Elsevier

Journal of Cardiac Failure

Volume 15, Issue 10, December 2009, Pages 856-863
Journal of Cardiac Failure

Clinical Investigation
Comparison of Ivabradine Versus Metoprolol in Early Phases of Reperfused Anterior Myocardial Infarction With Impaired Left Ventricular Function: Preliminary Findings

https://doi.org/10.1016/j.cardfail.2009.05.013Get rights and content

Abstract

Background

β-blockers in ST-segment elevation myocardial infarction (STEMI) are indicated for patients without a contraindication, particularly in patients with high heart rates (HR) or blood pressures. Epidemiological studies have shown that elevated HR represents a risk factor for cardiovascular morbidity. The study investigates the feasibility, tolerability, and the effects after 30 days of follow-up of ivabradine (IVA) versus metoprolol (METO) in early phases of anterior STEMI reperfused by percutaneous coronary intervention (PCI).

Methods and Results

Patients with a first anterior STEMI, Killip class I-II, an acceptable echocardiographic window, and admitted within 4 hours of the onset of symptoms, with an ejection fraction <50%. METO or IVA, 12 hours after PCI (double blind), were administered twice per day. Blood pressure (BP), heart rate (HR), electrocardiogram (ECG), and laboratory parameters were monitored during the study. At entry, day 10, day 30, and day 60, by echocardiography, the ESV, EDV, E/A ratio, E wave deceleration time, isovolumetric relaxation time were measured. A total of 155 (50 females, 105 males) patients were randomized in 2 groups: a group received METO (76 patients) 12 hours after PCI and a group received IVA (79 patients) 12 hours after PCI. The 2 groups were similar for clinical characteristics. No difference was evidenced in HR, systolic blood pressure, diastolic blood pressure, age (range, 39-73 years), sex, ejection fraction (EF), creatine kinase peak, between the 2 groups at entry. Both groups were similar for time to angiography and interventional procedures and number of vessels diseased. IVA group: the 79 patients showed 2 side effects and 5 readmissions: 4 for ischemic events and 1 for heart failure, and 1 sudden death; METO group: the 76 patients had 4 ischemic events, 2 side effects, and 1 patient died during re–acute MI (intrastent thrombosis) and 8 readmissions for heart failure signs. The systolic blood pressure and diastolic blood pressure showed a significant reduction in both groups, P < .0001, respectively), and significant lower values were observed in METO group, P = .0001). The HR was significantly reduced in both groups, P < .0001). IVA group showed a significant increase in EF, P = .0001, with concomitant reduction in ESV and EDV (P = .0001, and .048, respectively). The diastolic parameters were similar in both groups during study period.

Conclusions

Our results suggest that ivabradine may be administered early (12 hours after PCI) to patients with successful PCI for anterior STEMI with an impaired left ventricular function and high HR and sinus rhythm. A larger sample of patients and further studies are required to evaluate the effects of ivabradine on clinical end points.

Section snippets

Population

Between December 2007 and January 2009, 567 consecutive patients were admitted with STEMI.

Eligibility Criteria

Patients had to have a first anterior episode of STEMI, Killip class I–II, an acceptable echocardiographic window, and had to be admitted within 4 hours of the onset of symptoms (pain). On electrocardiogram (ECG), there had to be an ST elevation of 0.1 mm in the peripheral leads or 2 mm in precordial leads, involving more than 1 lead, with concomitant alterations of the segmentary kinetics in the

Results

Of the 567 consecutive patients admitted with acute myocardial infarction, only 155 patients (50 female, 105 males) with anterior STEMI met the entry criteria and were included into the study. These patients were randomized (double blind) in 2 groups: a group received β-blockers (76 patients) 12 hours after successful PCI and the other group received ivabradine (79 patients) 12 hours after successful PCI.

The 2 groups were similar for clinical characteristics. Table 1 shows the baseline clinical

Discussion

The most interesting results of this study were the feasibility, tolerability, and safety in patients with anterior STEMI with impaired LV function receiving interventional reperfusion. The ivabradine group showed a significant reduction in ESV and EDV compared with the metoprolol group after 2 months (P < .0001). The EF showed a significant improvement after 30 and 60 days (P < .0001) and a significant increase in comparison with the metoprolol group (P < .017 and .01). In addition, both

References (45)

  • E.M. Antman et al.

    ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction)

    Circulation

    (2004)
  • Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) phase II trial

    N Engl J Med

    (1989)
  • R. Roberts et al.

    Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study

    Circulation

    (1991)
  • P. Di Pasquale et al.

    Effects of administration of captopril, metoprolol, and captopril-metoprolol combination as adjuvant therapy during thrombolysis in acute myocardial infarction

    Int J Cardiol

    (1994)
  • A.R. Dyer et al.

    Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiologic studies

    Am J Epidemiol

    (1980)
  • G.B. Mensink et al.

    The relationship between resting heart rate and all-cause, cardiovascular and cancer mortality

    Eur Heart J

    (1997)
  • E. Kristal-Boneh et al.

    The association of resting heart rate with cardiovascular, cancer and all-cause mortality: eight year follow-up of 3527 male Israeli employees (the CORDIS Study)

    Eur Heart J

    (2000)
  • A. Reunanen et al.

    Heart rate and mortality

    J Intern Med

    (2000)
  • P. Bois et al.

    Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells

    Br J Pharmacol

    (1996)
  • A.J. Camm et al.

    Electrophysiological effects of a single intravenous administration of ivabradine (S 16257) in adult patients with normal baseline electrophysiology

    Drugs R D

    (2003)
  • D. DiFrancesco et al.

    Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease

    Drugs

    (2004)
  • F. Custodis et al.

    Heart rate reduction by ivabradine reduces oxidative stress, improves endothelial function, and prevents atherosclerosis in apolipoprotein E-deficient mice

    Circulation

    (2008)
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