Centro Hospitalar Lisboa Norte, Lisbon, Portugal; Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Centro Hospitalar Lisboa Norte, Lisbon, Portugal; Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Eur J Intern Med. 2018 May;51:1-10. doi: 10.1016/j.ejim.2018.02.020. Epub 2018 Mar 2.
Acute heart failure (AHF) contributes largely to the worldwide burden of heart failure (HF) and is associated with high mortality, poor prognosis and high rehospitalization rate. The pharmacologic therapy of AHF includes diuretics and vasodilators, which are a keystone when fluid overload and congestion are present. However, vasodilators are mainly focused on controlling symptoms, and drugs that also improve long-term mortality and morbidity seem to be in high demand. In this review, we summarize the existing evidence on mortality benefits of IV vasodilators in AHF. There is lack of evidence on the mortality benefits of IV vasodilators in AHF, as well as well-designed and large-scale trials for some of them. The existing trials on nitrates have conflicting results and are insufficient to establish definitive conclusions. Other vasodilators, such as enalaprilat, clevidipine, carperitide, and ularitide, have been evaluated only in a few trials assessing mortality. Levosimendan, nesititide and carperitide are approved by some regulatory agencies; however, data regarding mortality are also conflicting and large-scale post-marketing studies would be important. Serelaxin is a recent therapy with a novel mechanism of action and seemed to be promising; although serelaxin was safe and well tolerated in earlier trials, the results of a larger phase III trial failed to meet the primary endpoints of reduction in cardiovascular death at day 180 and reduction of worsening heart failure at day 5. The absence of definitive mortality benefits and high-quality and large-scale data not allow firm conclusions to be drawn about the role of IV vasodilators in AHF. Well-designed studies are needed to clarify the role of these drugs in the long-term outcome of AHF, as well as new therapies entering the clinical investigation.
急性心力衰竭(AHF)是全球心力衰竭(HF)负担的主要原因,与高死亡率、预后不良和高再住院率相关。AHF 的药物治疗包括利尿剂和血管扩张剂,当存在液体超负荷和充血时,这些是基石。然而,血管扩张剂主要侧重于控制症状,而那些也能改善长期死亡率和发病率的药物似乎需求很高。在这篇综述中,我们总结了 IV 血管扩张剂在 AHF 中降低死亡率的现有证据。一些血管扩张剂在 AHF 中降低死亡率的证据不足,而且缺乏针对它们的设计良好且规模较大的试验。关于硝酸盐的现有试验结果相互矛盾,不足以得出明确的结论。其他血管扩张剂,如依那普利拉、可乐定、卡培肽和乌拉肽,仅在一些评估死亡率的试验中进行了评估。左西孟旦、奈西立肽和卡培肽已被一些监管机构批准;然而,关于死亡率的数据也存在矛盾,大规模的上市后研究将非常重要。雷洛昔芬是一种具有新作用机制的最近治疗方法,似乎很有前途;尽管雷洛昔芬在早期试验中安全且耐受良好,但一项更大的 III 期试验的结果未能达到降低 180 天心血管死亡和 5 天内心力衰竭恶化的主要终点。由于缺乏明确的死亡率益处和高质量、大规模的数据,无法就 IV 血管扩张剂在 AHF 中的作用得出确定的结论。需要进行精心设计的研究,以阐明这些药物在 AHF 的长期结局中的作用,以及新的治疗方法进入临床研究。