{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:06:43Z","timestamp":1790050003616,"version":"4.0.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2008,11,29]],"date-time":"2008-11-29T00:00:00Z","timestamp":1227916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Crataegus preparations have been used for centuries especially in Europe. To date, no proper data on their efficacy and safety as an add-on-treatment are available. Therefore a large morbidity\/mortality trial was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate the efficacy and safety of an add-on treatment with Crataegus extract WS\u00ae 1442 in patients with congestive heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this randomised, double-blind, placebo-controlled multicenter study, adults with NYHA class II or III CHF and reduced left ventricular ejection fraction (LVEF\u226435%) were included and received 900 mg\/day WS\u00ae 1442 or placebo for 24 months. Primary endpoint was time until first cardiac event.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>2681 patients (WS\u00ae 1442: 1338; placebo: 1343) were randomised. Average time to first cardiac event was 620 days for WS\u00ae 1442 and 606 days for placebo (event rates: 27.9% and 28.9%, hazard ratio (HR): 0.95, 95% CI [0.82;1.10]; p=0.476). The trend for cardiac mortality reduction with WS\u00ae 1442 (9.7% at month 24; HR: 0.89 [0.73;1.09]) was not statistically significant (p=0.269). In the subgroup with LVEF \u2265 25%, WS\u00ae 1442 reduced sudden cardiac death by 39.7% (HR 0.59 [0.37;0.94] at month 24; p=0.025). Adverse events were comparable in both groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this study, WS\u00ae 1442 had no significant effect on the primary endpoint. WS\u00ae 1442 was safe to use in patients receiving optimal medication for heart failure. In addition, the data may indicate that WS\u00ae 1442 can potentially reduce the incidence of sudden cardiac death, at least in patients with less compromised left ventricular function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.ejheart.2008.10.004","type":"journal-article","created":{"date-parts":[[2008,11,26]],"date-time":"2008-11-26T08:34:41Z","timestamp":1227688481000},"page":"1255-1263","source":"Crossref","is-referenced-by-count":99,"title":["The Efficacy and Safety of Crataegus Extract WS\u00ae 1442 in Patients with Heart Failure: The SPICE Trial"],"prefix":"10.1093","volume":"10","author":[{"given":"Christian J.F.","family":"Holubarsch","sequence":"first","affiliation":[{"name":"Median Clinics Bad Krozingen , Bad Krozingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson S.","family":"Colucci","sequence":"additional","affiliation":[{"name":"Cardiology Department, Boston Medical Center , Boston 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