NEW YORK—An investigational triple regimen of olmesartan medoxomil (OM), amlodipine besylate (AML), and hydrochlorothiazide (HCTZ) may result in significantly greater mean reductions in BP compared with a combination of any two of these drugs in patients with moderate to severe hypertension, new data show.

“Many patients with hypertension fail to reach recommended blood pressure targets even when taking more than one therapy,” said study investigator Suzanne Oparil, MD, Professor of Medicine and Physiology and Biophysics at the University of Alabama School of Medicine in Birmingham. “This study demonstrates that treating patients with a triple combination therapy regimen, each component of which has a different mechanism of action, is more effective at lowering blood pressure than the dual combination of any two individual components and was well tolerated among the patients’ studied.”

The new findings emerged from the TRINITY (Triple Therapy with Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients) study, a phase 3, multi-center, randomized, parallel-group trial that included 2,492 patients with moderate to severe hypertension.  The study, presented here at the American Society of Hypertension’s 25th Annual Scientific Meeting and Exposition, consisted of a 12-week double-blind treatment period followed by a 40-week open-label treatment period. The triple therapy consisted of 40 mg of OM, 10 mg of AML, and 25 mg of HCTZ). The results from the 12-week treatment period, which were presented by Dr. Oparil, found that the percentage of patients reaching the current recommended BP target was greater with the triple therapy regardless of gender, age, race, and hypertension severity.

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At week 12, 64.3% of patients in the triple combination arm reached their BP goal (below 130/80 mm Hg for patients with diabetes, CKD, or cardiovascular disease and below 140/90 mm Hg for other patients) compared with 34.9% of patients treated with combinations of any two of the drugs, a significant difference in favor of the triple regimen. Additionally, the triple regimen was well tolerated, with most reported adverse events considered mild or moderate.

In a subset of 380 patients, the researchers also measured 24-hour ambulatory BP at baseline and at week 12 and found a larger decrease in this value in the triple-regimen group. The 100 patients receiving the triple combination experienced a drop in 24-hour ambulatory BP from a mean of 147/87 at baseline to 117/69 at week 12. Among the patients receiving two-drug regimens, the 24-hour ambulatory BP values ranged from 147/89 to 149/89 at baseline. The declines in these values ranged from 126/74 to 128/77 at week 12.

A pre-specified subgroup analysis of 740 black and 1,718 non-black patients showed that both race subgroups experienced significant reductions in diastolic and systolic pressure from baseline to week 12.

Across all groups, drug-related treatment adverse events were reported by 25.4% of patients.  More discontinuations due to adverse events occurred in the triple therapy group compared with the dual combination groups (4.0% vs. 1.0%-2.1%).  Events leading to discontinuation included dizziness, hypotension, and syncope.

“Nephrologists should care about these findings because people with resistant hypertension don’t usually respond to single therapy or dual therapy and so triple combinations are needed, and triple combinations in proper doses are needed,” Dr. Oparil said.

A fixed-dose, single pill containing OM, AML, and HCTZ for the treatment of hypertension is under review by the FDA.