{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:58:40Z","timestamp":1768521520131,"version":"3.49.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Renin\u2013angiotensin system inhibitors (RASi) have been shown to lower haemoglobin levels, potentially related to reductions in erythropoietin levels and haematopoiesis. We examined whether sacubitril\/valsartan might attenuate this effect of RASi alone on incident anaemia in patients with heart failure (HF) with mildly reduced or preserved ejection fraction (HFmrEF\/HFpEF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>PARAGON-HF was a global, multicentre randomized clinical trial of sacubitril\/valsartan versus the RASi valsartan in patients with HF and left ventricular ejection fraction \u226545%. We evaluated haemoglobin trajectory and risks of incident anaemia and new iron therapy initiation during follow-up. Among 4795 participants, 1111 (23.2%) had anaemia at randomization and 5.6% were treated with iron at baseline. Over a median follow-up of 2.9\u2009years, patients with anaemia were at significantly higher risk for total HF hospitalizations and cardiovascular death, compared with those without anaemia (21.6 vs. 11.5 per 100 patient-years; adjusted rate ratio 1.31; 95% confidence interval [CI] 1.12\u20131.54; p\u2009=\u20090.001). Sacubitril\/valsartan slightly slowed the decline in haemoglobin levels by 0.1\u2009g\/dl (95% CI 0.0\u20130.2\u2009g\/dl; p\u2009=\u20090.005). Participants treated with sacubitril\/valsartan were at significantly lower risk of developing anaemia (30.3% vs. 37.6%; hazard ratio [HR] 0.76; 95% CI 0.68\u20130.85; p\u2009&amp;lt;\u20090.001) and starting iron therapy (8.1% vs. 10.0%; HR 0.81; 95% CI 0.67\u20130.97; p\u2009=\u20090.026). Treatment effects of sacubitril\/valsartan versus valsartan on total HF hospitalizations and cardiovascular death were consistent among patients across the haemoglobin spectrum (pinteraction\u2009=\u20090.60).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among patients with HFmrEF\/HFpEF, treatment with sacubitril\/valsartan resulted in modestly smaller declines in haemoglobin, lower rates of incident anaemia, and fewer new initiations of iron therapy compared with RASi.<\/jats:p>\n                    <jats:p>Clinical Trial Registration: ClinicalTrials.gov ID NCT01920711.<\/jats:p>\n                  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