March 27, 2020JAMA168 citationsOpen Access
Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes
Key Result
Apabetalone added to standard therapy did not significantly reduce the risk of cardiovascular death, nonfatal MI, or stroke compared to placebo (HR 0.82; 95% CI 0.65-1.04; P=.11).
Study Design
Type
RCT (n=2,425)
Blinding
Double-blind
Randomization
1:1
Multicenter
Yes
Structured PICO
Does apabetalone reduce major adverse cardiovascular events in patients with recent acute coronary syndrome, type 2 diabetes, and low HDL cholesterol?
P
Population
2,425 patients with recent acute coronary syndrome, type 2 diabetes, and low high-density lipoprotein cholesterol levels, followed for a median of 26.5 months.
I
Intervention
Apabetalone 100 mg orally twice daily added to standard care
C
Comparator
Matching placebo added to standard care
O
Outcome
Composite of time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, or strokecomposite
In patients with recent ACS, T2D, and low HDL-C, the BET inhibitor apabetalone did not significantly reduce major adverse cardiovascular events compared to placebo.
Main Result
Hazard Ratio: 0.82 (95% CI 0.65–1.04)
Absolute Event Rate: 10.3% vs 12.4%
p-value: p=.11
Abstract
Importance: Bromodomain and extraterminal proteins are epigenetic regulators of gene transcription. Apabetalone is a selective bromodomain and extraterminal protein inhibitor targeting bromodomain 2 and is hypothesized to have potentially favorable effects on pathways related to atherothrombosis. Pooled phase 2 data suggest favorable effects on clinical outcomes. Objective: To test whether apabetalone significantly reduces major adverse cardiovascular events. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled trial, conducted at 190 sites in 13 countries. Patients with an acute coronary syndrome in the preceding 7 to 90 days, type 2 diabetes, and low high-density lipoprotein cholesterol levels were eligible for enrollment, which started November 11, 2015, and ended July 4, 2018, with end of follow-up on July 3, 2019. Interventions: Patients were randomized (1:1) to receive apabetalone, 100 mg orally twice daily (n = 1215), or matching placebo (n = 1210) in addition to standard care. Main Outcomes and Measures: The primary outcome was a composite of time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, or stroke. Results: Among 2425 patients who were randomized (mean age, 62 years; 618 women 25.6%), 2320 (95.7%) had full ascertainment of the primary outcome. During a median follow-up of 26.5 months, 274 primary end points occurred: 125 (10.3%) in apabetalone-treated patients and 149 (12.4%) in placebo-treated patients (hazard ratio, 0.82 95% CI, 0.65-1.04; P = .11). More patients allocated to apabetalone than placebo discontinued study drug (114 9.4% vs 69 5.7%) for reasons including elevations of liver enzyme levels (35 2.9% vs 11 0.9%). Conclusions and Relevance: Among patients with recent acute coronary syndrome, type 2 diabetes, and low high-density lipoprotein cholesterol levels, the selective bromodomain and extraterminal protein inhibitor apabetalone added to standard therapy did not significantly reduce the risk of major adverse cardiovascular events. Trial Registration: ClinicalTrials.gov Identifier: NCT02586155.