Ramipril-based versus diuretic-based antihypertensive primary treatment in patients with pre-diabetes (ADaPT) study.
BACKGROUND
Previous randomized controlled trials demonstrated a protective effect of renin angiotensin system blocking agents for the development of type-2 diabetes in patients with pre-diabetes. However, there are no real-world data available to illustrate the relevance for clinical practice.


METHODS
Open, prospective, parallel group study comparing patients with an ACE inhibitor versus a diuretic based treatment. The principal aim was to document the first manifestation of type-2 diabetes in either group.


RESULTS
A total of 2,011 patients were enrolled (mean age 69.1±10.3 years; 51.6% female). 1,507 patients were available for the per-protocol analysis (1,029 ramipril, 478 diuretic group). New-onset diabetes was less frequent in the ramipril than in the diuretic group over 4 years. Differences were statistically different at a median duration of 3 years (24.4% vs 29.5%; p<0.05). Both treatments were equally effective in reducing BP (14.7±18.0/8.5±8.2 mmHg and 12.7±18.1/7.0±8.3 mmHg) at the 4 year follow-up (p<0.001 vs. baseline; p=n.s. between groups). In 38.6% and 39.7% of patients BP was below 130/80 mmHg (median time-to-target 3 months). There was a significant reduction of cardiovascular morbidity and mortality in favour of ramipril (p=0.033). No significant differences were found for a change in HbA1c as well as for fasting blood glucose levels during follow-up. The rate of adverse events was higher in diuretic treated patients (SAE 15.4 vs. 12.4%; p<0.05; AE 26.6 vs. 25.6%; p=n.s).


CONCLUSIONS
Ramipril treatment is preferable over diuretic based treatment regimens for the treatment of hypertension in pre-diabetic patients, because new-onset diabetes is delayed.
Medizinische Klinik IV, Charité-Universitätsmedizin Berlin, Campus Benjamin-Franklin, Berlin, Germany. walter.zidek@charite.de
Walter
W
Zidek
Joachim
J
Schrader
Stephan
S
Lüders
Stephan
S
Matthaei
Christoph
C
Hasslacher
Joachim
J
Hoyer
Claudia
C
Zemmrich
Peter
P
Bramlage
Claus-Dieter
CD
Sturm
W Dieter
WD
Paar
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D018450:Disease Progression; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood / Q000453:epidemiology*; D011446:Prospective Studies; D017257:Ramipril / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D001786:Blood Glucose; D004232:Diuretics; D006442:Glycated Hemoglobin; D017257:Ramipril; C517652:hemoglobin A1c protein, human