{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:36:24Z","timestamp":1791765384600,"version":"4.3.4"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":458,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T00:00:00Z","timestamp":1731801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Engdahl Family Chair for Heart Failure Research and in part by the National Institutes of Health","award":["R01 HL-122744"],"award-info":[{"award-number":["R01 HL-122744"]}]},{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Patients with heart failure with preserved ejection fraction (HFpEF) tend to have low resting and exercise heart rates. Phosphodiesterase-3 (PDE-3) inhibitors improve heart rates, haemodynamics and symptoms in patients with HFpEF. Cilostazol is an oral PDE-3 inhibitor used in peripheral artery disease. This study thought to evaluate the short-term effects of cilostazol on health status, N-terminal brain natriuretic peptide (NT-proBNP) levels and mechanisms of action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The effect of cilostazol was evaluated in 23 patients with HFpEF in a randomized placebo controlled multiple crossover trial (CLIP-HFpEF). Participants received placebo or cilostazol for 1 week followed by three crossovers to the alternate assignment at weeks 2, 3 and 4. The primary endpoint was the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) overall summary score obtained at the end of each treatment period. NT-proBNP was the secondary endpoint. In an exploratory mechanistic analysis, pulmonary artery (PA) pressures and heart rates were followed amongst the five participants with implanted pressure monitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cilostazol improved the KCCQ score by 4.8 points (95% confidence interval, 2.0\u20137.7, P = 0.003). NT-proBNP levels were 448 (154\u20131056) pg\/mL on placebo and 375 (68\u2013974) pg\/mL on cilostazol (P = 0.006). In patients with PA pressure monitors, diastolic pressure was 20.5 (18.7\u201323.0) mmHg on placebo and 18.0 (17.0\u201320.0) mmHg on cilostazol, an effect linked to higher heart rates (P &amp;lt; 0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Amongst patients with HFpEF, short-term treatment with cilostazol leads to improvements in health status and NT-proBNP when compared with placebo. These effects are likely conveyed by a heart rate-dependent reduction in cardiac filling pressures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov Identifier: NCT05126836.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.15162","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T02:20:05Z","timestamp":1731896405000},"page":"1437-1446","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cilostazol in Patients with Heart Failure and Preserved Ejection Fraction\u2014The CLIP-HFpEF Trial"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-7356","authenticated-orcid":false,"given":"Norman","family":"Aiad","sequence":"first","affiliation":[{"name":"Department of Medicine, Cardiology, University of 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