Statin Therapy Lowered Coronary Artery Disease Risk in Familial Hypercholesterolemia

Moderate-to-high intensity statin therapy lowered the risk of coronary artery disease (CAD) and mortality in patients with heterozygous familial hypercholesterolemia, according to data published in the Journal of the American College of Cardiology.

Joost Besseling, MD, of the Department of Vascular Medicine at the Academic Medical Center in Amsterdam, and colleagues set out to determine the relative risk reduction of CAD and mortality using statins.

A total of 1559 patients with heterozygous familial hypercholesterolemia, but free of CAD at baseline were selected from “the linkage between the database of the national FH [familial hypercholesterolemia] cascade screening program in the Netherlands and the Pharmo Record Linkage System (RLS).”

Dr Besseling and colleagues describe the Pharmo RLS as a “patient-centric data network of multiple health care databases. Relevant databases for our study include the national registries on mortality and hospitalization (Dutch National Medical Registration), as well as in- and outpatient pharmacies, representing virtually complete longitudinal follow-up of patients since January 1, 1995.”

Patients were prescribed either simvastatin (40 mg) or atorvastatin (40 mg). The primary outcome was a composite end point of first hospitalization for a CAD event and all-cause mortality.

Among the statin users (n=1041), there were 89 CAD events and 17 deaths during 11 674 person-years of follow-up compared to patients who had never used statins (n=518) who had 22 CAD events and 9 deaths during 4892 person-years. The combined rates were 8.8 vs 5.3 per 1000 person-years, respectively (P<.001).

In addition, when applying the inverse-probability-for-treatment weighting, 72 statin users had a CAD event vs 37 “never-users,” and 31 statin users died during 5412 patient-years (event rates 7.5 per 1000 patient-years vs 11.9 per 1000 patient-years, respectively; P=.002).

The hazard ratio (HR) of statin use for CAD and all-cause mortality was 0.56 (95% confidence interval [CI]: 0.33-0.96), after adjusting for other medications and applying the inverse-probability-for-treatment weighting.

Using Cox proportional hazards models, statin use was associated with an increased risk for CAD and all-cause mortality in the unweighted model (HR: 1.65; 95% CI: 1.06-2.57). However, using a stabilized inverse-probability-for-treatment model, the risk decreased (HR: 0.62; 95% CI: 0.37-1.04).

In addition, after adjustment for other cardioprotective medications, statins were found to be protective for CAD and all-cause mortality in the unweighted model (HR: 0.96; 95% CI: 0.58-1.59). In the weighted model, this effect was even more pronounced (HR: 0.56; 95% CI: 0.33-0.96). Ultimately, statin therapy lowered the risk for CAD and all-cause mortality by approximately 44%.

“The increased risk for premature CAD in heterozygous FH, in conjunction with its high prevalence of around 1:250, has an important impact on public health,” the authors concluded. “Moreover it is estimated that 80% of these patients will not reach LDL-cholesterol levels <100 mg/dL despite efficacious therapy.”

They encouraged future studies to evaluate patients with familial hypercholesterolemia in other countries to determine if this risk reduction can be generalized to other populations.

Disclosures: Dr Kastelein has received consulting fees or honoraria from Aegerion, Amgen, AstraZeneca, Boehringer Ingelheim, Catabasis, Cerenis, Cymabay, CSL Behring, Dezima Pharmaceuticals, Eli Lilly, Esperion, Gemphire, ISIS, The Medicines Company, MSD, Novartis, Pfizer, Pronova, Regeneron, Sanofi, and UniQur.

Reference

Besseling J, Hovingh GK, Huijgen R, Kastelein JJP, Hutten BA. Statins in familial hypercholesterolemia. Consequences for coronary artery disease and all-cause mortality. J Am Coll Cardiol. 2016;68(3):252-260. doi: 10.1016/j.jacc.2016.04.054.