart rate-lowering effect of ivabradine. Third, DM also does not have a negative effect on the antianginal
References (28)
Funny channels in the control of cardiac rhythm and mode of action of selective blockers
Pharmacol Rev
(2006)- et al.
Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial
Lancet
(2008) - et al.
Modulation of rate by autonomic agonists in SAN cells involves changes in diastolic depolarization and the pacemaker current
J Mol Cell Cardiol
(2007) - et al.
Prolonged anginal perceptual threshold in diabetes: effects on exercise capacity and myocardial ischemia
J Am Coll Cardiol
(1990) - et al.
Antihypertensive medications and blood sugar: theories and implications
Can J Cardiol
(2006) - et al.
Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial
Lancet
(2005) - et al.
Electrophysiological effects of a single intravenous administration of ivabradine (S 16257) in adult patients with normal baseline electrophysiology
Drugs R D
(2003) - et al.
A single dose of ivabradine, a novel I(f) inhibitor, lowers heart rate but does not depress left ventricular function in patients with left ventricular dysfunction
Cardiology
(2003) - et al.
Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise
Br J Clin Pharmacol
(2006) - et al.
Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial
Circulation
(2003)
Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina
Eur Heart J
Antianginal efficacy and safety of ivabradine compared with amlodipine in patients with stable effort angina pectoris: a 3-month randomised, double-blind, multicentre, noninferiority trial
Drugs
Guidelines on the management of stable angina pectoris: executive summary
Eur Heart J
Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial
Eur Heart J
Cited by (49)
Type 2 Diabetes Mellitus and Heart Failure, A Scientific Statement From the American Heart Association and Heart Failure Society of America
2019, Journal of Cardiac FailureCitation Excerpt :There are no data on the impact of ivabradine on glycemic control in patients with HF. In patients with angina and DM, ivabradine was associated with a modest (mean 0.1%) decrease in HbA1c.224 Overall, ACE inhibitors, ARBs, and ARNIs have favorable effects on the development of DM and glycemic control in patients with HFrEF and should be used according to guideline recommendations.
Ivabradine versus propranolol given orally in microlaryngoscopic surgeries in attenuating stress response: A comparative prospective double blind randomized study
2016, Egyptian Journal of AnaesthesiaCitation Excerpt :It is useful in patients with angina pectoris, coronary artery disease and heart failure. Ivabradine is quite different from a beta blocker as it reduces the heart rate without jeopardizing hemodynamics in unhealthy, compromised patients [9]. The drug can be used not only in hypertensive patients but also in normotensive patients, diabetic patients and patients with bronchial asthma where beta blockers are contraindicated [10].
Evaluation of pharmacokinetic and pharmacodynamic profiles and tolerability after single (2.5, 5, or 10 mg) and repeated (2.5, 5, or 10 mg bid for 4.5 days) oral administration of ivabradine in healthy male korean volunteers
2013, Clinical TherapeuticsCitation Excerpt :The current study evaluated PK/PD characteristics and tolerability of ivabradine in healthy Korean males after single and repeated BID oral administration at doses of 2.5-, 5-, or 10-mg. In terms of PK profile aspects, the plasma and urinary PK parameters of ivabradine and its metabolite S18982 were consistent with the previous results on PK parameters in both healthy white subjects and patients with heart disease.29–31,42,43 For example, healthy volunteers studied to evaluate the drug’s interaction with Hypericum perforatum had a mean Cmax of 32.7 ng/mL, attained at 1.67 hours after single administration of 10 mg of ivabradine.29
This study was supported by Servier, Neuilly-sur-Seine, France; Drs. Borer and Tardif are paid consultants to Servier.