Key result
Moderate- to high-intensity statin therapy linked to ~44% lower risk of CAD events and mortality in HeFH.
Why the study?
The reduction in CAD events and mortality resulting from statin therapy had not been adequately quantified in patients with heterozygous familial hypercholesterolemia.
Does moderate- to high-intensity statin therapy reduce the composite of myocardial infarction, coronary revascularization, and all-cause mortality in adult patients with heterozygous familial hypercholesterolemia without prior coronary artery disease?
Cohort (n=1,559)
Does moderate- to high-intensity statin therapy reduce the composite of myocardial infarction, coronary revascularization, and all-cause mortality in adult patients with heterozygous familial hypercholesterolemia without prior coronary artery disease?
In adult patients with heterozygous familial hypercholesterolemia without baseline coronary artery disease, moderate- to high-intensity statin therapy was associated with a 44% reduction in the risk of coronary artery disease events and all-cause mortality.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“This is certainly an improvement, but a substantial residual risk remains in these patients compared with CAD event rates in their unaffected family members (29 per 100,000 person-years).”
“It was unkown to what extent statin therapy reduces the risk for coronary artery disease and mortality in patients with heterozygous familial hypercholesterolemia (FH). One previous study found that the relative risk reduction was 76%, but the study population in this study consisted of with a very severe FH phenotype. This result is therefore an overestimation of the risk reduction in the general heterozygous familial hypercholesterolemia population.”
“For instance, for all the negative press about statins, one of this study’s big conclusions is that, for FH patients, the most important potential ‘side effect’ of statins is increased longevity, and for those who cannot take statins or have elevated residual risk, we need to use other treatment modalities and work to remove barriers to care.”
May support statin use in FH; hypothesis-generating and should not yet change practice.
Background A statin-induced reduction of coronary artery disease (CAD) events and mortality has not been adequately quantified in patients with heterozygous familial hypercholesterolemia (FH). Objectives This study estimated the relative risk reduction for CAD and mortality by statins in heterozygous FH patients. Methods The authors included all adult heterozygous FH patients, identified by the Dutch screening program for FH between 1994 and 2013, who were free of CAD at baseline. Hospital, pharmacy, and mortality records between 1995 and 2015 were linked to these patients. The primary outcome was the composite of myocardial infarction, coronary revascularization, and death from any cause. The effect of statins (time-varying) was determined using a Cox proportional hazard model, while correcting for the use of other lipid-lowering therapy, thrombocyte aggregation inhibitors, and antihypertensive and antidiabetic medication. The authors applied inverse-probability-for-treatment weighting (IPTW) to account for differences at baseline between statin users and never-users. Results The authors obtained medical records of 2,447 patients, of whom 888 were excluded on the basis of age <18 years or previous CAD. Simvastatin 40 mg and atorvastatin 40 mg accounted for 23.1% and 22.8% of all prescriptions, respectively. Statin users (n = 1,041) experienced 89 CAD events and 17 deaths during 11,674 person-years of follow-up versus statin never-users (n = 518), who had 22 CAD events and 9 deaths during 4,892 person-years (combined rates 8.8 vs. 5.3 per 1,000 person-years, respectively; p < 0.001). After applying IPTW and adjusting for other medications, the hazard ratio of statin use for CAD and all-cause mortality was 0.56 (95% confidence interval: 0.33 to 0.96). Conclusions In patients with heterozygous FH, moderate- to high-intensity statin therapy lowered the risk for CAD and mortality by 44%. This is essential information in all cost-effectiveness studies of this disorder, such as when evaluating reimbursement of new lipid-lowering therapies.
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Besseling et al. (2016) conducted a cohort in Heterozygous familial hypercholesterolemia (n=1,559). Statin therapy (predominantly simvastatin 40 mg and atorvastatin 40 mg) vs. Statin never-users was evaluated on Composite of myocardial infarction, coronary revascularization, and death from any cause (HR 0.56, 95% CI 0.33-0.96, p=<0.001). Moderate- to high-intensity statin therapy lowered the risk of CAD events and all-cause mortality in heterozygous FH vs never-use (adjusted HR 0.56; 95% CI 0.33-0.96).
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