Study results of triple combination therapy in patients with diabetes and hypertension presented at ADA 2010

Preliminary results of a pre-specified subgroup study analysis of patients with diabetes and hypertension demonstrated that the investigational triple combination therapy of olmesartan medoxomil / amlodipine / hydrochlorothiazide (40/10/25 mg) resulted in a statistically significant greater Least Squares (LS) mean reduction in blood pressure from baseline at week 12 (37.9/22.0 mm Hg versus 26.4-28.0/14.7-17.6 mm Hg, P less than or equal to 0.0013) as compared to corresponding dual combination therapy [olmesartan medoxomil (40 mg) / amlodipine (10 mg); olmesartan medoxomil (40 mg) / hydrochlorothiazide (25 mg); or amlodipine (10 mg) and hydrochlorothiazide (25 mg)]. Blood pressure is more difficult to control among patients with hypertension and diabetes compared to patients with hypertension alone. These findings were presented today during a poster presentation at the American Diabetes Association (ADA) 70th Annual Scientific Sessions in Orlando, FL.

This analysis of the TRINITY study (Triple Therapy with Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients Study) also demonstrated that the investigational triple combination therapy (40/10/25 mg) enabled more patients with hypertension and diabetes to achieve blood pressure goal of <130/80 mm Hg at week 12 as compared to corresponding dual combination therapies (41.1 percent in the triple combination group versus 10.1 to 16.3 percent in the dual combination groups, P less than or equal to 0.0002).(1) Baseline blood pressures for those patients receiving the triple combination therapy and corresponding dual combination therapies were 170.7/98.3 mm Hg and 170.7-173.1/97.8-99.3 mm Hg, respectively.

Approximately 70 percent of people with diabetes have high blood pressure, which puts them at greater risk of developing long-term complications such as cardiovascular and renal disease. In order to achieve recommended blood pressure control of <130/80 mm Hg, the majority of people with diabetes are likely to need to take two or more antihypertensive medications.

About 15.5 percent (387 of 2,492) of the entire patient population of the TRINITY study were hypertensive patients with diabetes, and were thus included in this subgroup analysis. In these patients, the triple combination therapy was well tolerated with most reported adverse events defined as mild or moderate in severity.

"In addition to taking medications to treat high blood pressure, patients with diabetes often need to take several other medications to ensure glucose and cholesterol levels also are within recommended target levels," said Suzanne Oparil, MD, Professor of Medicine and Physiology and Biophysics at the University of Alabama School of Medicine. "Therefore, having a blood pressure-lowering treatment option that combines three medications into one pill will likely help patients take all of their medications as prescribed. Results of this subgroup analysis are important because it shows that this investigational triple combination therapy can help some of the most challenging patients significantly lower their blood pressure."

The triple combination therapy (40/10/25 mg) also demonstrated superior efficacy in the non-diabetes cohort with 68.6 percent of patients achieving goal compared to 39.0 to 52.8 percent in the dual combination therapy groups (P<0.0001). Treatment with the triple combination therapy (40/10/25 mg) also resulted in greater LS mean reductions in systolic and diastolic blood pressure in the non-diabetes cohort compared to the dual combination therapy groups (38.5/21.5 mm Hg versus 28.9 to 31.9/14.7 to 17.8 mm Hg, respectively, p<0.0001). Mean baseline blood pressure for the non-diabetes cohort was 167.4/101.4 mm Hg in the triple combination therapy group compared to 167.3-168.6/101.2-101.6 mm Hg in the dual combination therapy groups.

Publication-Only Abstract on Ethnicity and BMI Subgroup Analysis

Two additional pre-specified subgroup analyses of the TRINITY study by ethnicity (Hispanic/Latino or non-Hispanic/Non-Latino) and body mass index (BMI) category of <30 kg/m2 or greater than or equal to 30 kg/m2 found that the triple combination therapy was similarly more effective than dual regimens, regardless of the ethnicity and BMI of the patient.

It is estimated that hypertension affects 21 percent of Hispanic adults (18 years or older) in the U.S.  Additionally, the majority of patients with high blood pressure are overweight, with the condition being six times more frequent in obese people.

Results for the ethnicity subgroup analysis [Hispanic or Latino>

Additionally, in both the ethnicity and BMI subgroups of the study, the triple combination of olmesartan medoxomil / amlodipine / hydrochlorothiazide (40/10/25 mg) resulted in a greater percentage of patients reaching blood pressure goal compared with each dual combination group. The incidence of treatment-emergent events in the BMI and ethnicity subgroup analyses was comparable between groups and adverse events were mild or moderate.

TRINITY Study Design

At total of 2,492 patients with moderate to severe hypertension were enrolled into the Phase 3, multicenter, randomized, double-blind, parallel-group study, which examined the safety and efficacy of the triple combination of olmesartan medoxomil / amlodipine / hydrochlorothiazide (40/10/25 mg).(1,4) Patients were randomized to receive one of three dual combination therapies>

Safety & Tolerability

Across all groups, drug-related treatment adverse events (TEAEs) were reported in 25.4 percent of patients.  Most TEAEs and drug-related TEAEs were mild or moderate in severity. More discontinuations due to TEAEs occurred in the olmesartan medoxomil / amlodipine / hydrochlorothiazide (40/10/25 mg) (4.0 percent) versus the dual combination therapy groups (1.0 to 2.1 percent) and were due to adverse events such as dizziness and hypotension. These discontinuations can potentially be attributed to the more pronounced pharmacodynamic effect of the triple combination therapy. Peripheral edema also was a cause for discontinuation.

In addition, discontinuations for patients on triple combination therapy also included subjects who experienced an adverse event on earlier treatment (i.e. placebo or dual), prior to initiation of the triple combination regimen.