Per cent reduction LDL-C following statins is directly related to CVD incidenceRidker PM, et al. Eur Heart J 2016
Per cent reduction in LDL cholesterol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents
Ridker PM, Mora S and Rose L
Eur Heart J 2016; published online ahead of print
BackgroundIt has recently been shown that the percentage reduction of low-density lipoprotein cholesterol (LDL-C) following statin therapy is highly variable between individuals . This observation may impact future statin therapy guidelines. Currently, statin guidelines differ between Europe and Canada, and the US. Whereas Europe and Canada accept to achieve a fixed low-density LDL-C level or to decrease LDL-C levels with at least 50% [2,3], US guidelines allow a reduction of less than 50% when moderate intensity statin therapy is administered or ≥50% when high intensity statin therapy is given . The variability in per cent LDL-C reduction may have impact on clinical outcome as well as on the effectiveness of PCSK9 inhibitors, since enrolment criteria for PCSK9 inhibitors typically include the attainments of fixed LDL-C levels on statin therapy.
To address the effect of the LDL-C reduction variability on clinical outcome, a secondary data analysis was performed using data derived from the Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial . LDL-C reduction as well as non-HDL-C and apolipoprotein B (apoB) reduction levels were assessed and related to cardiovascular events.
The JUPITER randomized trial of rosuvastatin 20 mg (high-intensity) versus placebo enrolled 17802 asymptomatic woman ≥60 years and men ≥50 years who had LDL-C levels <130 mg/dL, hsCRP >2.0 mg/L and triglycerides <500 mg/dL with 5 years follow-up . Individuals with prior history of cardiovascular disease, diabetes or lipid-lowering therapy were excluded. The interquartile range of lipid levels at baseline was relatively narrow (LDL-C 94-119, non-HDL-C 118-147, apoB 95-122 mg/dL and median 108, 134, 109 mg/dL respectively).
Main resultsThe magnitude of per cent reductions in lipids was directly related to the incidence rates of first cardiovascular events:
Groups assigned: reduction ≥50%, 0-50%, none or increase
- Per cent individuals (within those allocated to rosuvastatin): 46.3%, 42.8%, 10,8% respectively
- Incidence rates: Respectively 9.2, 6.7, 4.8 per 1000 individuals. Placebo 11.2
- On-treatment reduction HR: 0.91; CI 95%: 0.54-1.53, HR: 0.61; CI 95%: 0.44-0.83, HR: 0.42; CI 95%: 0.30-0.60 respectively (compared to placebo group), P-trend <0.00001
- Adjusted for covariates (including lower baseline lipid levels): HR: 0.86; CI 95% 0.50-1.49, HR: 0.61; CI 95% 0.44-0.83, HR: 0.41; CI 95% 0.29-0.58 respectively (compared to placebo group), P-trend <0.00001
- There was a significant relationship between per cent cholesterol reduction and incident event rates, within individuals allocated to rosuvastatin, P =0.01
- Similar analyses of percentage non-HDL-C and apoB reduction showed comparable results
- Similar findings were obtained using tertiles of per cent LDL-C reduction for group assignment
- Analyses that were limited to individuals within specific on-treatment achieved LDL-C windows (50-75 mg/dL) lead to a similar conclusion
ConclusionThe variability in per cent reduction of LDL-C, non-HDL-C and apoB following statin therapy is wide between individuals. The magnitude of these reductions is directly related to this of risk reduction. The percentage LDL-C reduction may be considered for inclusion into statin therapy guidelines as well as for enrolment criteria regarding adjunctive lipid-lowering PCSK9 inhibitors, in addition to absolute lipid targets. PCSK9 inhibitors may be clinically less effective in individuals with a highly reduced percentage LDL-C following statin therapy, and vice versa.
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