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Calcium Channel Blockers May Not Add to ACE Inhibition in Nondiabetic Nephropathy: Presented at WCN

By Paula Moyer

BERLIN, GERMANY -- June 12, 2003 -- Adding the calcium channel blockers verapamil or amlodipine does not appear to significantly increase the antiproteinuric effect of totrandolapril in patients with nondiabetic nephropathy.

"Neither verapamil nor amlodipine increased the antiproteinuric effect in patients treated with the [angiotensin-converting enzyme] ACE inhibitor trandolapril," reported Robert Boero, MD, a staff nephrologist at the S.G. Bosco Hospital, in Turin, Italy.

In addition, Dr. Boero and colleagues found that the combination of trandolapril and verapamil was better tolerated than trandolapril and amlodipine. He presented the findings here June 9^th at the World Congress of Nephrology.

The investigators conducted their study to see whether the combination of the non-dihydropyridine calcium channel blocker verapamil or the dihydropyridine calcium channel blocker amlodipine, when combined with trandolapril, reduced proteinuria more than trandolapril alone in patients with nondiabetic proteinuric nephropathies. They also intended to evaluate the effects of these treatments on the selectivity of proteinuria, such as clearance of immunoglobulin G (IgG) or albumin, and the drugs' safety in these patients.

The team recruited 49 men and 20 women with nondiabetic nephropathies and an average of 54 years of age. Mean baseline serum creatinine level was 1.9 mg/dL, and mean baseline blood pressure was 136/90 mm Hg.

Patients went through a 1-month washout period from any ACE inhibitor or any angiotensin receptor blocker. Then they all received 2 mg daily of trandolapril in an open-label fashion for 1 month, after which they were randomly assigned to receive either 180 mg of verapamil or 5 mg of amlodipine daily for 8 months, in a double-blind phase. There were 33 patients in the verapamil arm and 36 in the amlodipine arm.

After 1 month on trandolapril monotherapy, the mean 24-hour proteinuria level was significantly reduced, from 3,078 mg to 2,537± 204 mg (P=0.005).

In the randomised phase, the investigators saw still more reduction of proteinuria in both groups, but no differences within and between groups. Patients treated with verapamil had a mean 24-hour proteinuria level of 2,335 mg at the beginning of combination therapy, and 2,124 mg at the end of the study. In the amlodipine group, the proteinuria levels decreased from a mean of 2,715 mg to a mean of 2,671 mg.

The selectivity of proteinuria was slightly and not significantly reduced in patients treated with the verapamil combination, from a median of 0.20 to a median of 0.16. In amlodipine-treated patients, this parameter significantly increased from a median of 0.20 to a median of 0.30 (P=0.0001). After randomisation, the verapamil group's serum creatinine level increased from 1.8 mg/dL to 1.9 mg/dL, a change the investigators did not find statistically significant. In the amlodipine group, that level increased from 2.2 mg/dL to 2.5 mg/dL (P=0.001).

In the overall patient group, the investigators found the changes in selectivity of proteinuria and serum creatinine from randomisation to the end of the study to be significantly and directly correlated (r=0.45, P=0.001).

Blood pressure levels at the end of the study were 127/83 mm Hg in the verapamil group and 125/83 mm Hg in the amlodipine group, a difference the investigators did not find to be statistically significant.

In the amlodipine group, 63.8% of patients reported adverse effects that the researchers considered to be related to this medication; in the verapamil group, the adverse events rate was 33.3% (P=0.016).

The researchers concluded that these findings show that neither verapamil nor amlodipine significantly adds any benefit to trandolapril's antiproteinuric effect. Dr. Boero urged further study to determine the possibility that amlodipine has an adverse effect of the selectivity of proteinuria and on renal function.


[Study title: The VVAMMTT Study: Verapamil Versus Amlodipine In Nondiabetic Nephropathies Treated With Trandolapril. Abstract M250]

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