More evidence needed for ADP-antagonists to prevent CVD in type 2 diabetes

ECG readout

This Cochrane systematic review looked at whether adenosine-diphosphate (ADP) receptor antagonists such as clopidogrel and ticlopidine,  can prevent cardiovascular disease (CVD) in type 2 diabetes mellitus.

These drugs have been shown to reduce the risk of cardiovascular outcomes in non-diabetic patients.  However, few studies have looked at the diabetic population.  As people with type 2 diabetes are at a substantially increased risk of CVD, we might expect ADP receptor antagonists to offer some benefit.

Clinical question

In patients with type 2 diabetes, do ADP receptor antagonists, compared with placebo or alternative treatments, reduce the risk of CVD?

Outcomes of interest included overall mortality, myocardial infarction, stroke and peripheral vascular disease.

Methods

This was a good quality systematic review in which it is unlikely that the reviewers missed important evidence.

To find relevant publications, the reviewers searched MEDLINE, EMBASE, the Cochrane Library and reference lists and they contacted authors of key papers.

Two independent reviewers performed study selection and evaluation.

Vascular diseaseResults

These methods turned up eight randomised trials comprising 21,379 participants.

They included:

  • two studies comparing ticlopidine with aspirin
  • one study comparing ticlopidine with placebo
  • one study comparing clopidogrel to aspirin
  • one study comparing clopidogrel to aspirin and dipyridamole
  • three studies comparing clopidogrel and aspirin to aspirin

Only three studies were included in the meta-analysis, however.  This was because the trials all included diabetic and non-diabetic particicpants.  Only in three trials was it possible to identify the outcomes for participants with type 2 diabetes.

Conclusion

When they pooled the data from these three trials, the reviewers drew the following conclusion:

Available data did not demonstrate a significant benefit of ADP receptor antagonists over placebo or other antiplatelet drugs in reducing all-cause mortality, vascular mortality, stroke or myocardial infarction.

Comments

  • The reviewers report important clinical differences between the studies, in the populations studied and in the interventions compared.  This limited the applicability of their findings.
  • The mean follow-up period of the studies was around 3 years.
  • Overall, the reviewers rated the trials as being of high quality.
  • This review does not suggest type 2 diabetics are so different from the general population that they cannot benefit from ADP receptor antagonists.
  • There was some indication from one study that ticlopidine might reduce the risk of stroke compared with aspirin.
  • However, further trials are warranted that specifically report outcomes data for people with type 2 diabetes so that the benefits and harms can be assessed fully.
  • Such trials are needed for primary and secondary prevention of CVD.

Reference

Valentine N, Van de Laar FA, van Driel ML. Adenosine-diphosphate (ADP) receptor antagonists for the prevention of cardiovascular disease in type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2012, Issue 11. Art. No.: CD005449. DOI: 10.1002/14651858.CD005449.pub2