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Heart failure with preserved ejection fraction in older adults
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Bharathi Upadhya, Dalane W. Kitzman
The natriuretic peptides play a crucial role in fluid homeostasis. Neprilysin is a zinc-dependent metalloprotease that degrades biologically active natriuretic peptides and does not affect the biologically inactive NT-proBNP (42). LCZ696 is a new combination drug of the angiotensin II type-1 receptor blocker valsartan and the neprilysin inhibitor pro-drug AHU377. This angiotensin receptor-neprilysin inhibitor (ARNI) combination exerts a powerful vasodilatory and natriuretic effect by blocking angiotensin II activity while augmenting plasma levels of natriuretic peptides, such as BNP. In the Prospective comparison of ARNI with ARB on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) trial, LCZ696 significantly lowered NT-proBNP levels, and at 36 weeks decreased LA size and showed a trend toward improved functional class (42). The promising findings of this phase-2 study led to an ongoing large, multicenter trial, Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF (PARAGON), which is comparing LCZ696 to valsartan in patients with HFpEF with the primary composite outcome of CV death or first hospitalization for HF (ClinicalTrials.gov NCT01920711). Other novel therapies tried in HFpEF are summarized in Table 22.3.
The effects of sacubitril/valsartan on heart failure with preserved ejection fraction: a meta-analysis
Published in Acta Cardiologica, 2022
Jiao Yuheng, Li Yanyan, Zhang Song, Zha Yafang, Meng Xiaowei, Zhang Jiayan
The NYHA class and Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary scores are vital criteria to evaluate the cardiac function and symptoms of HF patients. PARALLAX [27] has compared sacubitril/valsartan with IMT and showed no additional benefits on the NYHA class among HFpEF patients with a pooled OR of 1.01, 95%CI 0.75–1.37, p = 0.93. In contrast, PARAMOUNT[26] has demonstrated that the NYHA class improved significantly at 36 weeks in the sacubitril/valsartan group (p = 0.05), while there was no difference at 12 weeks (p = 0.11). In the PARAGON trial [24], the NYHA class improved by 15.0% and 12.6% in the S/V and valsartan groups, respectively, with a pooled OR of 1.45, 95%CI 1.13–1.86. Although there was no difference in the PARAMOUNT trial [25], the PARAGON trial [24] suggested that changes in the KCCQ clinical summary score at 8 months are −1.6 ± 0.4 and −2.6 ± 0.4, respectively. Moreover, PARALLAX [27] showed the mean change from baseline in sacubitril/valsartan and IMT group, which were 12.3 (11.3 to 13.4) and 11.8 (10.8–12.8), indicating no difference in the improvement of the KCCQ clinical summary score (95%CI −0.93–1.97, p = 0.48).
Real world experience on maintenance chemotherapy with gemcitabine in second line setting for advanced non-small cell lung carcinoma
Published in Journal of Chemotherapy, 2020
Wang Chun Kwok, David Chi Leung Lam, Ka Yan Chiang, James Chung Man Ho, Mary Sau Man Ip, Terence Chi Chun Tam
Maintenance therapy after induction chemotherapy with pemetrexed has been shown to prolong progression-free survival (PFS) and overall survival (OS). In the PARAMOUNT trial, for patients who have objective response or stable disease after four cycles of doublet chemotherapy, those that received maintenance pemetrexed have improved PFS by 1.3 months and OS by 2.9 months, when compared with observation alone.1 In a post hoc analysis, patients older than 70 years of age had a similar improvement when compared with their younger counterparts, but with more severe anemia and neutropenia.2 The effectiveness of maintenance pemetrexed in real world setting has also been shown to be similar to that observed in published randomized controlled trials.3–5 The use of maintenance pemetrexed has also been assessed in specific subgroups with similar outcomes, such as in Japanese population,6 EGFR mutant patients7 and even those with renal impairment.8 There were also studies conducted to investigate the use of pemetrexed with bevacizumab, and pembrolizumab as maintenance therapy, with promising results.9–11
Randomized phase III trial comparing switch-maintenance pemetrexed with observation followed by pemetrexed at progression in advanced NSCLC
Published in Acta Oncologica, 2020
Tarje O. Halvorsen, Kristin Stokke, Kristin T. Killingberg, Sunil X. Raj, Sveinung Sørhaug, Odd Terje Brustugun, Øystein Fløtten, Nina Helbekkmo, Kjersti Hornslien, Tesfaye Madebo, Sverre Fluge, Bjørn Henning Grønberg
Two other phase III trials (JMEN and PARAMOUNT) have demonstrated a benefit from maintenance pemetrexed after platinum-based chemotherapy for advanced non-squamous NSCLC [8–10]. The main difference between these studies is that the induction chemotherapy in the PARAMOUNT trial contained pemetrexed, while the regimens in the JMEN trial did not. The median age was lower in these trials; 61 years in the PARAMOUNT trial and 60 years in the JMEN trial, and PS 2 patients were not allowed. Only 18% of patients in the control arms received pemetrexed at progression in the JMEN trial, and the fraction was even lower in the PARAMOUNT trial (3.9%), while 73% of patients on our control arm received pemetrexed at progression. Numerically, the benefit in terms of prolonged PFS we observed was similar as in these trials (1.2 vs. 1.3–1.9 months), while the survival benefit was smaller (2.0 vs. 2.9–5.2 months). Similar to these studies, we did not find any negative impact on HRQoL from pemetrexed maintenance therapy [8–10].