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Atherosclerosis driven by high LDL-C is the underlying cause of CVD2

Over the past decades, a wealth of evidence has definitively established that LDL-C has a causal role in the development of atherosclerotic CVD.2
Atherogenesis is a multi-step process that begins early in life.3 Unstable or ruptured plaques occlude blood flow and increase the risk of CV events;4 early and aggressive treatment of elevated LDL-C and atherosclerosis may therefore reduce the risk of CV events.5

Progression of atherosclerosis3

Figure adapted from Pepine 1998.
LDL-C is a major modifiable risk factor for CVD2
Abnormal lipids are the single most important risk factor for acute myocardial infarction, accounting for ~50% of the total risk.6

Population-attributable risks associated with six risk factors for MI*6

*Data from the INTERHEART case-control study of acute myocardial infarction (15,152 cases, 14,820 controls) in 52 countries worldwide. Population-attributable risks were calculated for the following comparisons: Smoking: current vs never; diet: daily consumption of fruit and vegetables, yes vs no; exercise: regular moderate or strenuous physical exercise, yes vs no; history of hypertension, yes vs no; history of diabetes, yes vs no; lipids: ApoB/ApoA1 ratio, top vs bottom quintile.
In the study, 2690 recent MI patients received Repatha®, 2254 of whom achieved LDL-C levels <55 mg/dl.
25% RRR reported as the key secondary endpoint: composite of cardiovascular death, MI or stroke. HR: 0.75; 95% CI: 0.62-0.91; p=0.003. ARR: 3.2%; 95% CI: 1.2-5.2.
ACS = Acute coronary syndrome; ARR = Absolute risk reduction; CV = Cardiovascular; CVD = Cardiovascular disease; EAS = European Atherosclerosis Society; ESC = European Society of Cardiology; EVOPACS = EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes; LDL-C = Low-density lipoprotein cholesterol; MI = Myocardial infarction; PCSK9 = Protein convertase subtilisin/kexin type 9; RRR = Relative risk reduction.
  1. European Cardiovascular Disease Statistics 2017. Fifth Edition: February 2017. European Heart Network, Brussels.
  2. Ference BA. Eur Heart J. 2017;38:2459-72.
  3. Pepine CJ. Am J Cardiol. 1998;82(10A):23S-27S.
  4. Ross R. N Engl J Med. 1999;340:115-26.
  5. Okazaki S, et al. Circulation. 2004;110:1061-8.
  6. Yusuf S, et al. Lancet. 2004;364:937-52.
  7. Gencer B, et al. JAMA Cardiol. 2020;5(8):1-6. Main paper & Supplementary appendix.

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