Treatment of elevated triglycerides has not been shown to improve cardiovascular outcomes in recent clinical trials. The PROMINENT study was published, showing that pemafibrate effectively reduced high levels but was not linked to a decreased risk for cardiovascular events.

Treatment of hypertriglyceridemia

Treating hypertriglyceridemia may be necessary for conditions other than cardiovascular ones. Given that the risk for pancreatitis rises with rising triglyceride levels, particularly in individuals with a history of the condition, it is the most often mentioned condition.

Lowering triglycerides may also be beneficial on a practical level. Due to the fact that most cholesterol panels use the Friedewald equation to calculate low-density lipoprotein cholesterol (LDL-C) as opposed to measuring it directly, extremely high triglyceride levels can invalidate the calculation and cause error readings to appear on lab reports.

Risk for cardiovascular disease and triglycerides association: causal or confounding?

The pertinent issue is whether elevated triglycerides constitute a standalone risk factor for cardiovascular disease if we are going to assess and treat them for cardiovascular reasons.

There is a sizable body of evidence that supports the claims made by supporters. Triglyceride levels and cardiovascular risk have been linked in several studies. The evidence even includes genetic studies, which shouldn't have some of the issues with observational cohorts, in addition to more conventional epidemiologic analysis.

However, it is challenging to determine if these connections are really causative or just confounding. Alcohol use and a poor diet both raise triglycerides. High triglyceride levels are seen in people with metabolic syndrome or diabetes. Patients receiving thiazide diuretics for hypertension as well as those with nephrotic syndrome, hypothyroidism, or both. Although incomplete, it is feasible to account for these baseline characteristics, and residual confounding is a constant problem.

A review of the Reykjavik and EPIC-Norfolk investigations revealed a link between triglyceride levels and the risk of cardiovascular disease. When the risk was controlled for conventional risk variables such as age, smoking, blood pressure, diabetes, and cholesterol, the risk of cardiovascular disease was reduced but not eliminated.

To determine whether hypertriglyceridemia causes cardiovascular disease or only identifies high-risk people, randomised studies of triglyceride-lowering treatments are necessary. Early studies seemed to confirm the existence of a causal connection.

In the Helsinki Heart Study, which randomly assigned participants to either gemfibrozil or a placebo, the fibrate was shown to reduce the relative risk of coronary artery disease by 34%. Gemfibrozil, however, did not only lower triglycerides. In comparison to placebo, it also raised HDL-C and decreased LDL-C, which might account for the observed effect.

The period before and after the introduction of statins

Participants in the FIELD study from 2005 were randomly assigned to receive either fenofibrate or a placebo. A statin was begun by 17% of the placebo group during the experiment, despite the patients not taking one before they entered the research.

The main outcome, a combination of coronary heart disease mortality and nonfatal myocardial infarction, was not decreased by fenofibrate. Nonfatal MI was one of the several secondary endpoints that showed a decrease in the fibrate-treated individuals, however, cardiovascular death did not. Simvastatin + fenofibrate or Simvastatin alone were the treatment options for participants in the 2010 ACCORD trial, which used a randomisation process.

The PROMINENT trial might be the clincher. Pemafibrate, the new agent, performed similarly to fenofibrate, its predecessor. Despite being very successful in lowering triglycerides (by more than 25%), pemafibrate had no effect on the study's main composite outcome of nonfatal MI, stroke, coronary revascularisation, or cardiovascular mortality. Compared to the placebo group, pemafibrate patients showed higher LDL-C and apoB levels. With that in mind, the study's findings are not all that unexpected.

Some use the REDUCE-IT findings as evidence that triglycerides are still a viable target for pharmaceutical treatment. REDUCE-IT was studied as both a medicine and a placebo, but that discussion may wait for another day. The important finding is that eicosapentaenoic acid (EPA) effects were shown independent of baseline or ultimate triglyceride levels. EPA may lower the chance of heart disease, but it's still controversial that it does so by cutting triglycerides. Additional ways of working may be involved.

Even if their utility as a target for medication treatment is debatable, elevated triglycerides may still be used to indicate danger. There was a period when triglyceride-lowering drugs were advantageous. However, some experts contend that this is the post-statin age and that period is now over.

Treatment with triglyceride-lowering medicine won't likely lessen a patient's risk of cardiovascular disease if they have high triglycerides. Better alternatives include dietary changes, promoting physical activity, and cutting down on alcohol. They'll lessen cardiovascular risk in addition to lowering cholesterol levels.

Clinical implications

1. What to deal with an ASCVD patient who has increased triglycerides (200 to 500 mg/dL) is a major concern for doctors. The ideal strategy is a treatment that is advised by guidelines and a lifestyle change.
2. Recognise that triglycerides are related to food obesity and glucose issues while optimising LDL reduction with statins and PCSK9 inhibitors if required.
3. This is something that requires a change in lifestyle including diet and physical activity since both have positive effects.
4. The trick is to stay away from alcohol processed carbs and sweets. But if that doesn't work some doctors recommend using icosapent ethyl or fibrates to bring triglyceride levels down to a more manageable level.
5. Although the administration of fibrates should not be based on the hope that they may prevent cardiovascular events.

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Monish Raut is a practising super specialist from New Delhi.