Prognostic Impact of Statin Intensity in Heart Failure Patients With Ischemic Heart Disease: A Report From the CHART-2 (Chronic Heart Failure Registry and Analysis in the Tohoku District 2) Study

Abstract

Background: The beneficial prognostic impact of statins has been established in patients with ischemic heart disease but not in those with heart failure (HF). In addition, it is still unclear whether patients benefit from statins regardless of low-density lipoprotein cholesterol levels.

Methods and results: We examined 2444 consecutive stage C or D HF patients with ischemic heart disease registered in CHART-2 (Chronic Heart Failure Registry and Analysis in the Tohoku District 2), a multicenter, prospective, observational cohort study in Japan. Patients were divided into 3 groups according to the Japanese standard doses of statins and statin-intensity categories defined by the 2013 American College of Cardiology and American Heart Association guidelines: higher (moderate-high)-intensity (n=868), lower (low)-intensity (n=526), and no statin (n=1050). The median follow-up period was 6.4 years (13929 person-years). Analysis with the inverse probability of treatment weighted using a propensity score for multiple treatment revealed that both the higher-intesity group (hazard ratio [HR]: 0.68; P<0.001) and the lower-intensity group (HR: 0.82; P<0.001) had significantly lower incidence of the primary end point-a composite of all-cause death and HF admission-compared with the no statin group. The higher-intensity statin group had significantly lower incidence of the primary end point (HR: 0.82; P<0.001), all-cause death (HR: 0.83; P<0.001), and HF admission (HR: 0.78; P<0.001) than the lower-intensity statin group. Moreover, the use of statins, either higher- or lower-intensity, was associated with reduced incidence of the primary end point, regardless of low-density lipoprotein cholesterol levels.

Conclusions: These results suggest that statin use, particularly the use of higher-intensity statins, has a beneficial prognostic impact in HF patients with ischemic heart disease, regardless of low-density lipoprotein cholesterol levels.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00418041.

Keywords: heart failure; ischemic heart disease; statin therapy.

Figure 1

Flowchart of the study population.

Figure 2

The diagnostic plots for propensity score with multiple treatments using generalized boosted models. ATE, average treatment effect; es, effect size; ks, Kolmogorov‐Smirnov.

Figure 3

Kaplan–Meier curves for primary and secondary end points.

Figure 4

Hazard ratios for primary and secondary end points (A) in univariable Cox proportional hazards models, (B) in Cox proportional hazards models adjusted by IPTW methods using propensity score for multiple treatments, and (C) in Cox proportional hazards models adjusted by IPTW methods using propensity score for multiple treatments and low‐density lipoprotein cholesterol levels. AMI indicates acute myocardial infarction; CI, confidence interval; CV, cardiovascular; HF, heart failure; HR, hazard ratio; IPTW, inverse probability of treatment weighted.

Figure 5

Hazard ratios for primary end point in Cox proportional hazards models adjusted by IPTW methods using propensity score for multiple treatments by subgroups: (A) higher‐ or lower‐intensity vs no statin; (B) higher‐ vs lower‐intensity. BMI indicates body mass index; BNP, brain natriuretic peptide; CI, confidence interval; CRP, C‐reactive protein; HR, hazard ratio; IPTW, inverse probability of treatment weighted; LDL‐C, low‐density lipoprotein cholesterol; LVDd, left ventricular dimension diastolic; LVEF, left ventricular ejection fraction; LVMI, left ventricular mass index; NYHA, New York Heart Association.

Figure 6

Association between LDL‐C level and risk of the primary end point in the additive Cox regression models. LDL‐C indicates low‐density lipoprotein cholesterol.