Impact of statin therapy on clinical outcomes in chronic heart failure patients according to beta-blocker use: results of CIBIS II.
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%), receiving 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.
Krum
Henry
H
NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. henry.krum@med.monash.edu.au
Bailey
Michael
M
Meyer
Wilfried
W
Verkenne
Patricia
P
Dargie
Henry
H
Lechat
Phillipe
P
Anker
Stefan
S
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000704:Analysis of Variance; D017298:Bisoprolol / Q000008:administration & dosage*; D002423:Cause of Death; D016009:Chi-Square Distribution; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D013318:Stroke Volume; D016019:Survival Analysis; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017298:Bisoprolol