Increased residual cardiovascular risk in patients with diabetes and high versus normal triglycerides despite statin‐controlled LDL cholesterol

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Aims To describe the real‐world prevalence and consequences of hypertriglyceridaemia. Materials and methods We searched two large patient databases, the National Health and Nutrition Examination Survey (NHANES) database (2007–2014) and the Optum Research Database, as well as electronic medical records from two Kaiser Permanente regions. Results The NHANES data showed that ~26% of US adults, including nearly one‐third of statin users, had at least borderline hypertriglyceridaemia (triglycerides [TGs] ≥1.69 mmol/L), and ~40% of adults with diabetes had levels of ≥150 mg/dL despite statin use. The Optum analyses demonstrated that those with TG levels ≥1.69 mmol/L who were on statins had a significantly increased risk of composite initial major cardiovascular (CV) events (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.19–1.34; P < 0.001 vs. patients with TGs <150 mg/dL). This was accompanied by increased healthcare utilization and direct healthcare costs (HR 1.12, 95% CI 1.08–1.16; P < 0.001). In the analyses of the Kaiser Permanente records, patients with diabetes and TG levels 2.26–5.64 mmol/L had significantly higher adjusted incidence rates of non‐fatal myocardial infarction (rate ratio 1.30, 95% CI 1.08–1.58; P = 0.006), non‐fatal stroke (rate ratio 1.23; 95% CI 1.01–1.49; P = 0.037) and coronary revascularization (rate ratio 1.21; 95% CI 1.02–1.43; P = 0.027), but not unstable angina (rate ratio 1.33; 95% CI 0.87–2.03; P = 0.185) compared with patients with TG levels <1.69 mmol/L. Conclusions Real‐world analyses suggest that elevated TGs are prevalent and commonly associated with increased CV risk. CV outcomes trials in patients with established hypertriglyceridaemia will clarify whether strategies to reduce TG levels can ameliorate residual CV risk in patients taking statins.

Section: Hypertriglyceridaemia In Real‐world Databasessupporting

confidence: 72%

Section: Strengths and Limitationsmentioning

confidence: 89%

Risk of cardiovascular events in patients with hypertriglyceridaemia: A review of real‐world evidence

Tóth

Fazio

Wong

et al. 2019

Self Cite

“…Icosapent ethyl, a manufactured omega‐3 fatty acid, is an emerging alternative for diabetic patients with cardiovascular disease and triglyceride level ≥150 mg/dL (1.7 mmol/L). Cardiovascular risk is higher in diabetic patients on treatment with statins and triglyceride levels more than 150 mg/dL (1.7 mmol/L) compared to normal levels (<150 mg/dL [1.7 mmol/L]) . Efficacy of Icosapent Ethyl 2 g twice daily reduced cardiovascular risk and mortality, in the recent REDUCE‐IT (Reduction of Cardiovascular Events Outcomes) trial and is an option for this high‐risk population .…”

Section: Add On Therapy For Secondary Prevention In Diabetes Mellitusmentioning

confidence: 99%

The extent to which statins have improved cardiovascular outcomes: Lessons from randomized trials and observational studies of “real world” practice in people with diabetes

Jayanna

Robinson

2019

Statins are the mainstay of therapy for cardiovascular risk reduction in patients with diabetes mellitus. It is estimated that there are more than half a billion patients with diabetes mellitus worldwide and the numbers of prevalent cases of diabetes are expected to increase in both developed and developing countries in the next decade. Statins reduce risk of mortality and morbidity mainly by reducing blood low density cholesterol. Statins, along with other medical treatments, are responsible for about half of the decrease in cardiovascular mortality over the past several decades. Multiple clinical trials have found evidence for statin use in patients with diabetes, for both primary prevention and secondary prevention. The benefit of statins in patients with coronary heart disease and diabetes in terms of absolute risk reduction is twice as much as compared to the risk in patients with coronary heart disease but no diabetes. The proportion of patients with diabetes treated with statins has increased steadily over the past few decades with concurrent decrease in cardiovascular deaths in this high‐risk population. However, there are significant unmet needs in cardiovascular risk reduction, due to underutilization of statins and due to residual cardiovascular risk despite maximal statin therapy. Future strategies in population risk reduction in diabetics should include maximal statin therapy, additional treatment with nonstatin therapy and new paradigms of prevention with early intervention with shorter, more intensive therapy to potentially “reverse” atherosclerosis with goals of reducing clinical cardiovascular disease later in life.

“…Nonetheless, despite these impressive reductions in LDL‐C, patients with T2D still have elevated risk of CVD (residual CVD risk): for example, patients with T2D treated with the PCSK9 inhibitor evolocumab still had a major adverse cardiac event rate of ~7%/y . This indicates that non‐LDL‐targeted therapies are likely needed for CVD protection …”

Section: Introductionmentioning

confidence: 99%

Residual cardiovascular risk among people with diabetes

Dash

Leiter

2019

Type 2 diabetes (T2D) is a growing health concern across both developed and developing countries. Cardiovascular disease (CVD) remains the major cause of increased mortality in this patient population. In recent years, effective low density lipoprotein lowering treatments and other risk reduction strategies have substantially reduced the risk of atherosclerotic CVD, yet patients with T2D continue to remain at increased risk for atherosclerotic CVD. Here, we will briefly review various proposed underlying mechanisms for this residual risk with a more in‐depth focus on the potential role of triglyceride‐rich lipoproteins in residual risk and potential avenues to target this pharmacologically.