Long-term up to 24-month efficacy and safety of concomitant prescription omega-3-acid ethyl esters and simvastatin in hypertriglyceridemic patients.
OBJECTIVE
Assess the long-term efficacy and safety of prescription omega-3-acid ethyl esters (P-OM3) coadministered with simvastatin in an extension of the Combination of Prescription Omega-3 Plus Simvastatin (COMBOS) trial.


METHODS
COMBOS included hypertriglyceridemic patients (triglyceride [TG] >or=200 mg/dL and <500 mg/dL or >or=2.26 mmol/L and <5.64 mmol/L) with low density lipoprotein cholesterol (LDL-C) level no greater than 10% above the National Cholesterol Education Program, Adult Treatment Panel III treatment goal. After an 8-week lead-in phase with simvastatin 40 mg/day (which continued throughout the trial), subjects were randomized to 8 weeks of P-OM3 4 g/day or placebo. Completers were eligible to participate in a 24-month extension study. Those who received placebo + simvastatin in COMBOS switched to open-label P-OM3 + simvastatin ('Switchers'); those who received P-OM3 + simvastatin during COMBOS continued the same regimen (open-label) in the extension phase ('Non-switchers'). The primary endpoint was the difference between Non-switchers and Switchers in median percent change in non-high-density lipoprotein-cholesterol (non-HDL-C) from COMBOS end of treatment to Month 4 of the extension phase.


RESULTS
At Month 4 from COMBOS end of treatment, non-HDL-C was reduced by a median of 9.4% in Switchers and increased by 0.9% in Non-switchers (p < 0.001). For the total population (combined Non-switcher + Switcher population), the median percent change from COMBOS baseline to Months 4, 12, and 24 was -8.3%, -7.3%, and -8.9%, respectively (all p < 0.001). This extension study revealed no unexpected safety findings. A limitation of this study was a gap between completion of COMBOS and enrollment in the extension phase for some patients; however, a post-hoc non-HDL-C sensitivity analysis performed at the 4-month primary endpoint revealed no influence of gap on study results.


CONCLUSIONS
In this 24-month extension study, P-OM3 was generally well tolerated, and produced sustained reductions in non-HDL-C levels in simvastatin-treated patients with TG levels between 200 and 500 mg/dL (2.26 mmol/L and 5.64 mmol/L).


BACKGROUND
NCT00903409.
Bays
Harold E
HE
Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, USA. HBaysMD@aol.com
Maki
Kevin C
KC
McKenney
James
J
Snipes
Rose
R
Meadowcroft
Amy
A
Schroyer
Rosemary
R
Doyle
Ralph T
RT
Stein
Evan
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects
D000924:Anticholesteremic Agents; D015525:Fatty Acids, Omega-3; D019821:Simvastatin