{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:51:52Z","timestamp":1790819512308,"version":"4.1.0"},"reference-count":34,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"<jats:sec id=\"ab-hoi230039-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>The association between changes in atherosclerotic plaque induced by lipid-lowering therapies (LLTs) and reduction in major adverse cardiovascular events (MACEs) remains controversial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230039-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the association between coronary plaque regression assessed by intravascular ultrasound (IVUS) and MACEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230039-6\">\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>A comprehensive, systematic search of publications in PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230039-7\">\n                    <jats:title>Study Selection<\/jats:title>\n                    <jats:p>Clinical prospective studies of LLTs reporting change in percent atheroma volume (PAV) assessed by IVUS and describing MACE components were selected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230039-8\">\n                    <jats:title>Data Extraction and Synthesis<\/jats:title>\n                    <jats:p>Reporting was performed in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The association between mean change in PAV and MACEs was analyzed by meta-regression using mixed-effects, 2-level binomial logistic regression models, unadjusted and adjusted for clinical covariates, including mean age, baseline PAV, baseline low-density lipoprotein cholesterol level, and study duration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230039-9\">\n                    <jats:title>Main Outcome and Measures<\/jats:title>\n                    <jats:p>Mean PAV change and MACE in intervention and comparator arms were assessed in an updated systematic review and meta-regression analysis of IVUS trials of LLTs that also reported MACEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230039-10\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This meta-analysis included 23 studies published between July 2001 and July 2022, including 7407 patients and trial durations ranging from 11 to 104 weeks. Mean (SD) patient age ranged from 55.8 (9.8) to 70.2 (7.6) years, and the number of male patients from 245 of 507 (48.3%) to 24 of 26 (92.3%). Change in PAV across 46 study arms ranged from \u22125.6% to 3.1%. The number of MACEs ranged from 0 to 72 per study arm (17 groups [37%] reported no events, 9 [20%] reported 1-2 events, and 20 [43%] reported \u22653 events). In unadjusted analysis, a 1% decrease in mean PAV was associated with 17% reduced odds of MACEs (unadjusted OR, 0.83; 95% CI, 0.71-0.98;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.03), and with a 14% reduction in MACEs in adjusted analysis (adjusted OR, 0.86; 95% CI, 0.75-1.00;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.050). Further adjustment for cardiovascular risk factors showed a 19% reduced risk (adjusted OR, 0.81; 95% CI, 0.68-0.96;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.01) per 1% decrease in PAV. A 1% reduction of PAV change between intervention and comparator arms within studies was also associated with a significant 25% reduction in MACEs (OR, 0.75; 95% CI, 0.56-1.00;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.046).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230039-11\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this meta-analysis, regression of atherosclerotic plaque by 1% was associated with a 25% reduction in the odds of MACEs. These findings suggest that change in PAV could be a surrogate marker for MACEs, but given the heterogeneity in the outcomes, additional data are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamacardio.2023.2731","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T11:34:14Z","timestamp":1693395254000},"page":"937","source":"Crossref","is-referenced-by-count":56,"title":["Atherosclerotic Coronary Plaque Regression and Risk of Adverse Cardiovascular Events"],"prefix":"10.1001","volume":"8","author":[{"given":"Iulia","family":"Iatan","sequence":"first","affiliation":[{"name":"Centre for Heart Lung Innovation, Department of Medicine, St Paul\u2019s Hospital, Providence Health Care, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijiao","family":"Guan","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Improved Cardiovascular Health, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin H.","family":"Humphries","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Improved Cardiovascular Health, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunice","family":"Yeoh","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Centre for Cardiovascular Innovation, Cardiovascular Imaging Research Core Laboratory, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. B. John","family":"Mancini","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Centre for Cardiovascular Innovation, Cardiovascular Imaging Research Core Laboratory, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"key":"hoi230039r1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpc.2022.100366","article-title":"Intensive lipid lowering agents and coronary atherosclerosis: insights from intravascular imaging.","volume":"11","author":"Di Giovanni","year":"2022","journal-title":"Am J Prev Cardiol"},{"issue":"24","key":"hoi230039r2","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1016\/j.jacc.2010.05.059","article-title":"Does carotid intima-media thickness regression predict reduction of cardiovascular events? a meta-analysis of 41 randomized trials.","volume":"56","author":"Costanzo","year":"2010","journal-title":"J Am Coll Cardiol"},{"key":"hoi230039r3","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.atherosclerosis.2019.03.005","article-title":"Coronary atheroma regression and adverse cardiac events: a systematic review and meta-regression analysis.","volume":"284","author":"Bhindi","year":"2019","journal-title":"Atherosclerosis"},{"issue":"21","key":"hoi230039r4","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1016\/j.jacc.2010.02.026","article-title":"Intravascular ultrasound-derived measures of coronary atherosclerotic plaque burden and clinical outcome.","volume":"55","author":"Nicholls","year":"2010","journal-title":"J Am Coll Cardiol"},{"issue":"18","key":"hoi230039r5","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1001\/jama.2022.5218","article-title":"Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infarction.","volume":"327","author":"R\u00e4ber","year":"2022","journal-title":"JAMA"},{"issue":"7","key":"hoi230039r6","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1016\/j.jcmg.2022.03.002","article-title":"Effect of evolocumab on coronary plaque phenotype and burden in statin-treated patients following myocardial infarction.","volume":"15","author":"Nicholls","year":"2022","journal-title":"JACC Cardiovasc Imaging"},{"issue":"11","key":"hoi230039r7","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1253\/circj.CJ-09-0358","article-title":"Effect of rosuvastatin on coronary atheroma in stable coronary artery disease: multicenter Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects (COSMOS).","volume":"73","author":"Takayama","year":"2009","journal-title":"Circ J"},{"issue":"13","key":"hoi230039r8","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1001\/jama.295.13.jpc60002","article-title":"Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial.","volume":"295","author":"Nissen","year":"2006","journal-title":"JAMA"},{"issue":"7","key":"hoi230039r9","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1253\/circj.CJ-15-1379","article-title":"Effects of 4 statins on regression of coronary plaque in acute coronary syndrome.","volume":"80","author":"Matsushita","year":"2016","journal-title":"Circ J"},{"issue":"7","key":"hoi230039r10","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.jcin.2009.04.016","article-title":"Effect of fluvastatin on progression of coronary atherosclerotic plaque evaluated by virtual histology intravascular ultrasound.","volume":"2","author":"Nasu","year":"2009","journal-title":"JACC Cardiovasc Interv"},{"issue":"9","key":"hoi230039r11","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1161\/01.CIR.0000140261.58966.A4","article-title":"Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH study.","volume":"110","author":"Okazaki","year":"2004","journal-title":"Circulation"},{"issue":"4","key":"hoi230039r12","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.jacc.2009.04.033","article-title":"Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: a multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome] study).","volume":"54","author":"Hiro","year":"2009","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"hoi230039r13","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1253\/circj.CJ-17-0598","article-title":"Effects of ezetimibe-statin combination therapy on coronary atherosclerosis in acute coronary syndrome.","volume":"82","author":"Hibi","year":"2018","journal-title":"Circ J"},{"issue":"9","key":"hoi230039r14","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1001\/jamacardio.2018.2121","article-title":"Effect of serial infusions of CER-001, a pre-\u00df high-density lipoprotein mimetic, on coronary atherosclerosis in patients following acute coronary syndromes in the CER-001 atherosclerosis regression acute coronary syndrome trial: a randomized clinical trial.","volume":"3","author":"Nicholls","year":"2018","journal-title":"JAMA Cardiol"},{"issue":"10","key":"hoi230039r15","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1253\/circj.CJ-19-0412","article-title":"Effect of alirocumab on coronary atheroma volume in Japanese patients with acute coronary syndrome-the ODYSSEY J-IVUS trial.","volume":"83","author":"Ako","year":"2019","journal-title":"Circ J"},{"issue":"4","key":"hoi230039r16","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1161\/hc2901.093188","article-title":"Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease.","volume":"104","author":"Schartl","year":"2001","journal-title":"Circulation"},{"issue":"9","key":"hoi230039r17","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1001\/jama.291.9.1071","article-title":"Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial.","volume":"291","author":"Nissen","year":"2004","journal-title":"JAMA"},{"issue":"2","key":"hoi230039r18","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.ahj.2011.11.004","article-title":"Statin treatment for coronary artery plaque composition based on intravascular ultrasound radiofrequency data analysis.","volume":"163","author":"Nozue","year":"2012","journal-title":"Am Heart J"},{"issue":"11","key":"hoi230039r19","doi-asserted-by":"publisher","first-page":"2662","DOI":"10.1253\/circj.CJ-12-0325","article-title":"Virtual histology findings and effects of varying doses of atorvastatin on coronary plaque volume and composition in statin-naive patients: the VENUS study.","volume":"76","author":"Lee","year":"2012","journal-title":"Circ J"},{"issue":"3","key":"hoi230039r20","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1536\/ihj.14-311","article-title":"Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in patients with coronary artery disease.","volume":"56","author":"Masuda","year":"2015","journal-title":"Int Heart J"},{"issue":"5","key":"hoi230039r21","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.jacc.2015.05.065","article-title":"Impact of dual lipid-lowering strategy with ezetimibe and atorvastatin on coronary plaque regression in patients with percutaneous coronary intervention: the multicenter randomized controlled PRECISE-IVUS trial.","volume":"66","author":"Tsujita","year":"2015","journal-title":"J Am Coll Cardiol"},{"issue":"8","key":"hoi230039r22","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1016\/j.amjcard.2016.01.013","article-title":"Comparison of the effect of rosuvastatin 2.5 mg vs 20 mg on coronary plaque determined by angioscopy and intravascular ultrasound in Japanese with stable angina pectoris (from the Aggressive Lipid-Lowering Treatment Approach Using Intensive Rosuvastatin for Vulnerable Coronary Artery Plaque [ALTAIR] randomized trial).","volume":"117","author":"Takayama","year":"2016","journal-title":"Am J Cardiol"},{"key":"hoi230039r23","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.amjcard.2021.05.039","article-title":"Effect of atorvastatin (10 mg) and ezetimibe (10 mg) combination compared to atorvastatin (40 mg) alone on coronary atherosclerosis.","volume":"154","author":"Oh","year":"2021","journal-title":"Am J Cardiol"},{"issue":"21","key":"hoi230039r24","doi-asserted-by":"publisher","first-page":"2004","DOI":"10.1056\/NEJMra1216063","article-title":"Mechanisms of acute coronary syndromes and their implications for therapy.","volume":"368","author":"Libby","year":"2013","journal-title":"N Engl J Med"},{"issue":"January","key":"hoi230039r25","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.atherosclerosis.2023.01.017","article-title":"Impact of lipid lowering on coronary atherosclerosis moving from the lumen to the artery wall.","volume":"367","author":"Di Giovanni","year":"2023","journal-title":"Atherosclerosis"},{"issue":"13","key":"hoi230039r26","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1056\/NEJMoa070635","article-title":"Effect of torcetrapib on the progression of coronary atherosclerosis.","volume":"356","author":"Nissen","year":"2007","journal-title":"N Engl J Med"},{"issue":"22","key":"hoi230039r27","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1056\/NEJMoa1110874","article-title":"Effect of two intensive statin regimens on progression of coronary disease.","volume":"365","author":"Nicholls","year":"2011","journal-title":"N Engl J Med"},{"issue":"22","key":"hoi230039r28","doi-asserted-by":"publisher","first-page":"2373","DOI":"10.1001\/jama.2016.16951","article-title":"Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial.","volume":"316","author":"Nicholls","year":"2016","journal-title":"JAMA"},{"issue":"11","key":"hoi230039r29","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1161\/ATVBAHA.114.303932","article-title":"Antiatherosclerotic effects of long-term maximally intensive statin therapy after acute coronary syndrome: insights from study of coronary atheroma by intravascular ultrasound: effect of rosuvastatin versus atorvastatin.","volume":"34","author":"Puri","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"13","key":"hoi230039r30","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1016\/j.jacc.2015.01.036","article-title":"Impact of statins on serial coronary calcification during atheroma progression and regression.","volume":"65","author":"Puri","year":"2015","journal-title":"J Am Coll Cardiol"},{"issue":"4","key":"hoi230039r31","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1093\/ehjci\/jet251","article-title":"Long-term effects of maximally intensive statin therapy on changes in coronary atheroma composition: insights from SATURN.","volume":"15","author":"Puri","year":"2014","journal-title":"Eur Heart J Cardiovasc Imaging"},{"issue":"5","key":"hoi230039r32","doi-asserted-by":"publisher","first-page":"H619","DOI":"10.1152\/ajpheart.00036.2012","article-title":"A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture.","volume":"303","author":"Maldonado","year":"2012","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"1","key":"hoi230039r33","doi-asserted-by":"publisher","first-page":"120","DOI":"10.21037\/cdt","article-title":"Assessing the impact of PCSK9 inhibition on coronary plaque phenotype with optical coherence tomography: rationale and design of the randomized, placebo-controlled HUYGENS study.","volume":"11","author":"Nicholls","year":"2021","journal-title":"Cardiovasc Diagn Ther"},{"issue":"6","key":"hoi230039r34","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.jjcc.2017.07.007","article-title":"A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins.","volume":"70","author":"Watanabe","year":"2017","journal-title":"J Cardiol"}],"container-title":["JAMA Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/articlepdf\/2809089\/jamacardiology_iatan_2023_oi_230039_1695753711.77692.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T11:12:10Z","timestamp":1697022730000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/fullarticle\/2809089"}},"subtitle":["A Systematic Review and Updated Meta-Regression Analysis"],"short-title":[],"issued":{"date-parts":[[2023,10,1]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamacardio.2023.2731","relation":{},"ISSN":["2380-6583"],"issn-type":[{"value":"2380-6583","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10,1]]}}}