Department of Cardiology, Université Pierre et Marie Curie Paris VI, La Pitié-Salpétrière Hospital, Paris, France.
Eur J Heart Fail. 2013 Jan;15(1):79-84. doi: 10.1093/eurjhf/hfs127. Epub 2012 Aug 14.
A post-hoc analysis of the SHIFT trial was performed to explore whether ivabradine is beneficial in patients with systolic heart failure, in sinus rhythm, with resting heart rate ≥70 b.p.m., and whose guideline-recommended background therapy includes a mineralocorticoid receptor antagonist (MRA).
The effect of ivabradine on the primary composite endpoint of cardiovascular death or hospitalization for worsening heart failure, and its components, was explored in 3922 SHIFT patients with MRAs at baseline vs. 2583 patients without. Patients with MRAs were younger and were more likely to have severe heart failure and less coronary artery disease or hypertension than those without these drugs. Event rates in the placebo group were higher in patients with MRAs (33%) than in those without (23%) for the primary composite endpoint, with a 40% increase in relative risk (hazard ratio 1.40, 95% confidence interval 1.22-1.61). This was also true for secondary endpoints related to mortality or hospitalization. The effect of ivabradine on reducing the primary endpoint was similar in patients with and without MRAs (P = 0.916 for interaction, adjusted for prognostic factors at baseline), as were its effects on cardiovascular death (P = 0.279), hospitalizations for heart failure (P = 0.304), and death from heart failure and from all causes (P = 0.723 and 0.366, respectively). There was no difference in the safety of ivabradine in the two subpopulations.
Ivabradine improves outcomes in heart failure patients with heart rate ≥70 b.p.m. receiving multiple neurohormonal modulation treatments (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, and MRA). The addition of ivabradine to multiple neurohormonal modulation should therefore be considered when the heart rate is ≥70 b.p.m.
SHIFT 试验的事后分析旨在探讨伊伐布雷定是否有益于窦性心律、静息心率≥70 次/分且指南推荐的背景治疗包括盐皮质激素受体拮抗剂（MRA）的射血分数降低的心力衰竭患者。
在基线时使用 MRA 的 3922 例 SHIFT 患者与未使用 MRA 的 2583 例患者中，探讨了伊伐布雷定对主要复合终点（心血管死亡或心力衰竭恶化住院）及其组成部分的影响。MRA 组患者更年轻，心力衰竭更严重，且冠心病或高血压的发生率低于未使用这些药物的患者。安慰剂组中 MRA 组患者的主要复合终点事件发生率（33%）高于未使用 MRA 组（23%），相对风险增加 40%（危险比 1.40，95%置信区间 1.22-1.61）。这对于与死亡率或住院相关的次要终点也是如此。在有和没有 MRA 的患者中，伊伐布雷定降低主要终点的效果相似（交互作用 P = 0.916，根据基线时的预后因素进行调整），对心血管死亡的影响也相似（P = 0.279）、心力衰竭住院（P = 0.304）和心力衰竭及所有原因死亡（P = 0.723 和 0.366）。在这两个亚组中，伊伐布雷定的安全性没有差异。
在接受多种神经激素调节治疗（血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂、β受体阻滞剂和 MRA）的静息心率≥70 次/分的心力衰竭患者中，伊伐布雷定改善了结局。因此，当心率≥70 次/分时，应考虑将伊伐布雷定加入多种神经激素调节。
