SAN FRANCISCO — A simple, aggressive hypertension treatment regimen controlled systolic hypertension in 77% of 1,005 hard-to-treat patients after 18 weeks, Elijah Saunders, M.D., said.
The initial treatment consisted of a diuretic alone. If blood pressure control was not achieved, patients were switched to a combination pill containing the same diuretic and an angiotensin II receptor blocker.
The study included at least 100 patients from each of several populations in which high blood pressure often is difficult to control: patients aged 65 years or older, African Americans and Hispanic patients, patients with type 2 diabetes, and patients with metabolic syndrome.
The study, known as the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions In Diverse Patient Populations (INCLUSIVE) trial, is the first large-scale hypertension study to include such a broad range of patient groups, Dr. Saunders said at the annual meeting of the American Society of Hypertension. Women comprised 52% of the cohort.
Some study participants had risk factors for cardiovascular disease including obesity, abnormal glucose tolerance, high triglycerides, or low HDL. A large proportion of hypertensive people have these risk factors, and they often need two or more medications to control hypertension.
Patients entered the trial with high blood pressure that was not controlled adequately with one medication. After a 4-week washout period in which patients received placebo, treatment began with the diuretic hydrochlorothiazide at 12.5 mg/day. After 2 weeks, blood pressures were under control in 27% of patients.
The remaining patients were switched to combination treatment with 12.5 mg of hydrochlorothiazide and 150 mg of the angiotensin II receptor blocker irbesartan in a single daily pill (Avalide) for 8 weeks. During this second phase of treatment, a majority of patients reached blood pressure control: systolic pressure was under control in 56% of patients, and diastolic was controlled in 72%.
Patients who still had high blood pressures 12 weeks into the study were switched to a double dose of Avalide: 25 mg of hydrochlorothiazide with 300 mg of irbesartan per day.
At the end of the 18-week study, the study regimen had controlled 77% of systolic blood pressures and 83% of diastolic pressures, said Dr. Saunders, professor of medicine at the University of Maryland, Baltimore. The other principal investigator in the study was Joel Neutel, M.D., of the Orange County Research Center, Tustin, Calif., and the University of California, Irvine.
No particular efforts were made by the study patients to alter diet or exercise habits, suggesting that the benefits could be attributed to the medications.
The study patients were seen in 119 clinics, showing that high rates of blood pressure control can be achieved in general clinic settings, Dr. Neutel added.
The study was funded by the two companies that distribute Avalide in partnership, Bristol-Myers Squibb Co. and Sanofi-Synthelabo. Dr. Saunders is a consultant to both companies. Dr. Neutel is a speaker for Bristol-Myers Squibb.
The treatment was well tolerated. Dizziness was the most common side effect, occurring in 3% of patients. The incidence of hypokalemia did not increase with the higher thiazide dose.
In the United States, 53% of patients treated for hypertension reach recommended blood pressure goals of less than 140/90 mm Hg for the general population or 130/80 mm Hg for people with diabetes or chronic kidney disease, a 2000 study found. The magnitude of success in the current study surprised investigators, Dr. Saunders said.
Systolic blood pressures in the study dropped an average of 21 mm Hg, from 154 to 133 mm Hg. Diastolic pressures fell 10 mm Hg, from 91 to 81 mm Hg on average.
Improvements in blood pressure were similar between the subgroups studied, with systolic pressures dropping 15–23 mm Hg on average. The subgroup of diabetic patients had the lowest rates of control, with systolic pressure controlled in 56% and diastolic pressure controlled in 63% of patients. In the other subgroups, 72%–82% achieved systolic pressure control and 77%–96% achieved diastolic pressure control.