Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2012

Open Access 01-12-2012 | Original investigation

Ramipril-based versus diuretic-based antihypertensive primary treatment in patients with pre-diabetes (ADaPT) study

Authors: Walter Zidek, Joachim Schrader, Stephan Lüders, Stephan Matthaei, Christoph Hasslacher, Joachim Hoyer, Claudia Zemmrich, Peter Bramlage, Claus-Dieter Sturm, W Dieter Paar

Published in: Cardiovascular Diabetology | Issue 1/2012

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
Bosch J, Yusuf S, Gerstein HC, Pogue J, Sheridan P, Dagenais G, Diaz R, Avezum A, Lanas F, Probstfield J, Fodor G, Holman RR: Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006, 355 (15): 1551-1562.CrossRefPubMed
2.
Moebus S, Hanisch JU, Aidelsburger P, Bramlage P, Wasem J, Jöckel K-H: Impact of four different definitions used for assessment of the prevalence of metabolic syndrome in a primary health care setting. The German Metabolic and Cardiovascular Risk Project (GEMCAS). Cardiovasc Diabetol. 2007, 6 (1): 22-10.1186/1475-2840-6-22.PubMedCentralCrossRefPubMed
3.
Lewington S, Clarke R, Qizilbash N, Peto R, Collins R: Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002, 360 (9349): 1903-1913.CrossRefPubMed
4.
Lipscomb ER, Finch EA, Brizendine E, Saha CK, Hays LM, Ackermann RT: Reduced 10-year risk of coronary heart disease in patients who participated in a community-based diabetes prevention program: the DEPLOY pilot study. Diabetes Care. 2009, 32 (3): 394-396. 10.2337/dc08-1622.PubMedCentralCrossRefPubMed
5.
Pollare T, Lithell H, Berne C: Insulin resistance is a characteristic feature of primary hypertension independent of obesity. Metabolism. 1990, 39 (2): 167-174. 10.1016/0026-0495(90)90071-J.CrossRefPubMed
6.
Economic costs of diabetes in the U.S. In 2007. Diabetes Care. 2008, 31 (3): 596-615.
7.
Verdecchia P, Reboldi G, Angeli F, Borgioni C, Gattobigio R, Filippucci L, Norgiolini S, Bracco C, Porcellati C: Adverse prognostic significance of new diabetes in treated hypertensive subjects. Hypertension. 2004, 43 (5): 963-969. 10.1161/01.HYP.0000125726.92964.ab.CrossRefPubMed
8.
Elliott WJ, Meyer PM: Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007, 369 (9557): 201-207. 10.1016/S0140-6736(07)60108-1.CrossRefPubMed
9.
Lam SK, Owen A: Incident diabetes in clinical trials of antihypertensive drugs. Lancet. 2007, 369 (9572): 1513-1514. author reply 1514-1515CrossRefPubMed
10.
Kjeldsen SE, Julius S, Mancia G, McInnes GT, Hua T, Weber MA, Coca A, Ekman S, Girerd X, Jamerson K, Larochelle P, MacDonald TM, Schmieder RE, Schork MA, Stolt P, Viskoper R, Widimsky J, Zanchetti A: Effects of valsartan compared to amlodipine on preventing type 2 diabetes in high-risk hypertensive patients: the VALUE trial. J Hypertens. 2006, 24 (7): 1405-1412. 10.1097/01.hjh.0000234122.55895.5b.CrossRefPubMed
11.
Yusuf S, Gerstein H, Hoogwerf B, Pogue J, Bosch J, Wolffenbuttel BH, Zinman B: Ramipril and the development of diabetes. JAMA. 2001, 286 (15): 1882-1885. 10.1001/jama.286.15.1882.CrossRefPubMed
12.
Yusuf S, Ostergren JB, Gerstein HC, Pfeffer MA, Swedberg K, Granger CB, Olofsson B, Probstfield J, McMurray JV: Effects of candesartan on the development of a new diagnosis of diabetes mellitus in patients with heart failure. Circulation. 2005, 112 (1): 48-53. 10.1161/CIRCULATIONAHA.104.528166.CrossRefPubMed
13.
Califf RM, Boolell M, Haffner SM, Bethel MA, McMurray J, Duggal A, Holman RR: Prevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance: rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial. Am Heart J. 2008, 156 (4): 623-632. 10.1016/j.ahj.2008.05.017.CrossRefPubMed
14.
Dahlof B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J: Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005, 366 (9489): 895-906. 10.1016/S0140-6736(05)67185-1.CrossRefPubMed
15.
Poulter NR, Wedel H, Dahlof B, Sever PS, Beevers DG, Caulfield M, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J, Pocock S: Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). Lancet. 2005, 366 (9489): 907-913. 10.1016/S0140-6736(05)67186-3.CrossRefPubMed
16.
Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, Hua T, Laragh J, McInnes GT, Mitchell L, Plat F, Schork A, Smith B, Zanchetti A: Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004, 363 (9426): 2022-2031. 10.1016/S0140-6736(04)16451-9.CrossRefPubMed
17.
McMurray, et al: Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010, 362 (16): 1477-1490.CrossRefPubMed
18.
Dusing R, Lehnert H: Diabetogenic effect of antihypertensive treatment: primum nil nocere. Nephrol Dial Transplant. 2004, 19 (3): 531-534. 10.1093/ndt/gfg543.CrossRefPubMed
19.
Frohlich ED: Treating hypertension - what are we to believe?. N Engl J Med. 2003, 348 (7): 639-641. 10.1056/NEJMe020179.CrossRefPubMed
20.
Whelton PK, Barzilay J, Cushman WC, Davis BR, Iiamathi E, Kostis JB, Leenen FHH, Louis GT, Margolis KL, Mathis DE, Moloo J, Nwachuku C, Panebianco D, Parish DC, Pressel S, Simmons DL, Thadani U, for the ACRG: Clinical Outcomes in Antihypertensive Treatment of Type 2 Diabetes, Impaired Fasting Glucose Concentration, and Normoglycemia: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med. 2005, 165 (12): 1401-1409. 10.1001/archinte.165.12.1401.CrossRefPubMed
21.
Luders S, Hammersen F, Kulschewski A, Venneklaas U, Zuchner C, Gansz A, Schnieders M, Pfarr E, Sturm CD, Paar WD, Schrader J: Diagnosis of impaired glucose tolerance in hypertensive patients in daily clinical practice. Int J Clin Pract. 2005, 59 (6): 632-638. 10.1111/j.1742-1241.2005.00518.x.CrossRefPubMed
22.
Zidek W, Schrader J, Luders S, Matthaei S, Hasslacher C, Hoyer J, Bramlage P, Sturm CD, Paar WD: First-line antihypertensive treatment in patients with pre-diabetes: rationale, design and baseline results of the ADaPT investigation. Cardiovasc Diabetol. 2008, 7: 22-10.1186/1475-2840-7-22.PubMedCentralCrossRefPubMed
23.
Mancia G, et al: 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Journal of hypertension. 2007, 25 (6): 1105-1187. 10.1097/HJH.0b013e3281fc975a.CrossRefPubMed
24.
Al-Mallah M, Khawaja O, Sinno M, Alzohaili O, Samra AB: Do angiotensin converting enzyme inhibitors or angiotensin receptor blockers prevent diabetes mellitus? A meta-analysis. Cardiol J. 2010, 17 (5): 448-456.PubMed
25.
Tocci G, Paneni F, Palano F, Sciarretta S, Ferrucci A, Kurtz T, Mancia G, Volpe M: Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers and Diabetes: A Meta-Analysis of Placebo-Controlled Clinical Trials. Am J Hypertens. 2011, 24 (5): 582-590. 10.1038/ajh.2011.8.CrossRefPubMed
26.
Jandeleit-Dahm KA, Tikellis C, Reid CM, Johnston CI, Cooper ME: Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes. J Hypertens. 2005, 23 (3): 463-473. 10.1097/01.hjh.0000160198.05416.72.CrossRefPubMed
27.
Abuissa H, Jones PG, Marso SP, O'Keefe JH: Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials. J Am Coll Cardiol. 2005, 46 (5): 821-826. 10.1016/j.jacc.2005.05.051.CrossRefPubMed
28.
Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, Khunti K: Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007, 334 (7588): 299-10.1136/bmj.39063.689375.55.PubMedCentralCrossRefPubMed
29.
Geng DF, Jin DM, Wu W, Xu Y, Wang JF: Angiotensin receptor blockers for prevention of new-onset type 2 diabetes: A meta-analysis of 59,862 patients. Int J Cardiol. 2010
30.
Norris K, Bourgoigne J, Gassman J, Hebert L, Middleton J, Phillips RA, Randall O, Rostand S, Sherer S, Toto RD, Wright JT, Wang X, Greene T, Appel LJ, Lewis J: Cardiovascular outcomes in the African American Study of Kidney Disease and Hypertension (AASK) Trial. Am J Kidney Dis. 2006, 48 (5): 739-751. 10.1053/j.ajkd.2006.08.004.CrossRefPubMed
31.
Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G: Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000, 342 (3): 145-153.CrossRefPubMed
32.
Gerstein HC, Yusuf S, Holman R, Bosch J, Pogue J: Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention: the DREAM trial. Diabetologia. 2004, 47 (9): 1519-1527.CrossRefPubMed
33.
Fukao K, Shimada K, Hiki M, Kiyanagi T, Hirose K, Kume A, Ohsaka H, Matsumori R, Kurata T, Miyazaki T, Daida H: Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between Azelnidipine and amlodipine on glucose tolerance and endothelial function - a crossover trial (AGENT). Cardiovasc Diabetol. 2011, 10: 79-10.1186/1475-2840-10-79.PubMedCentralCrossRefPubMed
34.
Ruggenenti P, Lauria G, Iliev IP, Fassi A, Ilieva AP, Rota S, Chiurchiu C, Barlovic DP, Sghirlanzoni A, Lombardi R, Penza P, Cavaletti G, Piatti ML, Frigeni B, Filipponi M, Rubis N, Noris G, Motterlini N, Ene-Iordache B, Gaspari F, Perna A, Zaletel J, Bossi A, Dodesini AR, Trevisan R, Remuzzi G: Effects of manidipine and delapril in hypertensive patients with type 2 diabetes mellitus: the delapril and manidipine for nephroprotection in diabetes (DEMAND) randomized clinical trial. Hypertension. 2011, 58 (5): 776-783. 10.1161/HYPERTENSIONAHA.111.174474.CrossRefPubMed
35.
Martin RM, Kapoor KV, Wilton LV, Mann RD: Underreporting of suspected adverse drug reactions to newly marketed ("black triangle") drugs in general practice: observational study. BMJ. 1998, 317 (7151): 119-120. 10.1136/bmj.317.7151.119.PubMedCentralCrossRefPubMed
36.
Vermes E, Ducharme A, Bourassa MG, Lessard M, White M, Tardif JC: Enalapril reduces the incidence of diabetes in patients with chronic heart failure: insight from the Studies Of Left Ventricular Dysfunction (SOLVD). Circulation. 2003, 107 (9): 1291-1296. 10.1161/01.CIR.0000054611.89228.92.CrossRefPubMed
37.
Nelson MR, Reid CM, Ryan P, Willson K, Yelland L: Self-reported adherence with medication and cardiovascular disease outcomes in the Second Australian National Blood Pressure Study (ANBP2). Med J Aust. 2006, 185 (9): 487-489.PubMed
38.
Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL, Johnston CI, McNeil JJ, Macdonald GJ, Marley JE, Morgan TO, West MJ: A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003, 348 (7): 583-592. 10.1056/NEJMoa021716.CrossRefPubMed
39.
ALLHAT Collaborative Research Group: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002, 288 (23): 2981-2997. 10.1001/jama.288.23.2981.CrossRef
40.
Rouleau JL, Warnica WJ, Baillot R, Block PJ, Chocron S, Johnstone D, Myers MG, Calciu CD, Dalle-Ave S, Martineau P, Mormont C, van Gilst WH: Effects of angiotensin-converting enzyme inhibition in low-risk patients early after coronary artery bypass surgery. Circulation. 2008, 117 (1): 24-31. 10.1161/CIRCULATIONAHA.106.685073.CrossRefPubMed
41.
Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J, Pfeffer MA, Rice MM, Rosenberg YD, Rouleau JL: Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med. 2004, 351 (20): 2058-2068.CrossRefPubMed
42.
Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A, Luomanmaki K, Dahlof B, de Faire U, Morlin C, Karlberg BE, Wester PO, Bjorck JE: Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet. 1999, 353 (9153): 611-616. 10.1016/S0140-6736(98)05012-0.CrossRefPubMed
43.
44.
Lindholm LH, Persson M, Alaupovic P, Carlberg B, Svensson A, Samuelsson O: Metabolic outcome during 1 year in newly detected hypertensives: results of the Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation (ALPINE study). J Hypertens. 2003, 21 (8): 1563-1574. 10.1097/00004872-200308000-00022.CrossRefPubMed
45.
Ogihara T, Nakao K, Fukui T, Fukiyama K, Ueshima K, Oba K, Sato T, Saruta T: Effects of candesartan compared with amlodipine in hypertensive patients with high cardiovascular risks: candesartan antihypertensive survival evaluation in Japan trial. Hypertension. 2008, 51 (2): 393-398. 10.1161/HYPERTENSIONAHA.107.098475.CrossRefPubMed
46.
Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H: Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002, 359 (9311): 995-1003. 10.1016/S0140-6736(02)08089-3.CrossRefPubMed
47.
Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003, 362 (9386): 759-766. 10.1016/S0140-6736(03)14282-1.CrossRefPubMed
48.
Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A, Olofsson B, Trenkwalder P, Zanchetti A: The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens. 2003, 21 (5): 875-886. 10.1097/00004872-200305000-00011.CrossRefPubMed
49.
50.
Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P: Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008, 372 (9644): 1174-1183.CrossRefPubMed
Metadata
Title
Ramipril-based versus diuretic-based antihypertensive primary treatment in patients with pre-diabetes (ADaPT) study
Authors
Walter Zidek
Joachim Schrader
Stephan Lüders
Stephan Matthaei
Christoph Hasslacher
Joachim Hoyer
Claudia Zemmrich
Peter Bramlage
Claus-Dieter Sturm
W Dieter Paar
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2012
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-11-1

Other articles of this Issue 1/2012

Cardiovascular Diabetology 1/2012 Go to the issue

Original investigation

Hyperglycemia raises the threshold of levosimendan- but not milrinone-induced postconditioning in rat hearts

Original investigation

Determinants of vascular function in patients with type 2 diabetes

Original investigation

Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions

Original investigation

Epicardial adipose tissue thickness is an indicator for coronary artery stenosis in asymptomatic type 2 diabetic patients: its assessment by cardiac magnetic resonance

Original investigation

Associations of sex hormone-binding globulin and testosterone with diabetes among men and women (the Saku Diabetes study): a case control study

Original investigation

Erythropoietin, ferritin, haptoglobin, hemoglobin and transferrin receptor in metabolic syndrome: a case control study

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits