Krum Henry, Bailey Michael, Meyer Wilfried, Verkenne Patricia, Dargie Henry, Lechat Phillipe, Anker Stefan
NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
Cardiology. 2007;108(1):28-34. doi: 10.1159/000095629. Epub 2006 Sep 8.
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.
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.
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.
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.
3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）被广泛用于已确诊的收缩性慢性心力衰竭（CHF）患者。然而，关于其在此种情况下的益处存在相当大的争议。因此，我们在第二项心脏功能不全比索洛尔研究中，根据他汀类药物的使用情况对NYHA III-IV级收缩性CHF患者（左心室射血分数<35%）的预后进行了事后分析，这些患者接受了背景性血管紧张素转换酶抑制剂和利尿剂治疗，同时使用了β受体阻滞剂比索洛尔。
根据他汀类药物的基线使用情况以及随后随机分配至安慰剂或比索洛尔的情况，对临床结局进行分析。使用Kaplan-Meier方法构建临床事件的累积发生率曲线，并通过对数秩统计检验其显著性。使用Cox比例风险回归模型进行多变量分析。
2647例患者中有226例（8.5%）在基线时接受他汀类药物治疗。4个研究组在基线时的性别、体重、NYHA分级和左心室射血分数方面匹配良好，但他汀类药物/比索洛尔组患者明显更年轻（p<0.05）。与未使用他汀类药物相比，基线时使用他汀类药物与显著的生存获益相关（p<0.005，风险比[HR]=0.60，95%置信区间[CI]=0.39-0.94）。在调整其他显著的生存预测因素后，这种获益仍然存在（p<0.05，HR=0.60，95%CI=0.39-0.94）。与比索洛尔存在显著的交互作用，他汀类药物/比索洛尔组的生存率最高（p<0.001，HR=0.14，95%CI=0.03-0.60）。他汀类药物/比索洛尔组的生存率为98.3%，他汀类药物/安慰剂组为82.1%，未使用他汀类药物/比索洛尔组为87.2%，未使用他汀类药物/安慰剂组为82.8%。与其他组相比，他汀类药物/比索洛尔组的心血管死亡（p<0.005）和心源性猝死（p<0.0005）也更少。
尽管本分析具有事后、非随机的性质，但这些观察结果表明，使用他汀类药物似乎对CHF有益。此外，在第二项心脏功能不全比索洛尔研究队列中，他汀类药物与β受体阻滞剂之间似乎存在有益的相互作用。需要对他汀类药物进行前瞻性研究，以明确这些药物在已确诊的CHF中的作用。
