Impact of Statin Therapy on Clinical Outcomes in Chronic Heart Failure Patients According to Beta-Blocker Use: Results of CIBIS II

Abstract

Background: HMG-CoA reductase inhibitors (statins) are widely prescribed in patients with established systolic chronic heart failure (CHF). However, there is considerable controversy regarding their benefit in this setting. We therefore conducted a post-hoc analysis of outcomes according to statin use within the Second Cardiac Insufficiency Bisoprolol Study of the beta-blocker, bisoprolol, in NYHA classes III–IV systolic CHF patients (left ventricular ejection fraction <35%), eceiving background ACE inhibitor and diuretics. Methods: Analysis of clinical outcomes was performed according to baseline use of statins and subsequent randomisation to placebo or bisoprolol. Cumulative incidence curves for clinical events were constructed using the Kaplan-Meier method and tested for significance by log-rank statistic. Multivariate analysis was performed using the Cox proportional hazards regression model. Results: Two hundred and twenty-six of 2,647 patients were receiving statins at baseline (8.5%). Patients were well-matched in the 4 study groups at baseline for gender, weight, NYHA class and LVEF, however statin/bisoprolol patients were significantly younger (p < 0.05). Statin use at baseline was associated with a significant survival benefit compared with no statin use (p < 0.005, hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.39–0.94). This benefit remained after adjusting for other significant predictors of survival (p < 0.05, HR = 0.60, 95%CI = 0.39–0.94). A significant interaction effect was noted with bisoprolol, survival being greatest in the statin/bisoprolol group (p < 0.001, HR = 0.14, 95% CI = 0.03–0.60). Survival was 98.3% in the statin/bisoprolol group, 82.1% in the statin/placebo group, 87.2% in the no statin/bisoprolol group and 82.8% in the no statin/placebo group. The statin/bisoprolol group was also associated with fewer cardiovascular (p < 0.005) and sudden deaths (p < 0.0005) compared with other groups. Conclusions: Despite the post-hoc, non-randomised nature of this analysis, these observations suggest that statin use appears to be beneficial in CHF. Furthermore, there appears to be a favourable interaction between statins and beta-blockade within the Second Cardiac Insufficiency Bisoprolol Study cohort. Prospective studies of statins are required to definitively address the role of these agents in established CHF.

Statins in non-ischaemic cardiomyopathy: an update on our current clinical and pathophysiological understanding

“…Reduction in sympathetic activity has been shown to prevent cardiac decompensation in HF patients (53,55,56). In a recent analysis of the Second Cardiac Insufficiency Bisoprolol Study (CIBIS‐II) statins and beta‐blockers were found to have a favourable therapeutic benefit in mortality in HF patients than with either agent used alone (57). Elevated cholesterol levels have been shown to correlate with elevated expression of angiotensin type I receptors which increase the vasoconstrictor impact of angiotensin II on the vasculature (58).…”

Effects of a Secondary Prevention Combination Therapy with beta-Blocker and Statin on Major Adverse Cardiovascular Events in Acute Coronary Syndrome Patients

“…Previous studies showed that combination therapy with a beta-blocker and a statin was beneficial in lowering short-term MACEs in patients with coronary arterial disease [ 10 – 12 , 16 , 17 ]. Combination therapy application at an early stage was suggested to be correlated with reduced mortality and morbidity in patients with MI complicated with heart failure [ 10 ].…”

Korean Guidelines for Diagnosis and Management of Chronic Heart Failure

“…Although some studies reported beneficial effects of statin in patients with HF, such findings were mostly obtained from observational or retrospective studies. 227) 242) 243) 244) 245) The two large randomized trials CORONA and GISSI-HF, which evaluated the effect of statin treatment in patients with chronic HF, did not demonstrate any improvement in long term outcome. 246) 247) Moreover, there are several reports describing increased mortality in patients with HF and low cholesterol levels.…”