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76 CPD ACTIVITY FROM PAGE 75 without evidence of CVD. They were randomised to receive 1g capsules containing either 840mg of marine n−3 PUFAs (460mg EPA and 380mg DHA) or a matching placebo capsule (olive oil), once daily. The trial concluded that among patients with diabetes without evidence of CVD, there was no significant difference in the risk of serious vascular events between those who were assigned to receive omega-3 supplementation and those who were assigned to receive placebo. Triglyceride levels were not measured in the trial. The VITAL (vitamin D and omega-3 trial) study assessed the CV and cancer benefits of omega-3 fatty acids and vitamin D3 supplementation compared with placebo among healthy participants. Patients were randomised to receive 2000IU per day of vitamin D3, 1g per day as a fish-oil capsule containing 840mg of n–3 PUFAs, including 460mg EPA and 380mg DHA, or placebo. A large cohort (n=25,871) was randomised, with a follow-up duration of five years. The participants had no known CVD or cancer. The results of this trial indicate that supplementation with either omega-3 at a dose of 1g/day, or vitamin D3 at a dose of 2000IU/day, was not effective for primary prevention of CV or cancer events among healthy middle-aged men and women over the five years of follow-up. There was some evidence to suggest that participants who took omega-3 supplements experienced a 28 per cent reduction in heart attacks, and that this benefit seemed to be most pronounced among African American participants. However, this result was not clinically significant and cannot inform clinical guidelines. Rather it is hypothesis generating and deserving of further study. The only statistically significant outcome favouring omega-3 supplements on major CV events was in the group with low average weekly fish consumption (<1.5 servings per week). This suggests that populations with lower average consumption of fish may benefit more from omega-3 supplementation. The REDUCE-IT study assessed the impact of a highly purified and stable EPA ethyl ester called icosapent ethyl (Vascepa). Patients were randomised to 4g icosapent ethyl daily or placebo. More than 8,000 patients were enrolled, all with elevated triglyceride levels despite the use of statins. The primary end point was a composite of CV death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularisation, or unstable angina. The risk of the primary end point was reduced by 25 per cent in the icosapent ethyl arm (hazard ratio, 0.74; 95% CI, 0.65 to 0.83; P<0.001). The study concluded that the risk of ischemic events, including CV death, was significantly lower among those who received 2g of icosapent ethyl twice daily than among those who received placebo. The results of this study are not applicable to regular omega-3 (fish oil) supplements as icosapent ethyl is considered to be a highly active and refined form of EPA. Icosapent ethyl is not marketed in Australia. The most recent Cochrane Rreview (2020) represents the most extensive systematic assessment of the effects of omega-3 fats on CV health available. The review included 86 randomised controlled trials totalling 162,796 participants. The trials lasted at least 12 months and involved supplementation with omega-3 PUFAs, and included adults at varying cardiovascular risk, mainly in high-income countries. Omega-3 supplementation doses were varied (0.5/day to more than 5g/day). Of the 86 trials, 19 gave at least 3g omega-3 daily. The review found little or no effect of increasing omega-3 fatty acids on all- cause mortality, CV mortality, CV events, stroke or arrhythmia. Increasing omega-3 consumption slightly reduces CHD mortality or CHD events. However, this was defined as ‘low-certainty evidence’ in the review. The review also concluded that the effect of long-chain omega-3 at intake on bleeding is unclear, as the evidence is of very low quality. Omega-3 supplementation appears safe, as it had little or no effect on serious adverse events, adiposity, lipids and blood pressure. However, supplementation with omega-3 did reduce triglycerides by about 15 per cent in a dose- dependent way (high-certainty evidence) as well as increase HDL. To prevent one person having a coronary event, 167 people would need to increase their EPA and DHA, while 334 people would need to increase their EPA and DHA to prevent one person dying from coronary disease. Common fish oil supplements contain 1000mg of EPA/DHA per capsule. It’s important to consider the daily dose of EPA/DHA for efficacy in lowering triglycerides, as this can often exceed the dose suggested on the label, and hence pharmacists have a role in recommending the appropriate dose required for triglyceride lowering. Patients with inadequate consumption of fish seem to be the most likely to benefit from supplementation, although the evidence supporting this is conflicting. Probiotics Probiotics are live microbes that exhibit beneficial effect on human health. They have become an intervention of recent interest with proprietary preparations widely available claiming to assist with a variety of conditions including the maintenance of normal cholesterol levels.15 Several double-blind placebo-controlled trials have been conducted assessing the impact of probiotics on lipids, and some bacterial strains have been shown to reduce lipoprotein cholesterol and TG levels16. Lactobacillus species have been of specific interest. Lactobacilli are RETAIL PHARMACY • AUG 2020