Objectives

This study aimed to assess the prognostic importance of hyponatremia and the effects of dapagliflozin on serum sodium in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial.

Background

Hyponatremia is common and prognostically important in hospitalized patients with heart failure with reduced ejection fraction, but its prevalence and importance in ambulatory patients are uncertain.

Methods

We calculated the incidence of the primary outcome (cardiovascular death or worsening heart failure) and secondary outcomes according to sodium category (≤135 and >135 mmol/L). Additionally, we assessed: 1) whether baseline serum sodium modified the treatment effect of dapagliflozin; and 2) the effect of dapagliflozin on serum sodium.

Results

Of 4,740 participants with a baseline measurement, 398 (8.4%) had sodium ≤135 mmol/L. Participants with hyponatremia were more likely to have diabetes, be treated with diuretics, and have lower systolic blood pressure, left ventricular ejection fraction, and estimated glomerular filtration rate. Hyponatremia was associated with worse outcomes even after adjustment for predictive variables (adjusted HRs for the primary outcome 1.50 [95% CI: 1.23-1.84] and all-cause death 1.59 [95% CI: 1.26-2.01]). The benefits of dapagliflozin were similar in patients with and without hyponatremia (HR for primary endpoint: 0.83 [95% CI: 0.57-1.19] and 0.73 [95% CI: 0.63-0.84], respectively, P for interaction = 0.54; HR for all-cause death: 0.85 [95% CI: 0.56-1.29] and 0.83 [95% CI: 0.70-0.98], respectively, P for interaction = 0.96). Between baseline and day 14, more patients on dapagliflozin developed hyponatremia (11.3% vs 9.4%; P = 0.04); thereafter, this pattern reversed and at 12 months fewer patients on dapagliflozin had hyponatremia (4.6% vs 6.7%; P = 0.003).

Conclusions

Baseline serum sodium concentration was prognostically important, but did not modify the benefits of dapagliflozin on morbidity and mortality in heart failure with reduced ejection fraction. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]: NCT03036124)

中文翻译：

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达格列净与血清钠的关系

目标

本研究旨在评估 DAPA-HF（达格列净和预防心力衰竭不良结局）试验中低钠血症的预​​后重要性和达格列净对血清钠的影响。

背景

低钠血症在射血分数降低的心力衰竭住院患者中很常见且对预后很重要，但其在非卧床患者中的患病率和重要性尚不确定。

方法

我们根据钠类别（≤135 和 >135 mmol/L）计算了主要结局（心血管死亡或心力衰竭恶化）和次要结局的发生率。此外，我们评估了：1）基线血清钠是否改变了达格列净的治疗效果；2）达格列净对血清钠的影响。

结果

在基线测量的 4,740 名参与者中，398 名 (8.4%) 的钠含量≤135 mmol/L。患有低钠血症的参与者更有可能患有糖尿病，接受利尿剂治疗，并且收缩压、左心室射血分数和估计的肾小球滤过率较低。即使在对预测变量进行调整后，低钠血症与较差的结果相关（主要结果的调整后 HR 为 1.50 [95% CI：1.23-1.84]，全因死亡为 1.59 [95% CI：1.26-2.01]）。达格列净在有和无低钠血症患者中的益处相似（主要终点的 HR 分别为 0.83 [95% CI: 0.57-1.19] 和 0.73 [95% CI: 0.63-0.84]，交互作用P = 0.54；HR全因死亡：分别为 0.85 [95% CI: 0.56-1.29] 和 0.83 [95% CI: 0.70-0.98]，P交互作用 = 0.96）。从基线到第 14 天，更多服用达格列净的患者出现低钠血症（11.3% 对 9.4%；P = 0.04）；此后，这种模式发生了逆转，在 12 个月时，使用达格列净的患者出现低钠血症的人数减少（4.6% 对 6.7%；P = 0.003）。

结论

基线血清钠浓度对预后很重要，但并未改变达格列净对射血分数降低的心力衰竭发病率和死亡率的益处。（评估达格列净对慢性心力衰竭患者心力衰竭恶化或心血管死亡发生率影响的研究 [DAPA-HF]：NCT03036124）