Effect of quinapril or losartan alone and in combination on left ventricular systolic and diastolic functions in asymptomatic patients with diabetic autonomic neuropathy.
OBJECTIVE
To investigate the effect of angiotensin converting enzyme inhibition (ACE-I) or angiotensin receptor blockade (ARB), and their combination, on both diabetic autonomic neuropathy (DAN) and left ventricular (LV) diastolic dysfunction (LVDD) in asymptomatic patients with diabetes mellitus (DM).


METHODS
Sixty-two patients (34 women) with long-term DM (24 with Type 1) and DAN, aged 51.7+/-13.9 years, free of coronary artery disease (CAD) or arterial hypertension (HT) at baseline, were studied for a 12-month period. Diagnosis of DAN was established if two or more of the standard cardiovascular reflex tests (CRT) were abnormal. Patients were randomly allocated to quinapril (20 mg/day), losartan (100 mg/day), or quinapril plus losartan (20 mg/day+100 mg/day). LV systolic and diastolic function was assessed using radionuclide ventriculography (RNV) at baseline and after 12 months of treatment.


RESULTS
In all three treatment groups, abnormal CRT values were improved. In the quinapril group, the first third filling fraction (1/3FF, 48.9+/-17.8% vs. 39.2+/-12.9% at baseline, P=.005) was increased and the atrial contribution to ventricular filling (25.1+/-6.3 vs. 30.1+/-7.8, P=.027) was reduced in the losartan group; the peak filling rate (PFR) was improved (3.41+/-.62 vs. 3.11+/-.44 volumes/s, P=.05), and in the combination group, the 1/3FF (39.4+/-11.8% vs. 29.6+/-11.9%, P=.018) was markedly increased, while the time to peak filling (TPF; 147+/-42 vs. 184+/-33 ms, P=.02) and the TPF/filling time (TPF/FT; 32.5+/-6.2% vs. 38.2+/-5.7%, P=.016) were reduced.


CONCLUSIONS
Early ACE-I or ARB improve both DAN and LVDD in asymptomatic patients with Type 1 or 2 DM, after 1 year of treatment. Their combination may be slightly better than monotherapies on DAN and LVDD. The clinical importance of these effects should be validated by larger studies.
Didangelos
Triantafillos P
TP
Diabetes Center, 2nd Propedeutic Clinic of Internal Medicine, Hippocration Hospital, Aristotelian University of Thessaloniki, 49 Konstantinoupoleos Street, 546 42 Thessaloniki, Greece. didang@med.auth.gr
Arsos
Georgios A
GA
Karamitsos
Dimitrios T
DT
Athyros
Vasilios G
VG
Georga
Stamatia D
SD
Karatzas
Nikolaos D
ND
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077583:Quinapril; D015635:Radionuclide Ventriculography; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D044005:Tetrahydroisoquinolines; D019808:Losartan; D000077583:Quinapril