Servicio de Cardiología, Hospital Universitario Gregorio Marañón, CIBERCV, Calle Doctor Esquerdo, 46, 28007, Madrid, Spain.
Servicio de Cardiología, Hospital Universitario de Móstoles, Madrid, Spain.
ESC Heart Fail. 2019 Dec;6(6):1161-1166. doi: 10.1002/ehf2.12527. Epub 2019 Nov 8.
Sacubitril/valsartan is safe when initiated during hospitalization in a clinical trial setting. Its safety in real-life population is not stablished. We compared the initiation of sacubitril/valsartan during hospitalization in a non-selected population, in the PIONEER-HF trial, and in non-selected outpatients.
Multicentre registry included 527 patients: 100 were started on sacubitril/valsartan during hospitalization (19.0%) and 427 as outpatients (81.0%). Compared with those in the pivotal trial, inpatients in our cohort were older (71 ± 12 vs. 61 ± 14 years; P < 0.001); had more frequently Functional Class II (41 [41.0%] vs. 100 [22.7%]; P < 0.001), higher levels of N-terminal pro-B type natriuretic peptide (4044 [1630-8680] vs. 2013 [1002-4132] pg/mL; P < 0.001), better glomerular filtration rate (63.5 [51.0-80.0] vs. 58.4 [47.5-71.5] mL/min; P = 0.01), and higher systolic blood pressure (121 [110-136] vs. 118 [110-133] mmHg; P = 0.03); and received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers more frequently (92 [92.0%] vs. 208 [52.7%]; P < 0.001). Compared with non-selected outpatients, inpatients were older (71 ± 12 vs. 68 ± 12 years, P = 0.02), had more frequent Functional Class III-IV (58 [58.0%] vs. 129 [30.3%], P < 0.001), had higher levels of N-terminal pro-B type natriuretic peptide (4044 [1630-8680] vs. 2182 [1134-4172]; P < 0.001), and were receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers target dose less frequently (55 [55.0%] vs. 335 [78.5%]; P < 0.001). They also started sacubitril/valsartan with a low dose (50 mg/12 h) more frequently (80 [80.0%] vs. 209 [48.8%], P < 0.001). The initiation of sacubitril/valsartan in outpatients was an independent predictor of high-dose use (OR 3.1; 95% confidence interval 1.7-5.6, P < 0.001). The follow-up time in both cohorts, including all patients enrolled, was similar (7.0 ± 0.1 vs. 7.2 ± 2.6 months, P = 0.72). All-cause admissions during follow-up were more frequent in inpatients (30 [30.0%] vs. 68 outpatients [15.9%], P = 0.001), with no relevant differences in all-cause mortality. There was no significant difference in sacubitril/valsartan withdrawal rate (17 inpatients [17.0%] vs. 49 outpatients [11.5%], P = 0.13). The incidence of adverse effects was also similar: hypotension (16 inpatients [16.0%] vs. 71 outpatients [16.7%], P = 0.88), worsening renal function (7 inpatients [7.0%] vs. 29 outpatients [6.8%], P = 0.94), and hyperkalaemia (1 inpatient [1.0%] vs. 21 outpatients [4.9%], P = 0.09). We did not register any case of angioedema.
It is safe to initiate sacubitril/valsartan during hospitalization in daily clinical practice. Inpatients have a higher risk profile and receive low starting doses more frequently than outpatients.
在临床试验环境下，住院期间开始使用沙库巴曲缬沙坦是安全的。但其在真实人群中的安全性尚未确定。我们比较了在非选择性人群中、在 PIONEER-HF 试验中以及在非选择性门诊患者中住院期间开始使用沙库巴曲缬沙坦的情况。
多中心注册登记研究纳入了 527 例患者：100 例在住院期间开始使用沙库巴曲缬沙坦（19.0%），427 例在门诊开始使用（81.0%）。与关键试验相比，我们队列中的住院患者年龄更大（71±12 岁 vs. 61±14 岁；P<0.001）；功能分级 II 级的比例更高（41[41.0%] vs. 100[22.7%]；P<0.001），N 末端脑利钠肽前体（NT-proBNP）水平更高（4044[1630-8680]pg/mL vs. 2013[1002-4132]pg/mL；P<0.001），肾小球滤过率（GFR）更好（63.5[51.0-80.0]mL/min vs. 58.4[47.5-71.5]mL/min；P=0.01），收缩压更高（121[110-136]mmHg vs. 118[110-133]mmHg；P=0.03）；并且更频繁地接受血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂（ACEI/ARB）治疗（92[92.0%] vs. 208[52.7%]；P<0.001）。与非选择性门诊患者相比，住院患者年龄更大（71±12 岁 vs. 68±12 岁，P=0.02），功能分级 III-IV 级的比例更高（58[58.0%] vs. 129[30.3%]，P<0.001），NT-proBNP 水平更高（4044[1630-8680]pg/mL vs. 2182[1134-4172]pg/mL；P<0.001），并且接受 ACEI/ARB 靶剂量治疗的比例更低（55[55.0%] vs. 335[78.5%]；P<0.001）。他们也更频繁地开始使用较低剂量的沙库巴曲缬沙坦（50mg/12h）（80[80.0%] vs. 209[48.8%]，P<0.001）。门诊开始使用沙库巴曲缬沙坦是高剂量使用的独立预测因素（OR 3.1；95%置信区间 1.7-5.6，P<0.001）。两个队列的随访时间相似（7.0±0.1 个月 vs. 7.2±2.6 个月，P=0.72），包括所有入组患者。随访期间全因住院的发生率更高（30 例住院患者[30.0%] vs. 68 例门诊患者[15.9%]，P=0.001），但全因死亡率无显著差异。沙库巴曲缬沙坦停药率（17 例住院患者[17.0%] vs. 49 例门诊患者[11.5%]，P=0.13）也无显著差异。不良反应的发生率也相似：低血压（16 例住院患者[16.0%] vs. 71 例门诊患者[16.7%]，P=0.88）、肾功能恶化（7 例住院患者[7.0%] vs. 29 例门诊患者[6.8%]，P=0.94）和高钾血症（1 例住院患者[1.0%] vs. 21 例门诊患者[4.9%]，P=0.09）。我们没有登记到血管性水肿的病例。
在日常临床实践中，住院期间开始使用沙库巴曲缬沙坦是安全的。住院患者的风险更高，更常起始使用较低剂量。
