Functional changes in the heart after sacubitril/valsartan use in 5 hemodialysis patients with hypertension. Case report.

The purpose of this report is to describe the efficacy of sacubitril/valsartan in 5 hemodialysis patients with hypertension, including a patient with heart failure with reduced ejection fraction (HFrEF) and a patient with preserved ejection fraction (HFpEF) focused on the functional changes in the heart. We switched from angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) to sacubitril/valsartan and compared blood pressure post dialysis, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the findings of echocardiography for a period of 6 months. A month after the initiation of sacubitril/valsartan, there was improvement of symptoms and blood pressure post-dialysis, the NT-pro-BNP levels decreased from 23,132.2 ± 16,561.3 pg/mL to 8327 ± 3334.3 pg/mL, and the echocardiography findings showed a decrease in the left atrial dimension from 37.7 ± 5.7 mm to 33 ± 4.9 mm and an increase in the left ventricular ejection fraction from 58.2 ± 16.9% to 66.4 ± 15.0%. These results were sustained for up to 6 months. Also, blood pressure post-dialysis changed from 164 ± 11/77 mmHg to 150 ± 13/72 mmHg over the 6-month period. There were no side effects, such as hyperkalemia and lymphoedema. In conclusion, 5 patients had hypertension, including 2 patients with heart failure. Sacubitril/valsartan improved blood pressure post-dialysis, heart failure symptoms, NT-pro- BNP, the left atrial dimension, the left ventricular ejection fraction, and E/e', E/A found via echocardiography for a 6-months period. Treatment with sacubitril/valsartan was effective in hemodialysis patients in the cardiac function.

Kuwae N 《-》

Association of Sacubitril/Valsartan vs Valsartan With Blood Pressure Changes and Symptomatic Hypotension: the PARAGLIDE-HF Trial.

In PARAGLIDE-HF, in patients with ejection fraction (EF) > 40%, stabilized after worsening heart failure (WHF), sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared to valsartan alone, despite more symptomatic hypotension (SH). Concern about SH may be limiting the use of sacubitril/valsartan in appropriate patients. We characterized patients by the occurrence of SH (investigator-reported) after randomization to either sacubitril/valsartan or valsartan. A key trial inclusion criterion was systolic blood pressure (SBP) ≥ 100 mmHg for the preceding 6 hours and no SH. We also compared outcomes based on baseline SBP stratified by the median blood pressure. The primary endpoint was time-averaged proportional change in NT-proBNP levels from baseline through weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: (1) cardiovascular death; (2) hospitalizations due to HF; (3) urgent HF visits; and (4) change in NT-proBNP levels. Among 466 randomized patients, 92 (19.7%) experienced SH (sacubitril/valsartan, n = 56 [24.0%]; valsartan, n = 36 [15.5%]; P = 0.020). The median time to the first SH event was similar between treatment arms (18 days vs 15 days, respectively; P = 0.42) as was the proportion of first SH events classified as serious by investigators. Patients who experienced SH with sacubitril/valsartan were more likely to be white (OR 1.87 [95% CI: 0.31, 11.15]), to have a lower baseline SBP (per 10 mmHg increase, OR 0.68 [95% CI: 0.55, 0.85]), or to have a left ventricular ejection fraction (LVEF) of > 60% (OR 2.21 [95% CI: 1.05, 4.65]). Time-averaged change in NT-proBNP levels did not differ between patients with baseline SBP ≥ 128 mmHg vs SBP < 128 mmHg (interaction, P = 0.43). The composite hierarchical outcome for sacubitril/valsartan in patients with baseline SBP ≥ 128 mmHg had a win ratio of 1.34 ([95% CI: 0.91, 1.99]; P = 0.096) vs SBP < 128 mmHg with a win ratio of 1.09 ([95%CI: 0.73, 1.66]; P = 0 .62; interaction P value = 0.42). Among patients with LVEF > 40% stabilized after WHF, incident SH was more common with sacubitril/valsartan compared with valsartan. SH was associated with lower baseline SBP, being white, and having higher LVEF. Treatment benefits with sacubitril/valsartan may be more pronounced in patients with higher baseline SBP and lower LVEF (≤ 60%). (Funded by Novartis Pharmaceutical Corporation; ClinicalTrials.gov number, NCT03988634.).

Fudim M ，Cyr DD ，Ward JH ，Hernandez AF ，Lepage S ，Morrow DA ，Sharma K ，Claggett BL ，Starling RC ，Velazquez EJ ，Williamson KM ，Desai AS ，Zieroth S ，Solomon SD ，Braunwald E ，Mentz RJ ，PARAGLIDE-HF investigators ... -  《-》

Comparison of the Efficacy and Safety of Sacubitril/Valsartan and Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Patients With Reduced Ejection Fraction Combined With Moderate-to-Severe Chronic Kidney Disease.

Zhang Z ，Chen S ，Xu X ，Luo G ，Huang J ... -  《-》

Angiotensin receptor-neprilysin inhibition and improved ventricular-arterial coupling in heart failure with reduced ejection fraction.

Stegmann T ，Parentin L ，Schirmer SH ，Lavall P ，Hagendorff A ，Laufs U ，Lavall D ... -  《-》

Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Shaddy R ，Burch M ，Kantor PF ，Solar-Yohay S ，Garito T ，Zhang S ，Kocun M ，Mao C ，Cilliers A ，Wang X ，Canter C ，Rossano J ，Wallis G ，Menteer J ，Daou L ，Kusa J ，Tokel K ，Dilber D ，Xu Z ，Xiao T ，Halnon N ，Daly KP ，Bock MJ ，Zuckerman W ，Singh TP ，Chakrabarti M ，Levitas A ，Senni M ，Grutter G ，Kim GB ，Song J ，Lee HD ，Chen CK ，Sanchez-de-Toledo J ，Law Y ，Wanitkun S ，Cui Y ，Anjos R ，Mese T ，Bonnet D ... -  《-》