Effects of verapamil added-on trandolapril therapy in hypertensive  type 2 diabetes patients with microalbuminuria: the BENEDICT-B randomized trial.
OBJECTIVE
To address whether nondihydropyridine calcium-channel blocker added-on angiotensin-converting-enzyme inhibitor therapy ameliorates albuminuria and cardiovascular outcomes in type 2 diabetes patients.


METHODS
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].


CONCLUSIONS
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.
Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, Villa Camozzi, Ranica, Italy.
Piero
P
Ruggenenti
Anna
A
Fassi
Aneliya  Parvanova
A
Ilieva
Ilian Petrov
IP
Iliev
Carlos
C
Chiurchiu
Nadia
N
Rubis
Giulia
G
Gherardi
Bogdan
B
Ene-Iordache
Flavio
F
Gaspari
Annalisa
A
Perna
Paolo
P
Cravedi
Antonio
A
Bossi
Roberto
R
Trevisan
Nicola
N
Motterlini
Giuseppe
G
Remuzzi
D000368:Aged; D000419:Albuminuria / Q000150:complications* / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy*; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014700:Verapamil / Q000008:administration & dosage*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D007211:Indoles; C052035:trandolapril; D014700:Verapamil