Effect of ivabradine on hospitalization of heart failure patients with reduced left ventricular ejection fraction: A retrospective cohort study

Background: Diuretics, ACE inhibitors or ARB, beta-blockers, and aldosterone antagonists are well established guideline directed medical therapies (GDMT) used in patients with left ventricular reduced ejection fraction (LVrEF) heart failure (HF). Hospitalization is an important marker of poor heart failure prognosis(1–2). Scientific reports have shown that ivabradine reduces cardiovascular outcomes (cardiovascular death and hospitalization due to worsening heart failure symptoms) in HF patients(3). However, in the SHIFT trial 8% of the ivabradine study group were from Asia, with 3% from other races and Caucasians making up the majority of the sample (89%)(3). No previous studies have investigated the effect of ivabradine on cardiovascular outcomes among Arabs and non-Arabs from Asia and Africa or Middle Eastern countries in general. The aim of this single-center retrospective study was to assess the effect of ivabradine in addition to GDMT in a group of HF patients with a heart rate (HR) of more than 70 bpm, LVrEF (EF < 40%) and New York Heart Association (NYHA) class II-IV, compared with another group of patients not taking ivabradine with HR of more than 70 bpm, LVrEF and NYHA class II-IV on GDMT. Methods: The study was a retrospective cohort study. It was conducted in the Heart Hospital (HH) at Hamad Medical Corporation (HMC) in Qatar. All patients registered in the HF clinic from April 2015 to September 2016 were enrolled in the study. They were either exposed or not to ivabradine (Figure 1). The primary outcomes studied were the associated risk, number and length of hospitalizations due to worsening HF, and cardiovascular mortality. The secondary outcome was mortality due to all causes. Patients’ follow up records for 18 months after recruitment were observed. Baseline characteristics were collected at enrollment. Logistic regression model was applied to assess both hospitalizations and cardiovascular mortality. The number of hospitalizations due to worsening HF was modeled using a Poisson regression model. Length of hospitalization (in days) was estimated and assessed between groups by a negative binomial regression. Results: The study included 111 patients (Figure 1): 37 (33.94%) ivabradine patients and 74 (66.67%) non-ivabradine patients. The number of ivabradine patients hospitalized were 23 (62.16%) vs 54 hospitalized non-ivabradine patients (72.97%) (OR 0.43, 95% CI 0.16-1.015, p = 0.094) (Table 1). Days of hospitalization for the ivabradine group were 464 (41.28%) vs 660 (58.72%) for non-ivabradine (IRR 1.63, 95% CI 0.79-3.38, p = 0.187). The death rate in ivabradine patients was three (two patients died due to CVD and one due to other causes) and it was also three in non-ivabradine patients (one due to CVD and two due to other causes). Testing the outcome by the factor of ethnicity instead of treatment group had different results. The number of Arabs admitted was 55 (78.57%) compared to 22 non-Arabs (53.66%) (chi-square, p = 0.006). The number of Arabs admitted in the ivabradine group 19 (76%) was significantly higher than for non-Arabs 4(33.33%) (Pearson chi-square, p = 0.012). Conclusion: The results of the study are not generalizable but showed that ivabradine patients with HFrEF along with GDMT had less risk of hospitalizations but lengthier stays and increased count of hospitalization compared to non-ivabradine patients. Though the study did not aim to explore the differences between Arab and non-Arab patients, significant differences were found in the statistical analysis highlighting the need for further research to investigate the reasons behind these differences.