{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:37:52Z","timestamp":1792103872469,"version":"4.4.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2020,5,19]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Patients with acute coronary syndrome are at risk for peripheral artery disease (PAD) events and venous thromboembolism (VTE). PCSK9 (proprotein convertase subtilisin\/kexin type 9) inhibitors reduce lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C) levels. Our objective was to ascertain whether PCSK9 inhibition reduces the risk of PAD events or VTE after acute coronary syndrome, and if such effects are related to levels of lipoprotein(a) or LDL-C.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      This was a prespecified analysis of the ODYSSEY OUTCOMES randomized clinical trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome), which was conducted in 18\u2009924 patients with recent acute coronary syndrome on intensive or maximum-tolerated statin treatment who were randomized to the PCSK9 inhibitor alirocumab or placebo. In a prespecified analysis, PAD events (critical limb ischemia, limb revascularization, or amputation for ischemia) and VTE (deep vein thrombosis or pulmonary embolism) were assessed. LDL-C was corrected (LDL-C\n                      <jats:sub>corrected<\/jats:sub>\n                      ) for cholesterol content in lipoprotein(a).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      At baseline, median lipoprotein(a) and LDL-C\n                      <jats:sub>corrected<\/jats:sub>\n                      were 21 and 75 mg\/dL, respectively; with alirocumab, median relative reductions were 23.5% and 70.6%, respectively. PAD events and VTE occurred in 246 and 92 patients, respectively. In the placebo group, risk of PAD events was related to baseline quartile of lipoprotein(a) (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>trend<\/jats:sub>\n                      =0.0021), and tended to associate with baseline quartile of LDL-C\n                      <jats:sub>corrected<\/jats:sub>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>trend<\/jats:sub>\n                      =0.06); VTE tended to associate with baseline quartile of lipoprotein(a) (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>trend<\/jats:sub>\n                      =0.06), but not LDL-C\n                      <jats:sub>corrected<\/jats:sub>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>trend<\/jats:sub>\n                      =0.85). Alirocumab reduced risk of PAD events (hazard ratio [HR], 0.69 [95% CI, 0.54\u20130.89];\n                      <jats:italic>P<\/jats:italic>\n                      =0.004), with nonsignificantly fewer VTE events (HR, 0.67 [95% CI, 0.44\u20131.01];\n                      <jats:italic>P<\/jats:italic>\n                      =0.06). Reduction in PAD events with alirocumab was associated with baseline quartile of lipoprotein(a) (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>trend<\/jats:sub>\n                      =0.03), but not LDL-C\n                      <jats:sub>corrected<\/jats:sub>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>trend<\/jats:sub>\n                      =0.50). With alirocumab, the change from baseline to Month 4 in lipoprotein(a), but not LDL-C\n                      <jats:sub>corrected<\/jats:sub>\n                      , was associated with the risk of VTE and the composite of VTE and PAD events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In statin-treated patients with recent acute coronary syndrome, risk of PAD events is related to lipoprotein(a) level and is reduced by alirocumab, particularly among those with high lipoprotein(a). Further study is required to confirm whether risk of VTE is related to lipoprotein(a) level and its reduction with alirocumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT01663402.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.120.046524","type":"journal-article","created":{"date-parts":[[2020,3,29]],"date-time":"2020-03-29T09:13:50Z","timestamp":1585473230000},"page":"1608-1617","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":188,"title":["Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome"],"prefix":"10.1161","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2954-0695","authenticated-orcid":false,"given":"Gregory G.","family":"Schwartz","sequence":"first","affiliation":[{"name":"Division of Cardiology, University of Colorado School of Medicine, Aurora (G.G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe Gabriel","family":"Steg","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France (P.G.S.)."},{"name":"INSERM-1148, Paris, France (P.G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Szarek","sequence":"additional","affiliation":[{"name":"State University of New York, Downstate School of Public Health, Brooklyn (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera A.","family":"Bittner","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham (V.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Diaz","sequence":"additional","affiliation":[{"name":"Estudios Cardiol\u00f3gicos Latinoam\u00e9rica, Instituto Cardiovascular de Rosario, Argentina (R.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun G.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.)."},{"name":"St. Michael\u2019s Hospital, University of Toronto, ON, Canada (S.G.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Un","family":"Kim","sequence":"additional","affiliation":[{"name":"Sanofi, Paris, France (Y.-U.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Wouter","family":"Jukema","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, The Netherlands (J.W.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Pordy","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Tarrytown, NY (R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T.","family":"Roe","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (M.T.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey D.","family":"White","sequence":"additional","affiliation":[{"name":"Green Lane Cardiovascular Services Auckland City Hospital, New Zealand (H.D.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital Heart &amp; Vascular Center and Harvard Medical School, Boston, MA (D.L.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"For the ODYSSEY OUTCOMES Committees and Investigators*","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61249-0"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2014.03.290"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.11.1197"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/1358863X08089277"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.004519"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.035432"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.19.2481"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2015.08.044"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.11.024"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.07.037"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.165.16.1896"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.11.042"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.255521"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.08.77"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu107"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.719369"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH09-11-0772"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1053\/ejvs.2001.1431"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11789-019-00097-1"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH09-04-0274"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2012.02.008"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022157"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900241"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12056"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1598002"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149427"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.162.10.1182"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.303505"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu080"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.032235"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801174"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.10.057"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.03.013"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2014.07.028"},{"key":"e_1_3_5_36_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/B978-0-12-620990-7.50014-0","volume-title":"In: Lipoprotein(a)","author":"Dahlen GH","year":"1990","unstructured":"Dahlen, GH. 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