{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T04:35:12Z","timestamp":1770438912818,"version":"3.49.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1995,8,15]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            Direct thrombin inhibitors are a new class of drugs that may offer a more effective and potentially simpler alternative to heparin. Hirulog is a synthetic peptide based on the leech-derived compound hirudin and, like hirudin, is a highly specific, direct inhibitor of free and clot-bound thrombin.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            TIMI 7 was a randomized, double-blind study of Hirulog, given with 325 mg\/d aspirin to 410 patients with unstable angina. Patients received a constant infusion of Hirulog for 72 hours at one of four doses: 0.02 (n=160), 0.25 (n=81), 0.5 (n=88), and 1.0 (n=81) mg \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 h\n            <jats:sup>\u22121<\/jats:sup>\n            . The primary efficacy end point was \u201cunsatisfactory outcome,\u201d defined as death, nonfatal myocardial infarction (MI), rapid clinical deterioration, or recurrent ischemic pain at rest with ECG changes by 72 hours. Unsatisfactory outcome was not different among the four dose groups: 8.1%, 6.2%, 11.4%, and 6.2% (\n            <jats:italic>P<\/jats:italic>\n            =NS). However, the secondary end point of death or nonfatal MI through hospital discharge occurred in 10.0% of patients treated with 0.02 mg \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 h\n            <jats:sup>\u22121<\/jats:sup>\n            compared with 3.2% of patients treated with the three higher doses of Hirulog (0.25, 0.5, and 1.0 mg \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 h\n            <jats:sup>\u22121<\/jats:sup>\n            ,\n            <jats:italic>P<\/jats:italic>\n            =.008). Only 2 of 410 patients (0.5%) experienced a major hemorrhage attributed to Hirulog.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            The direct thrombin inhibitor Hirulog is a promising new antithrombotic agent that deserves further study. The results of TIMI 7 lend support to the use of an antithrombin agent with aspirin in patients with unstable angina.\n          <\/jats:p>","DOI":"10.1161\/01.cir.92.4.727","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:34:42Z","timestamp":1339461282000},"page":"727-733","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":80,"title":["Hirulog in the Treatment of Unstable Angina"],"prefix":"10.1161","volume":"92","author":[{"given":"Joanna","family":"Fuchs","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham and Women\u2019s Hospital, Boston, Mass."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher P.","family":"Cannon","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Harvard Medical School, Brigham and Women\u2019s Hospital, Boston, Mass."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.53.4.363"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198610163151602"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.71.4.3971539"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(86)80455-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198610093151501"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(83)90059-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.77.6.3286036"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.89.4.8149520"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198308183090703"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198511283132201"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198810273191701"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)92336-G"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5242.1779"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(81)92399-0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.1986.tb07927.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)90407-V"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.88.5.8222097"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114723"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199105303242206"},{"key":"e_1_3_2_20_2","unstructured":"Maraganore JM Bourdon P Adelman B Cannon CP Theroux P. Heparin variability and resistance: comparisons with a direct thrombin inhibitor. Circulation. 1992;86(suppl I):I-386. Abstract."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00482a021"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.13.6040"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.4.1177"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1651573"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(93)90179-G"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.88.4.8403297"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(93)90823-U"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.87.5.8491018"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.90.1.8026048"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.89.4.1557"},{"key":"e_1_3_2_31_2","unstructured":"Cannon CP. Hirulog. In: Messerli FH ed. Cardiovascular Drug Therapy. Philadelphia Pa: WB Saunders Co. In press."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)81848-8"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2830893"},{"key":"e_1_3_2_34_2","first-page":"829","volume":"65","year":"1991","unstructured":"Maraganore JM, Chao BH, Weitz JI, Hirsh J. Comparison of antithrombin activities of heparin and hirulog-1: basis for improved antithrombotic properties of direct thrombin inhibitors. Thromb Haemost. 1991;65:829. Abstract.","journal-title":"Thromb Haemost"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","unstructured":"Maraganore JM. Pre-clinical and clinical studies on hirulog: a potent and specific direct thrombin inhibitor. In: Claeson G Scully MF Kakkar VV Deadman J eds. Design of Synthetic Inhibitors of Thrombin. New York NY: Plenum Press; 1993:227-236.","DOI":"10.1007\/978-1-4899-2418-6_20"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)90581-9"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.82.1.2194694"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.89.1.8281698"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(90)91155-Y"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.92.4.727","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T16:02:52Z","timestamp":1715529772000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.92.4.727"}},"subtitle":["Results of the Thrombin Inhibition in Myocardial Ischemia (TIMI) 7 Trial"],"short-title":[],"issued":{"date-parts":[[1995,8,15]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1995,8,15]]}},"alternative-id":["10.1161\/01.CIR.92.4.727"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.92.4.727","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,8,15]]},"assertion":[{"value":"1995-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1995-02-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1995-08-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}