BENICAR Reverses Blood Vessel Damage Independent Of Blood Pressure Lowering

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Hypertension treatment olmesartan medoxomil was effective in reversing the narrowing of the arteries that occurs in patients with hypertension. The study, titled VIOS (Vascular Improvement with Olmesartan medoxomil Study) was a one-year, exploratory study that evaluated the effects of an angiotensin receptor blocker (olmesartan medoxomil) vs. a beta-blocker (atenolol) on vascular function and structure in patients with Stage 1 hypertension, independent of the blood pressure lowering effects of these agents.

In the VIOS trial, olmesartan medoxomil, through early blockade of angiotensin II, improved the structure abnormalities of resistance arteries in patients with hypertension as measured by arterial wall to lumen ratio (W/L), returning arterial architecture to normal levels after one year of treatment. This protective effect was not seen with the comparator agent in the study, atenolol. Olmesartan medoxomil is marketed in the United States by Daiichi Sankyo, Inc., as BENICAR . BENICAR and BENICAR HCT (olmesartan medoxomil/hydrochlorothiazide) are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive agents. BENICAR HCT is not indicated for initial therapy. BENICAR and BENICAR HCT have not been FDA approved for other indications such as end organ disease or other hypertension related morbidity.

"We believe the VIOS data add to the growing evidence for the role of angiotensin receptor blockers in preventing or reversing vascular damage at many stages during this disease process," said Carlos M. Ferrario, M.D., one of the study's lead investigators and Professor and Director of Hypertension and Vascular Research Center, Wake Forest University School of Medicine.

Angiotensin II has been linked to vascular dysfunction and end-organ damage, including cardiac hypertrophy and renal injury. Previous studies have demonstrated a beneficial effect of ACE inhibitors or other angiotension II receptor blockers (ARBs) in the reversal of vascular hypertrophy in hypertensive subjects.

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Hypertension is one of the most prevalent conditions in the United States, affecting one in three Americans. Long-standing, uncontrolled hypertension can damage the brain, the eyes, the heart and the kidney. Antihypertensive agents that inhibit the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors or ARBs, have demonstrated substantially greater effects on end-organ repair in the kidney and the heart.

VIOS Study Design

The study was a randomized, controlled, open-label, one-year study. The primary endpoint of this study was the change in the morphological characteristics of resistance arteries as determined by differences in the wall (media)/lumen (W/L) ratio. This parameter was measured using a pressurized myograph procedure on arteriole biopsy samples obtained from a sub-group of 49 patients receiving treatment (27 were on olmesartan and 22 were on atenolol) and from 11 normotensive control subjects.

Non-diabetic patients with Stage 1 hypertension (61% male; age 38 to 67 years) were randomized after a 4-week washout period to olmesartan medoximil 20 to 40 mg or atenolol 50 to 100 mg plus additional agents (hydrochlorothiazide 12.5-25 mg, amlodipine 5-10 mg, or hydralazine 50-100 mg twice daily) as needed for a goal BP of < 140/90).(20) Stage 1 hypertension is defined by the JNC 7 as systolic blood pressure (SBP) of 140-159 mm Hg or diastolic blood pressure (DBP) of 90-99 mm Hg.(21)

VIOS Study Results

The arteriolar dimensions (W/L Ratios) in the olmesartan medoxomil and atenolol-based treatment groups were similar prior to drug treatment (14.9% and 16% respectively) whereas arteries from the normotensive subjects had significantly smaller W/L ratios (11%). At the end of the study the W/L ratio in the olmesartan medoxomil-based treatment group was significantly reduced (from 14.9% to a mean of 11.1%; P<0.01). No significant change was observed in arteries of atenolol-treated patients (from 16.0% to 15.5%; P=NS). The difference between olmesartan medoxomil-treated and atenolol-treated patients at 1 year was significant (11.1% vs. 15.5%; P<0.001). Blood pressure reductions from baseline occurred within 12 weeks for both treatments and were statistically significant (P<0.05); blood pressure reductions were similar between the two treatments for the remainder of the study.

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