Ischaemic heart disease

Ischaemic heart disease is arguably the most important complication of diabetes. It is certainly the leading cause of premature mortality amongst people with T2DM and cardiovascular risk modification is one of the most important goals of diabetes treatment.

Prevention

What are the main strategies for prevention of ischaemic heart disease?

The prevention of ischaemic heart disease is multifactorial and should include smoking cessation, blood pressure control, modification of lipids, good glycaemic control and lifestyle factors (diet, weight and exercise).

Smoking cessation

Smoking cessation is arguably the single most important macrovascular risk factor. Patients who smoke should be encouraged and helped to stop smoking at all costs.

They are much more likely to succeed if it is done with some sort of professional support and appropriate referral should be made.

Smoking cessation clinics provide one-to-one or group support and expertise in the full range of smoking cessation drugs (nicotine replacement products, bupropion and varenicline).

Blood pressure control

As long ago as the 1990s, the UKPDS study showed that effective antihypertensive therapy is as important as good glycaemic control in reducing macrovascular risk in T2DM.

Blood pressure targets of 140/80 in the absence of microalbuminura and 130/80 in the presence of microalbuminuria are currently recommended in the UK for T2DM, similar targets for those with T1DM would not be unreasonable.

Overzealous BP reduction carries risks of its own and the recent publication of ACCORD-BP highlighted the risks of attempting to reduce BP to less than 120/80 mm Hg in an elderly population with T2DM at increased risk of cardiovascular disease.

 Lipid modification

The precise details of treatment targets are still hotly debated topics. However, there is some agreement that most people with T2DM and T1DM over the age of 40 should probably be on a statin.

Some argue that total cholesterol target should be 4 mmol/L and LDL cholesterol target should be 2 mmol/L, however, these targets are not universally accepted. There's also a debate over whether patients receive additional fibrate therapy if they fail to reach these targets despite statin therapy.

There are many diabetes specialists who would actively consider fibrate therapy in a patient on maximal tolerated statin doses who still has a total cholesterol significantly above 4 mmol/L and/or a low (<1mmol/L) HDL cholesterol +/- elevated fasting triglycerides. A convenient fibrate is fenofibrate 200 mcg od and the safety of this in combination with a statin is actually very favourable. 

Aspirin

Aspirin is still included in NICE CG87 for primary prevention of ischaemic heart disease in T2DM in patients over the age of 50 and in those below the age of 50 with "significant other CV risk factors”.

However, following the publication of the AAA (aspirin for asymptomatic atherosclerosis) and ATT (antithrombotic trialists collaboration) studies in 2009, and a subsequent MHRA drug safety update highlighting the increased haemorhagic risks with aspirin, many in the diabetes world are veering away from aspirin for primary prevention except in obviously high risk individuals with diabetes (e.g. smokers, marked dyslipidaemia). Further information on the risks and benefits of aspirin for primary prevention will be available when the ASCEND trials reports.

What glycaemic targets should be applied?

The 'one size fits all' strategy of using a single HbA1c target for the whole diabetic population is a blunt approach and it is increasingly recognised that individualised targets should be set with each patient.

The fundamental challenge is that the lower the HbA1c, generally speaking, the more frequent hypoglycaemia will be. Thus for a newly diagnosed patient who is adapting well to life with diabetes and is actively engaging with education and other aspects of self management, setting a target of 6.5% (48mmol/mol) without experiencing unacceptably frequent hypoglycaemia is a realistic aim.

However, for a 75-year-old patient with a 10-year history of T2DM and an HbA1c of 9% (75 mmol/mol), attempting reduction to 6.5 % (48 mmol/mol) will probably confer no survival advantage and may even increase mortality rate as shown by the recent ADVANCE, ACCORD and VADT trials.

Lifestyle

There is evidence to suggest that patients who achieve target weight, eat diets low in saturated animal fats and exercise regularly are also less likely to suffer from ischaemic heart disease. 

Management

Secondary prevention measures

It is essential once a patient has had their first MI or other manifestation of ischaemic heart disease that all secondary prevention measures are vigorously pursued (smoking, cholesterol, blood pressure, and glycaemia although as discussed under 'glycaemic targets', it is important that HbA1c is not lowered too aggressively).

There is a large evidence base regarding the prognostic importance of taking anti platelet agents, statins, ACE inhibitors, beta blockers and to a lesser extent, fish oils after first MI. In addition, the cardiologists should actively pursue all appropriate revascularisation options.

Management of hyperglycaemia on the coronary care unit

The whole question of how best to manage hyperglycaemia (pre-existing diabetes or stress hyperglycaemia) on the CCU in patients with MI or other acute coronary syndromes is another area of active debate. There is an opinion that significantly elevated blood sugars should be brought under control in the acute setting in order to improve prognosis and that the best way to do this may be with insulin. However, what blood glucose threshold insulin should be started at, what the target blood sugar should be and how long insulin should be continued for or all areas of debate. 

Most would agree that metformin should be stopped during acute coronary syndrome and many would agree that TZD therapy should also be suspended.

Thus, a practical approach to this area is as follows:

1. Measure blood glucose level in all admitted to CCU. 

2. Act on blood glucoses above 11 mmol/L regardless of previous diagnosis of diabetes.

3. In those who are already taking metformin or a TZD, stop these.

4. Aim for a blood glucose of 5-8 mmol/L.

5. Insulin will usually be necessary to achieve this level of glycaemia, this should be given as qds basal bolus regimen in patients who are eating. In those who are acutely ill and not eating or who are NBM for other reasons, use an intravenous sliding scale.

6. Once the acute phase is over and the patient is recovering, those with known diabetes can go back on to their previous regimen as long as this is providing adequate glycaemic control.

7. In those not previously known to have diabetes, a fasting blood sugar should be measured (off treatment) and further management should be dependent upon the results. 

Should metformin be continued in patients with heart failure?

This is currently a slightly contentious issue. Safe guidance would be to recommend continuing metformin in NYHA class I and II heart failure, consider stopping it in class III failure patients and suspend metformin therapy in patients with NYHA class IV failure (replacing it with insulin).

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