Cost-Effectiveness of Icosapent Ethyl in REDUCE-IT USA: Results From Patients Randomized in the United States.

BACKGROUND: In 3146 REDUCE-IT USA (Reduction of Cardiovascular Events With Icosapent Ethyl Intervention Trial USA) participants, icosapent ethyl (IPE) reduced first and total cardiovascular events by 31% and 36%, respectively, over 4.9 years of follow-up. METHODS AND RESULTS: We used participant-level data from REDUCE-IT USA, 2021 US costs, and IPE costs ranging from $4.59 to $11.48 per day, allowing us to examine a range of possible medication costs. The in-trial analysis was participant-level, whereas the lifetime analysis used a Markov model. Both analyses considered value from a US health sector perspective. The incremental cost-effectiveness ratio (incremental costs divided by incremental quality-adjusted life-years) of IPE compared with standard care (SC) was the primary outcome measure. There was incremental gain in quality-adjusted life-years with IPE compared with SC using in-trial (3.28 versus 3.13) and lifetime (10.36 versus 9.83) horizons. Using an IPE cost of $4.59 per day, health care costs were lower with IPE compared with SC for both in-trial ($29 420 versus $30 947) and lifetime ($216 243 versus $219 212) analyses. IPE versus SC was a dominant strategy in trial and over the lifetime, with 99.7% lifetime probability of an incremental cost-effectiveness ratio <$50 000 per quality-adjusted life-year gained. At a medication cost of $11.48 per day, the cost per quality-adjusted life-year gained was $36 208 in trial and $9582 over the lifetime. CONCLUSIONS: In this analysis, at $4.59 per day, IPE offers better outcomes than SC at lower costs in trial and over a lifetime and is cost-effective at $11.48 per day for conventional willingness-to-pay thresholds. Treatment with IPE should be strongly considered in US patients like those enrolled in REDUCE-IT USA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361.

Increased residual cardiovascular risk in U.S. veterans with moderately-elevated baseline triglycerides and well-controlled LDL-C levels on statins.

Background: Recent studies have demonstrated a causal role for elevated triglycerides (TG) in incident cardiovascular (CV) events in patients with established coronary heart disease (CHD) and those with CV risk factors alone, particularly diabetes. Objective: Using a large cohort of U.S. veterans with statin-controlled LDL-C levels (40-100 mg/dL), we explored residual CV risk among patients with elevated baseline TG levels (150-499 mg/dL) vs. those with normal TG levels (<150 mg/dL). Methods: We identified veterans receiving a statin but not a TG-lowering agent from the VA electronic health records database, from 2010 to 2015. We compared composite CV event rates (MI, stroke, unstable angina, coronary revascularization, and CV death) between the elevated TG and normal TG groups. We stratified the study cohort according to 3 CV risk groups: (1) no diabetes and no prior CV event, (2) diabetes and no prior CV event, and (3) prior CV event. We calculated crude event rates, rate ratios, and event rate ratios adjusted for age, sex, systolic blood pressure, estimated glomerular filtration rate, and weight. Results: The cohort included 396,189 veterans (predominantly male and white) of whom 109,195 (28%) had elevated TG levels. Those with elevated TG were younger (age 73 vs. 77 years) and had a higher body mass index (31.3 vs. 28.3 Kg/M2). The overall composite crude and adjusted rate ratios comparing the elevated and normal TG groups were 1.10 (1.09, 1.12) and 1.05 (1.03, 1.06), respectively. For CV risk groups 1, 2 and 3, the adjusted rate ratios comparing the elevated and normal TG groups were 0.99 (0.96, 1.02), 1.05 (1.02, 1.08), and 1.07 (1.04, 1.10), respectively. An association of increased rate ratios did not hold for fatal events. Conclusion: Those with elevated TG levels and well-controlled LDL-C on statins showed a modest increase in CV events compared to those with normal TG. Elevated TG levels were associated with increased CV events in patients with established CV disease and with diabetes only, suggesting that elevated TG levels are associated with a similar degree of residual risk in high-risk primary prevention and secondary prevention settings.

The potential population health impact of treating REDUCE-IT eligible US adults with Icosapent Ethyl.

Objective: To explore the population health impact of treating all US adults eligible for the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) with icosapent ethyl (IPE), we estimated (1) the number of ASCVD events and healthcare costs that could be prevented; and (2) medication costs. Methods: We derived REDUCE-IT eligible cohorts in (1) the National Health and Nutrition Examination Surveys (NHANES) 2009-2014 and (2) the Optum Research Database (ORD). Population sizes were obtained from NHANES and observed first event rates (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, or coronary revascularization) were estimated from the ORD. Hazard ratios from REDUCE-IT USA estimated events prevented with IPE therapy. The National Inpatient Sample estimated event costs (facility and professional) and daily IPE treatment cost was approximated at $4.59. Results: We estimate 3.6 million US adults to be REDUCE-IT eligible, and the observed five-year first event rate without IPE of 19.0% (95% confidence interval [CI] 16.6%-19.5%) could be lowered to 13.1% (95% CI 12.8%-13.5%) with five years of IPE treatment, preventing 212,000 (uncertainty range 163,000-262,000) events. We projected the annual IPE treatment cost for all eligible persons to be $6.0 billion (95% CI $4.7-$7.5 billion), but saving $1.8 billion annually due to first events prevented (net annual cost $4.3 billion). The total five-year event rate (first and recurrent) could be reduced from 42.5% (95% CI 39.6%-45.4%) to 28.9% (95% CI 26.9-30.9%) with five years of IPE therapy, preventing 490,000 (uncertainty range 370,000-609,000) events (net annual cost $2.6 billion). Conclusions: Treating all REDUCE-IT eligible US adults has substantial medication costs but could prevent a substantial number of ASCVD events and associated direct costs. Indirect cost savings by preventing events could outweigh much of the incurred direct costs.

Global assessment improves risk stratification for major adverse cardiac events across a wide range of triglyceride levels: Insights from the KP REACH study.

OBJECTIVE: Patients with risk factors for or established atherosclerotic cardiovascular disease (ASCVD) remain at high risk for subsequent ischemic events despite statin therapy. Triglyceride (TG) levels may contribute to residual ASCVD risk, and the performance of global risk assessment calculators across a broad range of TG levels is unknown. METHODS: We performed a retrospective cohort study of Kaiser Permanente Northern California members aged ≥45 years with ≥1 ASCVD risk factor (primary prevention cohort) or established ASCVD (secondary prevention cohort) between 2010 and 2017 who were receiving statin therapy and had a low-density lipoprotein cholesterol between 41-100 mg/dL. Global ASCVD risk assessment was performed using both the Kaiser Permanente ASCVD Risk Estimator (KPARE) and the ACC/AHA ASCVD Pooled Cohort Equation (PCE). Outcomes included major adverse cardiovascular events (MACE) defined as myocardial infarction, stroke, or peripheral artery disease, and expanded MACE (MACE + coronary revascularization + hospitalization for unstable angina). RESULTS: Among 373,389 patients in the primary prevention cohort, median TG was 122 mg/dL (IQR 88-172 mg/dL) and there were 0.2 MACE events and 0.3 expanded MACE events per 100-person years. Among 97,832 patients in the secondary prevention cohort, median TG level was 116 mg/dL (IQR 84-164 mg/dL) and there were 9.6 MACE events and 22.0 expanded MACE events per 100-person years. KPARE and the ACC/AHA PCE stratified patients for MACE and expanded MACE over the entire range of TGs. CONCLUSION: In a cohort receiving statin therapy for primary or secondary prevention, we found global assessment further improves risk stratification for initial and/or recurrent ASCVD events irrespective of baseline TG level.

Triglyceride Levels and Residual Risk of Atherosclerotic Cardiovascular Disease Events and Death in Adults Receiving Statin Therapy for Primary or Secondary Prevention: Insights From the KP REACH Study.

Background Patients with risk factors or established atherosclerotic cardiovascular disease remain at high-risk for ischemic events. Triglyceride levels may play a causal role. Methods and Results We performed a retrospective study of adults aged ≥45 years receiving statin therapy, with a low-density lipoprotein cholesterol of 41 to 100 mg/dL, and ≥1 risk factor or established atherosclerotic cardiovascular disease between 2010 and 2017. Outcomes included death, all-cause hospitalization, and major adverse cardiovascular events (myocardial infarction, stroke, or peripheral artery disease). The study sample included 373 389 primary prevention patients and 97 832 secondary prevention patients. The primary prevention cohort had a mean age of 65±10 years, with 51% women and 44% people of color, whereas the secondary prevention cohort had a mean age of 71±11 years, with 37% women and 32% people of color. Median triglyceride levels for the primary and secondary prevention cohorts were 122 mg/dL (interquartile range, 88-172 mg/dL) and 116 mg/dL (interquartile range, 84-164 mg/dL), respectively. In multivariable analyses, primary prevention patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (hazard ratio [HR], 0.91; 95% CI, 0.89-0.94) and higher risk of major adverse cardiovascular events (HR, 1.14; 95% CI, 1.05-1.24). In the secondary prevention cohort, patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (HR, 0.95; 95% CI, 0.92-0.97) and higher risk of all-cause hospitalization (HR, 1.03; 95% CI, 1.01-1.05) and major adverse cardiovascular events (HR, 1.04; 95% CI, 1.05-1.24). Conclusions In a contemporary cohort receiving statin therapy, elevated triglyceride levels were associated with a greater risk of atherosclerotic cardiovascular disease events and lower risk of death.

Rationale and design of the pragmatic randomized trial of icosapent ethyl for high cardiovascular risk adults (MITIGATE).

OBJECTIVE: The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). BACKGROUND: IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs. METHODS: MITIGATE is a virtual, electronic health record-based, open-label, randomized, pragmatic clinical trial enrolling ∼16,500 participants within Kaiser Permanente Northern California - a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving ∼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (∼ 1,500 IPE: ∼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE 2 grams by mouth twice daily with meals) vs the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time. CONCLUSION: The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pretreatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.

Real-world analyses of patients with elevated atherosclerotic cardiovascular disease risk from the Optum Research Database.

More than 56 million Americans have hypertriglyceridemia, including over 12 million statin-treated individuals. However, the contribution of elevated and high triglyceride levels to cardiovascular disease and death has not been extensively studied using real-world analyses. We review recent analyses of the Optum Research Database, which included patients aged ≥45 years with diabetes and/or atherosclerotic cardiovascular disease and on statin therapy. Triglyceride levels ≥150 and 200-499 mg/dl were significantly associated with a 25.8 and 34.9% increased relative risk of cardiovascular events, respectively, versus patients with triglyceride levels <150 mg/dl. In addition, hypertriglyceridemia predicted peripheral arterial revascularization, new heart failure diagnosis and new-onset renal disease. Increased triglyceride levels were also significantly associated with increased healthcare resource utilization and costs. Interventions such as icosapent ethyl reduce triglycerides and associated cardiovascular disease risk.

Mineral oil: safety and use as placebo in REDUCE-IT and other clinical studies.

Mineral oil is often used as a clinical trial placebo. Pharmaceutical-grade mineral oil consists of a mixture of saturated hydrocarbons, with a purity and chemical structure that differs substantially from food-grade or technical-/industrial-grade mineral oils. Interest in mineral oil was piqued by suggestions that a portion of the substantially positive results of the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) might be attributable to the theoretical negative effects of mineral oil rather than being due to the clinical benefits of icosapent ethyl. The objective of this review was to explore possible mineral oil safety and efficacy effects and contextualize these findings in light of the REDUCE-IT conclusions. A literature search identified studies employing mineral oil placebos. Eighty studies were identified and relevant data extracted. Adverse events associated with mineral oil were generally gastrointestinal and consistent with use as a lubricant laxative. Changes in triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and other biomarkers were inconsistent and generally not statistically significant, or clinically meaningful with mineral oil, as were changes in blood pressure. There was no consistent evidence that mineral oil in the amounts used in the REDUCE-IT or Effect of Vascepa on Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides on Statin Therapy (EVAPORATE) trials affects absorption of essential nutrients or drugs, including statins. These results were then considered alongside publicly available data from REDUCE-IT. Based on available evidence, mineral oil does not appear to impact medication absorption or efficacy, or related clinical outcomes, and, therefore, does not meaningfully affect study conclusions when used as a placebo at the quantities used in clinical trials.

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.

Association Between Triglycerides and Residual Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease (From the Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D] Trial).

Triglyceride (TG) levels encompass several lipoproteins that have been implicated in atherogenic pathways. Whether TG levels independently associate with cardiovascular disease both overall and, in particular among patients with established coronary artery disease (CAD) and type 2 diabetes (T2DM), remains controversial. Data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was used to evaluate patients with T2DM and CAD. Cox proportional hazards models were used to determine the association between TG levels and outcomes. Stepwise adjustment was performed for demographics, clinical factors, lipid profile and statin treatment. The primary composite outcome was time to CV death, myocardial infarction (MI), or stroke and secondary outcome was CV death. Among 2,307 patients with T2DM and CAD, the mean (±SD) TG levels were 181 (±136) with a median (Q1-Q3) 148mg/dL (104-219). Overall, 51% of patients had TG <150 mg/dL, 18% 150-199 mg/dL, 28% 200-499 mg/dL and 3% ≥500 mg/dL. Participants with elevated TG levels (≥150 mg/dL) were younger (61 vs 63 years, p <0.001), had higher BMI (32 vs 30 kg/m2, p <0.001), more likely to have had prior MI (34.2 vs 30.1%, p = 0.033) and revascularization (25.8 vs 21.4%, p = 0.013), had lower HDL-C (34 vs 39 mg/dL, p <0.001) and higher HbA1c (8 vs 7%, p <0.001). In unadjusted analyses, baseline TG levels were linearly associated with both the primary composite and secondary outcomes. In fully adjusted analyses, every 50 mg/dL increase in TG level was associated with a 3.8% (HR 1.038, 95%CI 1.004-1.072, p <0.001) increase in the primary composite outcome and a 6.4% (HR 1.064 95%CI 1.018-1.113, p <0.001) increase in the secondary outcome. There was no interaction between TG and outcomes within key subgroups including female sex, additional non-coronary atherosclerotic disease, CKD or low LDL (<100 mg/dL). In conclusion, among patients with T2DM and CAD, elevated TG were independently associated with adverse cardiovascular outcomes, even after adjustment for clinical and simple biochemical covariates.

The association between triglycerides and incident cardiovascular disease: What is "optimal"?

BACKGROUND: Elevated triglycerides (TGs) are associated with increased risk of cardiovascular disease (CVD), but the best way to both measure TGs and assess TG-related risk remains unknown. OBJECTIVE: The objective of the study was to evaluate the association between TGs and CVD and determine whether the average of a series of TG measurements is more predictive of CVD risk than a single TG measurement. METHODS: We examined 15,792 study participants, aged 40-65 years, free of CVD from the Atherosclerosis Risk in Communities and Framingham Offspring studies, using fasting TG measurements across multiple examinations over time. With up to 10 years of follow-up, we assessed time-to-first CVD event, as well as a composite of myocardial infarction, stroke, or cardiovascular death. RESULTS: Compared with a single TG measurement, average TGs over time had greater discrimination for CVD risk (C-statistic, 0.60 vs 0.57). Risk for CVD increased as average TGs rose until an inflection point of ~100 mg/dL in men and ~200 mg/dL in women, above which this risk association plateaued. The relationship between average TGs and CVD remained statistically significant in multivariable modeling adjusting for low-density lipoprotein cholesterol, and interactions were found by sex and high-density lipoprotein cholesterol level. CONCLUSIONS: The average of several TG readings provides incremental improvements for the prediction of CVD relative to a single TG measurement. Regardless of the method of measurement, higher TGs were associated with increased CVD risk, even at levels previously considered "optimal" (<150 mg/dL).

Prevalence of US Adults with Triglycerides ≥ 150 mg/dl: NHANES 2007-2014.

INTRODUCTION: Hypertriglyceridemia is associated with increased atherosclerotic cardiovascular disease (ASCVD) event risk, which persists even in statin-treated patients. The objective of this analysis was to estimate the prevalence of triglyceride (TG) levels ≥ 150 mg/dl in statin-treated adults with diabetes or ASCVD in the United States. METHODS: Laboratory data, medical history, and prescription data from 40,617 subjects who participated in the US National Health and Nutrition Examination Survey (NHANES) spanning 8 years (four 2-year surveys; 2007-2014) were analyzed. Patients included were ≥ 20 years old and had morning fasting (at least 8.5 h) TG values available. The proportion and weighted number of individuals in the US population with TG ≥ 150 mg/dl was calculated according to statin use, as well as in key subgroups of statin-treated patients including those with low-density lipoprotein cholesterol (LDL-C) levels < 100 mg/dl, type 2 diabetes, ASCVD, and those with type 2 diabetes and ASCVD. RESULTS: A total of 9593 subjects, projected to represent 219.9 million Americans, met the study entry criteria and were included in the analysis. Of these, 2523 had TG levels ≥ 150 mg/dl, translating to a prevalence of 25.9% and representing 56.9 million Americans. Among statin-treated adults, the proportion with TG levels ≥ 150 mg/dl was 31.6% (12.3 million) and ranged from 27.6 to 39.5% for those who also had LDL-C levels < 100 mg/dl and type 2 diabetes or ASCVD. CONCLUSIONS: Over 12 million Americans are treated with a statin and have TG levels ≥ 150 mg/dl. Interventions such as icosapent ethyl that have been shown to reduce ASCVD event risk in this elevated TG population with type 2 diabetes or established ASCVD can provide substantial clinical benefit for these patients.

Estimated ASCVD risk according to statin use in US adults with borderline triglycerides: Results from National Health and Nutrition Examination Survey (NHANES) 2007-2014.

BACKGROUND: Elevated triglycerides (TGs) are associated with atherosclerotic cardiovascular disease (ASCVD). Despite statin therapy, many US adults have borderline or elevated TG levels. Not characterized is the ASCVD risk associated with borderline TG levels in statin users, including the estimated number of adults who will sustain ASCVD events. METHODS: We studied 4986 US adults (weighted to 113 million) aged 40-74 from the National Health and Nutrition Examination Surveys 2007-2014. The proportion of persons at low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), and high (≥20%) 10-year ASCVD risk among those on statins was quantified for low (<70 â€‹mg/dL, 70-<100 â€‹mg/dL), borderline (100-<135 â€‹mg/dL and 135-<150 â€‹mg/dL), borderline high (150-<200 â€‹mg/dL), and elevated (≥200 â€‹mg/dL) TGs. Multiple logistic regression examined these TG categories in relation to high risk status. RESULTS: Overall, 18.6% of participants had TG â€‹< â€‹70 â€‹mg/dL, 24.2% TG 70-<100 â€‹mg/dL, 22.0% TG 100-<135 â€‹mg/dL, 6.2% TG 135-<150 â€‹mg/dL, 15.0% TG 150-<200 â€‹mg/dL, and 14.0% TG â€‹≥ â€‹200 â€‹mg/dL. Mean 10-year ASCVD risk for these groups were 5.6%, 6.9%, 7.8%, 10.3%, 9.6% and 10.8%, respectively (p â€‹< â€‹0.0001). One-fifth or more of statin users with TGs over 135 â€‹mg/dL were at ≥ 20% 10-year ASCVD risk and ≥60% of persons in all TG groups were at borderline or higher ASCVD risk. Compared to those with TGs <70 â€‹mg/dL, multiple logistic regression showed odds ratios of 3.1 to 4.6 (p â€‹< â€‹0.05 to p â€‹< â€‹0.01) for those in TG groups ≥135 â€‹mg/dL in the overall sample, but 3.4 to 8.1 (p â€‹< â€‹0.05 to p < 0.01) for those in TG groups of ≥100 â€‹mg/dL in statin users, despite adjustment including HDL-C. CONCLUSION: Many US adults with borderline levels of TGs are at elevated ASCVD risk despite statin therapy, suggesting the need first for greater lifestyle modification efforts, and when indicated, evidence-based therapies known to reduce this residual ASCVD risk.

Elevated Triglycerides (≥150 mg/dL) and High Triglycerides (200-499 mg/dL) Are Significant Predictors of New Heart Failure Diagnosis: A Real-World Analysis of High-Risk Statin-Treated Patients.

PURPOSE: Real-world data may provide insight into relationships between high triglycerides (TG), a modifiable cardiovascular (CV) risk factor, and increased heart failure (HF) risk. PATIENTS AND METHODS: This retrospective administrative claims analysis included statin-treated patients aged ≥45 years with diabetes and/or atherosclerotic CV disease enrolled in 2010 and followed for ≥6 months to March 2016. Patients with TG ≥150 mg/dL and a comparator cohort with TG <150 mg/dL and high-density lipoprotein cholesterol >40 mg/dL were included. A sub-analysis was conducted in patients with TG 200-499 mg/dL. Hazard ratios (HR) were calculated from multivariate analyses controlled for patient characteristics and comorbidities using Cox proportional hazard modeling. New diagnosis of HF required diagnosis in the follow-up period without prior evidence of HF. RESULTS: Multivariate analyses revealed a 19% higher rate of new HF diagnosis in the TG ≥150 mg/dL cohort (HR=1.192; 95% confidence interval [CI]=1.134-1.252; P<0.001; n=24,043) and a 24% higher rate in the TG 200-499 mg/dL sub-cohort (HR=1.235; 95% CI=1.160-1.315; P<0.001; n=11,657), each versus the comparator cohort (n=30,218). CONCLUSION: In a real-world analysis of statin-treated patients with high CV risk, elevated and high TG were significant predictors of new HF diagnosis.

Prevalence of United States adults with triglycerides ≥ 135 mg/dL: NHANES 2007-2014.

n/a - brief communication.

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.

Long-term statin persistence is poor among high-risk patients with dyslipidemia: a real-world administrative claims analysis.

BACKGROUND: A decade ago, statin persistence was < 50% after 1 year, and recent short-term analyses have revealed very little progress in improving statin persistence, even in patients with a prior cardiovascular (CV) event. Data on longer-term statin persistence are lacking. We measured long-term statin persistence in patients with high CV risk. METHODS: This retrospective administrative claims analysis of the Optum Research Database included patients aged ≥ 45 years with diabetes and/or atherosclerotic CV disease (ASCVD) who had a statin prescription filled in 2010. It included an elevated triglycerides (TG) cohort of patients with index date in 2010 and TG ≥ 150 mg/dL (n = 23,181) and a propensity-matched comparator cohort with TG < 150 mg/dL and high-density lipoprotein cholesterol > 40 mg/dL (n = 23,181). Both cohorts were followed for ≥ 6 months up to March 2016. RESULTS: The probability of remaining on a prescription fill for index statin therapy was 47% after 1 year and 19% after 5 years in both cohorts. Statin persistence was worse among women than men, and among younger versus older patients (P < 0.001 for all comparisons). After 5 years, the probability of remaining on a prescription fill for index statin was < 25% across all subgroups assessed including patients with and without baseline revascularization, heart failure, peripheral artery disease and renal disease. Similar results were observed in a subcohort analysis of patients with TG 200-499 mg/dL. CONCLUSIONS: Long-term statin persistence after 5 years is alarmingly low (< 25%) and is a public health concern.

Association of Elevated Triglycerides With Increased Cardiovascular Risk and Direct Costs in Statin-Treated Patients.

OBJECTIVE: To retrospectively investigate the real-world impact of elevated triglyceride (TG) levels on cardiovascular (CV) outcomes, medical resource utilization, and medical costs using observational administrative claims data from the Optum Research Database. METHODS: Patients with one or more claims for statin therapy between January 1, 2010, and December 31, 2010, and 6 months or more of baseline data prior to the index date were eligible for inclusion in the study. Patients aged 45 years or older with diabetes and/or atherosclerotic CV disease were included and analyzed in an elevated TG cohort (≥150 mg/dL) vs a comparator cohort with TG levels less than 150 mg/dL and high-density lipoprotein cholesterol (HDL-C) levels greater than 40 mg/dL. RESULTS: In the elevated TG vs propensity-matched comparator cohorts (both N=23,181 patients), the mean age was 62.2 vs 62.6 years, mean follow-up was 41.4 vs 42.5 months, 49.7% (11,518) vs 49.5% (11,467) were female, 83.7% (19,392) vs 84.0% (19,478) had diabetes, and 29.8% (6915) vs 29.3% (6800) had atherosclerotic CV disease. In the elevated TG (N=27,471 patients) vs comparator (N=32,506 patients) cohorts, multivariate analysis revealed significantly greater risk of composite major CV events (hazard ratio [HR], 1.26; 95% CI, 1.19-1.34; P<.001), nonfatal myocardial infarction (HR, 1.32; 95% CI, 1.20-1.45; P<.001), nonfatal stroke (HR, 1.14; 95% CI, 1.04-1.24; P=.004), and need for coronary revascularization (HR, 1.46; 95% CI, 1.33-1.61; P<.001) but not unstable angina (P=.53) or CV death (P=.23). Increased CV risk was maintained with the addition of non-HDL-C to the multivariate model and with high and low HDL-C subgroup analysis. Total direct health care costs (cost ratio, 1.12; 95% CI, 1.08-1.16; P<.001) and inpatient hospital stays (HR, 1.13; 95% CI, 1.10-1.17; P<.001) were significantly higher in the elevated TG cohort vs the comparator cohort. CONCLUSION: Statin-treated patients with TG levels of 150 mg/dL or greater had worse CV and health economic outcomes than those with well-managed TG (<150 mg/dL) and HDL-C (>40 mg/dL) levels.

The economic burden of hypertriglyceridemia among US adults with diabetes or atherosclerotic cardiovascular disease on statin therapy.

BACKGROUND: Hypertriglyceridemia (HTG) is associated with increased cardiovascular disease (CVD) risk. However, the cost burden of HTG-related CVD in high-risk US adults on statins has not been well characterized. OBJECTIVE: We estimated the HTG-related health care cost burden among US adults with CVD or diabetes taking statin therapy. METHODS: We estimated population sizes and annual health care costs among US adults aged ≥45 years with diabetes or CVD taking statin therapy with normal triglycerides (TGs) defined as TG < 150 mg/dL compared with those with HTG defined as TG ≥ 150 mg/dL. Population sizes were estimated from the 2007-2014 National Health and Nutrition Examination Surveys. Adjusted mean total annual health care costs in 2015 US dollars were estimated using the Optum Research Database. The annual total health care cost burden was estimated by multiplying the population size by the mean annual total incremental health care costs overall and within subgroups. RESULTS: There were 6.2 (95% confidence interval [CI], 5.4 - 7.1) million and 12.0 (95% CI, 11.1 - 12.9) million US adults aged ≥45 years with diabetes and/or CVD on statin therapy with TG ≥ 150 mg/dL and TG < 150 mg/dL, respectively. The mean adjusted incremental total one-year health care costs in adults with TG ≥ 150 mg/dL compared with those with TG < 150 mg/dL was $1730 (95% CI, $1160 - $2320). This leads to a projected annual incremental cost burden associated with HTG in patients with diabetes or CVD on statins of $10.7 billion (95% CI, $6.8 B - $14.6 B). CONCLUSION: In US adults on statins and at high risk for CVD, the health care costs associated with HTG are substantial.