Effectiveness and Safety of Lipid-Lowering Drug Treatments in Japanese Patients with Familial Hypercholesterolemia: Familial Hypercholesterolemia Expert Forum (FAME) Study.

Autor:	Yamashita S; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.; Department of Community Medicine, Osaka University Graduate School of Medicine.; ＊Department of Cardiology, Rinku General Medical Center, Izumisano., Masuda D; Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.; ＊＊Rinku Innovation Center for Wellness Care and Activities (RICWA), Health Care Center, Department of Cardiology, Rinku General Medical Center., Harada-Shiba M; Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute., Arai H; The National Center for Geriatrics and Gerontology., Bujo H; Department of Clinical Laboratory and Experimental Research Medicine, Toho University, Sakura Medical Center., Ishibashi S; Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University., Daida H; Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine., Koga N; Shin Koga Hospital., Oikawa S; Diabetes and Lifestyle-related Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association (JATA).
Jazyk:	angličtina
Zdroj:	Journal of atherosclerosis and thrombosis [J Atheroscler Thromb] 2022 May 01; Vol. 29 (5), pp. 608-638. Date of Electronic Publication: 2021 May 13.
DOI:	10.5551/jat.62764
Abstrakt:	Aims: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high serum levels of low-density lipoprotein (LDL)-cholesterol (LDL-C), tendon and skin xanthomas, and premature coronary artery disease (CAD). In Japan, detailed information on the current status of drug therapies for patients with FH has not been reported so far, and their efficacy and safety have not been clarified. After the introduction of ezetimibe, which can further reduce serum LDL-C levels on top of statins, the changes of management for FH patients with these drugs are of particular interest. The current study aimed to evaluate the clinical status of FH heterozygotes and homozygotes, especially focusing on the real-world lipid-lowering drug therapy, attained serum LDL-C levels, and cardiovascular events at registration and during the follow-up. Methods: The FAME Study enrolled 762 heterozygous (including 17 newly diagnosed cases) and 7 homozygous FH patients from hospitals and clinics nationwide. Diagnosis of FH was based upon the criteria defined in the Study Report in 2008 of the Research Committee on Primary Hyperlipidemia supported by Grants-in-Aid for Scientific Research from the Japanese Ministry of Health, Labor and Welfare. Data analysis was primarily carried on heterozygous FH patients. Results: Xanthoma or thickening of the Achilles tendon was observed in more than 80% of the patients. CAD was recorded in 23% of patients. Patients with parental and sibling CAD accounted for 47% and 24%, respectively. At baseline, patients without CAD who had LDL-C ＜100 mg/dL accounted for 12.3% and those with CAD who had attained the target (LDL-C ＜70 mg/dL) in the secondary prevention accounted for only 1.8%. In the multiple logistic analysis, male sex, age ＞40, heterozygous FH score ＞20, hypertension, and sibling CAD were significantly and positively associated with prevalent CAD, whereas serum HDL-cholesterol levels showed a significant inverse association with CAD. Patients treated with statin alone, statin＋ezetimibe, statin＋resin, or statin＋probucol accounted for 31.1%, 26.3%, 4.0%, and 3.7%, respectively. Patients treated with three-drug combination (statin＋ezetimibe＋resin or statin＋ezetimibe＋probucol) accounted for 7.5%. Statins and ezetimibe were used in 88.0% and 48.0% at the baseline, respectively. Although high-intensity statins were mainly prescribed, statin doses were much lower than those reported in Western countries. The addition of ezetimibe resulted in ~20% reduction in serum LDL-C. CAD was diagnosed in 17 patients with 21 episodes during follow-up. The Cox hazard model analysis demonstrated that male sex, CAD at the baseline, and parental CAD were related to the development of atherosclerotic cardiovascular disease (ASCVD) events. Furthermore, an increase in serum HDL-C was associated with a significant reduction of ASCVD events, while serum LDL-C and triglyceride levels were not related to ASCVD events. Conclusion: The prevalence of CAD in Japanese patients with heterozygous FH is still very high. In most of the cases, the target level of serum LDL-C was not achieved for primary and secondary prevention of CAD, suggesting that a more aggressive LDL-C lowering and appropriate management of residual risks are necessary.
Databáze:	MEDLINE
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