Effectiveness of combined statin plus omega-3 fatty acid therapy for mixed dyslipidemia

Abstract

Combination therapy for the treatment of dyslipidemia and reduction of cardiovascular risk has been demonstrated to beneficially modify the lipid profile in multiple randomized clinical trials. As reported in the updated National Cholesterol Education Program Adult Treatment Panel III guidelines, low-density lipoprotein (LDL) cholesterol remains the primary treatment target, although the comprehensive management of dyslipidemia in high-risk patients includes the modification of secondary lipid parameters such as triglycerides, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol. Although statin therapy is the standard intervention for lowering LDL cholesterol, combination therapy has demonstrated added benefits on secondary lipid parameters and enhances statin-mediated reductions in LDL cholesterol. The benefits of modifying these secondary targets on all-cause or cardiovascular event-related mortality are currently under investigation in several clinical trials. Prescription omega-3 fatty acid (Lovaza) is a formulation of 2 highly purified omega-3-acid ethyl esters, eicosapentaenoic acid and docosahexaenoic acid. The recently completed Combination of Prescription Omega-3 With Simvastatin (COMBOS) study confirmed that prescription omega-3 fatty acid administered in combination with simvastatin achieves statistically significant improvements across a range of lipid indicators beyond the LDL primary target, including triglycerides, non-high-density lipoprotein cholesterol, and lipoprotein particle size. In conclusion, several classes of drugs, including omega-3 fatty acids, can be used in combination with statins to achieve more global improvements in lipid profiles.

Figure 1

Meta-analysis of randomized controlled trials of the effect of OM3-FAs on lipid values. Studies are arranged by OM3-FA dose (grams per day). The point estimates of the net changes (change in OM3-FA arm minus change in control arm) and the corresponding 95% confidence intervals for individual studies are indicated by circles and bars. The random-effects model summary results are indicated by squares and bars near the bottom. Black circles indicate that data came from text or tables; open circles indicate that data were estimated from graphs; thick solid 95% confidence interval indicates that the SE of the net change was reported; thin solid 95% confidence interval indicates that the SE of net change was estimated from either baseline and final SEs or SEs of cohort changes; dashed 95% confidence interval indicates that the SE of net change was estimated from other sources. Quality: A = Least bias; study mostly adheres to the commonly held concepts of good quality, including formal randomized study, clear description of the population, setting, interventions, and comparison groups; appropriate measurement of outcomes; appropriate statistical and analytic methods and reporting; no reporting errors; <20% dropout; clear reporting of dropouts; and no obvious bias. B = Susceptible to some bias; study has some deficiencies but none likely to cause major bias or may be missing information making assessment of the limitations and potential problems difficult. C = Significant bias; study has serious errors in design, analysis, or reporting or may have large amount of missing information or discrepancies in reporting. Applicability: I = Sample is representative of the population of interest; sufficiently large to cover both genders, a wide age range, and other important features of the target population, including baseline dietary intake broadly similar to that of the United States population. II = Sample is representative of a relevant subgroup of the target population, but not the entire population. III = Sample is representative of a narrow subgroup of subjects only and not well applicable to other subgroups. ^*N = 119 for HDL cholesterol (HDL-C) and n = 75 for total cholesterol. ^†Initial dose given for 2 to 3 months, followed by lower dose for remainder of study. D = docosahexaenoic acid; E = eicosapentaenoic acid; ED = E + D; F = fish oil; LDL-C = LDL cholesterol. Reprinted with permission from Atherosclerosis.