Comparison Efficacy of Ivabradine and Bisoprolol in Patients with Acute Inferior Wall Myocardial Infarction

Heart rate (HR) is a strong predictor of mortality and heart failure (HF) in patients with acute myocardial infarction (AMI). Beta-blockers are indicated for myocardial infarction patients with high heart rates (HR) or left ventricular (LV) dysfunction, but side effects can limit their use in appropriate dose. These are arterial hypotension, bronchial asthma, and especially atrioventricular (AV) blocks. They represent biggest concern for the use of beta blockers in inferior wall myocardial infarction (MI). Ivabradine lowers heart rate with a lesser risk of AV blocks. This study provides comparison of ivabradine and bisoprolol in acute inferior wall MI in terms of feasibility, tolerability and efficacy.

Keywords: heart rate, ivabradine, bisoprolol, inferior wall myocardial infarction.

Introduction: Acute myocardial infarction (AMI) is characterized by cellular death or necrosis of myocardial tissue due to severe or prolonged ischemia. ST-Segment Elevation Myocardial Infarction (STEMI) or Non ST-Segment Elevation Myocardial Infarction (NSTEMI), a fatal form of AMI, is supposed to be the result of complete occlusion in a coronary artery. The extent and location of the infarction are influenced by the degree of ischemic burden, availability of coronary collateral blood flow, rapidity of reperfusion and location of the plaque in the coronary artery (1). β-blockers lead to the heart rate slowing, reduced myocardial contractility, and lowered systemic blood pressure. However, bisoprolol reduces the oxygen requirements of the heart, thus providing its benefits in the long-term. The current guidelines for STEMI and NSTEMI give the strong recommendation (class I) to oral β-blocker therapy in patients without a contraindication, particularly with high HR or blood pressures (4). Ivabradine, the inhibitor of If current of cardiac pacemaker cells, without affecting other cardiac ionic currents, reduces heart rate and has no effect on cardiac contractility, repolarization, or atrioventricular conduction (5, 6). It has been recently approved as an alternate drug of choice for heart rate lowering in acute coronary syndrome especially in patients with clinical heart failure and in conditions where β-blockers are contraindicated, for instance in patients with asthma or severe chronic obstructive airway disease (2, 3).

Purpose of the Study. To compare the effectiveness of bisoprolol and ivabradine in patients with acute inferior STEMI or NSTEMI.

Materials and Methods. This observational, comparative, in-hospitalization study involved patients admitted in intensive cardiac care unit in Tashkent Medical Academy and Republican Specialized Scientific and Practical Medical Center of Cardiology. A total of 60 patients diagnosed with acute inferior MI were included in the study and were equally divided into two groups. Group 1 included patients who were administered bisoprolol for treatment, and group 2 included patients who were administered ivabradine (Coraxan).

Blood counts were obtained from all patients. Troponin I was also measured within 2–3 hours after the hospitalization. 12-lead ECG and Neb-ECG was recorded in each patient immediately after the hospitalization. After being diagnosed with inferior wall myocardial infarction, the patients were first treated with dual antiplatelet therapy followed by thrombolysis. Coronary angiogram followed by revascularization was done later as per the surgeon’s discretion. In group 1, after thrombolysis, patients received bisoprolol orally: initially 2.5 mg BID, 24–48 hours later the dose was increased to 5.0 mg BID in patients with HR >75 bpm if tolerated. In group 2, patients received 5 mg of ivabradine, the dose was increased to 7.5 mg BID for HR >75 bpm. Both drugs were titrated to achieve a HR target from 60 to 70 bpm. The heart rates and blood pressure were recorded on admission, and thereafter every 6 hours during hospitalization and on follow-up; and ejection fraction values were recorded on admission and on discharge. The NYHA class was also assessed. Patients were evaluated according to the Killip classification of the clinical examination [7]. Advanced heart failure was defined as classes 3 and 4 of the New York Heart Association (NYHA). Patients without diabetes were classified as patients without documented diabetes who did not take either oral hypoglycemic drugs or insulin treatment on admission. Hypercholesterolemia was defined as a total cholesterol level of at least 200 mg/dl or in case of taking drugs that lower cholesterol level. A family history of coronary heart disease (CHD) was defined as a documented case of coronary artery disease in parents or siblings under the age of 60.

Assaying was performed using SPSS Statistics, version 17.0 (SPSS Inc, Chicago, Illinois). Data were summarized as mean standard deviation, median and interquartile range or proportions. Student's T-test was used to compare data with a normal distribution, and the Mann-Whitney U-test was used to compare data without a normal distribution, p-value <0.05 was considered statistically significant for all assays.

Results and Discussion. Atotal of 60 patients were included in the study, with 30 patients in each group. Two patients were of age between 30–40, 30 patients were of age between 41–60, and 28 patients were of age between 61–78. 32 patients were male and 28 were female. Diabetes (43.3% and 70.0%) and hypertension (60% and 70.0%) were most prevalent conditions in patients of both groups. Smoking was a co-morbid condition in 12 and 11 patients, respectively in both groups. The details about the prevalence of co-morbid conditions are presented in Table 1.

Table 1: Co-morbid conditions in patients of both groups.

Table 2: Ejection fraction and NYHA class details

NYHA — New York Heart Association

Table 3: Heart rates of patients at different time points.

HR1, 2, 3, 4, 9 = Heart rate of day 1, 2, 3, 4, 9, respectively

The changes in heart rate over the treatment period are given in Table 3. Ivabradine reduced mean heart rate from 85.6 bpm at baseline to 78.2 bpm. Heart rate in the Bisoprolol group was reduced from 85.9 bpm to 76.5 bpm over the same time period. No significant difference was found in the mean heart rate reduction between the two groups in the prescribed period of the study.

β-blockers are a first-line treatment in secondary coronary prevention after acute myocardial infarction with a marked reduction in mortality (7). On the other hand, ivabradine reduces heart rate but does not pose any inotropic or lusitropic effect, thus maintaining ventricular contractility (8).

Thus, it can be postulated that ivabradine leads to better heart rate reduction and better improvement in ejection fraction than bisiprolol, though the difference was not statistically significant. In addition, ivabradine offers some other advantages like it is devoid of most of the adverse effects of beta-blockers (and of calcium channel blockers) and it can be suitably used as an alternative when the first line drugs cannot be adequately tolerated (9).

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