Yeoh Su Ern, Docherty Kieran F, Jhund Pardeep S, Petrie Mark C, Inzucchi Silvio E, Køber Lars, Kosiborod Mikhail N, Martinez Felipe A, Ponikowski Piotr, Sabatine Marc S, Bengtsson Olof, Boulton David W, Greasley Peter J, Langkilde Anna Maria, Sjöstrand Mikaela, Solomon Scott D, McMurray John J V
BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut, USA.
JACC Heart Fail. 2022 May;10(5):306-318. doi: 10.1016/j.jchf.2022.01.019. Epub 2022 Apr 6.
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.
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.
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.
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).
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).
本研究旨在评估低钠血症的预后重要性以及达格列净对DAPA-HF（达格列净与心力衰竭不良结局预防）试验中血清钠的影响。
低钠血症在射血分数降低的住院心力衰竭患者中很常见且具有预后重要性，但其在门诊患者中的患病率和重要性尚不确定。
我们根据钠类别（≤135和>135 mmol/L）计算主要结局（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。
在4740名进行了基线测量的参与者中，398名（8.4%）的钠≤135 mmol/L。低钠血症患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，低钠血症仍与更差的结局相关（主要结局的调整后风险比为1.50 [95% CI：1.23 - 1.84]；全因死亡的调整后风险比为1.59 [95% CI：1.26 - 2.01]）。达格列净在有和没有低钠血症的患者中的获益相似（主要终点的风险比分别为0.83 [95% CI：0.57 - 1.19]和0.73 [95% CI：0.63 - 0.84]，交互作用P值 = 0.54；全因死亡的风险比分别为0.85 [95% CI：0.56 - 1.29]和0.83 [95% CI：0.70 - 0.98]，交互作用P值 = 0.96）。在基线和第14天之间，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，这种模式逆转，在12个月时服用达格列净的患者中低钠血症患者较少（4.6%对6.7%；P = 0.003）。
基线血清钠浓度具有预后重要性，但并未改变达格列净对射血分数降低的心力衰竭患者发病率和死亡率的获益。（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）
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