Irbesartan-HCTZ combination lowered blood pressure

The INCLUSIVE trial results show the combination treatment reduced systolic blood pressure in 77% of previously uncontrolled patients.

Combination therapy using irbesartan and hydrochlorothiazide was shown to effectively lower blood pressure levels in a large group of hypertensive patients.

“The INCLUSIVE [Irbesartan/HCTZ blood pressure reductions in diverse patient populations] trial showed that 77% of patients reached systolic goal blood pressure in a traditionally difficult-to-control population, and several treatment regimens achieved blood pressure goals in every eight out of 10 patients.

We also showed that it was well tolerated,” said Elijah Saunders, MD, who presented the results of the INCLUSIVE trial at the American Society of Hypertension 20th Annual Scientific Meeting and Exposition in San Francisco.

Saunders, chief of hypertension at the University of Maryland School of Medicine and an editorial board member of Cardiology Today’s Hypertension and Vascular Disease section, was one of the principal investigators.

INCLUSIVE trial

The INCLUSIVE trial was a prospective, open-label, single-arm study that included more than 1,000 patients with hypertension at 119 sites throughout the United States.

Included patients were elderly and patients with diabetes and metabolic syndrome. Patients had to have uncontrolled systolic blood pressure on monotherapy for at least four weeks. More than half were women; 25% were aged 65 or older; 23% were black, and 30% had type 2 diabetes. Eighty percent were on medications such as statins, aspirin, drugs for diabetes and nonsteroidals.

After a four to five week washout period, monotherapy with hydrochlorothiazide (HCTZ) was administered for two weeks. Therapy combining the angiotensin receptor blocker irbesartan and HCTZ was given in two doses to assess the effects on systolic blood pressure. Patients were given a dose of 150/12.5 mg of irbesartan-HCTZ for eight weeks. If they did not achieve goal BP, the dose was increased to 300/25 mg for another eight weeks.

The primary endpoint was systolic blood pressure from baseline at the end of the placebo period to 18 weeks of observation. The secondary endpoint was diastolic blood pressure, the mean change in systolic and diastolic at 10 weeks and the change in the total blood pressure at weeks 10 and 18, Saunders said.

BP goals achieved

Seventy-seven percent of patients on the larger dose of irbesartan-HCTZ achieved systolic blood pressure goals and 83% achieved diastolic goals, Saunders said. Sixty-nine percent of patients achieved dual systolic/diastolic goals.

From baseline to week 18, the mean reduction in systolic BP was 21.5 mm Hg (P<.001) and the reduction in diastolic blood pressure was 10.4 mm Hg (P<.001). In patients older than 65, the mean systolic reduction was 23 mm Hg; blacks, 20.7 mm Hg; and patients with type 2 diabetes, 18.2 mm Hg.

“There was a very good drop … roughly a 20 mm Hg drop in systolic blood pressure in all the groups,” Saunders said.

BP control was achieved in 82% of women and 56% of those with diabetes.

According to Saunders, previous therapies did not predict a response in the INCLUSIVE trial, and there were few drug-related adverse side effects in the study.

“The sad news is that we’re not controlling people very well. It does not require much hypertension to have significant risk. The fact that the combination was better than monotherapy was no surprise. What is a surprise is the extent that we got 77% of people controlled,” Saunders said. – by Nancie Brown

For more information:

• Saunders E. The efficacy and safety of irbesartan/HCTZ 150/12.5 mg and irbesartan/HCTZ 300/25 mg in patients with hypertension uncontrolled on monotherapy. Presented at the American Society of Hypertension 20th Annual Scientific Meeting and Exposition. May 14-18, 2005. San Francisco.