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The Trial of Intravenous
Insulin Infusion in the Management of Hyperglycaemia in
Acute Coronary Syndrome
THE TITAN-ACS STUDY
Joint venture ABCD, NHS Diabetes,
British Cardiovascular Society, Myocardial Ischaemia
National Audit project (MINAP) |
Background
Approximately 85% patients presenting with acute coronary
syndromes (ACS) have dysglycaemia. There is increasing
evidence that high blood glucose (BG) levels in patients
with known diabetes and also those with new stress
hyperglycaemia, is associated with worse outcomes in ACS and
that strict glycaemic control may improve outcomes[1-5]
There have been no randomised control trials (RCTs)
comparing strict glycaemic control versus less strict;
hence, there are no agreed targets for glycaemic control in
the management of ACS. However, there is evidence from one
RCT that treatment with insulin in the acute phase and for 3
months after the event has a mortality benefit for up to 3
years [6]. Observational data from the MINAP database showed
that treatment with insulin in patients without known
diabetes and ACS with a glucose ≥ 11mmol was associated with
a reduced adjusted hazard ratio of death within 7 days [7].
A recent study from the US showed improved outcomes for
those in whom hyperglycaemia resolved spontaneously or with
insulin treatment [8].
Aims of TITAN-ACS Study
To evaluate effectiveness of a variable rate intravenous
insulin (VRIII) administered with concomitant 5% dextrose
and potassium (40 mmol/L) infusion for patients with ACS
presenting with an admission glucose of ≥ 10 mmol/L.
To use the information derived from these data develop
practical guidance for management of hyperglycaemia in ACS
that would be applicable for use nationally and in agreement
with other consensus guidance under the auspices of the
Joint British Diabetes Societies Inpatient care Group.
The following primary outcomes are be examined:
To confirm that use of a standardised VRIII with 5% glucose
and potassium
• Was effective in achieving normoglycaemia – time to reach
8mmol
• Was effective in maintaining normoglycaemia - median
glucose measurements within the range 4-8 mmol in the first
24 hours
• Was not associated with increased frequency of either mild
hypoglycaemia BG < 4mmol/L or severe hypoglycaemia BG < 3
mmol/L
• Was not associated with insulin-induced hypokalaemia
• Was not associated with an excess of cardiac arrythmias
The following secondary outcomes are to be examined:
• To use the MINAP audit data to examine whether there was a
mortality benefit for those in the TITAN-ACS STUDY receiving
a standardised VRIII titrated to achieve normoglycaemia .
Principal investigator: Dr M Sinclair Hammersley,
Oxford University Hospitals
MINAP Coordinator: Dr John Birkhead, National
Institute of Clinical Outcomes, The Heart Hospital, London
Time Frame
Start: January 2010
Finish: December 2011
Primary outcome data: Diabetes UK APC 2012 Posters 577
and 581
Secondary outcome data: June 2012
Guideline: For completion by March 2013
References
1) Hadjadj S, Coisne D, Mauco G, Ragot S, Duengler F, Sosner
P, Torremocha F, Herpin D, Marechaud R. Prognostic value of
admission plasma glucose and HbA1c in acute myocardial
infarction. Diabetic Medicine 2004; 21 (4), 305–310
2) Stranders I, Diamant M, Van Gelder R E, Spruijt H J,
Twisk JWR, Heine R J, Visser F C. Admission Blood Glucose
Level as Risk Indicator of Death After Myocardial Infarction
in Patients With and Without Diabetes Mellitus. Arch Intern
Med 2004;164:982-988.
3) Ceriello, A. Acute hyperglycaemia: a ‘new’ risk factor
during myocardial infarction. European Heart Journal 2005;
26: 328 - 331.
4) Zarich SW, Nesto RW, Implications and Treatment of Acute
Hyperglycemia in the Setting of Acute Myocardial Infarction
Circulation. 2007;115:e436-e439.
5) Iwakura K, Ito H, MD, Ikushima M, MD*, Kawano S, Okamura
A, Asano K, Kuroda T, Tanaka K, Masuyama T, Hori M, and
Fujii K. Association between hyperglycemia and the no-reflow
phenomenon inpatients with acute myocardial infarction. Am
Coll Cardiol, 2003; 41:1-7
6) Malberg and DIGAMI Study group. Prospective randomised
study of intensive insulin treatment on long term survival
after acute myocardial infarction in patients with diabetes
mellitus. BMJ 1997; 314: 1512-1515
7) Weston C, Walker L, Birkhead J. Early impact of insulin
treatment on mortality for hyperglycaemic patients without
known diabetes who present with an acute coronary syndrome.
Heart 2007; 93: 1542 – 1546
8) Kosiborod M, Inzucchi SE, Krumholz HM, Masoudi FA, Goyal
A, Xiao L, Jones PG, Fiske S, Spertus JA. Glucose
normalization and outcomes in patients with acute myocardial
infarction. Arch Intern Med. 2009 169:438-46. |
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