Key question:

What is the evidence that cardiovascular risk in patients with Type 2 diabetes and nephropathy can be reduced by specific interventions?

Evidence table ref: 3

Only two studies have assessed cardiovascular risk reduction in patients with Type 2 diabetes and nephropathy. Both studies were methodologically of good quality, but in only one (the HOPE study) was cardiovascular disease risk reduction the primary endpoint. In the other study (the Steno Study), cardiovascular disease risk reduction was a tertiary endpoint and so the study was not adequately powered to detect a significant difference.

None of the major intervention studies of hypoglycaemic therapy, lipid-lowering therapy, anti-hypertensive therapy, smoking cessation or dietary modification have specifically addressed issues of cardiovascular disease risk reduction in patients with Type 2 diabetes and nephropathy.

In patients with chronic renal failure and coronary artery disease, no large-scale trials have compared aggressive cardiovascular risk reduction by medical therapy with coronary revascularisation.

Fully applicable.

3. Generalisability
Comment here on how reasonable it is to generalise from the results of the studies used as evidence to the target population for this guideline.

Highly reasonable.

4. Consistency
Comment here on the degree of consistency demonstrated by the available of evidence. Where there are conflicting results, indicate how the group formed a judgement as to the overall direction of the evidence

High degree of consistency - no conflicting results.

5. Clinical impact
Comment here on the potential clinical impact that the intervention in question might have - e.g. size of patient population; magnitude of effect; relative benefit over other management options; resource implications; balance of risk and benefit.

Large potential impact - large numbers of patients with Type 2 diabetes are likely to be prescribed ACE inhibitor therapy.

None

7. Evidence statement
Please summarise the development group's synthesis of the evidence relating to this key question, taking all the above factors into account, and indicate the evidence level which applies.

Evidence level

In patients with Type 2 diabetes and nephropathy:

Treatment with the Angiotensin Converting Enzyme (ACE) Inhibitor Ramipril significantly reduces, all-cause mortality, cardiovascular mortality, and cardiovascular events. The effect of ramipril on cardiovascular outcomes appears to be out of proportion to its anti-hypertensive effects.

Therapy with Vitamin E does not affect cardiovascular outcomes. There is no direct trial evidence that aggressive management of other cardiovascular risk factors affects cardiovascular outcomes. Evidence from blood pressure and lipid intervention trials in diabetic patients (whose nephropathy status has generally not been documented) would indicate that cholesterol reduction with statin agents and blood pressure reduction are likely to be of benefit in reducing cardiovascular events. Glucose-lowering therapy with metformin may also be of benefit in obese patients without significant impairment of renal function.

Coronary angiography (with subsequent revascularisation if coronary artery disease is identified) is often advocated in patients who are being considered for renal replacement therapy. There is no direct trial evidence to support this, nor have any trials compared coronary revascularisation with aggressive medical management of cardiovascular risk factors in such circumstances.

1⁺⁺


1⁺⁺

4








4

8. Recommendation
What recommendation(s) does the guideline development group draw from this evidence? Please indicate the grade of recommendation(s) and any dissenting opinion within the group.

Grade of recommendation

Patients with Type 2 diabetes and microalbuminuria should be commenced on therapy with Ramipril. There is no trial evidence that supports the use of other ACE inhibitors, in terms of cardiovascular risk reduction, although a class effect could be anticipated.

In patients with Type 2 diabetes and nephropathy, targets for glycaemic control, blood pressure and cholesterol concentrations should be the same as for patients with established cardiovascular disease. Advice on smoking cessation should be given.

A

D