Randomised control trial
Malmberg K, Ryden L, Efendic S, et alRandomized Trial of Insulin-Glucose Infusion Followed by Subcutaneous Insulin Treatment in Diabetic Patients with Acute Myocardial Infarction (DIGAMI Study): Effects on Mortality at 1 Year
JACC
1995; (26) 57-65
- Submitted by:Craig Ferguson - SPR
- Institution:Salford Royal Foundation Trust
- Date submitted:22nd July 2007
1
Objectives and hypotheses
1.1
Are the objectives of the study clearly stated?
Yes. To test the hypothesis that improvement of metabolic control in diabetic patients with acute myocardial infarction by means of an insulin-glucose infusion would decrease mortality.
2
Design
2.1
Is the study design suitable for the objectives
Yes. There are multiple centres recruiting patients with suspected myocardial infarctions and randomising them to either insulin-glucose therapy or standard care.
2.2
Who / what was studied?
Patients with a suspected myocardial infarction within the preceding 24h and a blood glucose >11 mmol/l. Included patients not known to be diabetic but with high blood glucose on attendance but did not include patients who were known to be diabetic but had blood glucose <11 mmol/l on attendance. Excluded patients who were too ill to consent.
2.3
Was this the right sample to answer the objectives?
Looked at patients with suspected MIs rather than patients with true MIs but I suppose this is actually more relevant for clinical practice. I would commence the DIGAMI regime in a patient I suspected of having an MI without waiting for confirmation.
2.4
Is the study large enough to achieve its objectives? Have sample size estimates been performed?
Sample size estimates were performed although they had hoped to see a reduction in mortality by 30% from a 35% rate in the control group. In actual fact the control group only had a mortality of 15.6% at 3 months.
2.5
Were all subjects accounted for?
Yes. Give numbers and reasons for excluded patients. Not clear how many patients were lost to follow up, does state at 1 year visit (n=376) which presumably means that 376/620 patients were reviewed at clinic at 1 year.
2.6
Were all appropriate outcomes considered?
Yes. Have provided data on short and longer term mortality, episodes of hypoglycaemia, rates of re-infarction, ventricular fibrillation and PTCA and CABG over the following year.
2.7
Has ethical approval been obtained if appropriate?
Yes.
2.8
Were the patients randomised between treatments?
Yes.
2.9
How was randomisation carried out?
States that patients were randomised in blinded fashion after inclusion and exclusion criteria were applied. Following randomisation the management of the patients was not blind.
2.10
Are the outcomes clinically relevant?
Yes. There is a non-significant decrease in mortality at the 3 month period, which was the primary out-come that this study was looking for.(38/306 (12.4%) patients in treatment group vs. 49/314 (15.6%) in the control group.) There was a decrease in mortality at 1 year which approaches conventional statistical significance. (57/306 (18.6%) in the treatment group vs. 82/314 (26.1%) in the control group, p=0.0273.)
3
Measurement and observation
3.1
Is it clear what was measured, how it was measured and what the outcomes were?
Yes, main outcome is death. Not clear how this was obtained, is there a national database?
3.2
Are the measurements valid?
Yes. If have sound method of measuring all mortality.
3.3
Are the measurements reliable?
Yes.
3.4
Are the measurements reproducible?
Yes.
3.5
Were the patients and the investigators blinded?
No, neither groups were blinded following randomisation. Would have been very difficult to do. Not clear how the diabetes or high blood sugars of the control group were managed other than the statement that they did not receive insulin unless clinically indicated.
4
Presentation of results
4.1
Are the basic data adequately described?
Yes.
4.2
Were groups comparable at baseline?
Yes.
4.3
Are the results presented clearly, objectively and in sufficient detail to enable readers to make their own judgement?
Yes.
4.4
Are the results internally consistent, i.e. do the numbers add up properly?
Yes, no errors spotted.
4.5
Were side effects reported?
Yes.
5
Analysis
5.1
Are the data suitable for analysis?
Yes.
5.2
Are the methods appropriate to the data?
Yes.
5.3
Are any statistics correctly performed and interpreted?
Yes, appear to be.
6
Discussion
6.1
Are the results discussed in relation to existing knowledge on the subject and study objectives?
Yes, good wide ranging discussion.
6.2
Is the discussion biased?
Mention the surprisingly low mortality rate in both groups but don't reflect that this may be due the fact that they looked at patients with suspected MI rather than confirmed MI (although the confirmation rate was 88% in the treatment group and 84% in the control group) and also that the main inclusion criteria was a blood glucose >11mmol/l rather than a previous diagnosis of diabetes. They may be excluding patients with diabetes who happened to have a lower blood glucose at the time of admission and including patients who had a stress response to having an MI but would not necessarily have the risks associated with long term diabetes.
7
Interpretation
7.1
Are the authors' conclusions justified by the data?
The authors conclude that this paper supports the use of insulin-glucose infusion in patients with MI. They also state that it is particularly beneficial in patients who were not already receiving insulin on the basis of sub-group analysis, stratifying the patients for pre-existing risk factors and demonstrating a significant benefit in the lowest risk patients.
This paper certainly show a tendency towards improved mortality rates in the patients that have received more intensive metabolic control and although the figures only achieve borderline significance there is a good theory to support the use of insulin in patients with MI.
The sub-group analysis does show a significant improvement in mortality rates in low risk patients (stratified on basis of age <70, previous MI, previous heart failure and digitalis therapy) but the numbers involved at this level are very small and I don't think that they should be extrapolated to the wider population.
This paper certainly show a tendency towards improved mortality rates in the patients that have received more intensive metabolic control and although the figures only achieve borderline significance there is a good theory to support the use of insulin in patients with MI.
The sub-group analysis does show a significant improvement in mortality rates in low risk patients (stratified on basis of age <70, previous MI, previous heart failure and digitalis therapy) but the numbers involved at this level are very small and I don't think that they should be extrapolated to the wider population.
7.2
What level of evidence has this paper presented? (using CEBM levels)
1b
7.3
Does this paper help me answer my problem?
Certainly suggests that starting glucose-insulin infusion to control glucose levels in patients with MI is likely to benefit them in the longer term.
8
Implementation
8.1
Can any necessary change be implemented in practice?
Yes.
8.2
What aids to implementation exist?
Production of sliding scale sheets to be make it easy to prescribe insulin for these patients.
8.3
What barriers to implementation exist?