NEW ORLEANS — Monotherapy with the direct renin inhibitor aliskiren was more effective at lowering blood pressure in hypertensive patients with metabolic syndrome than the angiotensin-receptor blocker irbesartan in a randomized study with 138 evaluable patients.
Aliskiren monotherapy also resulted in a significantly higher percentage of patients reaching their goal blood pressure, compared with those on irbesartan, Dr. Wilhelm Krone, professor and chairman of the second department of internal medicine at the University of Cologne (Germany), and his associates reported in a poster at the annual scientific sessions of the American Heart Association.
“Chronic activation of the renin system has been implicated in many of the key features of metabolic syndrome,” they said. “We hypothesize that the greater blood pressure-lowering effects by aliskiren relative to irbesartan in metabolic syndrome may be the result of more complete renin system inhibition by aliskiren in the kidney and/or adipose tissue. Adipocytes may contribute to blood pressure elevation in obesity-related hypertension through the generation of angiotensin II.” They also noted that metabolic syndrome occurs in more than a third of patients with hypertension.
The study was supported by Novartis, which markets aliskiren (Tekturna).
The subjects were aged 40-75 (average 59), 65% were men and 96% were white, and had metabolic syndrome. They all had essential hypertension (systolic pressure of at least 130 mm Hg or diastolic pressure of at least 85 mm Hg) and a waist circumference that met the definition for metabolic syndrome (at least 102 cm in men and 88 cm in women). In addition, they had to either have a plasma triglyceride level of more than 150 mg/dL or a fasting plasma glucose level between 100.8 mg/dL and 126 mg/dL.
Sixty-six were randomized to treatment with aliskiren and 75 were assigned to treatment with irbesartan. The average blood pressure at baseline was 156/94 mm Hg in the aliskiren group and 154/92 in the irbesartan group.
During the first 2 weeks of treatment, patients received either 150 mg of aliskiren once daily or 150 mg irbesartan once daily. After 2 weeks, the daily dosage in both arms was doubled to 300 mg once daily, and that dosage was maintained for an additional 10 weeks.
After a total of 12 weeks of treatment, blood pressure was cut by an average of 13.8/7.1 mm Hg in the 66 aliskiren-treated patients who completed the study and an average of 5.8/2.8 mm Hg in the 72 irbesartan-treated patients who finished the study. The differences in average reduction in both systolic and diastolic blood pressure were statistically significant. The percent of patients reaching the goal blood pressure of less than 135/85 mm Hg was 29% in the aliskiren group and 17% in the irbesartan group, a statistically significant difference.
Both treatments were generally well tolerated, with no serious adverse events in either arm. Neither drug was associated with a significant change in blood glucose or lipid profile and neither led to hyperkalemia or an increase in serum creatinine or blood urea nitrogen.
The study tracked changes in the levels of several biomarkers of inflammation, thrombosis, fibrosis, and oxidative state. No differences were seen between the two drugs for any of these, except that aliskiren therapy led to greater reductions of renin-system biomarkers, and irbesartan raised the level of eotaxin, an inflammatory cytokine.