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Take a look at a selection of our recent media coverage:

Elevated LDL triglycerides linked to higher risk of atherosclerotic cardiovascular disease

1st February 2023

Higher LDL triglyceride levels are associated with a greater risk of atherosclerotic cardiovascular disease and its components

Danish and UK researchers examining data from the Copenhagen General Population Study, have determined that higher LDL triglyceride levels are linked to an elevated risk of atherosclerotic cardiovascular (ASCV) disease and its components such as myocardial infarction, ischaemic stroke and peripheral artery disease.

It is well recognised that a higher low-density lipoprotein (LDL) level is directly linked with the development of ASCV. Moreover, it has previously been shown that LDL contains a mixture of phospholipids, cholesterol and its esters and around 6% triglycerides. However, the role of triglycerides in ASCV has achieved much less attention in comparison to LDL, possibly because of a lack of randomised, clinical trial evidence.

As a result, in the current study, researchers wanted to better understand the potential role of LDL triglycerides (LDLT) in the development of ASCV and hypothesised that it was likely that higher LDLT levels would in fact be linked to greater risk of ASCV. The team used data obtained in the Copenhagen Population study, in which the lipid levels were measured in nearly 70,000 patients, either by a direct assay or from assessment by nuclear magnetic resonance. The researchers then performed a meta-analysis incorporating their findings from the Copenhagen study with previous studies.

LDL triglycerides and atherosclerotic cardiovascular disease

Levels of LDLT had been measured via a direct assay in 38,081 individuals and by NMR in 30,208 and who were followed for a median of 3 and 9.2 years respectively.

Using the results from measurement of LDLT direct assay, researchers calculated that for every 0.1mmol/l increase in LDLT, there was a 26% higher risk of ASCV (hazard ratio, HR = 1.26, 95% CI 1.17 – 1.35). The risks were similarly elevated for ischaemic heart disease (HR = 1.27), myocardial infarction (HR = 1.28), ischaemic stroke (HR = 1.22) and slightly higher for peripheral artery disease (HR = 1.38). Using the NMR-derived data gave rise to similar elevated risks for ASCV and its components.

When these results were included into the meta-analysis, giving a total participant population in excess of 110,000, a comparison of the highest to lowest LDLT quartile, revealed a risk ratio (RR) for ASCV of 1.5 (95% CI 1.35 – 1.66). Again, the risk ratios were also significantly elevated for ASCV components.

The authors concluded that elevated LDLT were robustly associated with an increased risk of ASCV and its components.

Citation
Balling M et al. Elevated LDL Triglycerides and Atherosclerotic Risk. Am J Coll Cardiol 2023

Moderate-intensity statin therapy and ezetimibe non-inferior to high-intensity mono-therapy

22nd July 2022

A moderate-intensity statin and ezetimibe regime in atherosclerotic cardiovascular disease is non-inferior to high-intensity statin therapy

A moderate-intensity dose statin combined with ezetimibe is non-inferior to high-intensity statin mono-therapy in patients with atherosclerotic cardiovascular disease (ASCVD) and has a lower incidence of drug discontinuation or dose reduction due to adverse statin events, according to a 3-year randomised trial by South Korean researchers.

High-intensity statin regimes lower LDL cholesterol and improve vascular outcomes in comparison to less intense regimes. This was clearIy shown in a meta-analysis of 26 randomised trial with over 170,000 patients, in which high-intensity statin therapy produced a highly significant reduction in major vascular events such as coronary death or non-fatal myocardial infarction, compared to less intensive regimens. Nevertheless, whilst effective, statin drugs are associated with intolerance and which has an overall prevalence of 9.1% but which reduces to 5.9%, depending on the definition used by various organisations. In addition, higher potency statins have been found to be associated with a 15% higher risk of new onset diabetes compared to lower potency agents.

One potential solution to using high-intensity (or high dose) statins is to use a moderate-intensity regime but with the addition of ezetimibe. Indeed, one 2014 systematic review of 36 trials found that moderate-intensity statin therapy with ezetimibe, decreased LDL cholesterol level 5% to 15% more than high-intensity mono-therapy among patients with ASCVD. Although the authors of the review advocated a lower-intensity statin-ezetimibe combination for high-risk patients who were either intolerant or unresponsive to statins, they cautioned on the absence of long-term clinical benefits and harms from using this approach. Consequently and with a need to gather much needed evidence, the South Korean team undertook the RAndomised Comparison of Efficacy and Safety of lipid lowerING with statin mono-therapy versus statin–ezetimibe combination for high-risk cardiovascular disease (RACING) trial. The purpose of the trial was to compare the 3-year clinical efficacy and safety of moderate-intensity statin with ezetimibe to high-intensity statin mono-therapy in patients who are at very high risk for cardiovascular disease. Individuals were randomised 1:1 to either ezetimibe and rosuvastatin 10 mg daily or high-intensity mono-therapy (rosuvastatin 20 mg daily). The primary endpoint was the occurrence of cardiovascular death, major cardiovascular events or non-fatal strokes within 3 years. For the secondary endpoints, the researchers considered the proportion of patients whose LDL cholesterol was reduced to under 70 mg/dL (1.81 mmol/L) over the 3 years. They set the test for non-inferiority as an upper level of the 95% confidence interval between the two groups, of less than 2%.

Moderate-intensity statin therapy and cardiovascular outcomes

A total of 3780 patients with ASCVD and a mean age of 64 years (75% male) were randomised equally to either intervention and the median duration of follow-up was 3 years.

The primary endpoint occurred in 9.1% of those receiving combination therapy and 9.9% of those with mono-therapy (hazard ratio, HR = 0.92, 95% CI 0.75 – 1.13, p = 0.43). Since the upper level of the confidence interval was 1.3% (less than the pre-specified 2%) the authors declared non-inferiority for the two regimes. Moreover, the mortality rates were not significantly different (HR = 1.34, 95% CI 0.46 – 3.85, p = 0.59).

For the secondary outcome of LDL lowering, 72% in the combination regime and 58% of those on mono-therapy, achieved the target of < 70 mg/dL (p < 0.0001).

Interestingly, discontinuation rates or dose reductions due to adverse effects were significantly less for those receiving combination therapy (4.8% vs 8.2%, p < 0.0001).

The authors concluded that the combination of moderate-intensity statin therapy and ezetimibe was non-inferior to high-intensity statin therapy but also that the combination gave rise to a lower incidence of drug discontinuation or dose reduction due to adverse effects and a higher proportion of patients reaching their LDL cholesterol level.

Citation
Kin BK et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial Lancet 2022