Treatment of Hypertension

Canadian Diabetes Association Clinical Practice Guidelines Expert Committee

Richard E. Gilbert MBBS, PhD, FRCPC Doreen Rabi MD, FRCPC, MSc Pierre LaRochelle MD, PhD, FRCPC Lawrence A. Leiter MD, FRCPC, FACP, FAHA Charlotte Jones PhD, MD Richard Ogilvie MD, FRCPC, FACP Sheldon Tobe MD, FRCPC Nadia Khan MD, FRCPC, MSc Luc Poirier BPharm MSc Vincent Woo MD, FRCPC

  • Key Messages
  • Recommendations
  • Figures
  • Full Text
  • References

Chapter Headings

Key Messages

  • People with diabetes should be treated to achieve a blood pressure (BP) <130/80 mm Hg.

Introduction

Hypertension affects the vast majority of individuals with type 2 diabetes and many of those with type 1 diabetes also. Its pathogenesis is complex, involving interactions between genetic predisposition and a range of environmental factors that include sodium retention, obesity, premature arterial stiffening and endothelial dysfunction (1). Not only are patients with diabetes more likely to have coexistent hypertension, but, for any given systolic pressure, diabetes also is associated with an increase in the age-adjusted cardiovascular death rate.

Fortunately, several, large-scale, multicentre clinical trials have shown that antihypertensive therapy is highly effective at reducing death and disability in people with diabetes (1). These clinical trials also have provided some guidance in the choice of antihypertensive therapy, particularly among those with nephropathy or at high cardiovascular risk. Most recently, much discussion has focused on selecting an appropriate, evidence-based target for systolic blood pressure (SBP). These discussions have, to a large extent, been precipitated by the findings of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which compared the effects of targeting SBP <140 mm Hg with that <120 mm Hg (2). While the primary outcome (a composite of myocardial infarction, stroke, and cardiovascular death) was not significantly different between the 2 groups, stroke, a prespecified outcome, was reduced by 41% in the group targeted to achieve the <120 mm Hg systolic target. The findings of ACCORD are further supported by 2 meta-analyses, which similarly show that (3,4):

  1. 1.Little, if any, additional reduction in cardiac events is achieved by lowering SBP to <140 mm Hg.
  2. 2.Additional reduction in stroke can be achieved by lowering SBP to <120 mm Hg.
  3. 3.Lowering SBP is associated with an increased risk of adverse events, such as hypotension and hyperkalemia. However, the majority of these are associated with SBP <120 mm Hg.

Together, these findings provide the rationale for the current Canadian Hypertension Education Program (CHEP) and the Canadian Diabetes Association harmonized clinical practice recommendations, which continue to recommend blood pressure targets of <130/80 mm Hg in hypertensive patients with diabetes (5).

Recommendations

  1. 1.Persons with diabetes mellitus should be treated to attain SBP <130 mm Hg [Grade C, Level 3 (6,7)] and DBP <80 mm Hg [Grade B, Level 1 (8)]. (These target BP levels are the same as the BP treatment thresholds). Combination therapy using 2 first-line agents may also be considered as initial treatment of hypertension [Grade C, Level 3 (9,10)] if SBP is 20 mm Hg above target or if DBP is 10 mm Hg 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, patients with autonomic neuropathy).
  2. 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 (11–14)].
  3. 3.For persons with diabetes and hypertension not included in the above recommendation, appropriate choices include (in alphabetical order): ACE inhibitors [Grade A, Level 1A (15)], ARBs [Grade A, Level 1A (12)], dihydropyridine CCBs [Grade A, Level 1A (15)], and thiazide/thiazide-like diuretics [Grade A, Level 1A (15)].
  4. 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 (16)].

Abbreviations:
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; CCB, calcium channel blocker; DBP, diastolic blood pressure; SBP, systolic blood pressure.

References

  1. 1 N.R. Campbell R.E. Gilbert L.A. Leiter Hypertension in people with type 2 diabetes: update on pharmacologic management Can Fam Physician 57 2011 997 1002
  2. 2 W.C. Cushman G.W. Evans R.P. Byington Effects of intensive blood-pressure control in type 2 diabetes mellitus N Engl J Med 362 2010 1575 1585
  3. 3 S. Bangalore S. Kumar I. Lobach F.H. Messerli Blood pressure targets in subjects with type 2 diabetes mellitus/impaired fasting glucose: observations from traditional and bayesian random-effects meta-analyses of randomized trials Circulation 123 2011 2799 2810
  4. 4 G. Reboldi G. Gentile F. Angeli Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73,913 patients J Hypertens 29 2011 1253 1269
  5. 5 S.S. Daskalopoulou N.A. Khan R.R. Quinn The 2012 Canadian hypertension education program recommendations for the management of hypertension: blood pressure measurement, diagnosis, assessment of risk, and therapy Can J Cardiol 28 2012 270 287
  6. 6 A.I. Adler I.M. Stratton H.A. Neil Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study BMJ 321 2000 412 419
  7. 7 R.W. Schrier R.O. Estacio A. Esler P. Mehler Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes Kidney Int 61 2002 1086 1097
  8. 8 L. Hansson A. Zanchetti S.G. Carruthers Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial Lancet 351 1998 1755 1762
  9. 9 UK Prospective Diabetes Study Group Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38 BMJ 317 1998 703 713
  10. 10 W.C. Cushman C.E. Ford J.A. Cutler Success and predictors of blood pressure control in diverse north American settings: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) J Clin Hypertens 4 2002 393 404
  11. 11 E.J. Lewis L.G. Hunsicker W.R. Clarke Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes N Eng J Med 345 2001 851 860
  12. 12 L. Lindholm J. Ibsen B. Dahlof Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol Lancet 359 2002 1004 1010
  13. 13 The Heart Outcomes Prevention Evaluation Study Investigators Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients N Engl J Med 342 2000 145 153
  14. 14 B.M. Brenner M.E. Cooper D. de Zeeuw The losartan renal protection study: rationale, study design and baseline characteristics of RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) J Renin Angiotensin Aldosterone Syst 1 2000 328 335
  15. 15 P.K. Whelton J. Barzilay W.C. Cushman 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 165 2005 1401 1409
  16. 16 M.A. Weber G.L. Bakris K. Jamerson Cardiovascular events during differing hypertension therapies in patients with diabetes J Am Coll Cardiol 56 2010 77 85
 
Reproduced with permission from Canadian Journal of Diabetes © 2013 Canadian Diabetes Association. To cite this article, please refer to For citation.
 

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