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Diabetes and Stroke

5th Edition
2014 UPDATE
December 2014

The Canadian Stroke Best Practice Recommendations for the Secondary Prevention of Stroke, 5th Edition 2014 module is published in the International Journal of Stroke (IJS) (Online Open‑Access available December 2014; Printed Journal scheduled for April 2015).

To access the specific recommendations for Diabetes and Stroke and all other sections of the Secondary Prevention of Stroke module, please click on this URL which will take you to the recommendations online in the IJS:  http://onlinelibrary.wiley.com/doi/10.1111/ijs.12439/full. For the French version of these recommendations, open the appendix at this link : http://onlinelibrary.wiley.com/store/10.1111/ijs.12439/asset/supinfo/ijs12439-sup-0001-si.pdf?v=1&s=b0ed4fff1d7fc435cf4e2a83ccbcbffbdad767de.

All other supporting information, including performance measures, implementation resources, evidence summaries and references, remain available through www.strokebestpractices.ca, and not through the IJS.  Please click on the appropriate sections below for this additional content.

Rationale

Diabetes is a major risk factor for cardiovascular disease and is recognized as an independent risk factor for ischemic stroke. Most adults with type 1 or type 2 diabetes should be considered at high risk for vascular disease. The exceptions are younger adults with type 1 and type 2 diabetes with shorter duration of disease and without complications of diabetes (including established cardiovascular disease) and without other cardiovascular disease risk factors. Diabetes increases the risk of stroke and is a particularly potent risk factor in younger individuals, with studies suggesting an increase in stroke risk of as much as 10-fold in some younger subgroups. Overall, diabetes is considered a major risk factor for many conditions and is considered here as part of a comprehensive package supporting prevention and lifestyle management.

System Implications
  • Coordinated diabetes awareness programs at the provincial and community levels that involve community groups, primary care providers (including physicians, nurse practitioners and pharmacists), and other relevant partners.
  • Coordinated education and support programs for persons with diabetes to increase compliance and reduce ongoing risks for cardiovascular complications.
  • Increased availability and access to education programs for healthcare providers across the continuum of care on management of patients with diabetes and stroke
  • Continued alignment with recommendations and guidelines developed by the Canadian Diabetes Association.
Performance Measures
  1. Proportion of the population with a confirmed diagnosis of diabetes (type 1 and type 2).
  2. Proportion of persons with diabetes presenting to hospital with a new stroke event.
  3. Proportion of patients presenting to hospital with a stroke who receive a subsequent diagnosis of diabetes during their hospitalization for stroke care.

Measurement Notes

  • Performance measure 1: Rates may be obtained for Canada from the Public Health Agency of Canada Diabetes Surveillance database.
  • Performance measures 1 and 2 should be standardized for age and sex.
  • Data sources may include physician order sheets, physicians’ or nurses’ notes, discharge summaries, or copies of prescriptions given to patients.
  • Blood values should be taken from official laboratory reports where possible.
  • Trends and benchmarks may be monitored and tracked through the National Diabetes Surveillance System data.
Implementation Resources and Knowledge Transfer Tools

Health Care Provider Information

Patient Information

Summary of the Evidence, Evidence Tables and References

Diabetes Management Evidence Tables and Reference List

In persons with diabetes, the risk of stroke is increased 1.5- to three-fold, with a higher risk of ischemic, rather than hemorrhagic stroke (Irdis et al. 2006). However, it is difficult to determine the independent contribution of diabetes, since many risk factors for stroke are found more frequently in persons with diabetes such as hypertension, dyslipidemia and atrial fibrillation. (Karapanayiotides et al. 2004). The higher stroke risk in diabetes may be due to the complex interplay between the various hemodynamic and metabolic components of the diabetes syndrome. In addition to the traditional risk factors, those specifically associated with the metabolic syndrome (insulin resistance, central obesity, impaired glucose tolerance and hyperinsulinemia), which are common in diabetes; also contribute to the increased risk. In persons with diabetes, stroke outcomes are worse, and are associated with increased mortality, more residual neurologic and functional disability and longer hospital stays; however, there is no evidence to suggest that diabetes induces a larger area of cerebral infarction (Irdis et al. 2006). Lifestyle changes, tight glycemic control, antiplatelet drugs (ASA) and control of lipid levels, (e.g., using statins), can all have significant beneficial effects. Blood pressure control is another vital aspect in reducing risk, and a number of recent studies have provided evidence supporting the use of ACE inhibitors as first-line treatment in patients with diabetes.

The Treating to New Targets study (Shepherd et al. 2006) demonstrated that intensive lipid-lowering therapy with atorvastatin 80 mg/day provided significant clinical benefit beyond atorvastatin 10 mg/day in patients with patients with stable coronary artery disease and diabetes and LDL cholesterol levels of < 3.36 mmol/L. High-dose statin therapy was associated with a 25% reduction in major cardiovascular events. After a median follow-up period of 4.9 years, the primary end point (time to first major cardiovascular event), occurred less frequently in the high-dose group (17.9% vs. 13.8%, HR= 0.75, 95% CI 0.58–0.97; p = 0.026). Significant differences between the groups in favour of atorvastatin 80 mg were also observed for time to cerebrovascular event (HR 0.69, 95% CI 0.48–0.98; p = 0.037) and time to any cardiovascular event (HR 0.85, 95% CI 0.73–1.00; p = 0.044). There were no significant differences between the treatment groups in the rates of treatment-related adverse events or persistent elevations in liver enzymes.

The Action to Control Cardiovascular Risk in Diabetes Study (ACCORD, glucose-lowering arm) investigators (Gerstein et al. 2008) assessed whether intensive therapy to target normal A1C levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors.  In this study, 10, 251 patients with a median HbA1c level of 8.1 percent were randomly assigned to receive intensive therapy (targeting an HbA1c level below 6.0 percent) or standard therapy (targeting a level from 7.0 percent to 7.9 percent). The trial was stopped early due to mortality trends suggesting an increased rate of death from any cause associated with intensive therapy (HR=1.22, 95% CI 1.01-1.46, p=0.04). At 4 months, mean HbA1c values had fallen from 8.1% at baseline to 6.7% (intensive group) and 7.5% (control group) with no reduction in the risk of the primary outcome (nonfatal MI, nonfatal stroke or death from cardiovascular causes) associated with intensive glucose lowering (6.9% vs. 7.2%, HR=0.90, 95% CI 0.78-1.04, p=0.16 Patients in the intensive group required medical assistance for hypoglycemia more frequently (10.5% vs. 3.5%), and greater proportions of patients gained >10 kg from baseline (27.8% vs. 14.1%) and experienced a serious nonhypoglycemic adverse event (2.2% vs. 1.6%). The results of a Cochrane review (Marso et al. 2010) also suggest that intensive glucose control does not help to reduce the risk of stroke. The results from 6 studies (4 RCTs) including the results from 27,544 persons with type 2 diabetes examining the benefit of intensive glycemic control for the prevention of vascular events were examined. At the end of follow-up (mean of 5 years), the mean HbA1c values were 6.6% (intensive) and 7.4% (control). There was no reduction in the risk of all-cause mortality, stroke or cardiovascular mortality associated with intensive glycemic treatment. In the hypertension arm of the ACCORD trial (Cushman et al. 2010), patients were randomized to receive either intensive therapy (target = SBP <120mm Hg; n=2,362) or standard therapy (target SBP = 140mm Hg; n=2,371) using treatment strategies in current clinical practice. There was no significant reduction in the risk for the primary outcome associated with intensive HTN treatment (HR=0.88, 95% CI 0.73-1.06, p=0.20). There were significant reductions in the risk of any and non-fatal stroke associated with intensive hypertensive treatment (HR=0.59, 95% CI 0.39-0.89, p=0.01 and HR=0.63, 95% CI 0.41-0.96, p=0.03, respectively), although serious adverse events, attributed to therapy occurred more often in patients in the intensive group (3.3% vs. 1.3%, p<0.001).

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial (Patel et al. 2008) randomly assigned patients (n = 11 140) with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve an HbA1c value of 6.5% or less. After a median of 5 years of follow- up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1% v. 20.0% with standard control; HR 0.90, 95% CI 0.82–0.98; p = 0.01), as well as that of major microvascular events (9.4% v. 10.9%; HR 0.86, 95% CI 0.77–0.97; p = 0.01), primarily because of a reduction in the incidence of nephropathy (4.1% v. 5.2%; HR 0.79, 95% CI 0.66–0.93; p = 0.006), with no significant effect on retinopathy (p = 0.50). There was no significant difference between groups in the risk of death from any cause (HR=0.93, 95% CI 0.83-1.06, p=0.28) or in the risk of fatal or nonfatal stroke or all cerebrovascular events associated with intensive intervention. Severe hypoglycaemia was significantly more frequent in the intensive treatment group (HR=1.86, 95% CI 1.42-2.40, p<0.001). In the hypertension arm of the ADVANCE trial, patients were randomized to receive either a fixed combination of perindopril (2 mg) and indapamide (0.625 mg) or matching placebo. Active treatment was associated with reduction in the risk of combined micro/macrovascular events, all deaths and cardiovascular deaths, but was not associated with reductions in the risk of total cerebrovascular events or major cerebrovascular events.