Hypertension in Patients With Diabetes

Patients with diabetes can benefit from blood pressure control to reduce the risks of cardiovascular disease, retinopathy, and renal disease. The chart below provides information pertaining to common questions that arise when treating hypertension in these patients.

Abbreviations: ACC = American College of Cardiology; ADA = American Diabetes Association; AHA = American Heart Association; BP = blood pressure; CV = cardiovascular disease; DBP = diastolic blood pressure; eGFR = estimated glomerular filtration rate; ISH = International Society of Hypertension; LVH = left ventricular hypertrophy; MI = myocardial infarction SBP = systolic blood pressure

Clinical Question

Pertinent Information or Resources

What is the goal blood pressure in patients with diabetes?

ACC/AHA: <130/80 mmHg1

ADA: <140/90 mmHg for most patients, but suggests <130/80 mmHg for select patients (e.g., patients at high risk of CV disease who are able to reach this goal without significant side effects).4

JNC 8: <140/90 mmHg2

ISH: <140/90 mmHg7

Hypertension Canada: <130/80 mmHg8

Diabetes Canada: <130/80 mmHg9


Why do different guidelines recommend different blood pressure targets?

Variance is due to differences in which studies the guideline authors include and the weight they place on evidence.

ACC/AHA vs ADA

  • The ACCORD trial compared SBP goals of <140 mmHg vs <120 mmHg in type 2 diabetes patients with high CV risk.3 ACCORD did not show greater benefit from a lower target for a composite outcome of nonfatal MI, nonfatal stroke, and CV death.3 However, the event rate was low, and the ACC/AHA guidelines point out that ACCORD may have been underpowered.1,3 Although a target of <120 mmHg reduced stroke in diabetes patients, this was accompanied by serious side effects such as increased serum creatinine, hypotension, bradycardia, and hyper- or hypokalemia.3 ACC/AHA guidelines point out that these side effects were not associated with development of end stage renal disease or stroke.1 They also point to a secondary analysis that demonstrated a reduction in LVH for a SBP goal of <120 mmHg.1
  • SPRINT was a randomized trial comparing a SBP target of <140 mmHg to a target of <120 mmHg.6 This study did NOT include patients with diabetes. However, ACC/AHA guidelines point to a SPRINT substudy that showed that patients with prediabetes attained CV benefit.6 ADA guidelines acknowledge the SPRINT and HOT (described below) treat-to-target studies, but felt applicability of their results to patients with diabetes was unclear.4
  • ACC/AHA also based their recommendation on the results of three meta-analyses, two of which included only studies in which patients were randomized to different BP goals.1
  • ADVANCE enrolled patients with type 2 diabetes and high CV risk.5 Patients were randomized to perindopril/indapamide or placebo. Mean BP achieved in the treatment group was 136/73 mmHg, which led to a reduction in a composite endpoint of macro- or microvascular events, and reduced mortality. This study supports a goal of <140/80 mmHg, although it was not a “treat-to-target” study.4
  • ADA guidelines hold that while there is unequivocal Level A evidence that patients with type 1 and type 2 diabetes benefit from treating to <140/90 mmHg (including from UKPDS, which compared targets of <150/85 to <180/105 mmHg), there is less evidence that a goal of <130/80 mmHg provides net benefit for all patients with diabetes. However, select patients may benefit from reaching <130/80 mmHg.4

Other guidelines

  • Hypertension Canada’s recommended goal of 130/80 mmHg is, in part, supported by the diabetes subgroup of HOT (a treat-to-target study) in which there was a 51% relative reduction in CV events in patients assigned to a target DBP <80 mmHg vs 85 to 90 mmHg.12 However, only about 8% of patients enrolled in this study had diabetes.4 For support of their SBP target, they cite two meta-analyses, one of which was also considered by ACC/AHA.1,12 One showed benefit in patients with diabetes or impaired fasting glucose from achieving a SBP <135 mmHg (MI reduction) or <130 mmHg (stroke reduction). The other analysis showed that for every 5% reduction in SBP, there is a 13% relative reduction in stroke. They also point to cohort data showing that benefit (on mortality, CV disease, nephropathy, and retinopathy) increases as SBP deceases, in a linear fashion. Because these analyses were not exclusive to “treat-to-target” studies, they acknowledge that there is less support for their SBP goal compared to their DBP goal.12 They consider evidence for a SBP goal ≤120 mmHg in patients with diabetes “inconclusive.”8
  • Support for Diabetes Canada’s recommendations is based on UKPDS-38 (a randomized controlled trial comparing a goal of <150/85 mmHg to <180/105 mmHg), UKPDS-36 (a prospective observational study showing an approximately linear association between SBP reduction and reduction in diabetic complications), HOT, ADVANCE, ACCORD, and SPRINT (described above).9-11 They maintain that the results of ACCORD and SPRINT, taken together, support lower targets for high-risk patients, diabetes or not.9 Goals were also based on ABCD, in which patients were randomized to a DBP goal of 80 to 89 mmHg or 10 mmHg below baseline (intensive treatment). In ABCD, patients in the intensive group reached a BP of 128/75 mmHg and had a lower incidence of stroke, and slower progression to retinopathy and overt nephropathy.16 (Diabetes Canada recommendations now align with Hypertension Canada.9)
  • JNC 8 based their recommendations on randomized controlled trials. SHEP, UKPDS, and Syst-EUR showed evidence of benefit of SBP goal <150 mmHg. There are no RCTs comparing a goal of <150 mmHg to a goal of <140 mmHg.2 ADVANCE (described above) did not meet the panel’s inclusion criteria due to lack of randomization to different BP goals. JNC 8’s rationale for the systolic goal of <140 mmHg is based on the ACCORD results. Their rationale for a diastolic goal of <90 mmHg was lack of quality RCTs with mortality as an a priori outcome measure that support a lower goal. The JNC 8 authors point out that the positive outcome measure in the HOT study used by some to support a diastolic goal of <80 mmHg was a subgroup analysis. In regard to UKPDS, they argue that because a diastolic of <85 mmHg was compared to a diastolic goal of <105 mmHg, the results do not prove that a goal of <80 mmHg is better than a goal of <90 mmHg. The JNC 8 authors also feel that having one goal for patients with or without diabetes will facilitate guideline adherence.2
  • ISH: states there is unproven benefit of a target below 140/90 mmHg for patients with diabetes.7


Which antihypertensives are recommended for patients with diabetes?

Choose an agent shown to reduce CV events in patients with diabetes: ACEI, ARB, dihydropyridine CCB, or thiazide/thiazide-like diuretic (Hypertension Canada and Diabetes Canada give preference to chlorthalidone or indapamide due to evidence supporting CV benefit with these longer-acting diuretics9,15).1,2,4,7-9 (Note that neither JNC 8 nor ACC/AHA specify “dihydropyridine,” and ACC/AHA does not specify “thiazide.” ISH recommends ACEI or ARB first-line, except in black patients, in which a CCB or thiazide could be used first-line.7)

  • ALLHAT: chlorthalidone, amlodipine, lisinopril: similar impact on CV disease.12 Chlorthalidone reduced some events more than amlodipine or lisinopril.1

Hypertension Canada and Diabetes Canada recommend a dihydropyridine CCB as the preferred add-on to an ACEI or ARB.8,9

Some guidelines recommend specific agents for comorbidities in the context of diabetes:

  • Albuminuria: ACEI or ARB (ACC/AHA, ADA, Diabetes Canada, Hypertension Canada)1,4,8,9
    • Diabetes Canada and Hypertension Canada include renal disease or microalbuminuria (e.g., persistent albumin to creatinine ratio ≥2 mg/mmol)8,9
    • ACC/AHA specifies ≥300 mg/day, or ≥300 mg/g albumin-to-creatinine ratio or equivalent in first morning void.1 ACEI preferred.1
    • ADA specifies urine albumin-to-creatinine ratio ≥300 mg/g creatinine (recommended) or 30 to 299 mg/g creatinine (suggested).4
  • Hypertension Canada: can use a loop diuretic in patients with chronic renal failure and fluid overload.8
  • CV disease or CV risk factors: ACEI or ARB (Diabetes Canada, Hypertension Canada)8,9

For considerations in other comorbidities (e.g., heart failure, stroke, MI) see our chart, Treatment of Hypertension (U.S.), and algorithm, Stepwise Treatment of Hypertension (Canada).


Why doesn’t intensive blood pressure reduction show clear benefit in diabetes?

Lack of clear benefit may be a result of study limitations. For example, ACCORD (described above) had a low event rate, included patients who had low CV risk, may have been underpowered to detect a benefit, and used hydrochlorothiazide, a short-acting thiazide with less consistent evidence of CV benefit vs chlorthalidone (which was used in SPRINT, described above).13,14

Diabetes affects arteriolar function and blood flow as it relates to blood pressure, such that reducing blood pressure below a point that might be tolerated in a nondiabetic might significantly reduce blood flow to end organs in patients with diabetes.13

Diabetes may potentiate vascular damage such that vacular structure and function may not be amenable to the benefits of a lower SBP.17

How should treatment of hypertension in diabetes patients be individualized?

Age

  • The elderly may be unable to tolerate a significant reduction in BP.12
  • Age itself does not preclude a lower goal. Almost 30% of the patients randomized to intensive treatment in SPRINT were 75 years of age or older.6 Consider using a cardiovascular risk calculator and/or frailty score in decision-making.
  • Although there is less evidence to determine an optimal target in type 1 vs type 2 diabetes patients, DBP could be targeted in younger adults because DBP seems to be a more important CV event predictor in patients <50 years of age. Also, young patients with type 1 diabetes might more easily/safely reach a lower target, and derive benefit over the long-term.4
  • There is limited or no evidence to support a SBP goal of ≤120 mmHg in institutionalized elderly.8

Comorbidities

  • Patients with high CV risk, especially stroke risk, or albuminuria may benefit from a lower BP target, assuming it can be achieved easily and without significant side effects.4
  • Patients with autonomic neuropathy may be unable to tolerate a significant reduction in blood pressure.12
  • Patients with multiple comorbidities or polypharmacy may be less suited to a lower target.4
  • Choice of antihypertensive as it relates to comorbidities is described above.
  • There is limited or no evidence to support a SBP goal of ≤120 mmHg in patients with left ventricular ejection fraction <35% or a MI within the last three months.8
  • Only inconclusive evidence supports a SBP goal ≤120 mmHg in patients with prior stroke or eGFR
    <20 mL/min/1.73m2.

Other considerations

  • Choose a target using shared decision-making. Discuss treatment burdens such as side effects and costs. Explain that the benefits of lower targets for a given individual are uncertain.4
  • Consider patient motivation and socioeconomic resources when choosing a BP target.4 Hypertension Canada recommends that targets of 120 mmHg should be avoided in patients unwilling or unable to adhere to multiple meds.8


Should patients with diabetes be encouraged to check blood pressure at home?


The ADA recommends home blood pressure monitoring to identify white coat hypertension or masked hypertension (i.e., normal blood pressure in office; elevated blood pressure at home), and to promote adherence and interest.4

Hypertension Canada recommends home blood pressure monitoring in patients with diabetes.8

Get our chart, Blood Pressure Monitoring, for information to help patients get accurate readings. Give patients our patient education handout, How to Check Your Blood Pressure, to take home.


Project Leader in preparation of this clinical resource (340501): Melanie Cupp, Pharm.D., BCPS

References

  1. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017 Nov 13 [Epub ahead of print].
  2. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507-20.
  3. ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-85.
  4. De Boer IH, Bangalore S, Benetos A, et al. Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care 2017;40:1273-84.
  5. Patel A, MacMahon S, Chalmers J, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007;370:829–840.
  6. SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373:2103-16.
  7. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich) 2014;16:14-26.
  8. Nerenberg KA, Zamke KB, Leung AA, et al. Hypertension Canada’s 2018 Guidelines for diagnosis, risk assessment, prevention, and treatment of hypertension in adults. Can J Cardiol 2018. [Epub ahead of print].
  9. Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2018(Suppl 1): S1-325.
  10. Adler A, Stratton IM, Neil HA, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000;321:412-9.
  11. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703–13.
  12. Hypertension Canada. Treatment of hypertension in association with diabetes mellitus. http://guidelines.hypertension.ca/prevention-treatment/hypertension-with-diabetes/. (Accessed April 11, 2018).
  13. Grossman A, Grossman E. Blood pressure control in type 2 diabetes patients. Cardiovasc Diabetol 2017;16:3. doi: 10.1186/s12933-016-0485-3.
  14. Hypertension Canada. Choice of therapy for adults with hypertension without compelling indications for specific agents. http://guidelines.hypertension.ca/prevention-treatment/uncomplicated-hypertension-therapy/. (Accessed April 11, 2018).
  15. Leung AA. Daskalopoulou SS, Dasgupta K, et al. Hypertension Canada’s 2017 guidelines for diagnosis, risk assessment, prevention, and treatment of hypertension in adults. Can J Cardiol 2017; 33(5): 557-576.
  16. Schrier RW, Estacio RO, Esler A, Mehler P. Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopaty and strokes. Kidney Int 2002;61:1086-97.
  17. Wan EYF, Yu EYT, Chin WY, et al. Effect of achieved systolic blood pressure on cardiovascular outcomes in patients with type 2 diabetes mellitus: a population-based retrospective cohort study. Diabetes Care 2018 Mar 28. doi: 10.2337/dc17-2443.

Cite this document as follows: Clinical Resource, Hypertension in Patients With Diabetes. Pharmacist’s Letter/Prescriber’s Letter. May 2018.

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