How low can you go? The lower the better, at least when it comes to low-density lipoprotein cholesterol (LDL-C). That’s according to new findings from the FOURIER-OLE study, which found the lowest rates of cardiovascular disease among individuals with the lowest LDL-C levels.
High LDL-C is a well-known cardiovascular disease risk factor, but cholesterol-lowering drugs like statins have been remarkably successful in helping people reduce their lipid levels. Currently, optimal LDL-C is considered to be under 100 mg/dL.
In FOURIER-OLE, researchers examined how reducing LDL-C to different levels below the optimal threshold impacted cardiovascular disease incidence. They examined a subset of 6,635 participants from the FOURIER study, which itself had 27,564 individuals who received either a placebo or Amgen’s cholesterol-lowering drug Repatha (evolocumab).
FOURIER-OLE researchers followed this subset of individuals for an additional five years to determine the relationship between LDL-C levels and major cardiovascular events, finding that:
- The rates of cardiovascular events tended to be lowest for those with the lowest LDL-C levels (<20 mg/dL).
- There was no statistically significant association between lower LDL-C levels and increased risk of safety outcomes from use of Repatha – which had been an issue in a recent reanalysis of FOURIER study data.
- Despite lowering cardiovascular events, Repatha use had no statistically significant impact on all-cause mortality.
The study and related Cardiology Twitter chatter raise a number of questions:
- Should established clinical guidelines for LDL-C be lowered even further to spread the benefits of lipid-lowering drugs to more individuals?
- If so, what would be the cost of such an expansion?
- How concerning is FOURIER-OLE’s lack of an impact on all-cause mortality?
The same chatter also revealed some lingering misconceptions about Repatha’s cost, which most seem to believe is still $14,000 annually. However, Repatha was reduced by 60% to $6,600 in 2018, bringing it in line with the standard of care.
In addition to reinforcing the benefits of lipid-lowering drugs, the new FOURIER-OLE findings revive the debate over the cost-effectiveness of population-based cardiovascular interventions. Sure, lower is better – but at what cost?