Date of Award

Spring 2020

Degree Name

Master of Medical Science (Physician Assistant)

Department

Physician Assistant; College of Health Sciences

First Advisor

Zachary T. Weik, MHS, PA-C

Abstract

Introduction: Coronary artery disease (CAD) is a chronic medical condition caused by the buildup of plaque within the coronary artery endothelium. If left untreated it can progress to an acute coronary syndrome (ACS) which can lead to myocardial ischemia and death. Statins are lipid lowering agents used in clinical practice for the medical management of CAD. However, incidence of major adverse cardiovascular (CV) events still occurs despite optimal statin therapy. Currently eicosapentaenoic acid (EPA) has been promoted to be effective when added to statin therapy in lowering the incidence of CV events in patients with hypercholesterolemia. This paper will address the efficacy of adding EPA to statin therapy compared to statins alone to prevent the progression of CAD to ACS in adults over 45.

Methods: A literature search was completed utilizing PubMed and ClinicalKey in November 2018. A total of seven randomized control trials were selected based on publication date, outcome measurements, and relevance to the research question.

Results: Based on the literature review, there is evidence for the use of adjunct EPA in the primary prevention of ACS in patients with CAD. All seven studies demonstrated a reduction in the progression of baseline disease through measurements of various outcome measures. One study concluded that addition of EPA helps to decrease the pro-inflammatory marker pentraxin-3, which is associated with arterial inflammation. Other studies utilized various imaging techniques to determine coronary plaque stability in those receiving EPA. This was evidenced by significant reductions in fibrous plaque volume, increases in fibrous cap thickness, and reductions in macrophage accumulation. Significant improvements in flow mediated vasodilation and arterial stiffness through reduction of oxidative stress were also found by two other studies in participants taking the combination EPA and statin therapy. Only one study however found a significant decrease in CV events in participants taking EPA. Meanwhile, no significant increase in CV events was reported in any of the seven studies.

Discussion: While all seven articles had positive results for the use of adjunct EPA to statin therapy in patients with CAD, each study had limitations in its design that hindered its overall validity. Inadequate recruitment strategies and the use of an open label design in all seven articles introduces the possibility for bias. All but one study was conducted in Japan, where consumption of fish is about five times greater than the United States, which may have also skewed the results. Longer treatment timelines, and larger, more representative sample sizes are also points of emphasis for future studies to consider for improvement.

Conclusion: The seven articles analyzed in this meta-analysis all highlight statistically significant results of adjunct EPA to statin therapy in the treatment of CAD. While these articles also show that addition of EPA produces minimal risk to increasing morbidity and mortality, the validity of these results, along with the differences noted between the subjects and the actual targeted patient population limit its clinical significance. Thus, a recommendation cannot be made at this time for a change in the standard clinical practice for the treatment of CAD. These results however indicate adjunct EPA as a viable treatment option in the future and further research is warranted to investigate its potential role.

Additional Files

Poster Presentation.mp4 (19060 kB)
Poster Presentation Video

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The Efficacy of Adding Eicosapentaenoic Acid to Statin Monotherapy in the Prevention of Acute Coronary Syndrome in Patients with Coronary Artery Disease

Introduction: Coronary artery disease (CAD) is a chronic medical condition caused by the buildup of plaque within the coronary artery endothelium. If left untreated it can progress to an acute coronary syndrome (ACS) which can lead to myocardial ischemia and death. Statins are lipid lowering agents used in clinical practice for the medical management of CAD. However, incidence of major adverse cardiovascular (CV) events still occurs despite optimal statin therapy. Currently eicosapentaenoic acid (EPA) has been promoted to be effective when added to statin therapy in lowering the incidence of CV events in patients with hypercholesterolemia. This paper will address the efficacy of adding EPA to statin therapy compared to statins alone to prevent the progression of CAD to ACS in adults over 45.

Methods: A literature search was completed utilizing PubMed and ClinicalKey in November 2018. A total of seven randomized control trials were selected based on publication date, outcome measurements, and relevance to the research question.

Results: Based on the literature review, there is evidence for the use of adjunct EPA in the primary prevention of ACS in patients with CAD. All seven studies demonstrated a reduction in the progression of baseline disease through measurements of various outcome measures. One study concluded that addition of EPA helps to decrease the pro-inflammatory marker pentraxin-3, which is associated with arterial inflammation. Other studies utilized various imaging techniques to determine coronary plaque stability in those receiving EPA. This was evidenced by significant reductions in fibrous plaque volume, increases in fibrous cap thickness, and reductions in macrophage accumulation. Significant improvements in flow mediated vasodilation and arterial stiffness through reduction of oxidative stress were also found by two other studies in participants taking the combination EPA and statin therapy. Only one study however found a significant decrease in CV events in participants taking EPA. Meanwhile, no significant increase in CV events was reported in any of the seven studies.

Discussion: While all seven articles had positive results for the use of adjunct EPA to statin therapy in patients with CAD, each study had limitations in its design that hindered its overall validity. Inadequate recruitment strategies and the use of an open label design in all seven articles introduces the possibility for bias. All but one study was conducted in Japan, where consumption of fish is about five times greater than the United States, which may have also skewed the results. Longer treatment timelines, and larger, more representative sample sizes are also points of emphasis for future studies to consider for improvement.

Conclusion: The seven articles analyzed in this meta-analysis all highlight statistically significant results of adjunct EPA to statin therapy in the treatment of CAD. While these articles also show that addition of EPA produces minimal risk to increasing morbidity and mortality, the validity of these results, along with the differences noted between the subjects and the actual targeted patient population limit its clinical significance. Thus, a recommendation cannot be made at this time for a change in the standard clinical practice for the treatment of CAD. These results however indicate adjunct EPA as a viable treatment option in the future and further research is warranted to investigate its potential role.

 
 

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