PracticeUpdate: Cardiology | Vol1 - No.2 - 2016

CORONARY HEART DISEASE

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Benefits of omega-3 fatty acids from fish oil after acute MI: an off and on affair? Comment by Paul Thompson, MD I was pleasantly surprised by the

death via a fish oil effect on cardiac arrhythmia. Subsequent studies were less supportive of a beneficial effect of fish oil on cardiac arrhyth- mias and on AMI treatment in general. The OMEGA-REMODEL trial suggests that concentrated fish oil may have a beneficial effect on cardiac remodelling, and it offers a different possibility for GISSI’s success. OMEGA-REMODEL is a relatively small study, but well- designed and well-performed and suggests that cardiology’s affair with fish oil may be on again. So what are clinicians to do? This study was well-done, but it is premature to translate these promising results directly into patient care. We do not yet know whether these putative improve- ments in myocardial function and

fibrosis from concentrated fish oil, 4 gm daily, will have clinical significance. A larger, clinical out- comes study will be required before concentrated fish becomes standard of care. Some patients may learn of these results and start themselves on fish oil. Clinicians and such pa- tients should be aware that the fish oil preparation used in this study was highly concentrated, similar to the brand compound Omacor. Over-the-counter fish oil capsules have approximately one-third of the omega-3 fatty acids available in the concentrated products; so, over-the- counter fish oil would not provide the dose used in this study without taking 12 tablets daily.

change in non-infarct myocardial fibrosis (r = 0.65; P < 0.0001). The authors speculated that the omega-3 fatty acids decreased inflammation in the non-infarcted myocardium, thereby preserving LV function. Modern cardiology has had an on/off affair with concentrated fish oil. The GISSI, or Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico, study as- signed 11,324 AMI patients to 1 gm daily of omega-3 fatty acids or placebo in an open-label design. The patients receiving fish oil had a 20% reduction in mortality, which many attributed to a reduction in sudden

recently released results of the Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction, or OMEGA-REMODEL trial. The study randomised patients with documented acute myocardial in- farction (AMI) treated by acute an- gioplasty to either placebo (n=178) or 4 gm daily of concentrated fish oil using tablets containing ≈ 465 mg of ethyl esters of eicosapentae- noic acid (EPA) and ≈ 375 mg of docosahexaenoic acid (DHA). The placebo contained corn oil with ≈ 600 mg linoleic acid, no omega-3 fatty acids, and <0.05% of trans-fatty acids. Participants started treatment 14 to 28 days after their AMI and were treated for 6 months. Cardiac magnetic resonance imaging (cMRI) was performed at baseline and at 6 months to measure cardiac function and structure. Studies were read by blinded readers. There was high adherence to guideline-based treat- ment for AMI. Patients treated with the concen- trated fish oil had a 5.8% decrease in their left ventricular systolic volume index (LVSVI; P = 0.017) and 5.6% less fibrosis in their non- infarcted myocardium. Those with the greatest increase in red blood cell omega-3 fatty acid concentra- tion had the greatest decrease in LVSVI, demonstrating a dose effect of treatment. Omega-3 treatment was associated with decreases in the inflammatory markers myelop- eroxidase and lipoprotein-associated phospholipase A2 (Lp-PLA2) as well as decreases in ST2, a marker of myocardial fibrosis. The decrease in ST2 correlated directly with the

Dr Thompson is Chief of Cardiology, Hartford Hospital, Connecticut.

Effect of omega-3 acid ethyl esters on left ventricular remodeling after acute myocardial infarction: the OMEGA-REMODEL randomised clinical trial Circulation Take-home message • In this multicentre, double-blind trial, patients who suffered an acute MI were randomly assigned to 6 months of high-dose omega-3 fatty acids (n=180) or placebo (n=178). Significant reductions in left ventricular systolic volume index (−5.8%l; P = 0.017), non-infarct myocardial fibrosis (−5.6%; P = 0.026), and serum biomarkers of inflammation and myocardial fibrosis were observed in the omega-3 fatty acids group compared with the placebo group. In addition, increases in red blood cell omega-3 fatty acid correlated with decreases in left ventricular systolic volume index. • Following acute MI, high-dose omega-3 fatty acids had a beneficial effect on left ventricular remodeling, non-infarct myocardial fibrosis, and biomarkers of inflammation beyond standard-of-care therapy. Abstract

ventricular systolic volume index (–5.8%, P=0.017), and noninfarct myocardial fibrosis (–5.6%, P=0.026) in comparisonwith placebo. Per-protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13% reduction in left ventricular systolic volume index in comparisonwith the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serumbiomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with highdose omega-3 fatty acid therapy. CONCLUSIONS Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflam- mation beyond current guidelinebased standard of care. Circulation 2016;134:378-391, Heydari B, Abdullah S, Pottala JV, et al.

BACKGROUND Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown. METHODS In a multicenter, double-blind, placebo-controlled trial, participants presentingwith an acutemyocardial infarction were randomly assigned 1:1 to 6 months of high-dose omega-3 fatty acids (n=180) or placebo (n=178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue char- acteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size. RESULTS By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left

Weekend admissions for non-STEMI associated with higher rates of inhospital mortality and lower rates of coronary angiography Comment by Shaista Malik, MD, PhD, MPH T he paper by Agarwal et al comparing in-hospital mortal- ity and frequency of coronary does not impact outcomes when it comes to STEMI due to concerted efforts to make medical care uniform in time-sensitive acute illnesses.

papers have found that significant differences in outcomes between weekend and weekday admission had largely dissipated, but many did not look at contemporary or large representative samples of the national inpatient population, and many didn’t examine NSTEMI and STEMI separately. Previous studies have shown that the day of the week

for utilisation of early invasive strat- egy. These results suggest that a targeted approach to improving pro- cesses of care in NSTEMI, as has been done in the past for STEMI, can have a significant impact on de- creasing mortality in these patients needing time-sensitive treatment. Uniformity in use of an early in- vasive approach and adherence to guidelines, regardless of day of the week, may ensure better quality of care and improved outcomes in patients admitted with NSTEMI.

angiography on weekend versus weekday admissions in patients with non-ST-segment elevation myocar- dial infarction (NSTEMI) shows that higher mortality on weekends may be explained by decreased use of an early invasive approach. Previous

Agarwal et al have shown in a large representative sample (3,625,271) that those admitted with NSTEMI have 2% higher odds of mortality if admitted over the weekend, and this disparity dissipates when adjusted

Comparison of inhospital mortality and frequency of coronary angiography on weekend versus weekday admissions in patients with non-ST-segment elevation acute myocardial infarction Abstract

Dr Malik is Associate Professor of Medicine,

significant after adjustment for differences in rates of utilization of EIS (OR 1.01; 95% CI 0.99 to 1.03; P = 0.11). In conclusion, this study demonstrates that among patients admittedwith a diagnosis of an acute NSTEMI, admission on aweekendwas associatedwith higher inhospital mor- tality compared with admission on a weekday and that lower rates of utilization of EIS contributed significantly to this disparity. Am J Cardiol 2016;118:632-634, Agrawal S, Garg L, Sharma A, et al.

A total of 3,625,271 NSTEMI admissions were identified, of which 909,103 (25.1%) were weekend and 2,716,168 (74.9%) wereweekday admissions. Admission on aweek- end versus weekday was independently associatedwith lower rates of coronary angiography (odds ratio [OR] 0.88; 95% confidence interval [CI] 0.89 to 0.90; P < 0.001) or utilization of an early invasive strategy (EIS) (OR 0.480; 95% CI 0.47 to 0.48; P < 0.001). Unadjusted inhospital mortality was significantly higher for the cohort of patients admitted on weekends (adjusted OR 1.02; 95% CI 1.01 to 1.04; P < 0.001). However, this disparity was no longer

Patients withmyocardial infarction admitted onweekends have been reported to less frequently undergo invasive angiography and experience poorer outcomes. We used theNationwide Inpatient Sample database (2003 to 2011) to compare differences in all-cause inhospital mortality between patients admitted on a weekend versus week- day for an acute non-ST-segment elevation myocardial infarction (NSTEMI) and to determine if rates and timing of coronary revascularization contributed to this difference.

Director, Susan Samueli Center of Integrative Medicine, Medical Director, Preventive Cardiology and Cardiac Rehab Director, Women’s Heart Program, University of California.

VOL. 1 • No. 2 • 2016