Benicar Reductions In Seated Systolic Blood Pressure For Stage 2 Patients

Armen Hareyan's picture
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Fixed-dose combination BENICAR HCT was associated with a greater mean reduction in seated systolic blood pressure at 12 weeks in patients with Stage 2 hypertension, compared with amlodipine + benazepril study doses.

Systolic blood pressure is considered a better predictor of major cardiovascular adverse events than is diastolic blood pressure, particularly in older individuals. Blood pressure reductions with BENICAR HCT and amlodipine + benazepril were examined.

After 12 weeks of treatment, patients receiving BENICAR HCT 40 mg/12.5-25 mg saw their SeSBP drop a mean of 33* points from baseline (167/102 mm Hg vs. 133/84 mm Hg), compared with a mean of 27* points from baseline (167/101 mm Hg vs. 140/86 mm Hg) for patients receiving amlodipine + benazepril 5/20 mg and 10/20 mg, according to the study.

The purpose of this study was to compare the blood pressure (BP) lowering effect of fixed dose combinations of BENICAR HCT 40/12.5 mg and 40/25 mg and amlodipine + benazepril 5/20 mg and 10/20 mg. No comparisons were made with amlodipine + benazepril 10/40 mg, the current maximum dose of this combination, because it was not available at the time this study was designed and initiated.

"The efficacy data results show a benefit for patients receiving either therapy, while those receiving BENICAR HCT showed a greater reduction," said Henry Punzi, MD, of the Punzi Medical Center and Hypertension Research Institute, Carrollton, TX, one of the study investigators.

When these data were examined to determine the blood pressure goal endpoint, more patients treated with the BENICAR HCT study doses reached blood pressure goals recommended by JNC 7 (<140/90 mm Hg and <130/80 mm Hg) than those treated with the amlodipine + benazepril study doses. In patients receiving BENICAR HCT combination therapy (40/12.5-40/25 mg), 66 percent achieved a BP goal of <140/90 mm Hg and 33 percent achieved a BP goal of <130/80 mm Hg. In patients receiving amlodipine 5-10 mg + benazepril 20 mg, 45 percent achieved a BP goal of <140/90 mm Hg and 14 percent achieved a BP goal of <130/80 mm Hg.

In specifically examining the highest dose studied in both treatment arms, Dr. Punzi reported that 61 percent of the patients receiving BENICAR HCT 40/25 mg at week 12 reached a goal of BP<140/90 mm Hg, nearly 42 percent reached BP<130/85 mm Hg, and 30 percent reached BP<130/80 mm Hg, compared to 39 percent, 19 percent and 13 percent, respectively, of patients who were treated with amlodipine 10 mg + benazepril 20 mg.

Hypertension, also known as high blood pressure, affects approximately 72 million people in the United States and approximately one billion worldwide. Called the "silent killer" because it often has no specific symptoms, hypertension increases the risk of cardiovascular and related diseases such as stroke, heart attack, heart failure and kidney disease. Of those diagnosed with high blood pressure, 64.9 percent did not have the condition under control(5).

The purpose of this study was to compare the blood pressure lowering effect of fixed dose combinations of BENICAR HCT with combinations of amlodipine + benazepril. Patients who failed to achieve the desired goal (<120/80 mm Hg) at any visit underwent dosage titration and were switched to combination therapy and titrated to the maximum available dose at the time of the study.

Patients were randomized to either 2 weeks of double-blind titration with olmesartan medoxomil 20 mg and then uptitrated to olmesartan medoxomil 40 mg for 2 weeks or 2 weeks of benazepril 10 mg uptitrated to 20 mg for 2 weeks. If BP remained greater than or equal to 120/80 mm Hg, then patients were uptitrated to the next treatment period; two 4-week periods with the combination of olmesartan 40 mg/HCTZ 12.5 and 25 mg or amlodipine + benazepril 5/20 mg to 10/20 mg. Patients exited the study at any visit if blood pressure <120/80 mm Hg was achieved.

Angiotensin II is a hormone that interacts with a receptor on arterial blood vessels, which results in constriction and increasing blood pressure. In addition, angiotensin II stimulates the release of another hormone that causes enhanced sodium and chloride (salt) retention, with a resultant increase in vascular water retention and blood volume that also contributes to an elevation in blood pressure. BENICAR is a member of the ARB class of antihypertensive medications that help lower blood pressure by blocking the angiotensin II receptor on the blood vessels and antagonizing the release of the hormone which causes salt retention and increased blood volume. BENICAR HCT combines BENICAR with the diuretic hydrochlorothiazide.

BENICAR and BENICAR HCT 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.

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When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, BENICAR or BENICAR HCT should be discontinued as soon as possible. See WARNINGS, Fetal/Neonatal Morbidity and Mortality in the prescribing information.

In patients with an activated renin-angiotensin system, such as volume-and/or salt-depleted patients (eg, those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with BENICAR. Treatment should start under close medical supervision. If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.

In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported. There has been no long-term use of olmesartan medoxomil in patients with unilateral or bilateral renal artery stenosis, but similar results may be expected.

The prescribing information for BENICAR HCT also includes the following warnings regarding its hydrochlorothiazide component:

BENICAR HCT is not recommended in patients with severe renal impairment and is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.

Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Lithium generally should not be given with thiazides.

In clinical trials, the withdrawal rates due to adverse events (AEs) were similar with BENICAR and BENICAR HCT to placebo: BENICAR (2.4 percent vs 2.7 percent); BENICAR HCT (2.0 percent vs 2.0 percent). The incidence of AEs with BENICAR and BENICAR HCT were similar to placebo. The only AE that occurred in >1 percent of patients treated with BENICAR and more frequently than placebo was dizziness (3 percent vs 1 percent). AEs reported in >2 percent of patients taking BENICAR HCT and more frequently than placebo included nausea (3 percent vs 0 percent), hyperuricemia (4 percent vs 2 percent), dizziness (9 percent vs 2 percent), and upper respiratory tract infection (7 percent vs 0 percent).

No initial dosage adjustments are recommended with BENICAR in elderly, in moderate to marked renal impairment (creatinine clearance <40 mL/min), or in hepatic dysfunction. In patients with possible depletion of intravascular volume (e.g., patients on diuretics, particularly with impaired renal function), BENICAR should be initiated under close medical supervision and consideration given to use of a lower starting dose. For BENICAR HCT, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosage range.

Both products are co-promoted in the United States by Daiichi Sankyo, Inc. and Forest Laboratories, Inc.

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