no cognitive impairment with sacubitril/valsartan

no cognitive impairment with sacubitril/valsartan

Barcelona, ​​Spain – One of the novelties of the European recommendations published last year was that the sacubitril/valsartan combination could be considered first-line instead of ACE inhibitors and AIIRAs in heart failure with reduced LVEF. What about the risk of using sacubitril on cognitive functions? According to the results of the study PERSPECTIVE which were presented during a hot line session of the 2022 ESC Congress there is no need to worry. Specifically, this trial showed that patients treated with the sacubitril/valsartan combination for three years had no more cognitive adverse effects than those in the group treated with valsartan alone.

A request from the FDA

When the FDA approved sacubitril/valsartan, it requested that a randomized trial be conducted to assess its effect on cognitive function compared to the use of valsartan alone in patients with chronic heart failure.

Valsartan is an angiotensin II receptor antagonist (ARA-II) or sartan. Sacubitril is the first representative of the class of inhibitors of neprilysin, an enzyme involved in the breakdown of various peptides, including β-amyloid peptides. By inhibiting the degradation of the latter, doctors feared a possible cerebral accumulation of β-amyloid peptides, as is the case in Alzheimer’s disease, with an acceleration of cognitive decline, which is already commonly observed in patients with AD. ‘ic.

According to the results of PERSPECTIVE, “there is no evidence that neprilysin inhibition increases the risk of impaired cognitive function due to an accumulation of β-amyloid peptides in patients suffering from ‘an IC with a reduced or preserved ejection fraction’ indicated the Prof. John McMurray (cardiologist, University of Glasgow, UK) during his presentation. The speaker pointed out that if the participants selected for the study had a CI with an ejection fraction greater than 40%, there was no reason why these results would not be valid for a population of patients with AD. IC with reduced LVEF.

Cognitive tests and PET imaging

PERSPECTIVE is the first prospective randomized trial to assess the effects of long-term treatment with the sacubritil/valsartan combination, compared to valsartan alone, on the cognition of patients with preserved or slightly reduced LVEF HF, it is i.e. greater than 40%.

The participants, aged at least 60, came from 137 centers in 20 different countries. The average age was 72 and more than two-thirds of the participants were over 75 years old. Those who had a cognitive impairment at the time of inclusion were excluded. Overall, the investigators randomized the participants to receive either the sacubitril/valsartan combination (N=295) at the target dose of 97/103mg twice daily or valsartan alone (N=297) at the target dose target of 160 mg twice a day, in addition to their basic treatment, represented mainly by a beta-blocker, a diuretic or a statin.

The primary endpoint was performance on seven cognitive tests, measured at baseline and then every six months during follow-up for up to three years. Investigators managed to collect data for at least 30 months follow-up for 71-73% of participants. They found that about 60% of participants had impaired cognitive function during follow-up. John McMurray reported that the score changes over time were similar in the two arms of the study and that the sacubitril/valsartan combination met the non-inferiority criterion compared to valsartan alone. Cohen’s d was 0.0277 (95% CI [-0,1101-0,0778]which showed non-inferiority.

Concerning the results of PET imaging – which makes it possible to quantify the cerebral accumulation of β-amyloid peptides –, they showed that the deposits of β-amyloid peptides were finally lower in patients treated with sacubitril/valsartan in comparison with those treated with valsartan alone.

A reassuring study

Discussing the session, with Professor Biykem Bozkurt (Baylor College of Medicine, Houston, USA)

said that “it was a well-designed trial” whose results, “very reassuring”, “confirm the absence of risk and are exciting because this question has plagued many heart failure patients, especially older ones”

Concerning the limited duration of PERSPECTIVE’s follow-up, Pr Mc Murray recalled that a three-year follow-up was relevant insofar as life expectancy was limited at the time of the diagnosis of HF. “Three years is a long time for patients with heart failure,” he said.

The PERSPECTIVE study was funded by Novartis, which markets sacubitril/valsartan (Entresto).

The article originally appeared on under the title “Sacubitril/Valsartan Shows Cognitive Safety in Heart Failure: PERSPECTIVE.” Translated by Marine Cygler.

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