ATLANTA — A new hormone therapy for postmenopausal symptoms also has a significant antihypertensive effect; the popular β-blocker carvedilol comes in a once-daily formulation; and an analysis of more than 600 patients with hypertension quantified the potential for reducing coronary heart disease by controlling blood pressure and serum lipids. These three poster reports were among the hypertension studies presented at the annual meeting of the American College of Cardiology.
New Progestin Lowers Blood Pressure
Drospirenone is a new progestin with antialdosterone effects that is being developed for use with 17-β estradiol to treat postmenopausal symptoms. The effect of drospirenone and estradiol on blood pressure was assessed in a dose-ranging study with 750 women. All participants were postmenopausal women with mild to moderate hypertension, with a systolic pressure of 140–179 mm Hg and a diastolic pressure of 90–109 mm Hg when off treatment.
The women were randomized to treatment with estradiol alone; estradiol plus 1 mg, 2 mg, or 3 mg of drospirenone daily; or placebo. After 8 weeks of treatment, average clinical BP readings in the placebo group had fallen by 8.7 mm Hg (systolic) and by 5.0 mm Hg (diastolic), compared with baseline. Estradiol treatment alone produced no significant reduction in BP, compared with the placebo effect.
Women treated with 1 mg of drospirenone daily had an average additional systolic pressure reduction of 0.9 mm Hg and a diastolic pressure reduction of 2.0 mm Hg, compared with the placebo group; this was of borderline statistical significance. The higher dosages of drospirenone had a more marked effect. Women taking a 2-mg daily dosage had an average additional fall in systolic pressure of 3.4 mm Hg and in diastolic pressure of 4.0 mm Hg, compared with the placebo group, which were statistically significant declines, reported Dr. William B. White, chief of the section of hypertension and clinical pharmacology at the University of Connecticut, Farmington, and his associate. Similar drops in pressure were also seen in women who received 3 mg of drospirenone daily.
All three dosages of drospirenone were “well tolerated, with modest subjective or objective adverse events,” said Dr. White and his associate in their poster. The percentage of patients who developed hyperkalemia while on treatment was similar in all five treatment groups. Other details of adverse effects were not reported. The study was sponsored by Berlex, which is developing drospirenone.
Once-Daily Dosing of Carvedilol
Carvedilol is a widely used β-blocker that is effective for lowering blood pressure and is especially popular for treating patients with heart failure. The only available formulation of carvedilol requires twice-daily dosing. A placebo-controlled, dose-ranging study with a total of 338 patients was done to assess the BP-lowering effects of a controlled-release (CR) once-daily formulation of carvedilol.
The study enrolled patients with diastolic blood pressures of 90–109 mm Hg. Patients were randomized to treatment with 20 mg, 40 mg, or 60 mg of carvedilol CR or placebo once daily for 6 weeks. The study's primary end point was the change in mean diastolic BP, measured by ambulatory BP monitoring, in the treatment groups, compared with those on placebo.
Placebo use led to an average 0.4 mm Hg decline in mean, 24-hour diastolic pressure. The three dosages of carvedilol CR led to significantly larger declines in a dose-dependent manner. The average falls in diastolic pressure were 4.4 mm Hg, 7.9 mm Hg, and 9.6 mm Hg in the 20-mg, 40-mg, and 60-mg groups, respectively, reported Dr. Michael A. Weber, professor of medicine at the State University of New York, Brooklyn, and his associates. Similar drops were also seen in systolic pressure. Blood pressure control was maintained for 20–24 hours after a dose of carvedilol CR.
The rates of adverse effects and of adverse effects leading to withdrawal from treatment were similar in all four treatment groups.
GlaxoSmithKline is developing carvedilol CR (Coreg CR), and submitted a new drug application to the Food and Drug Administration last year to have carvedilol CR approved as hypertension treatment.
CHD Risk Tied to Hypertension and Lipids
In patients with hypertension, a third to a half of their coronary heart disease events could be prevented by reductions in their BP and improved serum levels of LDL and HDL cholesterol. Three-quarters of their events could be prevented by optimal control of these parameters, Dr. Nathan D. Wong and associates reported in a poster.
They made these estimates by analyzing data collected for 1,921 people in the National Health and Nutrition Examination Survey (NHANES) 2001–2002. The study, sponsored by Pfizer Inc., focused on the 676 people from this group who had hypertension, defined as a BP of at least 90 mm Hg diastolic or 140 mm Hg systolic, or at least 80 mm Hg diastolic or 130 mm Hg systolic in patients with diabetes.