General practice management of type 2 diabetes


Managing cardiovascular risk
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Recommendations

Reference

Grade*

Patients with pre-existing cardiovascular disease (CVD) are at high risk

149

NVDPA, 2012

A

All adults with type 2 diabetes and known prior CVD (except haemorrhagic stroke) should receive the maximum tolerated dose  of a statin, irrespective of their lipid levels

Note: The maximum tolerated dose should not exceed the maximum available dose (eg 80 mg atorvastatin, 40 mg rosuvastatin)

150

Baker IDI, 2015

A

Adults with any of the following conditions do not require absolute CVD risk assessment using the Framingham risk equation because they are already known to be at clinically determined high risk of CVD:

  • Diabetes and aged >60 years
  • Diabetes with microalbuminuria (>20 mcg/min or urine albuminto-creatinine ratio [UACR] >2.5 mg/mmol for men and >3.5 mg/ mmol for women)
  • Moderate or severe chronic kidney disease (persistent proteinuria or estimated glomerular filtration rate [eGFR]) <45 mL/min/1.73 m2)
  • A previous diagnosis of familial hypercholesterolaemia
  • Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg
  • Serum total cholesterol >7.5 mmol/L

149

NVDPA, 2012

D

Calculate risk level using an evidence-based tool:

149
NVDPA, 2012

B

Aboriginal and Torres Strait Islander peoples are generally assumed to be at higher risk

149
NVDPA, 2012

B

*Refer to Summary, explanation and source of recommendations for an explanation of the level of evidence and grade of evidence


Clinical context


CVD is the leading cause of death in people with diabetes, making assessment of CVD risk a vital part of diabetes care.

Assessment of combined multiple risk factors (absolute CVD risk) is more accurate than the use of individual risk factors.149

As with glycaemic targets, treatment targets in CVD need to be made on an individual basis, balancing the benefits and risks of interventions. For example, the CVD risk associated with lipid and BP levels is continuous; hence, specific targets are somewhat arbitrary and should be used as a guide to treatment, and not as a mandatory requirement. Table 8 can be used when developing a management plan for patients.

The risks associated with the effort required to reach a particular target, as opposed to achieving a near-target value, may outweigh any small absolute benefit. Any reduction in risk factor values will be associated with some benefit.149

Recommendations are summarised from the Natural Vascular Disease Prevention

Alliance’s Guidelines for the management of absolute CVD risk.149
 

Table 8. Risk management summary

CVD risk

Lifestyle

Pharmacotherapy

Targets

Monitoring

High risk:

Clinically
determined or calculated using Framingham risk evaluation (FRE) as >15% absolute risk of cardiovascular disease events over five years

Frequent and sustained specific advice and support regarding diet and physical activity

Appropriate advice, support and pharmacotherapy for smoking cessation

Advice given simultaneously with blood pressure (BP) and lipid-lowering drug treatment

Treat simultaneously with lipid-lowering and BP-lowering unless contraindicated or clinically inappropriate

Aspirin not routinely recommended


Consider withdrawal of therapy for people who
make profound lifestyle changes

BP:

  • ≤140/90 mmHg in general or people with CKD
  • ≤130/80 mmHg in all people with diabetes*
  • ≤130/80 mmHg if microalbuminuria or macroalbuminuria (UACR >2.5 mg/mmol  in men and  >3.5 mg/mmol  in women)

Review response
6–12 weekly until sufficient improvement or maximum tolerated dose achieved


Adjust medication as required

Review of absolute risk according to clinical context

Moderate risk:

Calculated using FRE as 10–15% absolute CVD risk events over five years

Appropriate, specific advice and support regarding diet and physical activity

Appropriate advice, support and pharmacotherapy for smoking cessation

Lifestyle advice given in preference to drug therapy

Not routinely recommended


Consider BP-lowering and/or lipid-lowering in addition to lifestyle advice if three to six months of lifestyle intervention does not reduce risk or:

  • BP persistently ≥160/100 mmHg
  • Family history of premature CVD
  • Specific population where the FRE underestimates risk e.g. Aboriginal and Torres Strait Islander, South Asian, Maori, Pacific Islander and Middle Eastern peoples

Consider withdrawal of therapy for people who
make profound lifestyle changes

Lipids:
Total cholesterol <4.0 mmol/L; highdensity lipoproteincholesterol ≥1.0 mmol/L; low-density lipoproteincholesterol <2.0 mmol/L; NonHDL-C <2.5 mmol/L; triglycerides <2.0 mmol/L.


Lifestyle:

  • Smoking cessation  (if smoker)
  • Consume diet rich in vegetables and fruit, low in salt and saturated and trans fats
  • At least 30 min physical activity on most or preferably every day of the week
  • Limit alcohol intake

Review response 6–12 weekly
until sufficient improvement or maximum tolerated dose achieved


Adjust medication as required Review absolute risk every 6–12 months

Low risk:
Calculated using FRE as <10% absolute CVD risk events over five years

Brief, general lifestyle advice regarding diet and physical activity

Appropriate advice, support and pharmacotherapy for smoking cessation

Not routinely recommended
Consider BP-lowering therapy in addition to specific lifestyle advice if BP persistently ≥160/100 mmHg.

Consider withdrawal of therapy for people who
make profound lifestyle changes

 

Review response 6–12 weekly until sufficient improvement or maximum tolerated dose achieved


Adjust medication as required Review absolute risk every two years


Blood test results within five years can be used

Reproduced with permission from the National Vascular Disease Prevention Alliance from Guidelines for the management of absolute CVD risk, 2012, an initiative of the National Vascular Disease Prevention Alliance

*Refer to the ‘Antihypertensive medication to manage cardiovascular risk’ section opposite for further discussion of BP targets


In practice


There are several interventions for managing CVD risk.

Lifestyle interventions to reduce CVD risk

Lifestyle changes in nutrition, physical activity and smoking status fundamentally underpin a comprehensive approach to CVD risk minimisation. Lifestyle changes show excellent cost-effectiveness in lowering the burden of disease and remain the basis for the management of all CVD risk levels.151,152 However, the Look AHEAD study, showed improved HbA1c and quality of life benefit, but no reduction in risk of cardiovascular morbidity or mortality in people with type 2 diabetes who were obese (average BMI  36 kg/m2;82 refer to Chapter 6. Lifestyle modification).

Antihypertensive medication to manage cardiovascular risk

This section on antihypertensive interventions to reduce cardiovascular risk provides further discussion of BP targets.

Recommendations

Reference

Grade*

BP-lowering therapy in people with diabetes should preferentially include an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)

If monotherapy does not sufficiently reduce blood pressure (BP) add one of the following:

149
NVDPA, 2012

A

• Calcium channel blocker

149
NVDPA, 2012

B

• Low-dose thiazide or thiazide-like diuretic

149
NVDPA, 2012

C

*Refer to Summary, explanation and source of recommendations for an explanation of the level of evidence and grade of evidence

Lowering BP reduces cardiovascular events and all-cause mortality in people with type 2 diabetes in the same manner as for the general population.

While no difference is noted between different classes of BP-lowering therapy for CVD outcomes, there is clear evidence that in people with type 2 diabetes, antihypertensive therapy with an angiotensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) decreases the rate of progression of albuminuria, promotes regression to normoalbuminuria and may reduce the risk of decline in renal function. Combining an ARB and an ACEI is not recommended.149

The target level for optimum BP is controversial.

A number of international guidelines have changed their blood pressure targets to <140/90 mmHg, while others remain at <130/80 mmHg. The target levels for BP therapy have been based on little direct trial evidence. A number of meta-analyses have demonstrated that the benefits of intensive BP control needs to be balanced  with the risks. One meta-analysis demonstrated that more intensive BP control (SBP  ≤130 mmHg) compared to usual (<140/90 mmHg) was associated with further reduction in stroke but a 40% increase in serious adverse events.153 Two additional meta-analyses have recently been published. The analysis by Emdin at al48 found that risk reduction was attenuated below an SBP of 140mmHg. However, there did appear to be a lower risk of stroke, retinopathy and albuminuria when blood pressure was reduced to <130 mmHg. Another meta-analysis, however, found that treatment of an SBP <140 mmHg was associated with increased CVD death.154 This may in part be related to the selection of trials in this analysis which included patients with comorbidites such as CKD, heart failure and CVD.155

In line with these findings, it would be reasonable for GPs to shift the BP target to <140/90 mmHg for people with diabetes, with lower targets considered for younger people and those at high risk of stroke (secondary prevention), as long as the treatment burden is not high. The target BP for people with diabetes and microalbuminuria or proteinuria remains <130/80 mmHg. As always, treatment targets should be individualised and people with diabetes monitored for side effects from the use of medications to achieve lower targets.
 

Lipid medication to manage cardiovascular risk

 

Recommendations

Reference

Grade*

Use statins as first-line therapy

149 NVDPA, 2012

A

*Refer to Summary, explanation and source of recommendations for an explanation of the level of evidence and grade of evidence


GPs should consider treatable secondary causes of raised blood lipids before commencing drug therapy.

When commencing drug therapy, statins remain the clear first-line choice. The results from several systematic reviews are consistent, and suggest that people with diabetes gain at least similar benefits from statin therapy as people without diabetes. The data clearly demonstrate that statin therapy results in a significant decrease in CAD morbidity and mortality in type 2 diabetes for those at high CVD risk. This benefit is in contrast to the contentious effects of improved glycaemic control in CVD.

Apart from statins, the evidence for other lipid-lowering therapy in decreasing the risk of CAD is still accumulating. Ezetimibe has been studied in IMPROVE-IT (Improved reduction of outcomes: Vytorin efficacy international trial).156 Patients with existing acute coronary syndrome and diabetes had a 14% reduction in death from CVD, a major coronary event (eg nonfatal MI, documented unstable angina requiring hospital admission, or coronary revascularisation occurring at least 30 days after randomisation), or nonfatal stroke. Among the patients with diabetes, the rates of MI and stroke were reduced by approximately 21% and 42% respectively.

Nicotinic acid, bile-acid resins, and fibrates (fenofibrate, gemfibrozil) have been suggested as alternatives for people who cannot tolerate statins. Nicotinic acid has been shown in one trial to reduce CVD outcomes, although the study was done in a cohort of people without diabetes.157 More recent trials have not confirmed this initial result. The use of nicotinic acid, in particular, as well as gemfibrozil and cholestyramine is limited by a high rate of adverse effects.

The role of fibrates to decrease CVD is contentious. All large prospective randomised clinical trials of fibric acids have failed to decrease the primary cardiovascular end point. However, in all studies, predominantly post-hoc analyses, have shown that sub-groups having a low HDL-C level <0.9 mmol/L together with a raised triglyceride (generally >2.3 mmol/L) derive a significant benefit from fibrate therapy. Given these results, it may be reasonable to consider the introduction of fenofibrate in high-risk patients on statin therapy whose LDL-C is not at target and who have low HDL-C and raised triglyceride levels. Newer injectable lipid lowering agents called PCSK9 i (inactivate proprotein convertase subtilisin–kexin type 9 inhibitors) has TGA approval for combination with other lipid lowering agents in select high-risk patients. Mortality or morbidity outcomes are not yet established. Refer to the TGA website  for more information.

Antithrombotic therapy

 

Recommendations

Reference

Grade*

All adults with type 2 diabetes and known prior cardiovascular disease should receive long-term antiplatelet therapy unless there is a clear contraindication

150
Baker IDI, 2015

A

All adults with type 2 diabetes and a history of ischaemic stroke or transient ischaemic attack should receive:

150
Baker IDI, 2015

 

• low-dose aspirin or

 

A

• clopidogrel or

 

A

• combination low-dose aspirin and extended-release dipyridamole

 

B

All adults with type 2 diabetes and recent acute coronary syndrome and/or coronary stent should receive, for 12 months after the event or procedure:

150
Baker IDI, 2015

 

• combination low-dose aspirin and clopidogrel or

 

B

• combination low-dose aspirin and prasugrel or

 

B

• combination low-dose aspirin and ticagrelor

 

C

All adults with type 2 diabetes and a history of coronary artery disease, but no acute event in the past 12 months should receive

150
Baker IDI, 2015

 

• long-term low-dose aspirin, or

 

 A

• long-term clopidogrel if intolerant to aspirin

 

 B

In the presence of atrial fibrillation or other major risk factors for thromboembolism, there should be consideration of anticoagulant therapy according to other relevant guidelines

150
Baker IDI, 2015

Practice Point

*Refer to Summary, explanation and source of recommendations for an explanation of the level of evidence and grade of evidence

Prescription of antiplatelet therapy (eg aspirin, clopidogrel) is not usually recommended in primary prevention, but for secondary prevention, the strong positive effects in the following conditions need to be weighed against individual patient risks.


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