In patients with high blood pressure and type 2 diabetes, the blood pressure-lowering medication Diovan (valsartan) significantly reduced urinary protein excretion, with high doses providing the greatest sustained reduction, according to data presented at the Amer ican 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, M.D., Ph.D., 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 percent and 49 percent for 320 mg and 640 mg, vs. 25 percent 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 percent vs. 12 percent, 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 percent, 64 percent and 57 percent of patients in the Diovan 640 mg, 320mg and 160 mg groups, respectively. Other blood pressure medications were given to 37 percent, 42 percent and 46 percent 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).