May 22, 2026Journal of the American College of Cardiology
The Effect of Darapladib on Plasma Lipoprotein-Associated Phospholipase A2 Activity and Cardiovascular Biomarkers in Patients With Stable Coronary Heart Disease or Coronary Heart Disease Risk Equivalent
Key result
Darapladib inhibits Lp-PLA2 activity up to ~66% vs placebo in stable CHD on atorvastatin.
- 43% to 66% inhibition
- P<0.001
- n=959
Why the study?
Does darapladib reduce Lp-PLA2 activity and inflammatory biomarkers in patients with stable coronary heart disease or CHD-risk equivalent receiving atorvastatin?
Population
959 patients with stable coronary heart disease or CHD-risk equivalent receiving atorvastatin
Comparison
Oral darapladib 40 mg, 80 mg, or 160 mg once… vs Placebo once daily for 12 weeks
Design
RCT, randomized
Follow-up
12 weeks
Authors
Discussion
Loading...
Member takes
Implication
In patients with stable CHD on intensive atorvastatin therapy, darapladib produced sustained, dose-dependent inhibition of Lp-PLA2 activity and reduced IL-6 levels.
Key Points
- To determine the effects of darapladib, a selective lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, on enzyme activity and inflammatory cardiovascular risk biomarkers in patients with coronary heart disease or risk equivalents.
- Randomized, double-blind, placebo-controlled trial including 959 patients with stable coronary heart disease or coronary heart disease risk equivalents receiving background atorvastatin (20 or 80 mg).
- Participants received oral darapladib at doses of 40 mg, 80 mg, 160 mg, or placebo once daily for 12 weeks, with serial blood biomarker assessments.
- Darapladib at 40 mg, 80 mg, and 160 mg produced sustained dose-dependent Lp-PLA2 inhibition of approximately 43%, 55%, and 66% compared with placebo (p < 0.001 at weeks 4 and 12).
- At 12 weeks, darapladib 160 mg reduced interleukin-6 by 12.3% (95% CI, -22% to -1%; p = 0.028) and hs-CRP by 13.0% (95% CI, -28% to +5%; p = 0.15) compared with placebo.
- Lp-PLA2 inhibition produced no detrimental effects on platelet biomarkers (P-selectin, CD40 ligand, urinary 11-dehydrothromboxane B2), with no major safety concerns reported.
Study Design
Type
RCT (n=959)
Randomization
randomized
Structured PICO
Does darapladib reduce Lp-PLA2 activity and inflammatory biomarkers in patients with stable coronary heart disease or CHD-risk equivalent receiving atorvastatin?
P
Population
959 patients with stable coronary heart disease or CHD-risk equivalent receiving atorvastatin therapy, followed for 12 weeks.
I
Intervention
Oral darapladib 40 mg, 80 mg, or 160 mg once daily for 12 weeks
C
Comparator
Placebo once daily for 12 weeks (both groups received background atorvastatin 20 or 80 mg)
O
Outcome
Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity at 12 weekssurrogate
Main Result
Effect estimate: 43% to 66% inhibition
p-value: p=<0.001
In patients with stable CHD on intensive atorvastatin therapy, darapladib produced sustained, dose-dependent inhibition of Lp-PLA2 activity and reduced IL-6 levels.
Cite This Study
Mohler et al. (2008) conducted an RCT in Coronary heart disease (CHD) and CHD-risk equivalent (n=959). Darapladib vs. Placebo was evaluated on Lp-PLA(2) activity (43% to 66% inhibition, p=<0.001). Darapladib 40 to 160 mg daily inhibited Lp-PLA(2) activity by 43% to 66% compared with placebo in patients with stable CHD receiving atorvastatin (P<0.001).