Effects of verapamil added-on trandolapril therapy in hypertensive type 2 diabetes patients with microalbuminuria: the BENEDICT-B randomized trial

J Hypertens. 2011 Feb;29(2):207-16. doi: 10.1097/hjh.0b013e32834069bd.

Abstract

Objectives: To address whether nondihydropyridine calcium-channel blocker added-on angiotensin-converting-enzyme inhibitor therapy ameliorates albuminuria and cardiovascular outcomes in type 2 diabetes patients.

Design: The Bergamo Nephrologic Diabetes Complications Trial-B was a multicentre, prospective, double-blind, parallel-group trial comparing renal and cardiovascular outcomes in 281 hypertensive type 2 diabetes patients with microalbuminuria randomized to at least 2-year VeraTran (verapamil/trandolapril 180 mg/2 mg daily) or trandolapril (2 mg daily, identical image) treatment. Main outcome was persistent macroalbuminuria (albuminuria >200 µg/min in two consecutive visits). Treatment targets were SBP/DBP less than 120/80 mmHg and HbA1C less than 7%.

Results: Over a median follow-up of 4.5 years, 18 patients (13%) on VeraTran vs. 15 (10.5%) on trandolapril [unadjusted hazard ratio (95% confidence interval [CI]) 1.07 (0.54-2.12), P = 0.852] progressed to macroalbuminuria, respectively; 62 (44.9%) vs. 71 (49.7%) [0.80 (0.57-1.12), P = 0.198] regressed to normoalbuminuria (urinary albumin excretion <20 µg/min), and 20 (14.5%) vs. 21 (14.7%) [hazard ratio 0.93 (0.50-1.72), P = 0.816] had major cardiovascular events. BP and metabolic control were similar between groups. Patients with cardiovascular events were significantly less [13 (9.8%) vs. 28 (18.9%), hazard ratio: 0.37 (0.19-0.71), P = 0.003] among those regressing to normoalbuminuria than those without regression. Difference was independent of treatment allocation and was significant also after adjusting for baseline characteristics [0.40 (0.20-0.79), P = 0.009], follow-up SBP [0.40 (0.20-0.80), P = 0.010] or DBP [0.36 (0.18-0.73), P = 0.004] BP or HbA1C [0.43 (0.21-0.88), P = 0.021].

Conclusion: In hypertensive type 2 diabetes patients with microalbuminuria, verapamil added-on trandolapril did not improve renal or cardiovascular outcomes. Independent of verapamil, trandolapril normalized albuminuria in half of patients and this translated into significant cardioprotection.

Trial registration: ClinicalTrials.gov NCT00235014.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / complications*
  • Albuminuria / drug therapy*
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Calcium Channel Blockers / administration & dosage
  • Cardiovascular Diseases / prevention & control
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension / complications*
  • Hypertension / drug therapy*
  • Indoles / administration & dosage*
  • Male
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome
  • Verapamil / administration & dosage*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Indoles
  • trandolapril
  • Verapamil

Associated data

  • ClinicalTrials.gov/NCT00235014