Health economic analysis of polygenic risk score use in primary prevention of coronary artery disease - A system dynamics model.

Background: Primary prevention programs utilising traditional risk scores fail to identify all individuals who suffer acute cardiovascular events. We aimed to model the impact and cost effectiveness of incorporating a Polygenic risk scores (PRS) into the cardiovascular disease CVD primary prevention program in Australia, using a whole-of-system model. Methods: System dynamics models, encompassing acute and chronic CVD care in the Australian healthcare setting, assessing the cost-effectiveness of incorporating a CAD-PRS in the primary prevention setting. The time horizon was 10-years. Results: Pragmatically incorporating a CAD-PRS in the Australian primary prevention setting in middle-aged individuals already attending a Heart Health Check (HHC) who are determined to be at low or moderate risk based on the 5-year Framingham risk score (FRS), with conservative assumptions regarding uptake of PRS, could have prevented 2, 052 deaths over 10-years, and resulted in 24, 085 QALYs gained at a cost of $19, 945 per QALY with a net benefit of $724 million. If all Australians overs the age of 35 years old had their FRS and PRS performed, and acted upon, 12, 374 deaths and 60, 284 acute coronary events would be prevented, with 183, 682 QALYs gained at a cost of $18, 531 per QALY, with a net benefit of $5, 780 million. Conclusions: Incorporating a CAD-PRS in a contemporary primary prevention setting in Australia would result in substantial health and societal benefits and is cost-effective. The broader the uptake of CAD-PRS in the primary prevention setting in middle-aged Australians, the greater the impact and the more cost-effective the strategy.

Integrating the Biology of Cardiovascular Disease into the Epidemiology of Economic Decision Modelling via Mendelian Randomisation.

Health economic analyses are essential for health services research, providing decision-makers and payers with evidence about the value of interventions relative to their opportunity cost. However, many health economic approaches are still limited, especially regarding the primary prevention of cardiovascular disease (CVD). In this article, we discuss some limitations to current health economic models and then outline an approach to address these via the incorporation of genomics into the design of health economic models for CVD. We propose that when a randomised clinical trial is not possible or practical, health economic models for primary prevention of CVD can be based on Mendelian randomisation analyses, a technique to assess causality in observational data. We discuss the advantages of this approach, such as integrating well-known disease biology into health economic models and how this may overcome current statistical approaches to assessing the benefits of interventions. We argue that this approach may provide the economic argument for integrating genomics into clinical practice and the efficient targeting of newer therapeutics, transforming our approach to the primary prevention of CVD, thereby moving from reactive to preventive healthcare. We end by discussing some limitations and potential pitfalls of this approach.

New Cardiovascular Risk Assessment Techniques for Primary Prevention: JACC Review Topic of the Week.

Risk factor-based models fail to accurately estimate risk in select populations, in particular younger individuals. A sizable number of people are also classified as being at intermediate risk, for whom the optimal preventive strategy could be more precise. Several personalized risk prediction tools, including coronary artery calcium scoring, polygenic risk scores, and metabolic risk scores may be able to improve risk assessment, pending supportive outcome data from clinical trials. Other tools may well emerge in the near future. A multidimensional approach to risk prediction holds the promise of precise risk prediction. This could allow for targeted prevention minimizing unnecessary costs and risks while maximizing benefits. High-risk individuals could also be identified early in life, creating opportunities to arrest the development of nascent coronary atherosclerosis and prevent future clinical events.

A systematic review on assessment and management of preventive cardiovascular care in primary health for Aboriginal and Torres Strait Islander women and men.

In promoting positive cardiovascular health for Aboriginal and Torres Strait Islander peoples, there is a need to ensure provision of high-quality risk assessment and management in primary healthcare settings. There is some evidence of gender gaps for Australian women in the provision of cardiovascular risk assessment and management; however, there is little understanding of whether these gaps are also present for Aboriginal and Torres Strait Islander women. A mixed-method systematic review was utilised to synthesise existing evidence on the provision of assessment and management against guideline-recommended care for Aboriginal and Torres Strait Islander women, and determine whether gender disparities in provision of care exist for this population. Sixteen studies that report gender-specific data indicate there are significant gaps in the provision of assessment and management for Aboriginal and Torres Strait Islander women and men alike. There is no evidence of incorporation of social and emotional wellbeing into cardiovascular care and limited studies outlining the assessment and management of behaviours and factors that may be protective of cardiovascular health. Furthermore, little is known about the provision of care in mainstream primary health services for Aboriginal and Torres Strait Islander peoples.

Coronary computed tomography angiography-based assessment of vascular inflammation in patients with obstructive sleep apnoea and coronary artery disease.

Background: Obstructive sleep apnoea (OSA) is associated with increased coronary artery disease (CAD) plaque burden, but the role of vascular inflammation in this relationship is unclear. Coronary computed tomography angiography (CTA) enables surrogate assessment of systemic inflammation via subcutaneous adipose tissue attenuation (SCAT-a), and of coronary inflammation via epicardial adipose tissue volume and attenuation (EAT-v and EAT-a) and pericoronary adipose tissue attenuation (PCAT-a). We investigated whether patients with severe OSA and high plaque burden have increased vascular inflammation. Methods: Patients with overnight polysomnography within ≤12 months of coronary CTA were included. Severe OSA was classified as apnoea/hypopnoea index (AHI) >30. High plaque burden was defined as a CT-adapted Leaman score (CT-LeSc) ≥8.3. Patients with both severe OSA and high plaque burden were defined as 'Group 1', all other patients were classified as 'Group 2'. ScAT, PCAT and EAT attenuation and volume were assessed on semi-automated software. Results: A total of 91 patients were studied (59.3±11.1 years). Severe OSA was associated with high plaque burden (P=0.02). AHI correlated with CT-LeSc (r=0.24, P=0.023). Group 1 had lower EAT-a and PCAT-a compared to Group 2 (EAT-a: -87.6 vs. -84.0 HU, P=0.011; PCAT-a: -90.4 vs. -83.4 HU, P<0.01). However, among patients with low plaque burden, EAT-a was higher in the presence of severe OSA versus mild-moderate OSA (-80.3 vs. -84.0 HU, P=0.020). On multivariable analysis, severe OSA and high plaque burden associated with EAT-a (P<0.02), and severe OSA and high plaque burden (P<0.01) and hypertension (P<0.01) associated with PCAT-a. Conclusions: EAT and PCAT attenuation are decreased in patients with severe OSA and high plaque burden, but EAT attenuation was increased in patients with severe OSA and low plaque burden. These divergent results suggest vascular inflammation may be increased in OSA independent of CAD, but larger studies are required to validate these findings.

Implementation and prospective evaluation of the Country Heart Attack Prevention model of care to improve attendance and completion of cardiac rehabilitation for patients with cardiovascular diseases living in rural Australia: a study protocol.

INTRODUCTION: Despite extensive evidence of its benefits and recommendation by guidelines, cardiac rehabilitation (CR) remains highly underused with only 20%-50% of eligible patients participating. We aim to implement and evaluate the Country Heart Attack Prevention (CHAP) model of care to improve CR attendance and completion for rural and remote participants. METHODS AND ANALYSIS: CHAP will apply the model for large-scale knowledge translation to develop and implement a model of care to CR in rural Australia. Partnering with patients, clinicians and health service managers, we will codevelop new approaches and refine/expand existing ones to address known barriers to CR attendance. CHAP will codesign a web-based CR programme with patients expanding their choices to CR attendance. To increase referral rates, CHAP will promote endorsement of CR among clinicians and develop an electronic system that automatises referrals of in-hospital eligible patients to CR. A business model that includes reimbursement of CR delivered in primary care by Medicare will enable sustainable access to CR. To promote CR quality improvement, professional development interventions and an accreditation programme of CR services and programmes will be developed. To evaluate 12-month CR attendance/completion (primary outcome), clinical and cost-effectiveness (secondary outcomes) between patients exposed (n=1223) and not exposed (n=3669) to CHAP, we will apply a multidesign approach that encompasses a prospective cohort study, a pre-post study and a comprehensive economic evaluation. ETHICS AND DISSEMINATION: This study was approved by the Southern Adelaide Clinical Human Research Ethics Committee (HREC/20/SAC/78) and by the Department for Health and Wellbeing Human Research Ethics Committee (2021/HRE00270), which approved a waiver of informed consent. Findings and dissemination to patients and clinicians will be through a public website, online educational sessions and scientific publications. Deidentified data will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: ACTRN12621000222842.

Population genomic screening of young adults for familial hypercholesterolaemia: a cost-effectiveness analysis.

AIMS: The aim of this study was to assess the impact and cost-effectiveness of offering population genomic screening to all young adults in Australia to detect heterozygous familial hypercholesterolaemia (FH). METHODS AND RESULTS: We designed a decision analytic Markov model to compare the current standard of care for heterozygous FH diagnosis in Australia (opportunistic cholesterol screening and genetic cascade testing) with the alternate strategy of population genomic screening of adults aged 18-40 years to detect pathogenic variants in the LDLR/APOB/PCSK9 genes. We used a validated cost-adaptation method to adapt findings to eight high-income countries. The model captured coronary heart disease (CHD) morbidity/mortality over a lifetime horizon, from healthcare and societal perspectives. Risk of CHD, treatment effects, prevalence, and healthcare costs were estimated from published studies. Outcomes included quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio (ICER), discounted 5% annually. Sensitivity analyses were undertaken to explore the impact of key input parameters on the robustness of the model. Over the lifetime of the population (4 167 768 men; 4 129 961 women), the model estimated a gain of 33 488years of life lived and 51 790 QALYs due to CHD prevention. Population genomic screening for FH would be cost-effective from a healthcare perspective if the per-test cost was ≤AU$250, yielding an ICER of

Cognitive Effects of the BET Protein Inhibitor Apabetalone: A Prespecified Montreal Cognitive Assessment Analysis Nested in the BETonMACE Randomized Controlled Trial.

BACKGROUND: Epigenetic changes may contribute importantly to cognitive decline in late life including Alzheimer's disease (AD) and vascular dementia (VaD). Bromodomain and extra-terminal (BET) proteins are epigenetic "readers" that may distort normal gene expression and contribute to chronic disorders. OBJECTIVE: To assess the effects of apabetalone, a small molecule BET protein inhibitor, on cognitive performance of patients 70 years or older participating in a randomized trial of patients at high risk for major cardiovascular events (MACE). METHODS: The Montreal Cognitive Assessment (MoCA) was performed on all patients 70 years or older at the time of randomization. 464 participants were randomized to apabetalone or placebo in the cognition sub-study. In a prespecified analysis, participants were assigned to one of three groups: MoCA score≥26 (normal performance), MoCA score 25-22 (mild cognitive impairment), and MoCA score≤21 (dementia). Exposure to apabetalone was equivalent in the treatment groups in each MoCA-defined group. RESULTS: Apabetalone was associated with an increased total MoCA score in participants with baseline MoCA score of≤21 (p = 0.02). There was no significant difference in change from baseline in the treatment groups with higher MoCA scores. In the cognition study, more patients randomized to apabetalone discontinued study drug for adverse effects (11.3% versus 7.9%). CONCLUSION: In this randomized controlled study, apabetalone was associated with improved cognition as measured by MoCA scores in those with baseline scores of 21 or less. BET protein inhibitors warrant further investigation for late life cognitive disorders.

Translation and Impact of Funded Australian Cardiovascular Research: A Review With Perspective.

This aim of this paper is to set the scene for the need for impact assessment and return on investment in funded cardiovascular research in Australia, starting with the historical perspective on waste in health and medical research. Recently there has been a substantial move from discussion and policy about the need for research translation, into practice and application via the evolution of funding streams like the Australian Medical Research Future Fund (MRFF). Health and medical research funders play a critical role in both setting the expectations for research translation and impact and helping researchers to meet these expectations. As a leading cause of death, cardiovascular disease is a national health priority, recognised as such with a AUD$220 million MRFF allocation to the Cardiovascular Health Mission. Focussing on cardiovascular research, we address some of the barriers researchers face in prospectively planning for research translation and impact assessment, and call for an ecosystem that supports a return on investment for all stakeholders, especially the community and patient end-users.

Cardiac Computed Tomography Radiomics for the Non-Invasive Assessment of Coronary Inflammation.

Radiomics, via the extraction of quantitative information from conventional radiologic images, can identify imperceptible imaging biomarkers that can advance the characterization of coronary plaques and the surrounding adipose tissue. Such an approach can unravel the underlying pathophysiology of atherosclerosis which has the potential to aid diagnostic, prognostic and, therapeutic decision making. Several studies have demonstrated that radiomic analysis can characterize coronary atherosclerotic plaques with a level of accuracy comparable, if not superior, to current conventional qualitative and quantitative image analysis. While there are many milestones still to be reached before radiomics can be integrated into current clinical practice, such techniques hold great promise for improving the imaging phenotyping of coronary artery disease.

Cost-Effectiveness of Coronary Artery Calcium Scoring in People With a Family History of Coronary Disease.

OBJECTIVES: To assess the cost effectiveness of coronary artery calcium (CAC) compared with traditional risk factor-based prediction alone in those with an family history of premature coronary artery disease (FHCAD). BACKGROUND: The use of CAC scoring to guide primary prevention statin therapy in those with a FHCAD is inconsistently recommended in guidelines, and usually not reimbursed by insurance. METHODS: A microsimulation model was constructed in TreeAge Healthcare Pro using data from 1,083 participants in the CAUGHT-CAD (Coronary Artery Calcium Score: Use to Guide Management of HerediTary Coronary Artery Disease) trial. Outcomes assessed were quality-adjusted life years (QALYs): cost-effectiveness was assessed over a 15-year time horizon from the perspective of the US health care sector using real-world statin prescribing, accounting for the effect of knowledge of subclinical disease on adherence to guideline-directed therapies. Costs were assessed in 2020 USD, with discounting undertaken at 3%. RESULTS: Statins were indicated in 45% of the cohort using the CAC strategy and 27% using American College of Cardiology/American Heart Association (2019) treatment strategies. Compared with applying a statin treatment threshold of 7.5%, the CAC strategy was more costly ($145) and more effective (0.0097 QALY) with an incremental cost-effective ratio (ICER) of $15,014/QALY. CAC ICER was driven by CAC acquisition and statin prescription cost and improved with certain patient subgroups: male, age >60 years, and 10-year risk pooled cohort equation risk ≥7.5%. CAC scanning of low-risk patients (10-year risk <5%) or those 40 to 50 years of age was not cost-effective. CONCLUSIONS: Systematic CAC screening and treatment of those with FHCAD and subclinical disease was more cost-effective than management using statin treatment thresholds, in the US health care system.

A systematic review and meta-analysis of gender differences in long-term mortality and cardiovascular events in peripheral artery disease.

OBJECTIVE: Individual studies of peripheral artery disease (PAD) have indicated that gender discrepancies exist in the symptoms, functional status, and treatment usage. It remains uncertain whether these discrepancies result in different long-term outcomes. We examined the potential gender differences in mortality and major adverse cardiovascular events (MACE) in patients with symptomatic PAD. METHODS: The PubMed and Embase databases were searched for studies from 2000 to January 2019. After a review of 13,582 citations, 14 articles were analyzed. The reported age-adjusted hazard ratios (HRs) for gender differences in mortality and MACE were included in the meta-analysis. The mortality outcomes were stratified according to the clinical presentation and study context. RESULTS: Male gender was associated with a greater risk of all-cause mortality (HR, 1.13; 95% confidence interval [CI], 1.10-1.16; P < .001) and MACE (HR, 1.10; 95% CI, 1.06-1.14; P < .001). In a stratified analysis, male gender was associated with a higher mortality risk for patients presenting with either critical limb ischemia (HR, 1.08; 95% CI, 1.05-1.10; P < .001) or mixed clinical presentations (HR, 1.16; 95% CI, 1.11-1.21; P < .001) but not for those with intermittent claudication (HR, 1.13; 95% CI, 0.98-1.30; P = .09). Elevated mortality risk was evident after revascularization (HR, 1.11; 95% CI, 1.04-1.19; P = .003), hospitalization (HR, 1.15; 95% CI, 1.08-1.22; P < .001), and amputation (HR, 1.09; 95% CI, 1.08-1.10; P < .001), although not in outpatient clinics (HR, 1.13; 95% CI, 0.97-1.32; P = .13), in men compared with women. CONCLUSIONS: Greater mortality and MACE rates in men with PAD occurred despite other accepted gender disparities. The mechanisms underlying these gender differences in the outcomes for PAD patients require further investigation.

Lack of Strategic Funding and Long-Term Job Security Threaten to Have Profound Effects on Cardiovascular Researcher Retention in Australia.

BACKGROUND: Cardiovascular disease is the leading cause of death in Australia. Investment in research solutions has been demonstrated to yield health and a 9.8-fold return economic benefit. The sector, however, is severely challenged with success rates of traditional peer-reviewed funding in decline. Here, we aimed to understand the perceived challenges faced by the cardiovascular workforce in Australia prior to the COVID-19 pandemic. METHODS: We used an online survey distributed across Australian cardiovascular societies/councils, universities and research institutes over a period of 6 months during 2019, with 548 completed responses. Inclusion criteria included being an Australian resident or an Australian citizen who lived overseas, and a current or past student or employee in the field of cardiovascular research. RESULTS: The mean age of respondents was 42±13 years, 47% were male, 85% had a full-time position, and 40% were a group leader or laboratory head. Twenty-three per cent (23%) had permanent employment, and 82% of full-time workers regularly worked >40 hours/week. Sixty-eight per cent (68%) said they had previously considered leaving the cardiovascular research sector. If their position could not be funded in the next few years, a staggering 91% of respondents would leave the sector. Compared to PhD- and age-matched men, women were less likely to be a laboratory head and to feel they had a long-term career path as a cardiovascular researcher, while more women were unsure about future employment and had considered leaving the sector (all p<0.05). Greater job security (76%) and government and philanthropic investment in cardiovascular research (72%) were highlighted by responders as the main changes to current practices that would encourage them to stay. CONCLUSION: Strategic solutions, such as diversification of career pathways and funding sources, and moving from a competitive to a collaborative culture, need to be a priority to decrease reliance on government funding and allow cardiovascular researchers to thrive.

Coronary artery calcium scoring in cardiovascular risk assessment of people with family histories of early onset coronary artery disease.

OBJECTIVES: To assess the predictive value of the Australian absolute cardiovascular disease risk (ACVDR) calculator and other assessment tools for identifying Australians with family histories of early onset coronary artery disease (CAD) who have coronary artery calcification. DESIGN, SETTING, PARTICIPANTS: People without known CAD were recruited at seven Australian hospitals, October 2016 - January 2019. Participants were aged 40-70 years, had a family history of early onset CAD, and a 5-year ACVDR of 2-15%. MAIN OUTCOME MEASURES: CT coronary artery calcium score greater than zero (any coronary calcification) or greater than 100 (calcification warranting lipid therapy). RESULTS: 1059 participants were recruited; 477 (45%) had non-zero coronary artery calcium scores (median 5-year ACVDR, 4.8% [IQR, 2.9-7.6%]; median coronary artery calcium score, 41.7 [IQR, 8-124]); 582 (55%) did not (median 5-year ACVDR, 3.2% [IQR, 2.0-4.6%]). Of 151 participants with calcium scores of 100 or more, 116 (77%) were deemed to be at low cardiovascular risk by Australian guidelines, while 14 of 75 participants at intermediate risk (19%) had zero calcium scores. The sensitivity of the ACVDR calculator for identifying people with non-zero calcium scores (area under receiver operator curve [AUC], 0.674) was lower than that of the pooled cohort equation (AUC, 0.711; P < 0.001). ACVDR (10-year)- and Multi-Ethnic Study of Atherosclerosis (MESA)-predicted risk categories concurred for 511 participants (48%); classifications were concordant for 925 participants (87%) when the ACVDR was supplemented by calcium scores. CONCLUSIONS: Coronary artery calcium scoring should be considered as part of the heart health check for patients at intermediate ACVDR risk and with family histories of early onset CAD. Alternative risk calculators may better select such patients for further diagnostic testing and primary prevention therapy. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN 12614001294640; 11 December 2014 (prospective).

Optimising Secondary Prevention and Cardiac Rehabilitation for Atherosclerotic Cardiovascular Disease During the COVID-19 Pandemic: A Position Statement From the Cardiac Society of Australia and New Zealand (CSANZ).

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has introduced a major disruption to the delivery of routine health care across the world. This provides challenges for the use of secondary prevention measures in patients with established atherosclerotic cardiovascular disease (CVD). The aim of this Position Statement is to review the implications for effective delivery of secondary prevention strategies during the COVID-19 pandemic. CHALLENGES: The COVID-19 pandemic has introduced limitations for many patients to access standard health services such as visits to health care professionals, medications, imaging and blood tests as well as attendance at cardiac rehabilitation. In addition, the pandemic is having an impact on lifestyle habits and mental health. Taken together, this has the potential to adversely impact the ability of practitioners and patients to adhere to treatment guidelines for the prevention of recurrent cardiovascular events. RECOMMENDATIONS: Every effort should be made to deliver safe, ongoing access to health care professionals and the use of evidenced based therapies in individuals with CVD. An increase in use of a range of electronic health platforms has the potential to transform secondary prevention. Integrating research programs that evaluate the utility of these approaches may provide important insights into how to develop more optimal approaches to secondary prevention beyond the pandemic.

Quantitative and Qualitative Coronary Plaque Assessment Using Computed Tomography Coronary Angiography: A Comparison With Intravascular Ultrasound.

BACKGROUND: To compare computed tomography coronary angiography (CTCA) with intravascular ultrasound (IVUS) in quantitative and qualitative plaque assessment. METHODS: Patients who underwent IVUS and CTCA within 3 months for suspected coronary artery disease were retrospectively studied. Plaque volumes on CTCA were quantified manually and with automated-software and were compared to IVUS. High-risk plaque features were compared between CTCA and IVUS. RESULTS: There were 769 slices in 32 vessels (27 patients). Manual plaque quantification on CTCA was comparable to IVUS per slice (mean difference of 0.06±0.07, p=0.44; Bland-Altman 95% limits of agreement -2.19-2.08 mm3, bias of -0.06mm3) and per vessel (3.1mm3 ± -2.85mm3, p=0.92). In contrast, there was significant difference between automated-software and IVUS per slice (2.3±0.09mm3, p<0.001; 95% LoA -6.78 to 2.25mm3, bias of -2.2mm3) and per vessel (33.04±10.3 mm3, p<0.01). The sensitivity, specificity, positive and negative predictive value of CTCA to detect plaques that had features of echo-attenuation on IVUS was 93.3%, 99.6%, 93.3% and 99.6% respectively. The association of ≥2 high-risk plaque features on CTCA with echo attenuation (EA) plaque features on IVUS was excellent (86.7%, 99.6%, 92.9% and 99.2%). In comparison, the association of high-risk plaque features on CTCA and plaques with echo-lucency on IVUS was only modest. CONCLUSION: Plaque volume quantification by manual CTCA method is accurate when compared to IVUS. The presence of at least two high-risk plaque features on CTCA is associated with plaque features of echo attenuation on IVUS.

Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial.

It is uncertain whether omega-3 fatty acids are beneficial in statin-treated patients. Epanova is a mix of omega-3 free fatty acids, not requiring co-ingestion with food, which can lower triglycerides by up to 31%. STRENGTH will examine whether Epanova 4 g daily reduces the rate of cardiovascular events in statin-treated patients with hypertriglyceridemia and low levels of HDL-C at high risk for developing cardiovascular events. STRENGTH is a randomized, double-blind, placebo-controlled trial. Patients had a triglyceride level ≥ 180 to <500 mg/dL and HDL-C < 42 mg/dL (men) or < 47 mg/dL (women) in the presence of either (1) established atherosclerotic cardiovascular disease, (2) diabetes with one additional risk factor, or (3) were other high-risk primary prevention patients, based on age and risk factor assessment. Patients should be treated with a statin, for >4 weeks, and have LDL-C < 100 mg/dL, but were also eligible if LDL-C was ≥100 mg/dL while on maximum tolerated statin therapy. The study will extend from October 30, 2014 to October 30, 2019. 13 086 patients were randomized to Epanova 4 g or placebo daily in addition to standard medical therapy. The primary efficacy outcome is time to first event of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The trial will continue until 1600 patients reach the primary endpoint, with a median duration of therapy of 3 years. STRENGTH will determine whether Epanova 4 g daily will reduce cardiovascular events in statin-treated high-risk patients with hypertriglyceridemia and low HDL-C levels.