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Effect of perindopril in patients with stable coronary artery disease: results on inflammatory and thrombosis markers of the pertinent study
Authors:
C Ceconi, KM Fox1, WJ Remme2, ML Simoons3, M Bertrand4, C Kluft5, A Blann6, R Ferrari7, University Hospital - Ferrara - Italy, 1Royal Brompton Hospital - London - United Kingdom, 2Cardiovascular Research Foundation - Rhoon - Netherlands, 3Erasmus University - Rotterdam - Netherlands, 4Hopital Cardiologique - Lille - France, 5Gaubius Laboratory TNO-PG - Leiden - Netherlands, 6University of Birmingham - Birmingham - United Kingdom, 7Azienda Ospedaliera, Universita di Ferrara - Ferrara - Italy,
Topic(s):
ACE inhibitors and AT2 blockers
Endothelial function
Thrombosis / microcirculation, other
Prognosis
Rationale: The background hypothesis for the EUROPA Trial was a possible vascular and anti-atherosclerotic effect of perindopril.
Aim: To explore possible mechanisms explaining the beneficial effect of perindopril in secondary prevention in CAD patients, the Sub-Study PERindopril - Thrombosis, InflammatioN, Endothelial Dysfunction and Neurohormonal Activation Trial ``Perindopril - PERTINENT'' - examined the effect of perindopril (8 mg/day) on markers of inflammatory and thrombosis (vWF, CRP, fibrinogen and D-dimer).
Methods: We evaluated the predictive role in term of survival of von Willebrand factor (vWF); a marker of endothelial dysfunction and c-reactive protein (CRP), an index of systemic inflammation on an anticipated sample size of 1200 patients adopting a case-cohort study with the same events of the main EUROPA Trial. In 300 of the 1200 patients, the effect at one year of perindopril vs. placebo on fibrinogen and D-dimer as markers of thrombosis and inflammation was also determined. vWF, CRP, fibrinogen and D-dimer were determined with standard (ELISA) immunoassays or clotting rate methods.
Results: The levels of each marker in EUROPA patients at baseline were in the upper range with respect to normal values. Treatment with perindopril resulted in a significant reduction of vWF and D-dimer at one year (p < 0.05), but not CRP and fibrinogen.
The predictive role of vWf levels on cardiovascular events occurrence is confirmed by the current study that showed a significant difference in survival between patients with high (>142%/Unit) vs. those with low ( < 142%/Unit) levels of vWf (Log-Rank test: p < 0.01)
Conclusions: These data confirm the predictive role on cardiovascular events occurrence of vWF but not of CRP in 1200 patients with stable CAD enrolled in the EUROPA trial. One year treatment with perindopril significantly reduces vWF and D-dimer, 2 biomarkers of endothelial dysfunction.
Table 1. Markers of Thrombosis, Inflammation
Parameters |
Normal |
CAD Patients |
CAD Patients |
P values |
|
Ranges |
Baseline |
1 year |
(delta)Perindopril |
|
|
|
|
vs. placebo |
|
|
Placebo |
Perindopril |
Placebo |
Perindopril |
|
CRP (mg/L) |
<0.8 |
4.2±6.2 |
4.3±6.9 |
4.7±6.6 |
4.6±8.0 |
ns |
vWf (%/Unit) |
44-158 |
145±37 |
142±34 |
135±29 |
128±29 |
<0.05 |
Fibrinogen (g/L) |
<4.3 |
3.9±7.5 |
2.9±2.6 |
3.4±0.9 |
3.2±0.8 |
ns |
D-dimer (μg/mL) |
<0.5 |
0.3±0.5 |
0.5±0.7 |
0.3±0.5 |
0.3±0.3 |
<0.05 |
CAD indicates coronary artery disease, CRP, C-reactive Protein; vWf, von Willebrand factor.
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