Insight into LDL Lowering and Cardiovascular Events from Trials
Explore the implications of LDL lowering trials on cardiovascular events, including evidence from studies like GLAGOV, IVUS, and IMPROVE-IT. Discover how lipid drugs and therapies such as ezetimibe impact atheroma volume and secondary prevention post-ACS, shaping recommendations for managing cardiovascular risk.
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Presentation Transcript
LOOKING TO FOURIER: LOOKING TO FOURIER: What do the trials tell us What do the trials tell us about LDL lowering and about LDL lowering and cardiovascular events? cardiovascular events?
NICE CG 181 Continuum of CVD Risk and its treatment Acute coronary syndrome (ACS) Atorva 80mg (+ Eze 10mg) Post MI/Angina Atorva 80mg Secondary Prevention Other Atherosclerotic Manifestations Atorva 80mg Subclinical Atherosclerosis: Type 2 diabetes Atorva 20+ mg Primary Prevention Lifestyle then Atorva 20mg Multiple RFs QRISK>10% Low Risk Lifestyle Courtesy of CD Furberg.; modified to include NICE CG181
GLAGOV: Mean On-Treatment LDL-C vs. Change in PAV Locally Weighted Polynomial Regression (LOESS) Plot with 95% confidence limits Change Percent Atheroma Volume (%) On-Treatment LDL-C (mg/dL)
IVUS studies: Change in atheroma volume vs. LDL-C 2.5 y = 0.0004x2 + 0.0448x + 0.715 R = 0.39 Change in atheroma volume (%) 2 REVERSAL- P 1.5 y = 0.0256x + 0.7217 R = 0.36 1 0.5 REVERSAL- A 0 -70 -60 -50 -40 -30 -20 -10 0 10 20 -0.5 METEOR SATURN- A -1 GLAGOV-E SATURN- R -1.5 Change in LDL-C (%)
Meta-analyses of CHD vs LDL-C and Incremental effects of lipid drugs Cholesterol Treatment Trialists; Lancet 2010; 376: 1670 Charland SL & Stanek EJ; Pharmacother 2014; 34 : 452
IMPROVE IT : Ezetimibe in statin-treated ACS Lipids Events 20 10 4.20 1.35 1.10 2.46 (1.80) P=0.01 P=0.002 p=0.95 Change (%) 0 -10 1.40 -20 p=0.01 -30 Secondary prevention; n= 18144 Cannon CP et al ; NEJM 2015; 372 : 2387
Defining recommendations Targets Drug-based Consistent with trials Exception limits defined Common trial design Novel output Focused on overall risk Consistent with epidemiology Rare in clinical trials Traditional output Focused on single risk factor Set on 50th centile Requires multiple monitoring Centile-independent Minimal monitoring required
