Clinical Decision Support for Familial Hypercholesterolemia: a Cluster Randomized Trial in the Primary Care Setting

Familial Hypercholesterolemia (FH) is a common cause of premature coronary artery disease (CAD). The prevalence of heterozygous FH has been estimated to be 1 in 500, but recent studies estimate that the prevalence might be as high as 1 in 200. FH is an autosomal-dominant genetic disorder caused by defects in the hepatic uptake and degradation of LDL, primarily due to mutations in the genes coding for the LDL receptor, apolipoprotein B (APOB), proprotein convertase subtilisin kexin type 9 (PCSK9), or LDL-receptor associated protein 1 (LDLRAP1), resulting in high levels of LDL-C and total cholesterol . As a consequence, patients with heterozygous FH have a significantly increased risk of developing premature coronary artery disease (CAD).

FH is both underdiagnosed and undertreated, and it is estimated that only a few percent of patients are diagnosed adequately. In Sweden there are no official figures regarding the prevalence of FH, but the patient association for FH recently published a report estimating that only 21 % of the patients in Sweden have been diagnosed. Early treatment with lifestyle changes and high doses of statins has been shown to be effective in reducing the risk of cardiovascular disease, reducing the risk of CAD with 40 - 70 % or more in treated individuals as compared to not treated.

The diagnosis of FH has traditionally been based on a combination of clinical signs, family history and cholesterol concentrations. Recently more emphasis has been placed on genetic testing for establishing definitive diagnosis. In Sweden the long-term aim is to diagnose 80 % of all individuals with FH by 2025 according to the "National Guidelines for Cardiac Care 2015" published by The Swedish National Board of Health and Welfare.

Clinical decision support (CDS) systems have shown promising results in improving healthcare performance, but results are still conflicting and some studies have not been able to find any clear improvement in quality of care or patient outcomes. Computer-based CDS systems have previously been implemented to aid in the identification and management of patients with FH. The results from these studies are promising; however, to the best of our knowledge, no randomized controlled trial has been conducted investigating the effects of a computer-based CDS in FH.

Clinical decision support (CDS) systems are tools that can be used to raise awareness of specific conditions, leading to more individuals being diagnosed and treated in accordance to guidelines. Clinical decision support for Familial hypercholesterolemia (CDS-FH) is a cluster randomized trial that will be conducted in the primary care setting in the county of Östergötland, Sweden. The primary care clinics participating in the study will be randomized 1:1 to CDS intervention or to control. Before the study is initiated all of the physicians working at the participating primary care clinics will receive information regarding FH and the associated risk for cardiovascular disease. Information regarding the study, FH and technical aspects of CDS-FH will be available for the participating physicians throughout the entire study period. The investigators intend to include all primary care clinics in the County of Östergötland (n = 45). Participation is non-compulsory. The population in the County of Östergötland is 467 158 inhabitants (December 2020).