1. Canadian Diabetes Association Clinical Practice Guidelines Treatment of Hypertension Chapter 25 Richard E. Gilbert, Doreen Rabi, Pierre LaRochelle, Lawrence A. Leiter, Charlotte Jones, Richard Ogilvie, Sheldon Tobe, Nadia Khan, Luc Poirier, Vincent Woo

2. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association ASSESS for hypertension (≥130/80 mmHg) TREAT to target <130/80 mmHg USE multiple antihypertensive medications if needed to achieve target (often necessary) USE initial combination therapy if systolic blood pressure >20 mmHg above target or diastolic blood pressure >10 mmHg above target 2013 Hypertension Checklist

3. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association BP >130/80 mm Hg Confirmed on a second occasion in either the office, home or by appropriate ambulatory measurement. Making the Diagnosis of Hypertension in Patients with Diabetes

4. UKPDS Study Group. BMJ 1998; 317:703-13. 50 40 30 20 10 0 Years from randomization Patients with events (%) 0123456789 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) Hypertension in Diabetes (UKPDS) guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

5. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Arch Intern Med 2005;165:1410-1419 Benefits of BP Lowering in DM Meta-analysis of 27 randomized trials showed intense BP reduction (i.e., by 6/4.6 mmHg) resulted in: – 36% reduction in stroke – 27% reduction in total mortality – 25% reduction in major cardiovascular events

6. Hansson et al. Lancet. 1998;351:1755. P<0.005 MI, stroke, CV mortality/1000 pt-y Diabetes Subgroup  90 mm Hg (n=501)  85 mm Hg (n=501)  80 mm Hg (n=499) Goal of therapy: target diastolic BP 24.4 18.8 11.9 30 25 20 15 10 5 0 Hansson et al. Lancet. 1998;351:1755. HOT: BP Control Reduces CV Events guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

7. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association <130/80 mmHg Multiple anti-hypertensive agents may be needed to achieve the desired target Target Blood Pressure

8. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Threshold equal or over 130/80 mmHg and target below 130/80 mmHg With Nephropathy* or CVD or CV risk factors *Urinary albumin to creatinine ratio >2.0 mg/mmol Diabetes Without The above Isolated Systolic Hypertension Systolic-diastolic Hypertension A combination of 2 first line drugs may be considered as initial therapy if the blood pressure is >20 mmHg systolic or >10 mmHg diastolic above target Combinations of an ACEI with an ARB are specifically not recommended in the absence of proteinuria Pharmacotherapy for Hypertension in Patients with Diabetes *Based on at least 2 of 3 measurements CVD = Cardiovascular Disease; CV = Cardiovascular

9. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association THRESHOLD equal or over 130/80 mmHg and TARGET below 130/80 mmHg If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min (0.5 ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control of volume is desired DIABETES with Nephropathy or CVD or CV risk factors ACE Inhibitor or ARB IF ACEI and ARB are contraindicated or not tolerated, SUBSTITUTE Long-acting CCB or Thiazide diuretic Addition of a Dihydropyridine CCB is preferable to HCTZ 3 - 4 drugs in combination may be needed Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB CCB = Calcium Channel Blocker; HCTZ = Hydrochlorothiazide; CKD = Chronic Kidney Disease Pharmacotherapy of Hypertension with Nephropathy, CVD or CV Risk Factors

10. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association THRESHOLD equal or over 130/80 mmHg and TARGET below 130/80 mmHg DIABETES without Nephropathy, CVD or CV risk factors 1. ACE Inhibitor or ARB or 2. Dihydropyridine CCB or Thiazide diuretic IF ACE Inhibitor, ARB, DHP-CCB and Thiazide are contraindicated or not tolerated, SUBSTITUTE – Cardioselective BB* or – Long-acting NON DHP-CCB Combination of first line agents Addition of one or more of: Cardioselective BB or Long-acting CCB Combinations of an ACE Inhibitor with an ARB are specifically not recommended in the absence of proteinuria Pharmacotherapy of Hypertension in Diabetes without Nephropathy, CVD or CV Risk Factors *Cardioselective BB: Acebutolol, Atenolol, Bisoprolol, Metoprolol

11. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Threshold equal or over 130/80 mmHg and Target below 130/80 mmHg With Nephropathy, CVD or CV risk factors ACE Inhibitor or ARB Diabetes Without the above 1. ACE Inhibitor or ARB or 2. Thiazide diuretic or DHP-CCB Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB Combinations of an ACEI with an ARB are specifically not recommended in the absence of proteinuria More than 3 drugs may be needed to reach target values If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control of volume is desired Combination of 2 first line drugs may be considered as initial therapy if the blood pressure is >20 mmHg systolic or >10 mmHg diastolic above target > 2-drug combinations Summary of Pharmacotherapy for Hypertension in Patients with Diabetes

12. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 1.Persons with diabetes mellitus should be treated to attain a *SBP of <130 mmHg [Grade C, Level 3] and a **DBP of <80 mmHg [Grade A, Level 1]. (These target BP levels are the same as the BP treatment thresholds). Combination therapy using two first-line agents may also be considered as initial treatment of hypertension [Grade C, Level 3] if SBP is 20 mmHg above target or if DBP is 10 mmHg above target. However, caution should be exercised in patients in whom a substantial fall in BP is more likely or poorly tolerated (e.g., elderly patients and patients with autonomic neuropathy) *SBP= Systolic Blood Pressure **DBP= Diastolic blood pressure 2013 Recommendation 1

13. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 2.For persons with cardiovascular or kidney disease, including microalbuminuria, or with cardiovascular risk factors in addition to diabetes and hypertension, an ACE inhibitor or an ARB is recommended as initial therapy [Grade A, Level 1A] 3.For persons with DM and HTN not included in the above recommendation, appropriate choices include (in alphabetical order): ACE inhibitors [Grade A, Level 1A], ARBs [Grade A, Level 1A], dihydropyridine CCBs [Grade A, Level 1A], and thiazide/thiazide-like diuretics [Grade A, Level 1A]. Recommendations 2 and 3

14. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 4.If target BP levels are not achieved with standard- dose monotherapy, additional antihypertensive therapy should be used [Grade D, Consensus]. For persons in whom combination therapy with an ACE inhibitor is being considered, a dihydropyridine CCB is preferable to hydrochlorothiazide [Grade A, Level 1A] 2013 Recommendation 4

15. CDA Clinical Practice Guidelines www.guidelines.diabetes.cawww.guidelines.diabetes.ca – for professionals 1-800-BANTING (226-8464) www.diabetes.ca www.diabetes.ca – for patients