Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: a sub analysis of the Treat to Target post authorization survey. Prospective observational, two armed study in 14,200 patients.

Objectives: The metabolic syndrome is a cluster of cardiovascular risk factors leading to an increased risk for the subsequent development of diabetes and cardiovascular morbidity and mortality. Blocking the renin-angiotensin system has been shown to prevent cardiovascular disease and delay the onset of diabetes. Irbesartan is an angiotensin receptor blocker (ARB) which has been shown to possess peroxisome proliferator-activated receptor gamma (PPARgamma) activating properties, and to have a favorable metabolic profile. Current discussion is whether the addition of small doses of hydrochlorothiazide changes this profile. Therefore the efficacy, safety and metabolic profile of Irbesartan either as monotherapy or in combination therapy was assessed in patients with the metabolic syndrome in a large observational cohort in primary care.

Research Design And Methods: Multicenter, prospective, two-armed, post authorization study over 9 months in 14,200 patients with uncontrolled hypertension with and without the metabolic syndrome (doctors' diagnosis based on the Adult Treatment Panel III criteria 2001). Blood pressure was measured sphygmomanometrically and cardiovascular risk factors making up the criteria for the metabolic syndrome were assessed.

Main Outcome Measures: Systolic (SBP) and diastolic (DBP) blood pressure reduction, response, and normalization (systolic and diastolic), changes in fasting glucose, waist circumference (abdominal obesity), serum triglycerides and HDL cholesterol as well as the proportion of patients fulfilling the criteria for the metabolic syndrome. Number and nature of adverse events (AEs).

Results: After 9 month the use of Irbesartan in monotherapy resulted in a significant reduction of blood pressure (SBP: -26.3 +/- 10.1 mmHg/DBP-13.0 +/- 6.6 mmHg, both p < 0.0001) in patients with the metabolic syndrome. This was accompanied by a reduction in cardiovascular risk factors: HDL cholesterol (+3.6 +/- 7.2 mg/dl in men, +3.8 +/- 6.5 mg/dl in women, both p < 0.0001), serum triglycerides (-28.6 +/- 52.1 mg/dl, p < 0.0001), fasting blood glucose (-8.4 +/- 25.1 mg/dl, p < 0.0001) and waist circumference (-2.4 +/- 11.9 cm in men, -1.2 +/- 14.2 in women, both p < 0.0001) were significantly improved. Irbesartan combination therapy (12.5 mg HCTZ) in patients with the metabolic syndrome: blood pressure reduction (SBP: -27.5 +/- 10.1 mmHg/DBP: -14.1 +/- 6.6 mmHg, both p < 0.0001), improvement in HDL cholesterol (+4.0 +/- 6.8 mg/dl in men, +3.4 +/- 6.8 in women, both p < 0.0001), triglycerides (-34.1 +/- 52.6 mg/dl, p < 0.0001), fasting blood glucose (-10.0 +/- 24.7, p < 0.0001) and waist circumference (-3.2 +/- 12.7 cm in men, -1.7 +/- 14.4 in women, both p < 0.0001). Tolerability was excellent: only 0.6% of patients experienced an AE.

Conclusion: There was a significant improvement in blood pressure and metabolic risk factors as a result of Irbesartan treatment. There was no evidence of a difference between monotherapy and combination therapy with regard to the cardiovascular risk profile.