Physicians' Academy for Cardiovascular Education

Greater benefit of statin therapy in those with inherited high LDL, suggests 4S

News - May 28, 2019

More statin benefit in people with likely genetic vulnerability to high levels of bad cholesterol: new analysis from the Scandinavian Simvastatin Survival Study (4S)

Presented at EAS 2019 in Maastricht, The Netherlands, by Antonio J. Vallejo-Vaz (Imperial College, London, UK).

Introduction and methods

Individuals with familial hypercholesterolemia (FH) are at high risk of coronary events, such as heart attack, as a consequence of their long-term exposure to high LDL-c levels. The absolute CV risk of these individuals is therefore higher than in people who develop hypercholesterolemia during adult life, but who do not have a clinical history suggestive of FH.

The ‘Scandinavian Simvastatin Survival Study’ or 4S study was the first landmark trial to demonstrate the benefit of statin treatment in patients with established heart disease and high cholesterol levels (between 5.5-8.0 mmol/L or about 200-300 mg/dL) on a lipid-lowering diet. As this benefit depends on absolute cardiovascular risk, baseline LDL-C level and the absolute reduction in LDL-C levels, this suggests that patients with likely FH who have longer lifetime exposure to high LDL-C levels may gain more from LDL-C lowering with a statin.

In the current analysis of 4S data, individuals were categorized according to baseline LDL-c (<4.9 mmol/L or ≥4.9 mmol/L) and those with high LDL-c levels were further divided based on the presence or absence of (premature) CAD in the individual and/or a family history of CAD, suggestive of inherited high cholesterol.

Main results


A new analysis of the 4S data shows that people with characteristics suggestive of FH, i.e. the combination of high LDL-c, premature heart disease and a family history of heart disease, gain greater clinical benefit from statin therapy. In these patients, statin therapy lowered the risk of all-cause mortality by more than 80%, and the risk of recurrent MI was halved. This is the first randomized trial evidence in secondary prevention that suggests that statin therapy reduces CVD events in those with an FH phenotype.

Our reporting is based on the information provided at the EAS 2019 congress

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