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Article Excerpt
Business Editors/Health & Pharmaceutical Writers
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Sept. 19, 2002
Cozaar is the Only Medicine to Demonstrate Significant Reduction in
Progression to End-Stage Renal Disease in this Patient Population
The Food and Drug Administration has approved Merck & Co. Inc.'s hypertension drug Cozaar(R) (losartan potassium tablets) to reduce the rate of progression of nephropathy (kidney disease) in type 2 diabetic patients with hypertension and nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio 300 mg/g), the Company announced today.
The new indication is based on the landmark RENAAL (Reduction of Endpoints in Non-Insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan) study, published last September in The New England Journal of Medicine. In this study, Cozaar, an angiotensin II receptor blocker (ARB), significantly delayed the doubling of serum creatinine (a marker of kidney disease) and significantly delayed progression to end-stage renal disease (ESRD), a condition requiring dialysis or renal transplantation for survival, but had no effect on overall mortality.
Cozaar is the only medicine that has demonstrated a significant reduction in the risk of ESRD in patients with type 2 diabetes, nephropathy and hypertension.
"End-stage renal disease is a growing worldwide public health concern, and type 2 diabetes is the leading cause of this condition," said Barry Brenner, M.D., director emeritus, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, and lead investigator of the RENAAL trial. "No other drugs, including ACE inhibitors, have demonstrated a significant reduction in the risk of ESRD in this patient population. This new indication for Cozaar may help physicians better manage the course of this disease in their patients."
For the treatment of nephropathy in hypertensive type 2 diabetic patients, the American Diabetes Association guidelines support ARBs as preferred first line therapy.
There are approximately 17 million people in the United States who have diabetes. Type 2 diabetes, which accounts for 90 to 95 percent of the patients with diabetes, is nearing epidemic proportions, due to an increased number of older Americans, and a greater prevalence of obesity and sedentary lifestyles. Diabetes is the leading cause of ESRD in the United States and accounted for approximately 40 percent of all cases between 1994 and 1998.
Once-daily Cozaar demonstrated renal benefits in RENAAL study
The RENAAL study was a multi-center, double-blind, placebo-controlled study designed to evaluate the renal effects of Cozaar in type 2 diabetic patients with nephropathy. The trial included 1,513 patients from 28 countries who were followed for an average of 3.4 years. Almost all of the patients had a history of hypertension.
In the study, 751 patients were randomized to the group treated with Cozaar (50 mg to 100 mg once daily) and 762 to the placebo treatment group. Both treatment groups continued to receive conventional blood pressure medication as needed. Conventional blood pressure medications taken by both treatment groups included calcium channel blockers, diuretics, beta-blockers, alpha blockers or centrally-acting agents. Other ARBs and angiotensin converting enzyme (ACE) inhibitors were excluded from the study. Standard medical care for managing diabetes was continued throughout the study.
The primary endpoint of the study was the time to the first occurrence of any one of the following events: doubling of serum creatinine (a marker indicating more than 50 percent loss of kidney function), end-stage renal disease (the need for long-term dialysis or kidney transplantation), or death. Patients taking Cozaar once daily, in addition to conventional blood pressure therapy, had a significant reduction of 16 percent (p=0.022) in the risk of kidney disease progression as measured by this primary endpoint compared to patients taking placebo plus conventional blood pressure therapy. Results showed that 327 patients taking Cozaar experienced doubling of serum creatinine, end stage renal disease or death as a first event (the primary endpoint) compared to 359 patients given placebo.
Seventy-two percent of patients were taking Cozaar 100 mg once daily more than half of the time they were on the study drug.
"We have known for years that lowering blood pressure is critically important for patients with type 2 diabetes because they are at substantially increased risk for kidney damage," said Dr. Brenner. "Not only is it important that we lower blood pressure, but this trial has shown that it is also matters how we lower blood pressure."
Other results were:
-- Cozaar significantly reduced the risk of progression to end-stage renal disease that requires dialysis or kidney transplantation by 29 percent (p=0.002). In the group treated with Cozaar, 147 patients progressed to ESRD during the study compared to 194 patients in the placebo group. -- Cozaar significantly reduced the risk of doubling of serum creatinine by 25 percent (p=0.006). Among patients treated with Cozaar, 162 patients experienced a doubling of serum creatinine during the study versus 198 patients in the placebo group. -- The risk of death was not significantly different between study groups.
In the RENAAL study, Cozaar reduced proteinuria, demonstrated excellent tolerability
Changes in proteinuria also were assessed as a secondary endpoint in the study. Proteinuria is the presence of a protein in the urine and is a marker of kidney damage. In the study, Cozaar significantly reduced proteinuria by an average of 34 percent compared to the placebo group. The study also examined the effects of treatment on cardiovascular events. There was no significant difference in the incidence of the composite endpoint of cardiovascular morbidity and mortality.
In this study, the overall incidences of reported adverse experiences were similar between groups treated with Cozaar and placebo. Cozaar was generally well tolerated as evidenced by a similar incidence of discontinuations due to side effects compared to placebo (19 percent for Cozaar, 24 percent for placebo). The most common adverse events in RENAAL reported with an incidence of 4 percent in patients treated with Cozaar (n=751) and occurring at a rate of 4 percent above placebo (n=762) on a background of conventional antihypertensive therapy were: diarrhea (15 percent vs. 10 percent), asthenia/fatigue (14 percent vs. 10 percent), hypoglycemia (14 percent vs. 10 percent), chest pain (12 percent vs. 8 percent), hyperkalemia (7 percent vs. 3 percent), and hypotension (7 percent vs. 3 percent).
Important Information about Cozaar
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, Cozaar should be discontinued as soon as possible.
Cozaar is contraindicated in patients who are hypersensitive to any component of the product.
In patients who are volume-depleted (e.g., those treated with diuretics), symptomatic hypotension may occur after initiation of therapy with Cozaar. These conditions should be corrected prior to administration of Cozaar, or a lower starting dose should be used.
Cozaar is also indicated for the treatment of hypertension. It may be used...
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