NEJM: For type 2 diabetic patients, this "bet" did a lipid-lowering process, but it did not translate into cardiovascular benefits...

High triglyceride levels are associated with increased cardiovascular risk, but it is uncertain
whether lowering these levels reduces the incidence of cardiovascular events.
Peroxisome proliferator-activated selective receptor α modulator pemafibrate reduces triglyceride levels and improves other lipid levels
.

In a multinational, double-blind, randomized, controlled trial, researchers assigned patients with type 2 diabetes, mild to moderate hypertriglyceridemia (triglyceride levels, 200 to 499 mg/dl), and high-density lipoprotein (HDL) cholesterol levels of 40 mg/dl or less to pemafibrate (0.
2 mg tablets twice daily) or a matched placebo group
.
Eligible patients are receiving guided lipid-lowering therapy or are unable to receive statin therapy without adverse effects and have a low-density lipoprotein (LDL) cholesterol level of 100 mg/dl or less
.
The primary efficacy endpoint was a combination of nonfatal myocardial infarction, ischaemic stroke, coronary revascularization, or death from cardiovascular causes
.

Results showed that in 10,497 patients (66.
9% with prior cardiovascular disease), the median fasting triglyceride level at baseline was 271 mg/dl, the median HDL cholesterol level was 33 mg/dl, and the median LDL cholesterol level was 78 mg/dl
.
The median follow-up was 3.
4 years
.
Compared to placebo, the effect of pemafibrate on lipid levels at 4 months was: -26.
2% for triglycerides, -25.
8% for very low-density lipoprotein (VLDL) cholesterol, -25.
6% for residual cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.
6% for apolipoprotein C-III and 4.
8
% for apolipoprotein B 。 The primary endpoint event occurred in 572 patients in the pemafibrate group and 560 patients in the placebo group (hazard ratio, 1.
03; 95% CI, 0.
91-1.
15), no clear effect change
in any of the prespecified subgroups.

There was no significant difference in the overall incidence of serious adverse events between groups, but pemafibrate was associated with
a higher incidence of adverse renal events and venous thromboembolism, as well as a lower incidence of nonalcoholic fatty liver disease.

Overall, in patients with type 2 diabetes mellitus, mild to moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, patients receiving pemafibrate had no lower rates of cardiovascular events than those receiving
placebo, although pemafibrate reduced triglycerides, VLDL cholesterol, residual cholesterol, and apolipoprotein C-III levels.

Original source:

Das Pradhan A, Glynn RJ, Fruchart JC, MacFadyen JG, Zaharris ES, Everett BM, Campbell SE, Oshima R, Amarenco P, Blom DJ, Brinton EA, Eckel RH, Elam MB, Felicio JS, Ginsberg HN, Goudev A, Ishibashi S, Joseph J, Kodama T, Koenig W, Leiter LA, Lorenzatti AJ, Mankovsky B, Marx N, Nordestgaard BG, Páll D, Ray KK, Santos RD, Soran H, Susekov A, Tendera M, Yokote K, Paynter NP, Buring JE, Libby P, Ridker PM; PROMINENT Investigators.
Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.
N Engl J Med.
2022 Nov 24; 387(21):1923-1934.
doi: 10.
1056/NEJMoa2210645.
Epub 2022 Nov 5.
PMID: 36342113.