Abstract 4433: Comparative Effects of Aliskiren and Irbesartan on Blood Pressure, Renin System Activity, and Biomarkers of Cardiometabolic Risk in Patients with Hypertension and Metabolic Syndrome
Metabolic syndrome occurs in over one-third of patients with hypertension and conveys excessive cardiovascular risk. We compared the effects of the direct renin inhibitor aliskiren (ALI) and the angiotensin receptor blocker irbesartan (IRB) on blood pressure (BP) and biomarkers of renin system activity and cardiometabolic risk in 141 patients with a history of hypertension (BP ≥130/85 mmHg) and metabolic syndrome (NCEP ATP III criteria). After a 3-week washout, patients were randomized to once-daily double-blind ALI 150 mg (n=75) or IRB 150 mg (n=66) for 2 weeks, each titrated to 300 mg for 10 weeks. At week 12, ALI lowered systolic/diastolic BP from baseline (mean ± SEM) by 13.8/7.1 ± 1.5/0.9 mmHg (n=72), a significantly greater reduction than IRB (5.8/2.8 ± 1.6/0.9 mmHg; p≤0.001). ALI provided significantly higher responder rates than IRB for systolic BP (<135 or ≥20 mmHg reduction from baseline; 48.6% vs 30.3%, p=0.019) and significantly higher BP control rates (<135/85 mmHg) than IRB (29.2% vs 16.7%; p=0.017). Renin system biomarkers showed significant effects of both treatments on plasma renin activity (PRA; ALI -60% vs IRB +99%; p<0.001 for difference) and plasma renin concentration (PRC; ALI +425% vs IRB +157%; p<0.001), though prorenin (+27% with ALI or IRB) did not reach significance. ALI significantly lowered endothelin-1 (ET-1) levels by 28% (p<0.01); IRB reduced ET-1 by 22%, although this was not significant. Both ALI and IRB significantly reduced urinary F2 isoprostane levels by 13% from baseline (p<0.05), with no between treatment difference. There were no significant differences between groups for effects on a range of plasma biomarkers of inflammation (including C-reactive protein, GM-CSF, ICAM-1, pro- and anti-inflammatory interleukins, lymphotactin, MCP-1, MDC, MIP-1α, MIP-1β, RANTES, TNF-α, TNF-β or TNFRII) or cardiom-etabolic risk (including adiponectin, Apo-A1, -CIII or -H, ET-1, fibrinogen, insulin, leptin, lipoprotein [a], MMP-2, -3 or -9, PAI-1, TIMP-1, tissue factor, von Willebrand factor and MPO). In conclusion, ALI provided significantly better control of BP and renin system activity than IRB in patients with hypertension and metabolic syndrome, with similar effects on plasma biomarkers of cardiometabolic risk.