Bayer AG.

Background The angiotensin‐receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was shown to be superior to the angiotensin‐converting enzyme inhibitor enalapril in terms of reducing cardiovascular mortality in the PARADIGM‐HF (Prospective Comparison of ARNI with angiotensin‐converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study. However, the impact of ARNI on cardiac reverse remodeling (CRR) has not been established. Methods and Results We conducted a meta‐analysis to compare the effects of ARNI versus angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers on CRR indices. We searched databases for studies published between 2010 and 2019 that reported CRR indices following ARNI administration. Effect size was expressed as mean difference (MD) with 95% CIs. Twenty studies enrolling 10 175 patients were included. ARNI improved functional capacity in patients with heart failure (HF) and a reduced ejection fraction (EF), including increasing New York Heart Association functional class (MD −0.79, 95% CI −0.86, −0.71) and 6‐minute walking distance (MD 27.62 m, 95% CI 15.76, 39.48). ARNI outperformed angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers in terms of CRR indices, with striking changes in left ventricular EF, diameter, and volume. However, there were no significant improvements in indices except left ventricular mass index (MD −3.25 g/m 2 , 95% CI −3.78, −2.72) and left atrial volume (MD −7.20 mL, 95% CI −14.11, −0.29) in HF patients with preserved EF treated with ARNI. Improvements in CRR indices were observed at 3 months and became more significant with longer follow‐up to 12 months. The regression equation for the relationship between left ventricular EF and end‐diastolic dimension was y=0.041+0.071x+0.045x 2 +0.006x 3 . Conclusions ARNI distinctly improved left ventricular size and hypertrophy compared with angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers in HF with reduced EF patients, even after short‐term follow‐up. Patients appeared to benefit more in terms of CRR treated with ARNI as early as possible and for at least 3 months. Further large sample trials are required to determine the effects of ARNI on CRR in HF with preserved EF patients.

Cardiovascular disease (CVD) has become the leading cause of morbidity and mortality worldwide. A well-monitored diet with a sufficient intake of fruits and vegetables has been confirmed as a primary prevention of CVD. Plant constituents such as flavonoids have been shown to confer healthy benefits. Luteolin (Lut), a kind of flavonoid, possesses anti-oxidative, anti-tumor, and anti-inflammatory properties. Recent scientific literature has reported the cardiac protective effects of Lut in vitro and in vivo. Therefore, the aim of this review is to provide an update and detailed overview with cardio-protective molecular mechanisms of Lut with a focus on multiple intrinsic and extrinsic effectors. We further explore how these mechanisms participate in ischemia/reperfusion (I/R) injury, heart failure (HF) and atherosclerosis (AS). A proper understanding of the cardiovascular protective effects and the relative mechanisms of Lut may provide the possibility of new drug design and development for CVD. With the previous studies mainly focused on basic research, we need to advance the prospects of its further clinical utilization against CVD, large prospective clinical trials of Lut are needed to observe its therapeutic effects on patients with I/R injury, HF and AS, especially on the effective therapeutic dosage, and safety of long-term administration.