A drug that lowers triglyceride levels did not reduce the risk of heart attack, stroke or cardiovascular death

• In a randomized trial of more than 10,000 people with diabetes, a drug that lowered triglyceride levels did not reduce the risk of heart attack, stroke or cardiovascular death

• The researchers described the results as "both confusing and clinically significant.
  "
  

Triglyceride levels are routinely measured as part of a preventive heart disease workup, and lowering triglycerides with several medications is common medical practice
.
However, in a major randomized trial of the new drug parmaphenolate, researchers found that although the drug reduced triglycerides by 26% compared to placebo, there was no reduction
in heart attack, stroke or cardiovascular disease mortality over a 5-year period.
The study was led by researchers at Brigham and Women's Hospital, one of the founding members of the Brigham Health System at Massachusetts General Hospital, with more than 10,000 participants
.
The new data were presented today at the American Heart Association's annual scientific meeting and published in the New England Journal of
Medicine.

"Parmafenate is very effective at lowering triglycerides and what we call residual cholesterol," said lead author Aruna Pradhan, MD, MD, of the Brigham Division of Cardiovascular Medicine, who co-chaired
the trial.
"However, we did not see evidence of
a decrease in difficult clinical events that patients and clinicians feared.
These findings are both confusing and clinically significant
.
”

PPARalpha agonists, such as fibrin, are a class of drugs that lower triglyceride levels in the blood through a variety of
mechanisms.
Pemafibrate is a selective PPARα modulator (SPPARMα) developed by Kowa and approved for use in Japan and some other Asian countries.
Traditional fibrate drugs like fenofibrate have been approved for use around the world, including the United States

This prestigious clinical trial was conducted by Kowa Research Institute, Inc.
Sponsorships, including 10,497 patients with type 2 diabetes, elevated triglyceride levels and low levels of HDL cholesterol — a group that showed promising results
in fibrin trials conducted a decade ago.
However, 572 participants randomized to parmafilate and 560 to placebo experienced a significant primary endpoint of the trial, heart attack, stroke, need for coronary artery bypass grafting or angioplasty, or cardiovascular death, with no statistically significant difference
between groups.
However, Pemafibrate is generally well tolerated and appears to reduce the incidence of nonalcoholic fatty liver disease (NAFLD), an important condition
for people with diabetes and obesity.

The authors note that the results of pemafibrate's findings on NAFLD require external replication; Several other clinical trials
of pemafibrate in the NAFLD setting are currently underway.

"We are studying groups of high-risk patients, and the best treatment for them remains an open question," said senior author Paul Ridker, PhD, trial co-chair and director of
the Brigham Center for Cardiovascular Disease Prevention.
"Compared to the study of fibrin a decade ago, our trial was conducted at a time when almost all participants were receiving statin therapy, so the relevance of triglyceride reduction in contemporary medical practice remains uncertain
.
"

The new striking data add to the recent controversy and debate
about the utility of reducing triglycerides in the care of patients at risk of contemporary heart disease.
In 2020, the results of the STRENGTH trial of omega-3 fatty acids showed a reduction in triglycerides of about 20%, but no benefit
for clinical events.
In contrast, in 2019, the REDUCE-IT trial of eicospene ethyl esters did show a significant reduction in clinical events, but this was not related
to the 20% reduction in triglycerides observed in this trial.

Other trials using alternative pathways to lower triglycerides, such as ApoCIII and ANGPTL3 inhibition, may help clarify these issues
.

"The outstanding lessons tell us once again that we can't know the truth
without a major randomized controlled placebo clinical trial," Ridker said.