Reduced mortality associated with the use of ACE inhibitors in patients with type 2 diabetes.

OBJECTIVE ACE inhibitor therapy is widely used in lower-risk patients with type 2 diabetes to reduce mortality, despite limited evidence to support this clinical strategy. The aim of this study was to evaluate the association between ACE inhibitor use and mortality in patients with diabetes and no cardiovascular disease. RESEARCH DESIGN AND SETTINGS: Using the Saskatchewan health databases, 12,272 new users of oral hypoglycemic agents were identified between the years of 1991 and 1996. We excluded 3,202 subjects with previous cardiovascular disease. Of the remaining subjects, 1,187 "new users" of ACE inhibitors were identified (ACE inhibitor cohort). Subjects not receiving ACE inhibitor therapy throughout the follow-up period served as the control cohort (n = 4,989). Subjects were prospectively followed until death or the end of 1999. Multivariate Cox proportional hazards models were used to assess differences in all-cause and cardiovascular-related mortality between cohort groups. RESULTS Subjects were 60.7 +/- 13.7 years old, 43.6% female, and were followed for an average of 5.3 +/- 2.1 years. Mean duration of ACE inhibitor therapy was 3.6 +/- 1.8 years. We observed significantly fewer deaths in the ACE inhibitor group (102 [8.6%]) compared with the control cohort (853 [17.1%]), with an adjusted hazard ratio (HR) and 95% CI of 0.49 (0.40-0.61) (P < 0.001). Cardiovascular-related mortality was also reduced (40 [3.4%] vs. 261 [5.2%], adjusted HR, 0.63 [0.44-0.90]; P = 0.012). CONCLUSIONS The use of ACE inhibitors was associated with a significant reduction in all-cause and cardiovascular-related mortality in a broad spectrum of patients with type 2 diabetes and no cardiovascular disease.

[1]  D. Singer,et al.  The effect of interventions to prevent cardiovascular disease in patients with type 2 diabetes mellitus. , 2001, The American journal of medicine.

[2]  P. Sleight.  Angiotensin II and trials of cardiovascular outcomes. , 2002, The American journal of cardiology.

[3]  S. Yusuf,et al.  Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[4]  R. Hayward,et al.  Treatment of Hypertension in Type 2 Diabetes Mellitus: Blood Pressure Goals, Choice of Agents, and Setting Priorities in Diabetes Care , 2003, Annals of Internal Medicine.

[5]  A. Maggioni,et al.  Effect of the ACE inhibitor lisinopril on mortality in diabetic patients with acute myocardial infarction: data from the GISSI-3 study. , 1997, Circulation.

[6]  K. Teo,et al.  NITROGLYCERIN AS AN INDICATOR FOR THE PRESENCE OF CORONARY HEART DISEASE , 1999 .

[7]  Pierre Ernst,et al.  The Use of β-Agonists and the Risk of Death and near Death from Asthma , 1992 .

[8]  D. Grobbee,et al.  Cardiovascular risk factors and diseases precede oral hypoglycaemic therapy in patients with type 2 diabetes mellitus. , 2002, Journal of clinical epidemiology.

[9]  Donald Rubin,et al.  Estimating Causal Effects from Large Data Sets Using Propensity Scores , 1997, Annals of Internal Medicine.

[10]  P. Beck,et al.  Health Databases in Saskatchewan , 2002 .

[11]  S. Yusuf,et al.  Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[12]  W. Tierney,et al.  Comparing methods to identify general internal medicine clinic patients with chronic heart failure. , 2001, American heart journal.

[13]  P. Raskin,et al.  Report of the expert committee on the diagnosis and classification of diabetes mellitus. , 1999, Diabetes care.

[14]  K. Fox,et al.  Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study) , 2003, The Lancet.

[15]  P. Parfrey,et al.  Community pharmacist outreach program directed at physicians treating congestive heart failure. , 2000, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[16]  L. Køber,et al.  Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction. Trace Study Group. , 1999, Journal of the American College of Cardiology.

[17]  Gregory E. Simon,et al.  A Chronic Disease Score with Empirically Derived Weights , 1995, Medical care.

[18]  W A Ray,et al.  Benzodiazepines of long and short elimination half-life and the risk of hip fracture. , 1989, JAMA.

[19]  P. Passmore,et al.  The importance of validating the diagnosis of coronary heart disease when measuring secondary prevention: a cross‐sectional study in general practice , 2002, Pharmacoepidemiology and drug safety.

[20]  S. Majumdar,et al.  Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes. , 2002, Diabetes care.

[21]  S. Yusuf,et al.  Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection. , 1994, Circulation.

[22]  G. Nichols,et al.  Replicating the chronic disease score (CDS) from automated pharmacy data. , 1994, Journal of clinical epidemiology.

[23]  E H Wagner,et al.  A chronic disease score from automated pharmacy data. , 1992, Journal of clinical epidemiology.

[24]  Lawrence A Leiter,et al.  1998 clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes Association. , 1998, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[25]  Andrew M. Johanos.  The use of betaagonists and the risk of death and near death from asthma: Spitzer WO, Suissa S, Ernst P, et al N Engl J Med 326:501–506 Feb 1992 , 1992 .

[26]  L. Køber,et al.  Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction. Trace Study Group. , 1999, Journal of the American College of Cardiology.

[27]  D. Rubin,et al.  The central role of the propensity score in observational studies for causal effects , 1983 .

[28]  R. Pauwels,et al.  Low-dose inhaled corticosteroids and the prevention of death from asthma. , 2000, The New England journal of medicine.

[29]  R. D'Agostino.  Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. , 2005, Statistics in medicine.