Original Research

Comparison of Cardiovascular Outcomes Between Statin Monotherapy and Fish Oil and Statin Combination Therapy in a Veteran Population

Andrew Bentz is a Clinical Pharmacy Specialist at the Loveland Colorado VA Clinic and was a Pharmacy Resident at the time of the study; Patrick Netland and Renae Schiele are Clinical Pharmacy Specialists; William Newman was Chief Endocrinologist at the time of the study and is now retired; and Lisa Froemke and Regan Miller are Physician Assistants; all at Fargo VA Health Care System in North Dakota.
Correspondence: Andrew Bentz (andrew. bentz@va.gov)

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.



There are no studies examining fish oil and statin therapy in the veteran population and only limited studies comparing statin and fish oil combination therapy vs statin monotherapy for adverse cardiovascular outcomes and all-cause mortality. One of the few comparison studies was by Macchia and colleagues and consisted of 7,924 post MI patients in Italy. Over a 4-year period, researchers found a slight improvement in the adjusted paired-matched population for all-cause mortality in the fish oil and statin therapy cohort vs statin monotherapy (8.6% vs 13.6% P < .001).3 A benefit also was seen in the fish oil and statin cohort vs statin monotherapy in the adjusted paired-matched population for death or stroke (16.7% vs 11.5% P < .001).3

In contrast, this study did not address postmyocardial infarction patients exclusively. Rather, patients in this study had lower morbidity, which resulted in fewer adverse cardiovascular outcomes and a greater difficulty to detect a difference in this healthier population. These healthier patients may derive less benefit from primary or secondary prevention with statin and fish oil combination therapy.

In this study, there were extensive inclusion and exclusion criteria to assess the relationship between the cohorts for adverse cardiovascular events caused by atherosclerotic disease. Veterans were required to take fish oil and statin therapy or statin monotherapy for at least 1 year. Other literature has only examined clinical impact on adverse cardiovascular event outcomes if therapy was a year or longer.7 Therefore, to prevent confounders from other medications, veterans who used any hyperlipidemia agent other than fish oil and statin therapy for longer than 1 year were excluded. Extensive exclusion criteria eliminated many veterans. However, the robust exclusion of clotting disorders, arrhythmias, chronic anticoagulation other than aspirin, hormonal medication use, or illegal substance abuse prevented the potential confounder of nonatherosclerotic adverse cardiovascular events, for example, a stroke due to poorly controlled atrial fibrillation.

Comparison of demographic data showed both cohorts were of similar age, sex, and race. Of note the Fargo veteran population was primarily white (> 80% in both cohorts). This is slightly higher than the percentage of whites for all US veterans. The slight difference most likely had a minimal clinical impact. Laboratory values recorded within 90 days of initiation of therapy were largely clinically similar except for triglycerides being significantly higher in the fish oil and statin combination cohort (Table 4). This may reflect selection bias, where providers may be more likely to add fish oil therapy for the potential to further control triglycerides.

Diagnoses of hypertension, heart failure, and dyslipidemia were higher in the statin monotherapy cohort. However, body mass index, tobacco use, and pancreatitis were statistically higher in fish oil and statin combination cohort. Even though there was a statistically significant difference in disease diagnoses, this likely created a minor clinical difference between the groups. This is further illustrated by the similarity of the Charlson Comorbidity Index of 1.6 for fish oil and statin cohort and 1.4 in statin monotherapy cohort.


A strength of this study was its adherence rates. Adherence rates were high in both cohorts (Table 6). Fish oil and statin cohort did have slightly lower adherence compared with that of statin monotherapy. This may demonstrate extra pill burden influencing adherence. Overall demographics, laboratory values, disease, and adherence rates were clinically similar in both cohorts, thus reducing the potential for confounders.

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