ESRD is a serious condition which requires dialysis or transplantation for survival. The landmark study, called RENAALii, the renal protection study for losartan, which included 1,513 patients from 28 countries, is the first and only study to report that a hypertensive drug reduces ESRD and reduces hospitalizations due to heart failure in Type 2 diabetic patients with kidney disease. Previous studies with angiotensin converting enzyme (ACE) inhibitors have not yielded data on progression to ESRD in this growing patient population.
Losartan, a member of the newest class of antihypertensives known as angiotensin II antagonists (AIIA), is approved by the US Food & Drug Administration (US FDA) and Bureau of Food and Drug (BFAD) for the treatment and control of hypertension, commonly known as high blood pressure. An advantage of AIIAs is their excellent tolerability, compared to other classes of antihypertensives.
"When a patient has ESRD, the patient is faced with the extreme inconvenience and high costs of regular dialysis and possible kidney transplantation," said Lynn A. Gomez, M.D., clinical associate professor, UP-Philippine General Hospital. "Delaying the development of ESRD is therefore very crucial because of the potential of delaying or possibly taking away these treatment options. The RENAAL trial demonstrated that losartan can reduce the risk of ESRD. This is a landmark result for type 2 diabetes patients as this clearly illustrates the capacity of losartan to control the course of their disease."
Boon to millions of diabetics
Approximately 146 million people worldwide have Type 2 diabetes, the most common form of the disease affecting 90 to 95 percent of patients with diabetes. This form of diabetes usually occurs later in life and is often associated with increased body weight, hypertension and abnormalities of blood lipids. In fact, hypertension is two to three times more common in patients with Type 2 diabetes than in patients without diabetes.
Losartan lowers blood pressure, controls course of disease and demonstrates renal protection
In RENAAL, investigators followed patients for an average of 3.4 yearsiii. The primary endpoint of the study was a composite measure consisting of time to the first occurrence of either 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 losartan daily plus conventional blood pressure therapy had a significant reduction in the primary composite endpoint by 16 percent, p=0.024, compared to the placebo (inactive pill) group plus conventional blood pressure therapy. According to Dr. Gomez who discussed the RENAAL results with the media, the renal protective benefit of losartan was independent of its blood pressure lowering ability.
Dr. Gomez also reported the following results:
• Losartan significantly reduced the risk of progression to ESRD requiring dialysis or kidney transplantation by 28 percent, p=0.002.
• Losartan significantly reduced the risk of doubling of serum creatinine by 25 percent, p=0.006.
• Losartan significantly reduced the risk of ESRD or death by 20 percent, p=0.010.
• The risk of death was not significantly different between study groups.
The study also examined the effects of treatment on cardiovascular events and changes in proteinuria. The following observations were made:
• Hospitalization for heart failure, a component of the cardiovascular composite endpoint, was significantly reduced by 32 percent, p=0.005, in the patient group treated with losartan. There were similar effects in both treatment groups for the composite endpoint of cardiovascular events (heart attack, stroke, revascularization, hospitalization for unstable angina, hospitalization for heart failure and cardiovascular death).
• Proteinuria, or presence of protein in the urine and a marker of kidney damage, was significantly reduced by 35 percent in the patient group treated with losartan plus conventional blood pressure therapy compared to the placebo plus conventional blood pressure therapy group, p<0.001.
Losartan also provided excellent tolerabililty in this population. Discontinuations from study therapy due to clinical adverse events, not including deaths, were 17 percent in the group receiving losartan plus conventional blood pressure therapy versus 22 percent in the placebo plus conventional blood pressure therapy group. The most common clinical adverse events requiring discontinuation were heart failure, end-stage renal disease, heart attack, stroke and worsening renal insufficiency.
In the Philippines, losartan, a product of Merck Sharp & Dohme (MSD), is indicated for the treatment and control of high blood pressure.
Launched in 1994, losartan was the first in a new type of hypertension medications called angiotensin II antagonists (AIIAs). Losartan and its companion product losartan plus hydrochlorothiazide (Hyzaar) are the world’s most widely prescribed medications in this class and the second highest selling antihypertensives worldwide. One major and consistently observed advantage of these agents is their excellent tolerability, which is comparable to placebo, helping patients to stay on therapy and allowing physicians to help patients control the course of their disease. Losartan and losartan plus hydrochlorothiazide have been prescribed for more than ten million patients since their introduction.