Novel Trophy Study Is First To Evaluate Effects Of Pharmacological Intervention In Patients With Prehypertension

Main Category: Hypertension
Also Included In: Cardiovascular / Cardiology;  Clinical Trials / Drug Trials
Article Date: 18 Mar 2006 - 0:00 PDT

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Results of the TROPHY study (Trial Of Preventing Hypertension) were presented today in the late-breaking clinical trials session at the American College of Cardiology's 55th Annual Scientific Session. "The TROPHY study is groundbreaking because it's the first study to examine the potential to change the natural history of hypertension through early pharmacological intervention in patients diagnosed with prehypertension," said principal investigator Stevo Julius, MD, Professor of Internal Medicine and Physiology, University of Michigan. For the primary study end point of development of hypertension, there was a 15.6% relative risk reduction in the group treated with ATACAND® (candesartan cilexetil) compared with the group treated with placebo (53.2% vs 63.0% p<.007). According to Dr Julius, "The TROPHY study was designed to provide proof of principle for the feasibility of using a pharmacologic intervention to affect the natural history of hypertension."

Extensive clinical experience supporting the efficacy, safety and tolerability of ATACAND in hypertension made it an appropriate choice as the pharmacologic agent for investigation in TROPHY. ATACAND is indicated for the treatment of hypertension. ATACAND is not indicated to prevent the development of hypertension or for the treatment of prehypertension. In addition, ATACAND® (candesartan cilexetil) is indicated for the treatment of heart failure (NYHA class II-IV) in patients with left-ventricular systolic dysfunction (ejection fraction <=40%) to reduce cardiovascular death and to reduce heart failure hospitalizations. ATACAND also has an added effect on these outcomes when used with an ACE inhibitor.

Hypertension is defined as a blood pressure of 140/90 mm Hg or higher and is one of the most common cardiovascular diseases in the United States, affecting an estimated 65 million people or approximately one in three adults. Most of the mortality and morbidity from hypertension occur among subjects with stage 1 (mild) hypertension. The rationale behind TROPHY is that if it were possible to prevent the transition from prehypertension to stage 1 hypertension, there could be a positive benefit on public health.

The 7th report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) changed the classification "high normal blood pressure" to "prehypertension" in 2002, recognizing this condition as an increasing public health concern.

"Additional studies will be needed to determine the long-term benefits of delaying or preventing the development of hypertension," said Dr Julius.

About TROPHY

TROPHY was a four-year, multicenter (71 centers in the US), randomized, placebo-controlled study in 772 evaluable subjects (average age 48 years, 40% women) with prehypertension, defined as blood pressures (BP) of <=139/85-89 mm Hg or 130-139/<=89 mm Hg. The trial consisted of two years of double-blind treatment with candesartan (16 mg once daily) or matching placebo followed by 2 years of single-blind treatment with matching placebo in both groups. All subjects continued to receive non-pharmacologic interventions during the study. Blood pressure was measured by an automated device at the beginning of the study, and at 3-month intervals. The primary objective was to determine whether a 2-year period of active treatment with ATACAND® (candesartan cilexetil) would be sufficient to reduce the proportion of subjects developing hypertension over the 4-year duration of the trial. The primary study end point was the development of hypertension. Hypertension was defined as BP >=140/90 mm Hg on any 3 visits or at the 48-month visit, BP >=160/100 mm Hg at one visit, or clinical need for treatment. Patients reaching the hypertension end point were given active treatment and followed by clinics.

About Hypertension

An estimated 65 million Americans (one in three adults) have hypertension or high blood pressure. Thirty-one percent of patients with hypertension are unaware they have this condition, and among all hypertensive patients only 31% have their blood pressure under control. Of patients receiving treatment for hypertension, 47% do not have their blood pressure properly controlled. The prevalence of hypertension increases with age -- more than 50 percent of men and women ages 60-69 and approximately 75 percent of those age 70 and older have elevated blood pressure.

Lifestyle changes, such as weight loss, exercise, stopping smoking, and dietary adjustments can help reduce elevated blood pressure, and there are a number of classes of antihypertensive medications for those individuals who require drug treatment.

IMPORTANT SAFETY INFORMATION

The usual recommended starting dose of ATACAND is 16 mg once daily as monotherapy in patients who are not volume depleted. ATACAND can be administered once or twice daily with total doses ranging from 8 mg to 32 mg.

The recommended initial dose for treating heart failure is 4 mg once daily. The target dose is 32 mg once daily, which is achieved by doubling the dose at approximately 2-week intervals, as tolerated by the patient.

USE IN PREGNANCY: 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, ATACAND® (candesartan cilexetil) should be discontinued as soon as possible.

For full Prescribing Information for ATACAND, including boxed WARNING, call 1-800-236-9933 or visit http://www.atacand-us.com.

In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with diuretics), symptomatic hypotension may occur. These conditions should be corrected prior to administration of ATACAND, or the treatment should start under close medical supervision.

In heart failure patients receiving ATACAND, hypotension, increases in serum creatinine, and hyperkalemia have occurred. Caution should be observed for hypotension when initiating therapy. Evaluation of patients with heart failure should always include assessment of renal function and volume status. Monitoring of blood pressure, serum creatinine, and serum potassium is recommended during dose escalation and periodically thereafter.

During concomitant use of ATACAND and lithium, careful monitoring of serum lithium levels is recommended.

While overall incidence of adverse events of ATACAND in hypertension patients was similar to placebo in controlled clinical trials, some adverse events that occurred in at least 1% of patients treated with ATACAND were higher than with placebo, including upper respiratory infection (URI) (6% vs 4%), dizziness (4% vs 3%), back pain (3% vs 2%), pharyngitis (2% vs 1%), and rhinitis (2% vs 1%). The adverse event profile of ATACAND in heart failure patients was consistent with the pharmacology of the drug and the health status of the patients. In the CHARM program, comparing ATACAND in total daily doses up to 32 mg once daily (n=3803) with placebo (n=3796), 21.0% of patients discontinued ATACAND® (candesartan cilexetil) for adverse events versus 16.1% of placebo patients.

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