Reviewer: Dr. İbrahim Halil Özdemir

Name of the Study: PANTHER - P2Y12 inhibitor versus aspirin monotherapy in patients with coronary artery disease

Published Congress: ESC 2022

Link : https://www.escardio.org/The-ESC/Press-Office/Press-releases/Neprilysin-inhibition-does-not-affect-cognitive-function-in-patients-with-heart-failure

Background:

Heart failure (HF) patients are at higher risk of developing dementia compared to the general population. Sacubitril/valsartan combines the neprilysin inhibitor sacubitril with the angiotensin receptor blocker valsartan. Neprilysin is one of many enzymes involved in the proteolytic degradation of amyloid beta (ß) peptides associated with Alzheimer's-type dementia, and concern has been expressed that their accumulation in the brain during inhibition of neprilysin may cause or worsen cognitive impairment.

Objective:

The aim of this study was to investigate the effect of long-term treatment with valsartan and the sacubitril/valsartan combination on patients' cognitive function in patients with HF and mildly reduced HF (HFmrEF) and preserved ejection fraction HF (HFpEF).

Methods:

Adults over 60 years of age who had hospitalization for heart failure in the past year and/or had NT-proBNP above 200 pg/mL were included in the study. Those with known or suspected cognitive dysfunction were excluded from the study. The primary endpoint was change in cognitive function at three-year follow-up. Cognitive function was assessed using the CogState global cognition composite score (GCCS), which consists of seven tasks (assessing attention, episodic memory, and executive function).

Results:

Primary outcome; a total of 592 patients were randomized 1:1 to sacubitril/valsartan (target dose 97/103 mg twice daily) or valsartan (target dose 160 mg twice daily). No difference was observed between the two groups in GCCS at 3-year follow-up. The difference in least-squares mean change in the GCCS was -0.0180 (95% confidence interval [CI] -0.1230 to 0.0870; p=0.74). Cohen's d effect size was -0.0277 (95% CI -0.1101 to 0.0778), indicating non-inferiority. Secondary outcome; in 491 patients, amyloid ß deposition measured using PET was different from baseline. The difference in least-squares mean change in the standardised uptake value ratio was -0.0292 (95% CI -0.0593 to 0.0010; p=0.058), indicating that amyloid ß deposition in the brain tended to be less in patients treated with sacubitril/valsartan compared with valsartan.

Conclusion:

There is no evidence that inhibition of neprilysin increases the risk of cognitive impairment due to amyloid ß deposition in the brain in patients with HF and HFmrEF/ HFpEF.

Interpretations:

Concern for increased cerebral amyloid ß accumulation with sacubitril/valsartan has always been hypothetical. However, no data in this direction were obtained from the study. The absence of any adverse effects on cognitive function is important in alleviating physician concerns in long-term treatment with sacubitril/valsartan.