Cardiology, Department of Experimental and Applied Medicine, University of Brescia, Brescia, Italy.
Eur Heart J. 2011 Jun;32(12):1519-34. doi: 10.1093/eurheartj/ehr042. Epub 2011 Mar 8.
Dyspnoea and pulmonary and/or peripheral congestion are the most frequent manifestations of acute heart failure (AHF) and are important targets for therapy. We have assessed changes in dyspnoea, their relationship with mortality, and the effects of the adenosine A1 receptor antagonist rolofylline on these endpoints in patients enrolled in the PROTECT trial.
PROTECT was a prospective, double-blind, placebo-controlled study assessing the effect of rolofylline in patients hospitalized for AHF with dyspnoea, fluid overload, increased plasma natriuretic peptides, and mild-to-moderate renal dysfunction. Early dyspnoea relief, prospectively defined as moderately or markedly better dyspnoea at both 24 and 48 h after the start of study drug administration, occurred in 49.8% of the patients. Early dyspnoea relief was associated with greater weight loss and with reduced mortality at Days 14 and 30 [hazard ratio (HR) 0.28, 95% confidence interval (CI): 0.15, 0.50; and 0.35, 95% CI: 0.22, 0.55, respectively]. Rolofylline administration was associated with an increase in the proportion of patients showing early dyspnoea relief (HR 1.30; 95% CI: 1.08, 1.57) and with a numerically lower mortality at 14 and 30 days, largely driven by the mortality due to HF [at 30 days, HR (95% CI, P-value): 0.65 (0.38-1.10, P= 0.107)]. Rolofylline did not reduce episodes of in-hospital worsening HF or post-discharge re-admissions, nor did it improve survival at 60 or 180 days.
The present analysis from PROTECT demonstrated that more weight loss was associated with early dyspnoea relief and reduced short-term mortality.
呼吸困难和肺部及/或外周充血是急性心力衰竭（AHF）最常见的表现，也是治疗的重要目标。我们评估了呼吸困难的变化，及其与死亡率的关系，并评估了腺苷 A1 受体拮抗剂罗氟司特在 PROTECT 试验中这些终点的疗效。
PROTECT 是一项前瞻性、双盲、安慰剂对照研究，评估了罗氟司特对因呼吸困难、液体超负荷、血浆利钠肽增加和轻中度肾功能障碍而住院的 AHF 患者的疗效。早期呼吸困难缓解（定义为在研究药物治疗开始后 24 和 48 小时，呼吸困难明显或明显改善）在 49.8%的患者中发生。早期呼吸困难缓解与更大的体重减轻和 14 天和 30 天死亡率降低相关[风险比（HR）0.28，95%置信区间（CI）：0.15，0.50；和 0.35，95%CI：0.22，0.55]。罗氟司特治疗与早期呼吸困难缓解患者比例增加相关（HR 1.30；95%CI：1.08，1.57），14 天和 30 天死亡率降低，主要是心力衰竭所致死亡率降低[30 天，HR（95%CI，P 值）：0.65（0.38-1.10，P=0.107）]。罗氟司特并未减少住院期间心力衰竭恶化或出院后再入院的发作，也未改善 60 天或 180 天的生存率。
PROTECT 的本次分析表明，更多的体重减轻与早期呼吸困难缓解和降低短期死亡率相关。
