Efficacy of statins in familial hypercholesterolaemia: a long term cohort study

Abstract

Objective: To determine the efficacy of statin treatment on risk of coronary heart disease in patients with familial hypercholesterolaemia.

Design: Cohort study with a mean follow-up of 8.5 years.

Setting: 27 outpatient lipid clinics.

Subjects: 2146 patients with familial hypercholesterolaemia without prevalent coronary heart disease before 1 January 1990.

Main outcome measures: Risk of coronary heart disease in treated and "untreated" (delay in starting statin treatment) patients compared with a Cox regression model in which statin use was a time dependent variable.

Results: In January 1990, 413 (21%) of the patients had started statin treatment, and during follow-up another 1294 patients (66%) started after a mean delay of 4.3 years. Most patients received simvastatin (n=1167, 33 mg daily) or atorvastatin (n=211, 49 mg daily). We observed an overall risk reduction of 76% (hazard ratio 0.24 (95% confidence interval 0.18 to 0.30), P<0.001). In fact, the risk of myocardial infarction in these statin treated patients was not significantly greater than that in an age-matched sample from the general population (hazard ration 1.44 (0.80 to 2.60), P=0.23).

Conclusion: Lower statin doses than those currently advised reduced the risk of coronary heart disease to a greater extent than anticipated in patients with familial hypercholesterolaemia. With statin treatment, such patients no longer have a risk of myocardial infarction significantly different from that of the general population.

Conflict of interest statement

Competing interests: None declared.

Figures

Fig 1 Flow of patients through study

Fig 2 Kaplan-Meier curve estimates of cumulative coronary heart disease-free survival among patients with familial hypercholesterolaemia according to statin treatment (P<0.001 for difference)

Fig 3 Subgroup analyses for reduction in risk of coronary heart disease in patients with familial hypercholesterolaemia by statin use in a time dependent analysis. Smoking, diabetes, and hypertension were compared based on having ever been present. LDL cholesterol concentration was split based on the median value, and HDL cholesterol level split based on normal laboratory values. Hazard ratio (95% CI) by statin use is shown on a logarithmic scale

Fig 4 Kaplan-Meier curve estimates of cumulative myocardial infarct-free survival among patients with familial hypercholesterolaemia older than 55 years according to statin treatment compared with a sample from the general population (Rotterdam study). (P<0.001 for difference between untreated patients and general population; P=0.07 for difference between treated patients and general population)