Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients With Diabetes - PROMINENT

Feb 27, 2023
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Kowa Research Institute
Date Presented:
11/05/2022
Date Published:
11/05/2022
Date Updated:
02/27/2023
Original Posted Date:
11/05/2022
References

Contribution To Literature:

The PROMINENT trial failed to show that pemafibrate improved cardiovascular outcomes among patients with diabetes and hypertriglyceridemia.

Description:

The goal of the trial was to evaluate pemafibrate compared with placebo among patients with type 2 diabetes and hypertriglyceridemia. Pemafibrate is a selective peroxisome proliferator–activated receptor α (PPARα) modulator.

Study Design

  • Randomized
  • Parallel
  • Double-blind
  • Placebo

Patients with diabetes and elevated triglyceride levels were randomized to pemafibrate 0.2 mg twice daily (n = 5,240) vs. placebo (n = 5,257).

  • Total number of enrollees: 10,497
  • Median duration of follow-up: 3.4 years
  • Mean patient age: 64 years
  • Percentage female: 28%
  • Duration of diabetes ≥10 years: 46%

Inclusion criteria:

  • Type 2 diabetes
  • Triglyceride level 200-499 mg/dL
  • High-density lipoprotein cholesterol (HDL-C) ≤40 mg/dL

Exclusion criteria:

  • Type 1 diabetes
  • Uncontrolled diabetes
  • Untreated or inadequately treated hypothyroidism or hyperthyroidism
  • Severe heart failure
  • Severe kidney disease
  • Severe liver disease

Other salient features/characteristics:

  • Any statin, 96%
  • Median HDL-C, 33 mg/dL
  • Median LDL-C, 78 mg/dL

Principal Findings:

The primary outcome, cardiovascular death, nonfatal myocardial infarction, ischemic stroke, or coronary revascularization, occurred in 3.6% of the pemafibrate group vs. 3.5% of the placebo group (p = 0.67).

Secondary outcomes:

  • Median change in triglyceride level from baseline: -31.1% in the pemafibrate group vs. -6.9% in the placebo group
  • Median change in apolipoprotein B level from baseline: 3.2% in the pemafibrate group vs. -1.6% in the placebo group
  • All-cause mortality: 2.4% of the pemafibrate group vs. 2.3% of the placebo group
  • Any adverse renal event: 10.7% of the pemafibrate group vs. 9.6% of the placebo group (p = 0.004)
  • Venous thromboembolism: 0.4% of the pemafibrate group vs. 0.2% of the placebo group (p < 0.001)

Interpretation:

Among patients with diabetes and hypertriglyceridemia despite statin therapy, pemafibrate was associated with a significant reduction in triglyceride levels. However, pemafibrate was not associated with a reduction in adverse cardiovascular events. Pemafibrate was associated with an increased incidence of adverse renal events and venous thromboembolism. These results are consistent with the STRENGTH, AIM-HIGH, FIELD, and ACCORD trials. Among statin-treated patients, fibrates cannot be recommended for cardiovascular risk reduction.

References:

Das Pradhan A, Glynn RJ, Fruchart JC, et al., on behalf of the PROMINENT Investigators. Triglyceride Lowering With Pemafibrate to Reduce Cardiovascular Risk. N Engl J Med 2022;387:1923-34.

Editorial: Virani SS. The Fibrates Story — A Tepid End to a PROMINENT Drug. N Engl J Med 2022;387:1991-2.

Presented by Dr. Aruna D. Pradhan at the American Heart Association Scientific Sessions, Chicago, IL, November 5, 2022.

Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Cardiac Surgery and Arrhythmias, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and Vascular Medicine

Keywords: AHA Annual Scientific Sessions, AHA22, Apolipoproteins, Apolipoproteins B, Cholesterol, HDL, Cholesterol, LDL, Diabetes Mellitus, Type 2, Dyslipidemias, Heart Disease Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertriglyceridemia, Ischemic Stroke, Lipoproteins, HDL, Metabolic Syndrome, Myocardial Infarction, Myocardial Revascularization, Peroxisome Proliferator-Activated Receptors, Primary Prevention, Renal Insufficiency, Risk Factors, Triglycerides, Venous Thromboembolism


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