Real-world risk of cardiovascular outcomes associated with hypertriglyceridaemia among individuals with atherosclerotic cardiovascular disease and potential eligibility for emerging therapies

Abstract

Aims Hypertriglyceridaemia in patients with atherosclerotic cardiovascular disease (ASCVD) has been in focus following the REDUCE-IT trial showing benefit with icosapent ethyl. Among individuals with prevalent ASCVD, we sought to quantify the contemporary, real-world risk of ASCVD events associated with hypertriglyceridaemia, as well as estimate icosapent ethyl eligibility and compare trial participants with REDUCE-IT-like individuals in the population. Methods and results We examined data from 2 424 865 adults with lipid panels in the Ontario population. Among those with prevalent ASCVD, we examined adjusted associations between triglyceride (TG) and ASCVD events (first occurrence of myocardial infarction, unstable angina, stroke or transient ischaemic attack, coronary revascularization, or cardiovascular death). The proportion of patients with ASCVD potentially eligible for icosapent ethyl was estimated as those with TG 135–499 mg/dL (1.52–5.63 mmol/L) and low-density lipoprotein cholesterol (LDLc) 41–100 mg/dL (1.06–2.59 mmol/L), similar to the lipid cut-offs in REDUCE-IT, and their demographics and event rates examined. Among 196 717 individuals with ASCVD, median age was 69 years and 30% were female. A total of 24 097 composite ASCVD events occurred over a mean (standard deviation) 2.9 (0.5) years of follow-up. Increasing TG was associated with a graded, progressively higher hazard of ASCVD events. Twenty-five percent (49 886) of individuals with ASCVD had hypertriglyceridaemia and controlled LDLc; these patients were demographically similar to those in REDUCE-IT with comparable event rates. Conclusions Among patients with ASCVD, hypertriglyceridaemia is common, and is associated with higher ASCVD risk across a range of TG. It is possible that as many as one in four patients with ASCVD may be candidates for emerging therapies.

Triglyceride glucose index for the detection of asymptomatic coronary artery stenosis in patients with type 2 diabetes

“…Whether or not triglycerides are involved in the atherosclerotic process is still debated. Some data strongly suggest a relation between elevated triglyceride levels and cardiovascular disease [ 41 , 42 ] with a residual cardiovascular risk associated with triglycerides in patients with type 2 diabetes who have reached their LDL-cholesterol target [ 43 , 44 ]. A major role of the retention of cholesterol-rich and triglyceride-rich apoB-containing remnants within the arterial wall is to be considered in the pathogenesis of atherosclerosis [ 45 ].…”

Achievement of European guideline-recommended lipid levels post-percutaneous coronary intervention: A population-level observational cohort study

“…In keeping with our findings, a recent Canadian realworld study has found that approximately 25% of patients with atherosclerotic cardiovascular disease had moderately elevated TG with controlled LDL-C, identifying an increased event rate in these patients compared to those with TG <1.0 mmol/l. 5 Prescribing of HI-statins was considerably lower amongst patients with LDL-C levels above target. Whilst it is possible that a proportion of these patients were intolerant of HI-statins, it is more likely that a greater proportion of patients prescribed NI-statins with uncontrolled LDL-C, would be tolerant of HI-statins, acknowledging prior reported levels of statin intolerance in just 10-20% of statin-treated patients.…”

Applicability of the REDUCE‐IT trial to the FAST‐MI registry. Are the results of randomized trials relevant in routine clinical practice?

“…In the CLARIFY registry, 22 which involved patients with stable coronary artery disease (defined as a history of myocardial infarction, coronary stenosis >50%, symptomatic myocardial ischemia, or previous coronary revascularization procedure), 15.5% would have broadly met the enrolment criteria for REDUCE‐IT. One‐quarter of the ONTARIO study 23 population were reported to be eligible, but the population was broad based and included patients with a history of myocardial infarction, ischemic stroke, peripheral artery disease, or previous coronary revascularization procedure. The most similar study to FAST‐MI was a population‐based Danish cohort study in patients with myocardial infarction, 25 in which 21% met the enrolment criteria for REDUCE‐IT, substantially more than those in the FAST‐MI registries.…”

“…Several studies have applied the REDUCE-IT enrolment criteria to their study populations. [22][23][24][25] In the Veterans Affairs healthcare system, 24 14.5% of the population with ASCVD (defined as a history of myocardial infarction, ischemic stroke, or peripheral artery disease)…”