{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:32:15Z","timestamp":1792524735704,"version":"4.5.0"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2018,7,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The combination of statin therapy and PCSK9 (proprotein convertase subtilisin\/kexin type 9) inhibition markedly lowers low-density lipoprotein cholesterol (LDL-C) and reduces cardiovascular event rates. Whether residual inflammatory risk as measured by on-treatment high sensitivity C-reactive protein (hsCRP) remains an important clinical issue in such patients is uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We evaluated residual inflammatory risk among 9738 patients participating in the SPIRE-1 and SPIRE-2 cardiovascular outcomes trials (Studies of PCSK9 Inhibition and the Reduction in Vascular Events), who were receiving both statin therapy and bococizumab, according to on-treatment levels of hsCRP (hsCRP\n                      <jats:sub>OT<\/jats:sub>\n                      ) and LDL-C\n                      <jats:sub>OT<\/jats:sub>\n                      measured 14 weeks after drug initiation. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      At 14 weeks, the mean percentage change in LDL-C among statin-treated patients who additionally received bococizumab was \u221260.5% (95% confidence interval [CI], \u221261.2 to \u221259.8;\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001; median change, \u221265.4%) as compared to 6.6% (95% CI, \u22121.0 to 14.1;\n                      <jats:italic>P<\/jats:italic>\n                      =0.09; median change, 0.0%) for hsCRP. Incidence rates for future cardiovascular events for patients treated with both statin therapy and bococizumab according to hsCRP\n                      <jats:sub>OT<\/jats:sub>\n                      &lt;1, 1 to 3, and &gt;3 mg\/L were 1.96, 2.50, and 3.59 events per 100 person-years, respectively, corresponding to multivariable adjusted hazard ratios of 1.0, 1.16 (95% CI, 0.81\u20131.66), and 1.62 (95% CI, 1.14\u20132.30) (\n                      <jats:italic>P<\/jats:italic>\n                      -trend=0.001) after adjustment for traditional cardiovascular risk factors and LDL-C\n                      <jats:sub>OT<\/jats:sub>\n                      . Comparable adjusted hazard ratios for LDL-C\n                      <jats:sub>OT<\/jats:sub>\n                      (&lt;30, 30\u201350, &gt;50 mg\/dL) were 1.0, 0.87, and 1.21, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      -trend=0.16). Relative risk reductions with bococizumab were similar across hsCRP\n                      <jats:sub>OT<\/jats:sub>\n                      groups (\n                      <jats:italic>P<\/jats:italic>\n                      -interaction=0.87).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In this post hoc analysis of the SPIRE trials of bococizumab in a stable outpatient population, evidence of residual inflammatory risk persisted among patients treated with both statin therapy and proprotein convertase subtilisin-kexin type 9 inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial 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 identifiers: NCT01975376, NCT01975389.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.118.034645","type":"journal-article","created":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T05:20:12Z","timestamp":1525152012000},"page":"141-149","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":232,"title":["Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy"],"prefix":"10.1161","volume":"138","author":[{"given":"Aruna D.","family":"Pradhan","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, VA Boston Healthcare System, West Roxbury Campus, MA (A.D.P.)."},{"name":"Division of Preventive Medicine (A.D.P., A.W.A., L.M.R., P.M.R.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron W.","family":"Aday","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine (A.D.P., A.W.A., L.M.R., P.M.R.)"},{"name":"Department of Medicine, Division of Cardiovascular Medicine (A.W.A., P.M.R.), Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda M.","family":"Rose","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine (A.D.P., A.W.A., L.M.R., P.M.R.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M","family":"Ridker","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine (A.D.P., A.W.A., L.M.R., P.M.R.)"},{"name":"Department of Medicine, Division of Cardiovascular Medicine (A.W.A., P.M.R.), Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.9.839"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200106283442601"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042000"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042378"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.628909"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60447-5"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr310"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw024"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.310527"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615664"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1701488"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2014.07.028"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2016.05.010"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000148980.87579.5E"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0807646"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.033254"},{"key":"e_1_3_3_19_2","unstructured":"Tardif JC L\u2019Allier P. Montreal Heart Institute. Colchicine Cardiovascular Outcomes Trial (COLCOT). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02551094. Accessed March 8 2017."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2013.03.018"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1614062"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx450"},{"key":"e_1_3_3_23_2","volume-title":"American College of Cardiology Annual Scientific Session","author":"Steg P","unstructured":"Steg, P. The ODYSSEY outcomes trial: topline results. 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