{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T20:21:10Z","timestamp":1785270070001,"version":"3.55.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":3346,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor\u2013neprilysin inhibitor (ARNI) sacubitril\/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid-\u03b2 peptides from the brain, there is a theoretical concern about the long-term effects of sacubitril\/valsartan on cognition. Therefore, we have examined dementia-related adverse effects (AEs) in PARADIGM-HF and placed these findings in the context of other recently conducted HFrEF trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In PARADIGM-HF, patients with symptomatic HFrEF were randomized to sacubitril\/valsartan 97\/103\u2009mg b.i.d. or enalapril 10\u2009mg b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the Medical Dictionary for Regulatory Activities (MedDRA), using Standardized MedDRA Queries (SMQs) with \u2018broad\u2019 and \u2018narrow\u2019 preferred terms related to dementia. In PARADIGM-HF, 8399 patients aged 18\u201396 years were randomized and followed for a median of 2.25\u2009years (up to 4.3\u2009years). The narrow SMQ search identified 27 dementia-related AEs: 15 (0.36%) on enalapril and 12 (0.29%) on sacubitril\/valsartan [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.33\u20131.59]. The broad search identified 97 (2.30%) and 104 (2.48%) AEs (HR 1.01, 95% CI 0.75\u20131.37), respectively. The rates of dementia-related AEs in both treatment groups in PARADIGM-HF were similar to those in three other recent trials in HFrEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We found no evidence that sacubitril\/valsartan, compared with enalapril, increased dementia-related AEs, although longer follow-up may be necessary to detect such a signal and more sensitive tools are needed to detect lesser degrees of cognitive impairment. Further studies to address this question are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.687","type":"journal-article","created":{"date-parts":[[2016,11,20]],"date-time":"2016-11-20T23:26:40Z","timestamp":1479684400000},"page":"129-137","source":"Crossref","is-referenced-by-count":107,"title":["Dementia-Related Adverse Events in PARADIGM-HF and Other Trials in Heart Failure with Reduced Ejection Fraction"],"prefix":"10.1093","volume":"19","author":[{"given":"Jane A.","family":"Cannon","sequence":"first","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shen","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pardeep 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