Darapladib effect on circulating high sensitive troponin in patients with acute coronary syndromes
Héctor M García-García1, Rohit M Oemrawsingh, Salvatore Brugaletta
1Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands; Cardialysis, Rotterdam, The Netherlands. hect2701@gmail.com
Insights
Darapladib treatment reduced cardiac troponin I (hs-cTnI) increases in patients with acute coronary syndrome (ACS). This suggests darapladib may benefit patients with stable coronary artery disease (CAD) by reducing plaque necrosis.
Area of Science:
- Cardiology
- Biomarkers
- Pharmacology
Background:
- Elevated high-sensitivity troponin I (hs-cTnI) can indicate myocardial damage.
- Understanding long-term troponin trends in acute coronary syndrome (ACS) versus non-ACS patients is crucial for risk stratification.
- The role of novel therapeutics in modulating troponin levels in stable coronary artery disease (CAD) requires further investigation.
Purpose of the Study:
- To compare the incidence of late hs-cTnI increase between ACS and non-ACS patients.
- To evaluate the effect of darapladib, in addition to standard care, on hs-cTnI levels in ACS and non-ACS patients.
- To identify predictors of hs-cTnI level fluctuations in patients with CAD.
Main Methods:
- A prospective study included 323 patients (161 ACS, 162 non-ACS).
- High-sensitivity troponin I (hs-cTnI) was measured at baseline and at 4, 13, 26, and 52 weeks.
- Multivariate logistic regression analysis was used to identify predictors of hs-cTnI increases.
Main Results:
- ACS patients exhibited higher mean hs-cTnI levels during long-term follow-up compared to non-ACS patients (1.180 vs. 0.886 ng/L, p=0.02).
- Darapladib treatment was associated with a reduced risk of a 2-fold increase in hs-cTnI (adjusted OR 0.53).
- Initial ACS presentation (adjusted OR 0.42) and diabetes (adjusted OR 2.20) were also significant predictors of hs-cTnI changes.
Conclusions:
- Darapladib treatment significantly decreased the risk of hs-cTnI elevation in ACS patients.
- The findings suggest darapladib may mitigate cardiac troponin increases, potentially by reducing necrotic core in coronary plaques.
- Darapladib may offer a therapeutic benefit in managing patients with stable CAD.
Objectives:
We compared the incidence of late increase in hs-cTnI between ACS and non-ACS patients treated with standard of care with or without darapladib.
Methods:
A total of 323 (161 ACS and 162 non-ACS patients) were included. High sensitivity troponin I was measured at baseline and at 4, 13, 26 and 52 weeks.
Results:
ACS patients had statistically higher hs-cTnI values during longer term follow-up at which these patients were no longer in the acute setting of myocardial ischemia, but were regarded to have stable CAD (mean hsTnI value in ACS patients: 1.180 versus 0.886 ng/L in non-ACS patients, p = 0.02). Multivariate logistic regression revealed three predictors of any 2-fold increase in hs-cTnI levels compared to the previous visit when interactions were not considered. Treatment with darapladib (adjusted OR 0.53; 95% CI: 0.30-0.92) and initial presentation with ACS (adjusted OR 0.42; 95% CI: 0.23-0.77) were associated with less frequent occurrence of a 2-fold increase in hs-cTnI levels. In contrast, diabetes was associated with a higher incidence of 2-fold increases in hs-cTnI levels (adjusted OR 2.20; 95% CI: 1.04-4.64). Logistic regression to predict any 2-fold increase in hs-cTnI by ACS status showed that in the ACS group, treatment with darapladib decreased the risk of elevation of hs-cTnI (OR 0.219; 95% CI: 0.087, 0.553, p = 0.0013).
Conclusion:
In patients with ACS, treatment with darapladib is associated with less increase in cardiac troponin I compared to standard of care alone. This beneficial effect may be associated with darapladib's capability of reducing necrotic core in coronary plaques.
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