著者

Hiroyuki Tsutsui Shin-ichi Momomura Yoshihiko Saito Hiroshi Ito Kazuhiro Yamamoto Yasushi Sakata Tomomi Ohishi Pankaj Kumar Toshihito Kitamura

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-23-0174, (Released:2023-08-26)

参考文献数

38

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Background: The PARALLEL-HF study assessed the efficacy and safety of sacubitril/valsartan vs. enalapril in Japanese patients with chronic heart failure with reduced ejection fraction (HFrEF). This open-label extension (OLE) assessed long-term safety with sacubitril/valsartan.Methods and Results: This study enrolled 150 patients who received sacubitril/valsartan 50 or 100 mg, b.i.d., in addition to optimal background heart failure (HF) therapy. A dose level of sacubitril/valsartan 200 mg, b.i.d., was targeted by Week 8. At OLE baseline, higher concentrations of B-type natriuretic peptide (BNP) and urine cGMP, and lower concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP), were observed in the sacubitril/valsartan core group (patients who received sacubitril/valsartan in both the core and extension study) than in the enalapril core group (patients who received enalapril in the core study and were then transitioned to sacubitril/valsartan). The mean exposure to study drug was 98.9%. There was no trend of worsening of HF at Month 12. No obvious changes in cardiac biomarkers were observed, whereas BNP and urine cGMP increased and NT-proBNP decreased in the enalapril core group, which was evident at Weeks 2–4 and sustained to Month 12.Conclusions: Long-term sacubitril/valsartan at doses up to 200 mg, b.i.d., has a positive risk-benefit profile; it was safe and well tolerated in Japanese patients with chronic HFrEF.

著者

Hiroyuki Tsutsui Shin-ichi Momomura Yoshihiko Saito Hiroshi Ito Kazuhiro Yamamoto Yasushi Sakata Akshay Suvas Desai Tomomi Ohishi Takayuki Iimori Toshihito Kitamura Weinong Guo on behalf of the PARALLEL-HF Investigators

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-20-0854, (Released:2021-03-16)

参考文献数

21

被引用文献数

37

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Background:In the Prospective Comparison of angiotensin receptor neprilysin inhibitor (ARNI) With ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study, treatment with sacubitril/valsartan reduced the primary outcome of cardiovascular (CV) death and heart failure (HF) hospitalization compared with enalapril in patients with chronic HF and reduced ejection fraction (HFrEF). A prospective randomized trial was conducted to assess the efficacy and safety of sacubitril/valsartan in Japanese HFrEF patients.Methods and Results:In the Prospective comparison of ARNI with ACEi to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients (PARALLEL-HF) study, 225 Japanese HFrEF patients (New York Heart Association [NYHA] class II–IV, left ventricular ejection fraction [LVEF] ≤35%) were randomized (1 : 1) to receive sacubitril/valsartan 200 mg bid or enalapril 10 mg bid. Over a median follow up of 33.9 months, no significant between-group difference was observed for the primary composite outcome of CV death and HF hospitalization (HR 1.09; 95% CI 0.65–1.82; P=0.6260). Early and sustained reductions in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline were observed with sacubitril/valsartan compared with enalapril (between-group difference: Week 2: 25.7%, P<0.01; Month 6: 18.9%, P=0.01, favoring sacubitril/valsartan). There was no significant difference in the changes in NYHA class and Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score at Week 8 and Month 6. Sacubitril/valsartan was well tolerated with fewer study drug discontinuations due to adverse events, although the sacubitril/valsartan group had a higher proportion of patients with hypotension.Conclusions:In Japanese patients with HFrEF, there was no difference in reduction in the risk of CV death or HF hospitalization between sacubitril/valsartan and enalapril, and sacubitril/valsartan was safe and well tolerated.

著者

Hiroyuki Tsutsui Shin-ichi Momomura Yoshihiko Saito Hiroshi Ito Kazuhiro Yamamoto Yasushi Sakata Tomomi Ohishi Takayuki Iimori Toshihito Kitamura on behalf of the PARALLEL-HF Investigators

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-23-0349, (Released:2023-11-21)

参考文献数

18

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Background: Lower systolic blood pressure (SBP) is known to be associated with poor prognosis in heart failure (HF). We evaluated the efficacy and safety of sacubitril/valsartan according to baseline SBP tertiles in Japanese patients from the PARALLEL-HF study.Methods and Results: In all, 223 patients were stratified into tertiles according to baseline SBP (≤114 mmHg: n=75; >114 and ≤130 mmHg: n=76; and >130 mmHg: n=72). Patients with lower SBP (≤114 mmHg) had the highest median N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations at baseline (P=0.0184). No significant difference was observed between sacubitril/valsartan and enalapril for the composite outcome of cardiovascular death and HF hospitalization across SBP tertiles (P-interaction=0.2682). Although the P-interaction value was not significant (0.2106), a greater reduction in NT-proBNP with sacubitril/valsartan compared with enalapril was observed in patients with SBP >130 mmHg (P=0.0076). The incidence of hypotension-related events and reduction or discontinuation of treatment due to hypotension-related events was higher in the lower SBP subgroup, and these events were more frequent in the sacubitril/valsartan than enalapril group.Conclusions: The efficacy of sacubitril/valsartan compared with enalapril was consistent across baseline SBP tertiles in Japanese patients from the PARALLEL-HF study. Hypotension-related events were more common in patients treated with sacubitril/valsartan with lower SBP.

著者

Hiroyuki Tsutsui Shin-ichi Momomura Yoshihiko Saito Hiroshi Ito Kazuhiro Yamamoto Tomomi Ohishi Naoko Okino Toshihito Kitamura Weinong Guo

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.82, no.10, pp.2575-2583, 2018-09-25 (Released:2018-09-25)

参考文献数

17

被引用文献数

1 15

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Background: The objective of the present analyses was to describe the baseline characteristics and treatment of the Japanese patients with HFrEF in THE PARALLEL-HF study. Methods and Results: Key demographic, clinical and laboratory findings, along with treatment, were reported and compared with patients enrolled in the PARADIGM-HF trial and other contemporary randomized clinical trials and registries of Japanese patients with HFrEF. In addition, the MAGGIC and EMPHASIS-HF risk scores were calculated. A total of 225 Japanese patients were randomized in PARALLEL-HF with a mean age of 67.9 years and the majority of the patients being male (85.8%) and in NYHA Class II (93.8%). Key baseline characteristics in PARALLEL-HF were generally comparable with PARADIGM-HF, and other contemporary clinical trials and registries of Japanese HFrEF patients. Patients enrolled in PARALLEL-HF were well treated with conventional evidence-based therapy at baseline (angiotensin-converting enzyme inhibitor inhibitor/angiotensin receptor blocker, 62.7%/37.3%; β-blockers, 94.7%; mineralocorticoid receptor antagonist, 59.1%). Despite the evidence-based treatment and most patients being in NYHA Class II, these patients had a low LVEF (mean 28.1%) and were at high risk of cardiovascular mortality and morbidity as assessed by the MAGGIC and EMPHASIS-HF risk scores. Conclusions: Overall, the patients in PARALLEL-HF were largely representative of contemporary ambulatory patients with HFrEF who are well treated with evidence-based therapies. PARALLEL-HF will determine whether sacubitril/valsartan provides similar improvements in clinical outcomes in Japanese HFrEF patients as observed in the PARADIGM-HF study.

著者

Hiroyuki Tsutsui Shin-ichi Momomura Yoshihiko Saito Hiroshi Ito Kazuhiro Yamamoto Tomomi Ohishi Naoko Okino Toshihito Kitamura Weinong Guo

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-17-1424, (Released:2018-07-26)

参考文献数

17

被引用文献数

15

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Background:The objective of the present analyses was to describe the baseline characteristics and treatment of the Japanese patients with HFrEF in THE PARALLEL-HF study.Methods and Results:Key demographic, clinical and laboratory findings, along with treatment, were reported and compared with patients enrolled in the PARADIGM-HF trial and other contemporary randomized clinical trials and registries of Japanese patients with HFrEF. In addition, the MAGGIC and EMPHASIS-HF risk scores were calculated. A total of 225 Japanese patients were randomized in PARALLEL-HF with a mean age of 67.9 years and the majority of the patients being male (85.8%) and in NYHA Class II (93.8%). Key baseline characteristics in PARALLEL-HF were generally comparable with PARADIGM-HF, and other contemporary clinical trials and registries of Japanese HFrEF patients. Patients enrolled in PARALLEL-HF were well treated with conventional evidence-based therapy at baseline (angiotensin-converting enzyme inhibitor inhibitor/angiotensin receptor blocker, 62.7%/37.3%; β-blockers, 94.7%; mineralocorticoid receptor antagonist, 59.1%). Despite the evidence-based treatment and most patients being in NYHA Class II, these patients had a low LVEF (mean 28.1%) and were at high risk of cardiovascular mortality and morbidity as assessed by the MAGGIC and EMPHASIS-HF risk scores.Conclusions:Overall, the patients in PARALLEL-HF were largely representative of contemporary ambulatory patients with HFrEF who are well treated with evidence-based therapies. PARALLEL-HF will determine whether sacubitril/valsartan provides similar improvements in clinical outcomes in Japanese HFrEF patients as observed in the PARADIGM-HF study.