Irbesartan significantly reduced serum hsCRP (P<0.02), IL-6 (P<0.01), and platelet aggregation (P<0.001) compared with enalapril in patients with coronary artery disease and hypertension.
RCT (n=48)
double-blind
randomized
Does irbesartan improve markers of inflammation and platelet aggregation compared to enalapril in patients with CAD and hypertension post-angioplasty?
AT1-blockade with irbesartan exerts stronger systemic anti-inflammatory and anti-aggregatory effects compared with ACE inhibition with enalapril in patients with CAD.
p-value: p=<0.01
OBJECTIVES: We evaluated whether renin-angiotensin system (RAS) blockade attenuates cardiovascular events. BACKGROUND: Because inflammation and enhanced thrombogenesis are hallmarks of atherosclerosis, we assessed whether RAS inhibition elicits anti-inflammatory and anti-aggregatory effects. METHODS: Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), metalloprotease 9 (MMP-9), and interleukin 10 (IL-10) were determined in patients with coronary artery disease (CAD) and arterial hypertension six to eight weeks after coronary angioplasty (low-density lipoprotein serum levels <150 mg/dl). Patients were randomized double-blind to either 20 mg enalapril (ENAL, n = 27) or 300 mg irbesartan (IRB, n = 21) for 3 months. Blood samples were drawn at baseline and at three months. Thromboxane A2-induced platelet aggregation was determined turbidimetrically; urine bicyclo-prostaglandin E2 (PGE(2)) and inflammatory markers were measured by enzyme-linked immunosorbent assay technique. RESULTS: Both treatment regimens enhanced serum IL-10 levels (IRB p < 0.001, ENAL p < 0.03) and reduced serum MMP-9 protein (IRB p < 0.001, ENAL p < 0.05) and MMP-9 activity (IRB p < 0.005, ENAL p < 0.05). Only IRB reduced serum IL-6 and hsCRP levels significantly compared with baseline (p < 0.01), whereas ENAL did not (hsCRP p < 0.02 IRB vs. ENAL, p < 0.01 IRB vs. ENAL). Platelet aggregation was only reduced by IRB (p < 0.001, ENAL p < 0.06, IRB vs. ENAL p < 0.001) while urine PGE(2) levels remained unchanged. CONCLUSIONS: Angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1) blockade reduced serum MMP-9 protein/activity to a similar extent, and only AT1 blockade reduced hsCRP, IL-6, and platelet aggregation in patients with CAD. Thus, AT1-blockade appears to exert stronger systemic anti-inflammatory and anti-aggregatory effects compared with ACE inhibition.
Schieffer et al. (2004) conducted an RCT in Coronary artery disease and arterial hypertension (n=48). Irbesartan vs. Enalapril 20 mg was evaluated on Serum levels of inflammatory markers (IL-6, hsCRP, MMP-9, IL-10) and platelet aggregation (p=<0.01). Irbesartan significantly reduced serum hsCRP (P<0.02), IL-6 (P<0.01), and platelet aggregation (P<0.001) compared with enalapril in patients with coronary artery disease and hypertension.