statin and fish oil combination therapy

Last edited 11/2018 and last reviewed 08/2021

• prescription omega-3 acid ethyl esters (P-OM3) are commonly used for treatment of very high triglyceride levels, often in combination with a statin, to lower persistent hypertriglyceridemia
• statins and omega-3 fatty acids affect lipids through distinct mechanisms
  • P-OM3 primarily reduces the number and triglyceride content of VLDL particles secreted by the liver
    • omega-3 fatty acids are believed to influence triglyceride metabolism by decreasing triglyceride synthesis (through inhibition of acyl-coenzyme A:1,2 diacylglycerol acyltransferase), increasing hepatic fatty acid oxidation, and increasing triglyceride clearance (through increased lipoprotein lipase activity)
    • reductions in non-HDL-C with P-OM3 result mainly from lowering the concentrations of cholesterol carried by VLDL and other TG-rich lipoproteins
    • statins appear to lower non-HDL-C concentrations by increasing hepatic uptake of both LDL and TGrich lipoprotein particles
      • statins principally lower LDL cholesterol by inhibiting the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, which increases hepatic uptake of cholesterol by increasing LDL receptors
      • thus, the combination of omega-3 fatty acids plus a statin appears to have additive and complementary effects to reduce entry of TG-rich lipoproteins into the circulation (P-OM3 effect) and increase hepatic uptake of Apo B-containing lipoproteins (statin effect)
• a small 6 week study revealed that:
  • non-HDL cholesterol decreased from baseline (209 mg/dl) by 40% for P-OM3 + simvastatin compared with 34% for placebo + simvastatin (p <0.001)
  • favorable changes for P-OM3 + simvastatin versus placebo + simvastatin were also observed for very low-density lipoprotein (VLDL) cholesterol (-42% vs -22%), triglyceride (-44% vs -29%), total cholesterol (-31% vs -26%), HDL cholesterol (+16% vs +11%), apolipoprotein B (-32% vs -28%), total cholesterol:HDL cholesterol ratio (-39% vs -33%), triglyceride:HDL cholesterol ratio (-51% vs -37%), and systolic (-5.0 vs 0.3 mm Hg) and diastolic (-3.3 vs -1.8 mm Hg) blood pressures (p <0.05 for all)
    • because statins and P-OM3 act through distinct mechanisms, their combination is likely to have additive and complementary effects on lipid metabolism
    • P-OM3 + simvastatin produced greater decreases from baseline in systolic and diastolic blood pressures than simvastatin monotherapy
  • VLDL particle concentration and size decreased and LDL particle size increased significantly more with P-OM3 + simvastatin than with placebo + simvastatin (all p <0.05)
  • changes in LDL cholesterol, LDL particle concentration, HDL particle size and concentration, and apolipoprotein A-I did not differ significantly between treatments
  • findings from the present trial confirm previous results showing that non-HDL cholesterol is reduced with P-OM3 treatment when administered as monotherapy or when added to a statin
    • decrease in non-HDL cholesterol results mainly from lowering of concentrations of cholesterol carried by VLDL and other triglyceride-rich lipoproteins (intermediate-density lipoproteins and chylomicron remnants)
  • the authors concluded that P-OM3 + simvastatin appears to be a useful therapeutic option for the management of mixed dyslipidemia

Reference:

• 1. Effects of adding prescription omega-3 acid ethyl esters to simvastatin (20 mg/day) on lipids and lipoprotein particles in men and women with mixed dyslipidemia. Maki KC, McKenney JM, Reeves MS, Lubin BC, Dicklin MR. Am J Cardiol. 2008 Aug 15;102(4):429-33. Epub 2008 May 22. Erratum in: Am J Cardiol. 2008 Nov 15;102(10):1425.