Cardiovascular Risk Reduction and Other Co-Morbidities in Type 2 Diabetes

Transcription

1 Cardiovascular Risk Reduction and Other Co-Morbidities in Type 2 Diabetes Following this presentation, you will be able to: Describe the relationship between major CV risk factors and CVD outcomes Select therapeutic modalities available to practitioners to improve CV risk factors Discuss other co-morbid/microvascular conditions seen in patients with type 2 diabetes Recognize the implications of recent large trials on guiding clinical decisions and targets for blood pressure and lipid abnormalities Explain the role of pharmacologic intervention in the treatment of type 2 diabetes CV = cardiovascular; CVD = cardiovascular disease.

2 Type 2 Diabetes and CVD Type 2 diabetes is considered a CHD equivalent Atherosclerotic complications are responsible for: 80% of mortality among patients with diabetes More than 75% of all hospitalizations for diabetic complications 50% of patients with type 2 diabetes have preexisting CAD One-third of patients presenting with MI have undiagnosed diabetes mellitus CAD = coronary artery disease; CHD = coronary heart disease; CVD = cardiovascular disease; MI = myocardial infarction. Lewis GF. Can J Cardiol. 11(suppl C):24C-28C, 1995; Norhammar A, et.al. Lancet 359; , 2002; NCEP ATP III. Circulation. 2002;106(25):3143; Meigs, et al. Am J Med. 1997;102:38-47.

3 Compared with Individuals Without Diabetes, Patients with Diabetes Have a 2- to 4-Fold Increased Risk of Developing and Dying of CHD CVD Mortality Among Participants with and without DM CHD = coronary heart disease; CVD = cardiovascular disease; DM = diabetes mellitus. Preis, et al. Circulation. 119(13): , 2009.

4 No. events per 100 person- years Absolute Risk of MI Is Higher in Patients with DM Diabetes n = 379,003 No Diabetes n = 9,018,082 Database Diabetes Men Women No diabetes Men Women Age group All lines fitted according to a polynomial equation; R 2 = for each DM = diabetes mellitus; MI = myocardial infarction. Booth GL, et al. Lancet 368:29-36, 2006.

5 T2DM for >15 Years Duration Confers Similar Risk of Fatal CHD as Prior CHD and No Diabetes 20-year Follow-Up of 121,046 Women Aged 30 to 55 Years in Nurses Health Study CHD = coronary heart disease; DM = diabetes mellitus; T2DM = type 2 diabetes mellitus. Hu F, et al. Arch Intern Med. 161: , 2001.

6 Age-standardized Rates of Diabetes Complications: Rates of diabetes-related complications declined between 1990 and 2010 (relative risk reductions): Myocardial infarction -68.8%, death from hyperglycemic crisis -64.4%, end-stage renal disease -28.3%, stroke and amputation ~50% ESRD = end-stage renal disease. Gregg EW, et al. N Engl J Med 370: , 2014.

7 Event Rates/10,000 Adults/Year ESRD = end-stage renal disease. Gregg EW, et al. N Engl J Med 370: , 2014.

8 How Is CAD Different in Diabetes? > CAD extent Multi-vessel disease Distal disease more difficult to revascularize Silent ischemia/mi Younger Women Worse outcomes despite revascularization Increased re-stenosis after PCI even with stents ACB: worse perioperative and long-term outcomes ACB = aortocoronary bypass; CAD = coronary artery disease; MI = myocardial infarction; PCI = percutaneous coronary intervention.

9 Diabetes Mellitus and Factors That May Predispose to Atherosclerosis and Cardiovascular Disease AGE = advanced glycation end-product; CRP = c-reactive protein; DM = diabetes mellitus; HDL = high density lipoprotein; LDL = low density lipoprotein; PA = plasminogen activator; PAI-1 = plasminogen activator inhibitor-1; TGRL = triglyceride-rich lipoprotein. Hayden: Curr Opin Lipidol, (5) , 2000.

10 Abdominal Obesity and Increased Risk of Cardiovascular Events: HOPE Study Adjusted Relative Risk 1.4 Waist circumference (in): 1.29 Tertile 1 Tertile 2 Tertile 3 Men < > Women < > BMI = body mass index; C = cholesterol; CVD = cardiovascular disease; DM = diabetes mellitus; HDL = high density lipoprotein; MI = myocardial infarction. Dagenais GR, et al. Am Heart J. 149(1):54-60, Jan CVD death MI All-cause deaths *Adjusted for BMI, age, smoking, sex, CVD disease, DM, HDL-cholesterol, total-c

11 Adipose Tissue in Obesity Lean Obese Després J-P. Eur Heart J Suppl. 8(suppl B):B4-12, Gustafson. Arterioscler Thromb Vasc Biol, 27(11): , 2007.

12 Systemic Effects of Inflammation in Insulin Resistance and Cardiovascular Disease EC = endothelial cells; FFA = free fatty acid. Shoelson, et al. J. Clin. Invest. 116: , 2006.

13 Strategies For Reducing Macrovascular Complications Prevention proven by intervention Hyperglycemia Hypertension Dyslipidemia Antiplatelet therapy Smoking Cessation Exercise

14 Type 2 Diabetes: A1C Predicts CHD CHD Mortality Incidence (%) in 3.5 Years * All CHD Events Incidence (%) in 3.5 Years ** 0 Low <6% Middle 6-7.9% High >7.9% *P<0.01 vs lowest tertile 0 Low <6% Middle 6-7.9% High >7.9% **P<0.05 vs lowest tertile A1C = glycated hemoglobin; CHD = coronary heart disease. Kuusisto J, et al. Diabetes. 43: , 1994.

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16 ACCORD: Treatment Effects on Glucose Control Standard therapy A1C (%) Intensive therapy Time (years) A1C = glycated hemoglobin. ACCORD Study Group. N Engl J Med 358: , 2008.

17 ACCORD: Treatment Effect on Primary Outcome 25 Patients with events (%) HR 0.90 ( ) P = 0.16 Standard therapy Intensive therapy 2.29%/yr 2.11%/yr Time (years) HR = heart rate. ACCORD Study Group. N Engl J Med 358: , 2008.

18 ADVANCE: Treatment Effect on Glucose Control Mean A1C (%) Standard control P < Intensive control Follow-up (months) A1C = glycated hemoglobin. ADVANCE Collaborative Group. N Engl J Med 358: , 2008.

19 ADVANCE: Treatment Effect on Primary Macrovascular Outcome CV Death, MI, Stroke 25 Cumulative incidence (%) HR 0.94 ( ) P = 0.32 Standard control Intensive control Follow-up (months) CV = cardiovascular; HR = heart rate; MI = myocardial infarction. ADVANCE Collaborative Group. N Engl J Med 358: , 2008.

20 A1C (%) VADT-Median A1C +/- IQR STD INT Baseline 1 year 2 years 3 years 4 years 5 years 6 years Years on Study A1C = glycated hemoglobin; INT = intensive control; IQR = interquartile range; STD = standard control; VADT = Veterans Affairs Diabetes Trial. VADT Study Group. N Engl J Med 360: , 2009.

21 Proportion free of primary outcome VADT Primary Outcome 1.0 Time to primary outcome Hazard Ratio & CI (0.728, 1.036) P= Follow-up time (years) VADT = Veterans Affairs Diabetes Trial. VADT Study Group. N Engl J Med 360: , 2009.

22 Glycosylated hemoglobin (Percent) A1C During DCCT and EDIC Observation DCCT Intervention Conventional - mean A1C 9.1 % Training EDIC Observation Conventional - mean A1C 8.2 % 8 7 Intensive - mean A1C 8.0 % 6 Intensive - mean A1C 7.2 % Study year A1C = glycated hemoglobin; DCCT = Diabetes Control and Complications Trial; EDIC = Epidemiology of Diabetes Interventions and Complications. Nathan DM, et al. N Engl J Med 353: , 2005.

23 Cumulative incidence of any predefined cardiovascular outcome Cumulative Incidence of the First of Any Predefined Cardiovascular Disease Outcomes No. at Risk Risk reduction 42% 95% CI: 9, 63 Log-rank P = Years since entry Conventional treatment Intensive treatment Intensive Conventional Nathan DM, et al. N Engl J Med 353: , 2005.

24 Glucose Control and CHD Events ACCORD = Action to Control Cardiovascular Risk in Diabetes; ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; CHD = coronary heart disease; PROactive = Prospective Pioglitazone Clinical Trial in Macrovascular Events; UKPDS = United Kingdom Prospective Diabetes Study Group; VADT = Veterans Affairs Diabetes Trial. Ray KK, et al. Lancet. 373: , 2009.

25 Strategies for Reducing Macrovascular Complications Prevention proven by intervention Hyperglycemia Hypertension Dyslipidemia Antiplatelet therapy Smoking Cessation Exercise

26 CV mortality rate Per 10,000 person-years Association of SBP and CV Mortality in Men with T2DM No diabetes Diabetes < SBP (mmhg) 200 CV = cardiovascular; SBP = systolic blood pressure; T2DM = type 2 diabetes mellitus. Stamler J, et al. Diabetes Care. 16: , 1993.

27 Patients with events (%) Hypertension in Diabetes, UKPDS Less tight control (mean BP 154/87 mmhg) Tight control (mean BP 144/82 mmhg) Tight BP control: 24% reduction of events (95% CI 8-38) UKPDS Study Group. BMJ 317:703-13, Years from randomization BP = blood pressure; UKPDS = United Kingdom Prospective Diabetes Study Group.

28 % of patients Effect of Ramipril on Combined Outcome (MI, Stroke, Death) % Risk reduction 25% Risk reduction Placebo Ramipril Placebo Ramipril No diabetes, n=5720 Diabetes, n=3577 MI = myocardial infarction. The Lancet. 2000; 355(9200): Yusuf S, et al. NEJM. 2000:342(3):

29 Risk Reduction (%) Effect of Intensive BP Lowering on Risk of Microand Macrovascular Complications: UKPDS 0 Myocardial infarction Any diabetesrelated endpoint Diabetesrelated death Retinopathy Renal failure Stroke Vision deterioration Heart failure Benefits of 144/82 mmhg vs 154/87 mmhg -56 BP = blood pressure; UKPDS = United Kingdom Prospective Diabetes Study Group. UKPDS Group. UKPDS 38. BMJ. 317: , 1998.

30 Guideline Recommendations for Uncomplicated and Complicated Hypertension Type of hypertension BP goal (mmhg) Uncomplicated <140/90 Complicated Diabetes mellitus <130/80 Kidney disease <130/80* Other high risk (stroke, MI) <130/80 *Lower if proteinuria is >1 g/day. BP = blood pressure; MI = myocardial infarction. Chobanian, et al. Hypertension. 42: , Garber AJ, et al. Endocr Pract. 19(suppl 2):1-48, Handelsman Y, et al. Endocr Pract. 17(suppl 2):1-53, Torre JJ, et al. Endocr Pract. 12: , 2006.

31 AACE = American Association of Clinical Endocrinologists Garber AJ et al. Endocr Pract. 2017,doi: /EP CS

32 Strategies for Reducing Macrovascular Complications Prevention proven by intervention Hyperglycemia Hypertension Dyslipidemia Antiplatelet therapy Smoking Cessation Exercise

33 Percent 60 Diabetes and Lipid Extremes Framingham Offspring Men P<0.001 Diabetes No diabetes 30 P< P< HDL-C<35 Total-C 240+ LDL-C 160+ Trig 250+ HDL-C<35 Total-C 240+ mg/dl C = cholesterol; HDL-C = high density lipoprotein-cholesterol; LDL-C = low density lipoprotein-cholesterol. Siegel Metabolism 96:1267, 1996.

34 Priorities for Lipid Levels in Adult Patients with Diabetes LDL cholesterol lowering Statin at maximally tolerated dose HDL cholesterol raising Behavior: weight loss, physical activity, smoking cessation Glycemic control Triglyceride lowering Glycemic control first priority Fibric acid derivative (gemfibrozil, fenofibrate) Statins at high dose also have some TG lowering Niacin or high-dose omega-3 fatty acids Triglyceride goal presently <150 mg/dl HDL = high density lipoprotein; LDL = low density lipoprotein; TG = triglyceride. Handelsman Y et al. Endocr Pract. Vol 21; (Suppl 1). 2015

35 ACC/AHA 2013 Recommendations CVD Primary Prevention U.S. Adults Group Diabetes Mellitus ACC/AHA 2013 All individuals >40 y/o with diabetes are considered high CVD risk Rx high-potency statin No fixed LDL-C targets ACC = American College of Cardiology; AHA = American Heart Association; CVD = cardiovascular disease; LDL-C = low density lipoprotein-cholesterol. Goff DC et al. JACC Vol. 63; No. 25, 2014:

36 Statin Therapy in Diabetes American Diabetes Association 2016 Age (years) Risk Factors Statin Dose Lipid Monitoring <40 None ASCVD risk factor(s)** ASCVD*** No medication Moderate or high High Yearly or as needed >75 ACS = acute coronary syndrome; ASCVD = atherosclerotic cardiovascular disease; CVD = cardiovascular disease; LDL = low density lipoprotein; LDL-C = low density lipoprotein-cholesterol. ADA Diabetes Care 38:S63, None ASCVD risk factors ASCVD ACS and LDL> 50 mg/dl* None CVD risk factors Overt CVD ACS and LDL>50 mg/dl* * On basis of IMPROVE-IT subgroup ** LDL-C>100 mg/dl, hypertension, smoking, overweight or obesity Moderate High High Moderate + Ezetimibe Moderate Moderate or high High Moderate + Ezetimibe To monitor adherence To monitor adherence

37 Intensity of Statin Therapy (Doses in mg/day) Low-intensity daily statin Reduce LDL-C <30% Simvastatin 10 Pravastatin Lovastatin 20 Fluvastatin Pitavastatin 1 Boldface type indicates specific statins and doses that were evaluated in RCTs included in CQ1, CQ2, and the Cholesterol Treatment Trialists 2010 meta-analysis included in CQ3. All of these RCTs demonstrated a reduction in major cardiovascular events. Italic type indicates statins and doses that have been approved by the FDA but were not tested in the RCTs reviewed. Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice. There might be a biological basis for a less-than-average response. Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in the IDEAL (Incremental Decrease through Aggressive Lipid Lowering) study. Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA because of the increased risk of myopathy, including rhabdomyolysis. BID indicates twice daily; CQ, critical question; FDA, Food and Drug Administration; LDL-C, low-density lipoprotein cholesterol; and RCTs, randomized controlled trials. Stone NJ et al. Circulation. 2014;129[suppl 2]:S1-S45 Moderate-intensity daily statin Reduce LDL-C 30% to <50% Atorvastatin Rosuvastatin 5-10 Simvastatin Pravastatin Lovastatin 40 Fluvastatin XL 80 Fluvastatin 40 BID Pitavastatin 2-4 High-intensity daily statin Reduce LDL-C >50% Atorvastatin (40 )-80 Rosuvastatin 20-40

38 Cholesterol Lowering in High Risk Patients: The Heart Protection Study LDL lowering resulted in 22% reduction in CVD events across all LDL categories CHD = coronary heart disease; CVD = cardiovascular disease; LDL = low density lipoprotein; MI = myocardial infarction. HPS Collaborative Group. Lancet. 2002;360:7-22.

39 Statins and CVD in Patients with Diabetes: CTT Meta-analysis CTT = Cholesterol Trialists Collaboration; CVD = cardiovascular disease; RR = rate ratio. Cholesterol Treatment Trialists. Lancet 371: 117, 2008.

40 AACE Dyslipidemia Management Algorithm When atherogenic markers are not at goal: To lower LDL-C: To lower non-hdl-c, TG: To lower APO-B, LDL-P: Intensify statin and/or, add ezetimibe and/or PCSK9 and/or colesevelam and/or niacin Intensify statin and/or Rx-grade Omega-3 fatty acid and/or fibrates and/or niacin Intensify statin and/or add ezetimibe and/or PCSK9 and/or colesevelam AACE = American Association of Clinical Endocrinologists; APO-B = apolipoprotein-b; HDL-C = high density lipoprotein-cholesterol; LDL-C = low density lipoprotein-cholesterol; LDL-P = low density lipoprotein-particles; PCSK9 = proprotein convertase subtilisin/kexin type 9; TG = triglyceride. Garber et al. Endocr Pract. 2016; Vol 22 No. 1:

41 Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors Reduce LDL-C levels Have been shown to reduce cardiovascular endpoints LDL-C = low density lipoprotein-cholesterol; PCSK9 = proprotein convertase subtilisin/kexin type 9. New Eng J Med 372: , New Eng J Med 372: , 2015.

42 The Role of PCSK9 in the Regulation of LDL Receptor Expression For illustration purposes only LDL = low density lipoprotein; LDL-R = low density lipoprotein receptor; PCSK9 = proprotein convertase subtilisin/kexin type 9; SREBP = sterol response element binding protein. Lambert G, et al.. J Lipid Res. 2012; Vol 53:

43 PCSK9 Inhibitors IND1ICATIONS Adjunct to diet and maximally tolerated statin therapy in adults Heterozygous familial hypercholesterolemia Clinical atherosclerotic CV disease who require additional lowering of LDL-C SIDE EFFECTS Injection site reactions; myalgias; neurocognitive (confusion, impaired memory); nasopharyngitis; upper respiratory tract infection; back pain; influenza. DOSAGE: Alirocumab (Praluent R ) Evolucumab (Repatha R ) 75 mg/2 weeks or 150 mg /2 weeks 140 mg /2 weeks or 420mg/month CV = cardiovascular; LDL-C = low density lipoprotein-cholesterol; PCSK9 = proprotein convertase subtilisin/kexin type 9.

44 HeFH or high CV risk patients on maximally tolerated statin ± other LLT, with LDL >70 mg/dl Least-squares mean difference, baseline to week 24 Apo B=apolipoprotein B; CV=cardiovascular; DM=diabetes mellitus; HeFH=heterozygous familial hypercholesterolemia; Lp(a)= lipoprotein(a); LDL=low density lipoprotein; LLT=lipidlowering therapy Alirocumab in Individuals with and without Diabetes: ODYSSEY Study DM Entire Cohort no DM LDL-C Non-HDL-C Apo B Lp(a) Colhoun HM, et al. Presented September 19, 2015 EASD Stockholm, Sweden

45 Preliminary Analysis, ODYSSEY Long-term Study: Treatment-emergent MACE at 78 Weeks with Alirocumab HeFH or high CV risk patients on maximally tolerated statin ± other LLT, with LDL >70 mg/dl (baseline LDL 123 MACE = Major CV Events confirmed by adjudication: cardiac death, non-fatal MI, fatal/non-fatal stroke, unstable angina requiring hospitalization Percent 2.8 Placebo mg/dl) HR 0.52 MACE (0.31 to Events 0.90) n=1,489 n=838 n=2,341 HR 0.47 (0.22 to 1.00) 1.3 Alirocumab 150 mg q2wks 1.7 HR 0.58 (0.27 to 1.25) 2 Overall pop. No Diabetes Colhoun HM, et al. Presented at September 19, 2015 EASD Meeting, Stockholm, Sweden CV=cardiovascular; DM=diabetes mellitus; HeFH=heterozygous familial hypercholesterolemia; LDL=low density lipoprotein; LLT=lipidlowering therapy; MI=myocardial infarction; RRR=relative risk ratio Diabetes LDL in entire cohort by 62% ( mg/dl); CV event RRR by 48% LDL in patients without diabetes by 63% ( mg/dl); CV event RRR 53% LDL in diabetes group by 59% ( mg/dl) & CV event RRR 42%

46 Lipid Changes, Baseline To 12 Weeks: Evolocumab vs Ezetimibe or Placebo LDL TRIG Non-HDL Lp(a) HDL HDL=high-density lipoprotein; LDL=low density lipoprotein; Lp (a)=lipoprotein(a) TRIG=triglycerides Sattar M, et al. Lancet Diab Endocrinol. 2016:4(5)

47 Strategies for Reducing Macrovascular Complications Prevention proven by intervention Hyperglycemia Hypertension Dyslipidemia Antiplatelet therapy Smoking Cessation Exercise

48 What About ASA for 1⁰ Prevention of CVD? Included: 6 studies, N = 10,117 participants ASA = acetylsalicylic acid (aspirin); CVD = cardiovascular disease. De Berardis G, et al. BMJ 339:b4531, 2009.

49 ASA for 1⁰ Prevention in Diabetes: Meta Analysis of 6 Studies (N=10,117) Major CV events JPAD POPADAD WHS PPP ETDRS Total No. of events/no. in group ASA Control/placebo RR (95% CI) RR (95% CI) 68/ /638 58/514 20/ / / / /638 62/513 22/ / / ( ) 0.97 ( ) 0.90 ( ) 0.90 ( ) 0.90 ( ) 0.90 ( ) No overall benefit for: Major CV events MI Stroke CV mortality All-cause mortality Myocardial infarction JPAD POPADAD WHS PPP ETDRS PHS Total Stroke JPAD POPADAD WHS PPP ETDRS Total 28/ /638 36/514 5/ / / / / /638 15/514 9/519 92/ / / /638 24/513 10/ / / / / /638 31/513 10/512 78/ / ( ) 1.10 ( ) 1.48 ( ) 0.49 ( ) 0.82 ( ) 0.40 ( ) 0.86 ( ) 0.89 ( ) 0.74 ( ) 0.46 ( ) 0.89 ( ) 1.17 ( ) 0.83 ( ) ASA = acetylsalicylic acid (aspirin); CV = cardiovascular; ETDRS = Early Treatment Diabetic Retinopathy Study; JPAD = Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes; MI = myocardial infarction; PHS = Physicians Health Study; POPADAD = Prevention of Progression of Arterial Disease and Diabetes; PPP = Primary Prevention Project; RR = rate ratio; WHS = Women s Health Study. De Berardis G, et al. BMJ 339:b4531, Death from CV causes JPAD POPADAD PPP ETDRS Total All-cause mortality JPAD POPADAD PPP ETDRS Total 1/ /638 10/ / / / /638 25/ / / / /638 8/ / / / /638 20/ / / Favors ASA 0.10 ( ) 1.23 ( ) 1.23 ( ) 0.87 ( ) 0.94 ( ) 0.90 ( ) 0.93 ( ) 1.23 ( ) 0.91 ( ) 0.93 ( ) 2 8 Favors control/placebo

50 Antiplatelet Agents in Diabetes: 2013 Primary prevention ( mg/day) Type 1 or type 2 diabetes at increased CV risk (10-year risk >10%) Men >50 years of age or women >60 years with 1+ additional major risk factor Family history of CVD, HTN, smoking, dyslipidemia, or albuminuria Not sufficient evidence to recommend aspirin for primary prevention in lower-risk individuals Secondary prevention ( mg/day) Use aspirin therapy as a secondary prevention strategy in those with diabetes with a history of CVD CV = cardiovascular; CVD = cardiovascular disease; HTN = hypertension. American Diabetes Association. Diabetes Care. 36(Suppl 1):S11-66, Jan 2013.

51 ASA Not Routinely Recommended for First- Degree CVD Prevention in Patients with Diabetes Insufficient evidence to support use of ASA for primary prevention Risk of bleeding CVD protection ASA = acetylsalicylic acid (aspirin); CVD = cardiovascular disease.

52 STENO-2

53 STENO-2: Intensive Group Achieved Targets BP = blood pressure. Gaede, et al. NEJM. 348; , 2003.

54 STENO-2: Intensive Group Had Improved CV Outcomes P = Any CV event Conventional therapy Intensive therapy 53 % RRR NNT = Months of Follow-up CV = cardiovascular; NNT = number needed to treat; RRR = relative risk reduction. Gaede, et al. NEJM. 348; , 2003.

55 Gaede, et al. NEJM. 348; , STENO 2: Microvascular Disease

56 STENO 2: 21-Year Follow-up, Death, or CVD Events Median survival was 7.9 years longer in intensive vs conventional group CVD = cardiovascular disease Gaede, et al. Diabetologia. 2016;59:

57 The Prevalence of U.S. Adults with Diabetes Achieving A1C, Blood Pressure, and LDL-C Goals: : NHANES Percent (%) A1C<7.0% BP<130/80 LDL<100mg/dL All 3 at Goal Still a long way to go A1C = glycated hemoglobin; BP = blood pressure; LDL = low density lipoprotein; LDL-C = low density lipoprotein-cholesterol; NHANES = National Health and Nutrition Examination Survey. Casagrande SS, Cowie CC, Fradkin JE, Rust KF, Saydah SH. Diabetes Care 36: , 2013.

58 Treating the ABCs Reduces Diabetic Complications Strategy Blood glucose control (A1C) Blood pressure control Complication Reduction of Complication Myocardial infarction 16% 1 Cardiovascular disease Heart failure Stroke Diabetes-related deaths 51% 2 56% 3 44% 3 32% 3 Lipid control (Cardiovascular) Coronary heart disease mortality Major coronary heart disease event Any atherosclerotic event Cerebrovascular disease event 35% 4 55% 5 37% 5 53% 4 1 UKPDS Study Group (UKPDS 33). Lancet. 352: , Hansson L, et al. Lancet. 351: , UKPDS Study Group (UKPDS 38). BMJ. 317: , Grover SA, et al. Circulation. 102: , Pyŏrälä K, et al. Diabetes Care. 20: , 1997.

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