my personal edition > hypertension > news


  E-Mail this DGNews to a colleague

DGNews

Study Shows Valsartan Reduced Urinary Protein Excretion in Patients with Type 2 Diabetes and High Blood Pressure

High doses of Diovan provided greatest sustained reduction and were well-tolerated

Effective and sustained blood pressure lowering across all doses

CHICAGO, IL -- November 20, 2006 -- In patients with high blood pressure and type 2 diabetes, the blood pressure-lowering medication DiovanŽ (valsartan) significantly reduced urinary protein excretion, with high doses providing the greatest sustained reduction, according to data presented at the American Heart Association's (AHA) Annual Scientific Sessions.

The findings were from a study called DROP (Diovan Reduction Of Proteinuria), the largest and longest running trial to examine dose-related effects of an angiotensin receptor blocker (ARB) -- a class of medication used to treat hypertension -- on urinary protein excretion. DROP is also the first clinical study testing efficacy, safety and tolerability of Diovan 640 mg, a dose that is not currently approved.

"Recent research encouraged exploration into high doses of ARBs and their effects on microalbuminuria in addition to blood pressure," 7 said lead investigator Norman Hollenberg, MD, PhD, Professor of Medicine at Brigham and Women's Hospital and Harvard Medical School in Boston. "DROP found that high doses of Diovan provided a greater reduction in microalbuminuria than lower doses."

Study and Findings
The multi-center, double-blind study included 391 adult participants with type 2 diabetes, high blood pressure and high levels of urinary protein (urinary albumin excretion rate 20-700 mcg/min). All participants received Diovan 160 mg for the first 4 weeks, then were randomly assigned to continue that dose or receive 320 mg or 640 mg, twice the approved highest dose, for 26 more weeks.

Comparable urinary albumin excretion (UAE) reductions from baseline were seen in all groups at week 4 (p<0.001). However, by the end of the trial at week 30, participants taking the higher doses of Diovan achieved significantly greater reductions in UAE compared to those taking the lower dose: 51% and 49% for 320 mg and 640 mg, vs. 25% for 160 mg. Normal UAE rates (less than 20 mcg/min) were achieved by twice as many patients in the 640 mg dosage group than in the 160 mg group (24% vs. 12%, p=0.021). Except for slightly more dizziness and headache with the 640 mg dose, high doses were well-tolerated, with no dose-related increases in other adverse events, including hypotension (abnormally low blood pressure) and hyperkalemia (high blood potassium levels).

All doses of Diovan reduced blood pressure significantly (p<0.001) within 4 weeks, and that reduction was sustained throughout the study. In addition, an attempt was made to reduce blood pressure to less than 130/80 in all patients by providing, as needed, additional blood-pressure medications starting at week 6. This aggressive blood-pressure goal was achieved in 74%, 64% and 57% of patients in the Diovan 640 mg, 320mg and 160 mg groups, respectively. Other blood pressure medications were given to 37%, 42% and 46% of patients in these three groups, respectively. The most frequently prescribed add-on agents were amlodipine and hydrochlorothiazide. Despite the lower frequency of additional antihypertensive medications, the 640 mg Diovan dose induced a significantly greater reduction in blood pressure than the 320 mg dose at week 30 (p<0.05).

About Diovan and Diovan HCT
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, Diovan or Diovan HCT should be discontinued as soon as possible.

Diovan and Diovan HCT are contraindicated in patients who are hypersensitive to any component of these products. Because of the thiazide component, Diovan HCT is contraindicated in patients with anuria or hypersensitivity to sulfonamide-derived drugs.

Volume and or salt depletion should be corrected in patients prior to administering Diovan or Diovan HCT or symptomatic hypotension may occur.

Care should be exercised with dosing of Diovan in patients with severe renal impairment. As a consequence of inhibiting the renin-angiotensin system, changes in renal function may be observed in susceptible individuals (e.g. patients with renal artery stenosis or severe heart failure).

Important considerations due to the hydrochlorothiazide component: Thiazide diuretics should be used with caution in patients with impaired hepatic function or progressive liver disease; Lithium generally should not be given with thiazides. Thiazides have been reported to cause exacerbation or activation of systemic lupus erythematosus. Patients taking Diovan HCT should be observed for clinical signs of fluid or electrolyte imbalance.

No significant differences between adverse events, Diovan or Diovan HCT and placebo. AEs more frequent with Diovan than placebo: viral infection (3% vs 2%), fatigue (2% vs 1%), abdominal pain (2% vs 1%); the most common AEs: headache and dizziness. An increase in dizziness was observed with the 320 mg (8%) vs 10 mg to 160 mg (2% to 4%). AEs more frequent with Diovan HCT than placebo: nasopharyngitis (2.4% vs 1.9%). In individual studies, a dose-related increase in the incidence of dizziness was observed in Diovan HCT-treated patients.

Diovan HCT is for patients who need even more than Diovan or HCTZ alone and is not indicated for initial therapy.

Diovan and Diovan HCT are approved to treat high blood pressure, and are not approved to prevent heart attack, stroke, kidney disease or eye damage resulting from high blood pressure.

About Lotrel
Lotrel can harm an unborn baby and even cause death. If you get pregnant, stop taking Lotrel. Call your doctor right away. Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant.

Don't take Lotrel if you are allergic to any of the ingredients or to any ACE inhibitor. Your doctor or pharmacist can give you a complete list of the ingredients in Lotrel.

In rare cases with Lotrel, a potentially life-threatening allergic reaction (swelling of the mouth and throat) can occur. This potentially dangerous swelling of the mouth and throat has been reported more often in African American patients receiving ACE inhibitors than in non-African American patients.

Serious side effects such as low blood pressure (hypotension), low white blood cells, liver or kidney problems could occur. Rarely, worsening chest pain (angina) or heart attack has been reported, particularly in patients who already have severe heart disease.

The most common side effects include cough, dizziness, headache and edema (swelling of the feet, ankles, legs, or hands).

Lotrel is approved to treat high blood pressure, and is not approved to prevent heart attack, stroke, kidney disease or eye damage resulting from high blood pressure.


SOURCE: Novartis Pharmaceuticals

E-Mail this DGNews to a colleague

To print, use this version