Severe familial hypercholesterolemia treatment

Czech version

Authors: Michal Vrablík ¹; Tomáš Freiberger ²; Vladimír Bláha ³; Richard Češka ¹
Authors‘ workplace: Centrum preventivní kardiologie III. interní kliniky 1. LF UK a VFN v Praze ¹; Genetická laboratoř Centra kardiovaskulární a transplantační chirurgie, Brno ²; III. interní gerontometabolická klinika LF UK a FN Hradec Králové ³
Published in: Vnitř Lék 2016; 62(11): 895-901
Category: Reviews

Overview

Familial hypercholesterolemia (FH) represents the most frequent of inborn errors of metabolism. It is a group of disorders with a codominant mode of inheritance characterized by marked elevations of LDL-cholesterol as well as atherosclerotic cardiovascular disease risk. Clinical (phenotypic) picture of FH varies widely depending on genotype and concomitant risk factors. Identification of most seriously affected FH individuals is necessary for proper clinical management. The therapeutic approach must be complex and comprehensive. The corner stone of pharmacotherapy is high-intensity statin therapy usually combined with ezetimibe (possibly complemented with bile acid sequestrant). Even this multi-drug combination do not lead majority of patients to their treatment goals. Thus, combinations with other pharmacological (PCSK9 inhibitors, apoB-100 anti-sense therapy, MTP inhibition) and non-pharmacological (LDL-apheresis, liver transplantation) approaches is being used.

Key words:
ezetimibe – LDL-apheresis – lomitapide – mipomersen – PCSK9 inhibitors – severe familial hypercholesterolemia – statins

Sources

1. Gidding SS, Champagne MA, de Ferranti SD et al. The agenda for familial hypercholesterolemia: a scientifi c statement from the American Heart Association. Circulation 2015; 132(22): 2167–2192. Dostupné z DOI: <http://dx.doi.org/10.1161/CIR.0000000000000297>.

2. Benn M, Watts GF, Tybjaerg-Hansen A et al Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol-lowering medica-tion. J Clin Endocrinol Metab 2012; 97(11): 3956–3964. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2012–1563>. Erratum in J Clin Endocrinol Metab. 2014; 99(12): 4758–4759.

3. Cuchel M, Bruckert E, Ginsberg HN et al. Homozy¬gous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management – a position paper from the Consensus Panel on Familial Hypercholestero¬laemia of the European Atherosclerosis Society. Eur Heart J 2014; 35(32): 2146–2157. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehu274>.

4. Nordestgaard BG, Chapman MJ, Humphries SE et al. Familial hypercholesterolaemia is underdiagno¬sed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J 2013; 34(45): 3478–3490a. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/eht273>.

5. Lahtinen AM, Havulinna AS, Jula A et al. Prevalence and clinical correlates of fa¬milial hypercholesterolemia founder mutations in the general population. Atherosclerosis 2015; 238(11): 64–69. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosis.2014.11.015>.

6. Neil A, Cooper J, Betteridge J et al. Reductions in all-cause, cancer,and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study. Eur Heart J 2008; 29(21): 2625–2633. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehn422>.

7. Austin MA, Hutter CM, Zimmern RL et al. Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am J Epidemiol 2004; 160(5): 421–429.

8. Besseling J, Kindt I, Hof M et al. Severe heterozygous familial hypercholesterolemia and risk for cardiovascular disease: a study of a cohort of 14 000 mutation carriers. Atherosclerosis 2014; 233(1): 219–223. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosis.2013.12.020>.

9. Langsted A, Kamstrup PR, Benn M et al. High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: a prospective cohort study. Lancet Diabetes Endocrinol 2016; 4(7): 577–587. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(16)30042–0>.

10. Yeboah J, McClelland RL, Polonsky TS et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA 2012; 308(8): 788–795. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2012.9624>.

11. Cho I, Chang HJ, Hartaigh BO et al. Incremental prognostic utility of coronary CT angiography for asymptomatic patients based upon extent and severity of coronary artery calcium: results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study. Eur Heart J 2015; 36(8): 501–508. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehu358>.

12. McClelland RL, Jorgensen NW, Budoff M et al. 10-year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) study and the DHS (Dallas Heart Study). J Am Coll Cardiol 2015; 66(15): 1643–1653. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2015.08.035>.

13. Santos RD, Gidding S, Hegele RA et al. Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel. Lancet Diabetes Endocrinol 2016; 4(10): 850–861. Dostupné z DOI: <http://dx.doi.org/10.1016/ S2213–8587(16)30041–9>.

14. Versmissen J, Oosterveer DM, Yazdanpanah M et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ 2008; 337: a2423. Dostupné z DOI: <http://dx.doi.org/10.1136/bmj.a2423>.

15. Pisciotta L, Fasano T, Bellocchio A et al. Effect of ezetimibe coadministered with statins in genotype-confirmed heterozygous FH patients. Atherosclerosis 2007; 194(2): e116-e122.

16. Raal FJ, Stein EA, Dufour R et al. (RUTHERFORD-2 Investigators). PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 385(9965): 331–340. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(14)61399–4>.

17. Kastelein JJ, Ginsberg HN, Langslet G et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J 2015; 36(43): 2996–3003. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehv370>.

18. Ginsberg HN, Rader DJ, Raal FJ et al. Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia and LDL-C of 160 mg/dl or Higher. Cardiovasc Drugs Ther 2016; 30(5): 473–483.

19. Santos RD, Watts GF. Familial hypercholesterolaemia: PCSK9 inhibitors are coming. Lancet 2015; 385(9965): 307–310. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(14)61702–5>.

20. Cuchel M, Bloedon LT, Szapary PO et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 2007; 356(2): 148–156.

21. Kastelein JJ, Wedel MK, Baker BF et al. Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation 2006; 114(16): 1729–1735.

22. Jovin IS, Taborski U, Muller-Berghaus G. Analysis of the long-term efficacy and selectivity of immunoadsorbtion columns for low density lipoprotein apheresis. ASAIO J 2000; 46(3): 298–300.

23. Schamberger BM, Geiss HC, Ritter MM et al. Influence of LDL apheresis on LDL subtypes in patients with coronary heart disease and severe hyperlipoproteinemia. J Lipid Res 2000; 41(5): 727–33.

24. Bláha V, Bláha M, Lánská M et al. LDL-aferéza: indikace, kontraindikace, klinický význam a vlastní zkušenosti. Hypertenze a kardiovaskulární prevence 2015; 4(1): 47–51.

25. Thompson GR. The evidence-base for the efficacy of lipoprotein apheresis in combating cardiovascular disease. Atheroscler Suppl 2013; 14(1): 67–70. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosissup.2012.10.001>.

26. Moriarty PM, Parhofer KG, Babirak SP et al. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J 2016. pii: ehw388. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehw388>.

27. Bruckert E, Blaha V, Stein EA et al. Abstract 17016: Trial Assessing Long-Term Use of PCSK9 Inhibition in patients with Genetic LDL Disorders (TAUSSIG): Efficacy and Safety in Patients with Familial Hypercholesterolemia Receiving Lipid Apheresis. Circulation 2014; 130: A17016. Dostupné z WWW: <http://circ.ahajournals.org/content/130/Suppl_2/A17016>.

28. Cannon CP, Blazing MA, Giugliano RP et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372(25): 2387–2397. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1410489>.