Role of Newer Antiplatelet Therapies in the Patient with Diabetes - Can we Improve on Aspirin? Stephen Wiviott; ADA 2011.

There is doubt about the safety and efficacy of aspirin in diabetes. Combining clopidogrel with aspirin yields slight added benefit in non-diabetics, but those with diabetes showed no benefit or even a tendency to harm.

Thus in those with diabetes/multiple risk factors there is no evidence that adding clopidogrel adds any benefit beyond that of aspirin alone for primary prevention. That changes for acute coronary syndrome (ACS) or stent thrombosis however.

There is a 2-3 fold increase in stent thrombosis rates in diabetes. In the CURE Trial in ACS there was a significant benefit in favour of adding clopidogrel to aspirin in the medical therapy alone group, and there was a substantial and consistent benefit across all treatment groups in CURE in favour of clopidogrel. This benefit may be increased with Prasugrel (a newer generation agent) which improves benefit especially in those who get no response with clopidogrel. In the TRITON TIMI-38Trial there was a significant reduction in CV death/MI/stroke with an NNT of 43 in the diabetic subgroup.

In TRITON TIMI-38 Prasugrel increased risk of severe bleeding especially in the older patients although the difference did not reach significance. A second newer agent that is in the pipeline is Ticagrelor which has a very rapid onset of action and far greater inhibition of platelets/ It has been studied in the PLATO Trial which showed a significant reduction in MI & stroke. There was also a significant reduction in CV death with this agent.

New agents including a thrombin receptor inhibitor are in trial. The Thrombin Receptor Antagonist (TRA) programme is now running with enrollment complete in 2 trials. There is an increase in overall bleeding and this has led to premature closure of the trials.

In summary the is NO evidence for intensive (combined) anti-platelet therapy in diabetes EXCEPT in acute coronary syndromes as there is an increase in bleeding without benefit on ischaemic events. Newer intensive agents have shown greater reductions in ischaemic events but this is at the expense of increased bleeding rates. Studies of alternate pathways are ongoing.