Fixed-dose combinations in dyslipidemy treatment

Authors: M. Vráblík
Authors‘ workplace: Centrum preventivní kardiologie, III. interní klinika 1. LF UK a VFN v Praze
Published in: Kardiol Rev Int Med 2016, 18(2): 98-103


Combination pharmacotherapy is frequently being used in patients at high cardiovascular risk due to an accumulation of risk factors. Potential and real drug-drug interactions represent one of the important barriers to implementing guideline-recommended treatment strategies, but even more important might be decreasing adherence. One of the most feasible options seems to be fixed-dose combinations that have been used for the treatment of arterial hypertension and diabetes for some time. There are a few fixed-dose combinations of lipid lowering drugs currently available, such as the statin + ezetimibe combo and, more recently, statin + fenofibrate. The option of fixed-dose combinations of a lipid lowering agent with another representative drug class will soon become available. This will result in a simplification of drug regime, leading to better adherence to pharmacological treatment and a consequent reduction of residual cardiovascular risk.

statins –  fibrates –  ezetimibe –  antihypertensives –  fixed-dose combinations –  residual risk –  dyslipidemia


1. Catapano AL, Reiner Z, De Backer G et al. ESC/ EAS Guidelines for the management of dyslipidaemias. Atherosclerosis 2011; 217: 3– 46.

2. Perk J, De Backer G, Gohlke H et al. European Guide­lines on cardiovascular disease prevention in clinical practice (version 2012). The fifth joint task force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur Heart J 2012; 33: 1635– 1701. doi: 10.1093/ eurheartj/ ehs092.

3. Makani H, Bangalore S, Romero J et al. Ef­fect of renin-angiotensin system blockade on calcium chan­nel blocker-as­sociated peripheral edema. Am J Med 2011; 124: 128– 135. doi: 10.1016/ j.amjmed.2010.08.007.

4. Filipovský J, Widimský J jr., Ceral J et al. Dia­gnostické a léčebné postupy u arteriální hypertenze –  verze 2012. Doporučení České společnosti pro hypertenzi. Vnitř Lék 2012; 58: 785– 801.

5. Hatala R, Pel­la D, Hatalová K et al. Optimization of blood pres­sure treatment with fixed-combination perindopril/ amlodipine in patients with arterial hypertension. Clin Drug Investig 2012; 32: 603– 612. doi: 10.2165/ 11634530-000000000-00000.

6. Varbo A, Benn M, Nordestgaard BG. Remnant cholesterol as a cause of ischemic heart disease: evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment. Pharmacol Ther 2014; 141: 358– 367. doi: 10.1016/ j.pharmthera.2013.11.008.

7. Nordestgaard BG, Wootton R, Lewis B. Selective retention of VLDL, IDL, and LDL in the arterial intima of genetical­ly hyperlipidemic rabbits in vivo. Molecular size as a determinant of fractional loss from the intima-in­ner media. Arterioscler Thromb Vasc Biol 1995; 15: 534– 542.

8. Varbo A, Benn M, Tybjærg-Hansen A et al. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013; 61: 427– 436. doi: 10.1016/ j.jacc.2012.08.1026.

9. Nordestgaard BG, Chapman MJ, Humphries SE et al. Familial hypercholesterolemia is underdia­g­­-nosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease. Eur Heart J 2013; 34: 3478– 3890. doi: 10.1093/ eurheartj/ eht273.

10. Bruckert E, Hayem G, Dejager S et al. Mild to moderate muscular symp­toms with high-dosage statin therapy in hyperlipidemic patients-the PRIMO study. Cardiovasc Drugs Ther 2005; 19: 403– 414.

11. Barter P, Gotto AM, LaRosa JC et al. HDL cholesterol, very low levels of LDL cholesterol and cardiovascular events. N Engl J Med 2007; 357: 1301– 1310.

12. The ACCORD Study Group and ACCORD Eye Study Group. Ef­fects of combination lipid therapy in type 2 diabetes mel­litus. N Engl J Med 2010; 363: 233– 244. doi: 10.1056/ NEJMoa1001288.

13. Vrablík M. Není statin jako statin aneb jeden dělá to a co ten druhý? Practicus 2012; 6: 13– 15.

14. Davidson MH, Bal­lantyne CM, Kerzner B et al. Ef­ficacy and safety of ezetimibe coadministered with statins: randomised, placebo-control­led, blinded experience in 2382 patients with primary hypercholesterolemia. Int J Clin Pract 2004; 58: 746– 755.

15. Can­non CP, Blaz­ing MA, Giugliano RP et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015; 372: 2387– 2397. doi: 10.1056/ NEJMoa1410489.

16. Roth EM, Rosenson RS, Jones PH et al. Attainment of goal/ desirable lipid levels in patients with mixed dyslipidemia after 12 weeks of treatment with fenofibric acid and rosuvastatin combination ther­apy: a pooled analysis of control­led studies. J Clin Lipidol 2012; 6: 534– 544. doi: 10.1016/ j.jacl.2012.02.002.

17. Ginsberg HN, Elam MB, Lovato LC et al. ACCORD Study Group. Ef­fects of combination lipid therapy in type 2 diabetes mel­litus. N Engl J Med 2010; 362: 1563– 1574. doi: 10.1056/ NEJMoa1001282.

18. Vrablík M. Studie ACCORD lipid: první data o vlivu kombinace statinu s fibrátem na výskyt příhod. Remedia 2010; 20: 44– 46.

19. Scott R, O’Brien R, Fulcher G et al. Ef­fects of fenofibrate treatment on cardiovascular disease risk in 9795 individuals with type 2 diabetes and various components of the metabolic syndrome. Diabetes Care 2009; 32: 493– 498. doi: 10.2337/ dc08-1543.

20. Chew EY, Ambrosius WT, Davis MD et al. The ACCORD Study Group and ACCORD Eye Study Group. Ef­fects of combination lipid therapy in type 2diabetes mel­litus. N Engl J Med 2010; 363: 233– 244. doi: 10.1056/ NEJMoa1001288.

21. Cha KH, Cho KJ, Kim MS et al. Enhancement of the dis­solution rate and bio­availability of fenofibrate by a melt-adsorption method us­ing supercritical carbon dioxide. Int J Nanomedicine 2012; 7: 5565– 5575. doi: 10.2147/ IJN.S36939.

22. Foucher C, Aubon­net P, Reichert P et al. Cholib study Investigators. New fixed-dose combinations of fenofibrate/ simvastatin therapy significantly improve the lipid profile of high-risk patients with mixed dyslipidemia versus monotherapies. Cardiovasc Ther 2015; 33: 329– 337. doi: 10.1111/ 1755-5922.12148.

23. Noonan JE, Jenkins AJ, Ma JX et al. An update on the molecular actions of fenofibrate and its clinical ef­fects on diabetic retinopathy and other microvascular end points in patients with diabetes. Diabetes 2013; 62: 3968– 3975. doi: 10.2337/ db13-0800.

24. Saha SA, Arora RR. Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mel­litus –  a pooled metaanalysis of randomized placebo-control­led clinical trials. Int J Cardiol 2010; 141: 157– 166. doi: 10.1016/ j.ijcard.2008.11.211.

25. Jun M, Foote C, Lv J et al. Ef­fects of fibrates on cardiovascular outcomes: review and meta-analysis. Lancet 2010; 375: 1875– 1884. doi: 10.1016/ S0140-6736(10)60656-3.

26. Vrablík M. Reziduální riziko kardiovaskulárních příhod. Medicína po promoci 2009; 10: 60– 64.

27. Sever PS, Dahlöf B, Poulter NR et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial– Lipid Lower­ing Arm (ASCOT-LLA): a multicentre randomised control­led trial. Lancet 2003; 361: 1149– 1158.

28. Chapman RH, Ben­ner JS, Petril­la AA et al. Predictors of adherence with antihypertensive and lipid-lower­ing therapy. Arch Intern Med 2005; 165: 1147– 1152.

29. Sever P, Dahlöf B, Poulter N et al. Potential synergy between lipid-lower­ing and blood-pres­sure lower­ing in the Anglo-Scandinavian Cardiac Outcomes Trial. Eur Heart J 2006; 27: 2982– 2988.

30. Yusuf S, Lonn E, Pais P et al. HOPE-3 Investigators. Blood-pres­sure and cholesterol lower­ing in persons without cardiovascular disease. N Engl J Med 2016. In pres­s.

Paediatric cardiology Internal medicine Cardiac surgery Cardiology
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