Abstract 5143: Efficacy Of Statins In Familial Hypercholesterolaemia: A Long Prospective Follow-up Study
Background Placebo-controlled statin trials were never undertaken in patients with familial hypercholesterolaemia (FH), since it was considered unethical to withhold therapy in the causal pathway of this disorder. We recently showed that simvastatin 80 mg daily resulted in normal IMT of FH patients (ENHANCE study), but we still lack estimates of the true efficacy of statin treatment with regards to coronary heart disease (CHD). We therefore decided to study the consequences of statin treatment in a large prospective cohort study, the next best option to a randomized controlled trial.
Methods We initiated follow-up in 2146 FH patients free of CHD on January 1, 1990, at the time statin therapy became available in the Netherlands. We then used the delay of statin initiation as a model for a clinical trial comparing treated and untreated FH patients, with statin use as a time dependent variable in a Cox regression analysis. In addition, we compared the risk of CHD between our FH cohort and the large population-based prospective Rotterdam Study.
Findings At baseline, 21% of the patients had started statin treatment versus 88% at the end of follow-up with a mean delay of 4.3 years. Most patients received simvastatin (n=1167, 33 mg daily) or atorvastatin (n=211, 49 mg daily) and exhibited an overall risk reduction of 76% (95% CI 0.18 – 0.30; p<0.001). The risk reduction in females was comparable to that in males. Treated FH patients and a cohort of the general population had nearly identical risks of myocardial infarction (HR 1.44, 95% CI 0.80 –2.60; p=0.23).
Conclusion Our data show that much lower statin dosages than currently advised result in impressive reductions of CHD risk in FH patients. These findings warrant an immediate start of statin therapy after the diagnosis of FH has been made and emphasize that the treatment of FH has witnessed profound changes leading to near normalisation of arterial wall thickness in recent studies and of CHD risk in our patients.