REDUCE-IT Eligibility and Preventable Cardiovascular Events in the US Population (from the National Health and Nutrition Examination Survey [NHANES]).

The reduction of cardiovascular events with icosapent ethyl-intervention (REDUCE-IT) trial showed in persons with prior cardiovascular disease (CVD) or diabetes mellitus (DM) that icosapent ethyl (IPE) reduced CVD events by 25%. We projected the preventable initial and total CVD events if REDUCE-IT trial eligibility criteria were applied to US adults. We identified US adults with available REDUCE-IT inclusion criteria from NHANES Surveys 1999-2016 and estimated primary (CVD death, nonfatal myocardial infarction, stroke, revascularization, or unstable angina) and secondary composite (CVD death, nonfatal MI or stroke) events using REDUCE-IT published event rates in the IPE and placebo groups, the difference being the number of preventable events. From 11,445 adults aged ≥45 years (representing 111.1 million [M]), a total of 319 persons (3.0 M) fit key REDUCE-IT eligibility criteria: triglycerides of 135 to 499 mg/dL, HbA1c <10%, blood pressure <200/100 mm Hg, and on a statin with LDL-C of 40 to 99 mg/dL. 63% had prior CVD and 37% had DM + ≥1 risk factor (primary prevention cohort). If these persons are given IPE for the REDUCE-IT median trial period of 4.9 years, we estimated preventing a total 349,817 (71,391/year) primary CVD outcomes of which 146,011 (29,798/year) were initial events. Most (24,151) preventable events were from the secondary prevention cohort. Using FDA eligibility criteria, an estimated 4.6 million persons would be eligible for IPE, with 60,544 preventable primary CVD outcomes annually from REDUCE-IT USA event rates. In conclusion, many CVD events in US adults with known CVD or DM and well-controlled LDL-C on statin therapy can be prevented with IPE.

Residual Hypertriglyceridemia and Estimated Atherosclerotic Cardiovascular Disease Risk by Statin Use in U.S. Adults With Diabetes: National Health and Nutrition Examination Survey 2007-2014.

OBJECTIVE: Hypertriglyceridemia (HTG) is common in patients with diabetes, and statins remain the first-line therapy. However, the proportion of patients with diabetes having elevated triglycerides (TGs) on statin treatment and their atherosclerotic cardiovascular disease (ASCVD) risk has not been described. We quantified the prevalence of HTG in U.S. adults with diabetes currently treated versus not treated with statins and the estimated 10-year ASCVD risk. RESEARCH DESIGN AND METHODS: Among 1,448 U.S. adults aged 20 years and over with diabetes (projected to 24.4 million) in the 2007-2014 National Health and Nutrition Examination Survey (NHANES), we compared the prevalence of borderline HTG (TG 150-199 mg/dL) and HTG (TG ≥200 mg/dL) by statin use and LDL cholesterol (LDL-C) levels, and we used logistic regression to identify risk factors for HTG. We also estimated the 10-year ASCVD risk in those without prior ASCVD. RESULTS: The prevalence of borderline HTG and HTG was 20.0% and 19.5%, respectively, in statin users and 20.1% and 25.3%, respectively, in nonstatin users (P < 0.0001). Even among statin users with LDL-C <70 mg/dL, borderline HTG prevalence was 16.8% and HTG prevalence was 16.7%. Approximately 77.5% of those with HTG had an estimated 10-year ASCVD risk of ≥7.5%, with almost 40% of statin users having ASCVD risk ≥20%. CONCLUSIONS: Residual HTG occurs in over one-fifth (∼5.5 million) of U.S. adults with diabetes, including those on statin therapy and with well-controlled LDL-C. Over three-quarters of adults with diabetes with HTG are at moderate or high 10-year risk for ASCVD. Greater efforts are needed to promote lifestyle and pharmacologic means to address residual HTG.

Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey.

BACKGROUND: Statin therapy remains the primary treatment for mixed dyslipidemia, even with moderate triglyceride (TG) elevations. OBJECTIVE: We examined the prevalence of elevated TG levels in adults with and without statin use and the associated 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk. METHODS: We studied 9593 US adults aged ≥20 years (219.9 million projected) in the US National Health and Nutrition Examination Surveys, 2007 to 2014. We determined the proportions of TG categories (<150, 150-199, 200-499, and ≥500 mg/dL) according to statin use, as well as the 10-year estimated ASCVD risk and number of events. RESULTS: Among those not taking statin therapy, the prevalence of TG < 150, 150 to 199, and ≥200 mg/dL was 75.3%, 12.8%, and 11.9%; among statin users, these proportions were 68.4%, 16.2%, and 15.4%, respectively. Among persons with low-density lipoprotein cholesterol <100 mg/dL (or <70 mg/dL in those with ASCVD), despite statin use, 27.7% had TG ≥ 150 mg/dL. The odds of TG ≥ 150 mg/dL in statin users was associated with greater age, higher body mass index, lower high-density lipoprotein cholesterol, higher low-density lipoprotein cholesterol, and diabetes. Estimated mean 10-year ASCVD risk from TG < 150 to ≥500 mg/dL, ranged from 11.3% to 19.1% in statin users and 6.0% to 15.6% in nonusers, with an overall 3.4 million ASCVD events expected in the next 10 years. CONCLUSIONS: One-fourth of US adults overall, including nearly one-third of those on statin therapy, have suboptimal TG levels. More than 3 million ASCVD events are expected to occur over the next decade in those with TG ≥ 150 mg/dL, with approximately 1 million events expected in statin users.

Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on remnant-like particle cholesterol from the MARINE and ANCHOR studies.

BACKGROUND AND AIMS: Remnant-like particle cholesterol (RLP-C) is atherogenic and may increase atherosclerotic cardiovascular disease risk. Icosapent ethyl is a high-purity prescription eicosapentaenoic acid ethyl ester (approved as an adjunct to diet to reduce triglyceride [TG] levels in adult patients with TGs ≥500 mg/dL [≥5.65 mmol/L] at 4 g/day). In the MARINE and ANCHOR studies, icosapent ethyl reduced TG and other atherogenic lipid parameter levels without increasing low-density lipoprotein cholesterol (LDL-C) levels. This exploratory analysis evaluated the effects of icosapent ethyl on calculated and directly measured RLP-C. METHODS: MARINE (TGs ≥500 and ≤2000 mg/dL [≥5.65 mmol/L and ≤22.6 mmol/L]) and ANCHOR (TGs ≥200 and <500 mg/dL [≥2.26 and <5.65 mmol/L] despite statin-controlled LDL-C) were phase 3, 12-week, double-blind studies that randomized adult patients to icosapent ethyl 4 g/day, 2 g/day, or placebo. This analysis assessed median percent change from baseline to study end in directly measured (immunoseparation assay) RLP-C levels (MARINE, n = 218; ANCHOR, n = 252) and calculated RLP-C levels in the full populations. RESULTS: Icosapent ethyl 4 g/day significantly reduced directly measured RLP-C levels -29.8% (p = 0.004) in MARINE and -25.8% (p = 0.0001) in ANCHOR versus placebo, and also reduced directly measured RLP-C levels to a greater extent in subgroups with higher versus lower baseline TG levels, in patients receiving statins versus no statins (MARINE), and in patients receiving medium/higher-intensity versus lower-intensity statins (ANCHOR). Strong correlations were found between calculated and directly measured RLP-C for baseline, end-of-treatment, and percent change values in ANCHOR and MARINE (0.73-0.92; p < 0.0001 for all). CONCLUSIONS: Icosapent ethyl 4 g/day significantly reduced calculated and directly measured RLP-C levels versus placebo in patients with elevated TG levels from the MARINE and ANCHOR studies.