Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction.
Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction.
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DOI：
10.1093/eurheartj/ehab499
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发表时间：
2021-09-21
影响因子：
39.3
通讯作者：
McMurray JJV
中科院分区：
文献类型：
--
作者：
Jackson AM;Jhund PS;Anand IS;Düngen HD;Lam CSP;Lefkowitz MP;Linssen G;Lund LH;Maggioni AP;Pfeffer MA;Rouleau JL;Saraiva JFK;Senni M;Vardeny O;Wijkman MO;Yilmaz MB;Saito Y;Zile MR;Solomon SD;McMurray JJV
心力衰竭并保留射血分数(HFpEF)的患者经常患有难以控制的高血压。在Paragon-HF试验中，我们检测了neprilysin抑制对HFpEF患者“明显的顽固性高血压”的影响，该试验比较了萨舒必利-valsartan和valsartan的效果。在这项特殊的分析中，患者根据Valsartan磨合结束时的收缩压进行分类(n = 4795)。尽管接受了钙通道阻滞剂和利尿剂Valsartan的治疗，但“明显顽固性高血压”的定义是收缩压≥140 毫米汞柱(如果糖尿病，则为≥135 毫米汞)。尽管接受了上述治疗并接受了明显的盐皮质激素受体拮抗剂治疗，高血压的定义仍为收缩压≥140mMHg(如果糖尿病，则为≥135mmHg)。Paragon-HF试验的主要结果是因心力衰竭和心血管原因死亡而住院的总人数。我们根据高血压类别检查临床终点和萨舒比利-伐沙坦的安全性。我们还检查了从Valsartan磨合结束到随机化后第4周和第16周的血压下降情况。总体而言，731名患者(15.2%)有明显的抵抗性高血压，135名(2.8%)有明显的MRA抵抗性高血压。与控制收缩压的患者(13.4；12.7-14.3/100人年)相比，明显顽固性高血压患者的主要预后发生率更高[17.3；95%可信区间(CI)15.6-19.1/100人年]，调整后的比率为1.28(95%CI为1.05-1.57)。在显性难治性高血压[−4.8(−7.0~−2.5)和3.9(−6.6~−1.3)mm Hg]和明显MRA抵抗高血压[−8.8(−14.0~−3.5)和−6.3(−12.5~−0.1)mm Hg]的患者中，分别在第4周和16周时服用萨舒比利-Valsartan的患者的收缩压下降幅度大于Valsartan[−4.8(−7.0~−2.5)和3.9(−6.6~−1.3)mm Hg]。经调整的优势比(OR)为1.78，95%可信区间(CI)为1.30~2.43，16周时，萨舒比利-Valsartan组和Valsartan组明显难治性高血压患者的血压控制比例分别为47.9%和34.3%。在MRA明显抵抗的高血压患者中，这一比例分别为43.6%和28.4%(调整后OR为2.63，95%CI为1.18~5.89)。萨舒比利-valsartan可能对HFpEF患者的明显难治性高血压有用，即使在至少接受了包括MRA在内的四种降压药物治疗的情况下仍有高血压的患者也是如此。Paragon-HF：ClinicalTrials.gov标识符NCT01920711。在心力衰竭和射血分数保留的患者中，几乎每六名患者中就有一名在Paragon-HF中有明显的顽固性高血压，这与较差的临床结果有关；在这些患者中，neprilysin抑制显著降低了收缩压。
Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on ‘apparent resistant hypertension’ in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril–valsartan with valsartan. In this post hoc analysis, patients were categorized according to systolic blood pressure at the end of the valsartan run-in (n = 4795). ‘Apparent resistant hypertension’ was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite treatment with valsartan, a calcium channel blocker, and a diuretic. ‘Apparent mineralocorticoid receptor antagonist (MRA)-resistant’ hypertension was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite the above treatments and an MRA. The primary outcome in the PARAGON-HF trial was a composite of total hospitalizations for heart failure and death from cardiovascular causes. We examined clinical endpoints and the safety of sacubitril–valsartan according to the hypertension category. We also examined reductions in blood pressure from the end of valsartan run-in to Weeks 4 and 16 after randomization. Overall, 731 patients (15.2%) had apparent resistant hypertension and 135 (2.8%) had apparent MRA-resistant hypertension. The rate of the primary outcome was higher in patients with apparent resistant hypertension [17.3; 95% confidence interval (CI) 15.6–19.1 per 100 person-years] compared to those with a controlled systolic blood pressure (13.4; 12.7–14.3 per 100 person-years), with an adjusted rate ratio of 1.28 (95% CI 1.05–1.57). The reduction in systolic blood pressure at Weeks 4 and 16, respectively, was greater with sacubitril–valsartan vs. valsartan in patients with apparent resistant hypertension [−4.8 (−7.0 to −2.5) and 3.9 (−6.6 to −1.3) mmHg] and apparent MRA-resistant hypertension [−8.8 (−14.0 to −3.5) and −6.3 (−12.5 to −0.1) mmHg]. The proportion of patients with apparent resistant hypertension achieving a controlled systolic blood pressure by Week 16 was 47.9% in the sacubitril–valsartan group and 34.3% in the valsartan group [adjusted odds ratio (OR) 1.78, 95% CI 1.30–2.43]. In patients with apparent MRA-resistant hypertension, the respective proportions were 43.6% vs. 28.4% (adjusted OR 2.63, 95% CI 1.18–5.89). Sacubitril–valsartan may be useful in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have an elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA. PARAGON-HF: ClinicalTrials.gov Identifier NCT01920711. Almost one in six patients with heart failure and preserved ejection fraction had apparent resistant hypertension in PARAGON-HF and this was associated with worse clinical outcomes; neprilysin inhibition reduced systolic blood pressure significantly in these patients.
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影响因子：
158.5
作者：
Solomon, S. D.;McMurray, J. J. V.;Lefkowitz, M. P.
通讯作者：
Lefkowitz, M. P.
影响因子：
3.8
作者：
Sweeney M;Cole GD;Pabari P;Hadjiphilippou S;Tayal U;Mayet J;Chapman N;Plymen CM
通讯作者：
Plymen CM
DOI：
10.1161/hyp.0000000000000084
发表时间：
2018-11
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Carey RM;Calhoun DA;Bakris GL;Brook RD;Daugherty SL;Dennison-Himmelfarb CR;Egan BM;Flack JM;Gidding SS;Judd E;Lackland DT;Laffer CL;Newton-Cheh C;Smith SM;Taler SJ;Textor SC;Turan TN;White WB;American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council
通讯作者：
American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council
影响因子：
4.9
作者：
Mandviwala, Taher M.;Basra, Sukhdeep S.;Deswal, Anita
通讯作者：
Deswal, Anita
影响因子：
158.5
作者：
Pitt, Bertram;Pfeffer, Marc A.;McKinlay, Sonja M.
通讯作者：
McKinlay, Sonja M.