Effect of successful hypertension control by manidipine or lisinopril on albuminuria and left ventricular mass in diabetic hypertensive patients with microalbuminuria.
OBJECTIVE
The aim of this open-labelled, randomised, parallel-group study was to evaluate the effect of long-term monotherapy with manidipine or lisinopril on albumin excretion rate (AER) and left ventricular mass index (LVMI) in hypertensive patients with type-2 diabetes and microalbuminuria.


METHODS
After a 4-week wash-out period, 174 patients with essential hypertension [diastolic blood pressure (DBP) >80 mmHg and <100 mmHg], type-2 diabetes and microalbuminuria were randomised to manidipine 10 mg o.d. or lisinopril 10 mg o.d.; after 8 weeks, the dose was doubled in non-responders (DBP >80 mmHg); after 3 months, treatment was discontinued in the non-responder patients and in those complaining of side effects; the remaining 121 patients continued their therapy with manidipine or lisinopril, and 99 completed the 2-year study. At the end of the wash-out period, of the titration period and after 6, 12, 18 and 24 months of treatment, BP was measured, AER, creatinine clearance, glycosylated haemoglobin (HbA1c) and body mass index (BMI) were evaluated and an echocardiographic evaluation was performed.


RESULTS
The 99 patients who completed the study were statistically analysed according to a per-protocol evaluation. Manidipine and lisinopril significantly reduced systolic blood pressure (SBP) and DBP levels (at 24 months, --22.3/15.5 mmHg, P<0.001 versus baseline and --21.4/15.7 mmHg, P<0.01 versus baseline, respectively). Both drugs provided a significant decrease in AER, but it was significantly more pronounced with lisinopril (at 24 weeks, --37.2 mg/24 h, P<0.001 versus baseline) than with manidipine (--29.9 mg/24 h, P<0.05 versus baseline) and became evident earlier in the lisinopril group (after 3 months versus 6 months of treatment). Manidipine produced a greater reduction of LVMI than lisinopril (--14.9 g/m(2) versus --10.8 g/m(2) at 24 months). The effect was more pronounced in patients with left ventricular hypertrophy at baseline (--19.8 g/m(2) versus --12.8 g/m(2), P<0.05).


CONCLUSIONS
These data suggest that, despite similar BP lowering, non-haemodynamic factors play an important role in the pharmacological reduction of AER and LVMI in diabetic hypertensive patients.
Fogari
Roberto
R
Department of Internal Medicine and Therapeutics, Clinica Medica II, University of Pavia, IRCCS Policlinico S. Matteo, 27100, Pavia, Italy. r.fogari@smatteo.pv.it
Mugellini
Amedeo
A
Zoppi
Annalisa
A
Lazzari
Pierangelo
P
Destro
Maurizio
M
Rinaldi
Andrea
A
Preti
Paola
P
D000368:Aged; D000419:Albuminuria / Q000150:complications / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017706:Lisinopril / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009578:Nitrobenzenes; D010879:Piperazines
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; C054218:manidipine; D017706:Lisinopril