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Why?<\/jats:p>\n          <jats:p>Atherosclerosis begins early in life, yet clinical trials and mechanistic studies often emphasize terminal, end-stage plaques, meaning on the verge of causing heart attacks and strokes. Thus, current clinical evidence drives us to emphasize aggressive treatments that are delayed until patients already have advanced arterial disease. I call this paradigm \u201ctoo much, too late.\u201d<\/jats:p>\n          <jats:p>This brief review covers exciting efforts that focus on preventing, or finding and treating, arterial disease before its end-stage. Also included are specific proposals to establish a new evidence base that could justify intensive short-term interventions (induction-phase therapy) to treat subclinical plaques that are early enough perhaps to heal. If we can establish that such plaques are actionable, then broad screening to find them in early midlife individuals would become imperative\u2014and achievable. You have a lump in your coronaries! can motivate patients and clinicians.<\/jats:p>\n          <jats:p>We must stop thinking of a heart attack as a disease. The real disease is atherosclerosis. In my opinion, an atherosclerotic heart attack is a medical failure. It is a manifestation of longstanding arterial disease that we had allowed to progress to its end-stage, despite knowing that atherosclerosis begins early in life and despite the availability of remarkably safe and highly effective therapies.<\/jats:p>\n          <jats:p>The field needs a transformational advance to shift the paradigm out of end-stage management and into early interventions that hold the possibility of eradicating the clinical burden of atherosclerotic cardiovascular disease, currently the biggest killer in the world. We urgently need a new evidence base to redirect our main focus from terminal, end-stage atherosclerosis to earlier, and likely reversible, human arterial disease.<\/jats:p>","DOI":"10.1161\/atvbaha.123.320065","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T05:00:35Z","timestamp":1700110835000},"page":"48-64","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Eradicating Atherosclerotic Events by Targeting Early Subclinical Disease: It Is Time to Retire the Therapeutic Paradigm of Too Much, Too Late"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0000-2159","authenticated-orcid":true,"given":"Kevin Jon","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Sciences, Department of Medicine, Lewis Katz School of Medicine at Temple University, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e3182285a81"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000678"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz455"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39553.670231.25"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2021.1810"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2021.1980777"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.48030"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2021.4987"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.122.317963"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circoutcomes.122.009787"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2023-000908"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1976.tb43368.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.14.2.177"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000174795.62387.d3"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio1086"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.04.023"},{"key":"e_1_3_3_18_2","unstructured":"Thomas L. 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