De Vecchis R, Ariano C, Di Biase G, Noutsias M
Preventive Cardiologyand Rehabilitation Unit, DSB 29 "S. Gennaro dei Poveri Hospital", via S.Gennaro dei Poveri 25, 80136, Napoli, Italy.
Cardiology Unit, Presidio Sanitario Intermedio "Elena d'Aosta", ASL Napoli 1 Centro, via Cagnazzi 29, 80137, Napoli, Italy.
Herz. 2019 Nov;44(7):651-658. doi: 10.1007/s00059-018-4690-6. Epub 2018 Mar 8.
In heart failure with reduced left ventricular ejection fraction (HFREF) patients, the dosage of sacubitril/valsartan is modulated according to a gradual increase regimen. Nevertheless, if patients exhibit tolerability problems, a provisional reduction of the dose of sacubitril/valsartan or even its interruption are recommended.
This study provides estimates of respective proportions of patients receiving minimum or intermediate doses of sacubitril/valsartan. In addition, a comparison was made to detect possible differences regarding all-cause mortality and heart failure hospitalization in patients treated with the recommended optimum dose compared to those receiving submaximum maintenance doses of sacubitril/valsartan.
Patients treated with sacubitril/valsartan in addition to beta-blocker and mineralocorticoid receptor blocker were 68. Among them, 20 patients (29.4%), were identified as having clinical features that were contraindications to the administration of sacubitril/valsartan at full dose. The subsequent decision was to maintain an intermediate dose in 11 patients and to reduce the dose to the minimum level allowed, i.e., 24 mg/26 mg twice daily in nine patients. After a median follow-up of 5.25 months, no differences were found concerning the risk of all-cause death by comparing patients treated with reduced versus those subjected to target doses of sacubitril/valsartan (odds ratio [OR] = 1.666; 95% confidence interval [CI] = 0.256-10.823; p = 0.6266). Patients taking reduced doses had a similar risk of heart failure hospitalizations when compared to patients treated with the target dose (OR = 0.789; 95% CI: 0.077-8.0808; p = 1.00).
During a median follow-up of 5.25 months, in the group of patients who had proven to be intolerant to the maximum dose of sacubitril/valsartan, use of reduced doses of the drug did not result in increased all-cause mortality or heart failure hospitalization compared to patients treated with sacubitril/valsartan at the target dose.
在左心室射血分数降低的心力衰竭（HFREF）患者中，沙库巴曲缬沙坦的剂量根据逐步增加方案进行调整。然而，如果患者出现耐受性问题，建议暂时降低沙库巴曲缬沙坦的剂量，甚至中断用药。
本研究提供了接受最低或中等剂量沙库巴曲缬沙坦患者各自比例的估计值。此外，进行了一项比较，以检测接受推荐的最佳剂量治疗的患者与接受低于最大维持剂量沙库巴曲缬沙坦治疗的患者在全因死亡率和心力衰竭住院方面可能存在的差异。
除β受体阻滞剂和盐皮质激素受体阻滞剂外，接受沙库巴曲缬沙坦治疗的患者有68例。其中，20例患者（29.4%）被确定具有临床特征，这些特征是禁止使用全剂量沙库巴曲缬沙坦的禁忌症。随后的决定是，11例患者维持中等剂量，9例患者将剂量降至允许的最低水平，即每日两次，每次24毫克/26毫克。在中位随访5.25个月后，通过比较接受降低剂量与接受目标剂量沙库巴曲缬沙坦治疗的患者，未发现全因死亡风险存在差异（优势比[OR]=1.666；95%置信区间[CI]=0.256-10.823；p=0.6266）。与接受目标剂量治疗的患者相比，服用降低剂量的患者心力衰竭住院风险相似（OR=0.789；95%CI：0.077-8.0808；p=1.00）。
在中位随访5.25个月期间，在已证明对最大剂量沙库巴曲缬沙坦不耐受的患者组中，与接受目标剂量沙库巴曲缬沙坦治疗的患者相比，使用降低剂量的该药物不会导致全因死亡率增加或心力衰竭住院率增加。
