Observations from the Clopidogrel Resistance in Stent Thrombosis (CREST) registry
Previous studies have demonstrated significant heterogeneity in responses to APT, and high residual platelet reactivity is associated with the risk of ischaemic events, including ST.
The clinical impact of APT is unknown in the “real world’ setting
Aim of the study
The authors report the prevalence of APT hypo-responsiveness in a ‘real world’ registry of ST patients and the feasibility of personalising APT
This study prospectively evaluated 39 consecutive patients admitted to a single regional cardiothoracic centre with definite ST. Response to aspirin and clopidogrel was measured following discharge using short thrombelastography (TEG), a rapid, well validated near patient platelet function test. Treatment modification in hypo-responders comprised an increase in aspirin dose and/or changing clopidogrel to prasugrel or ticagrelor. Short TEG was repeated following treatment modification to ensure an adequate response had been achieved.
Twelve (31%) patients had an adequate response to both aspirin and clopidogrel, 16 (41%) were hypo-responsive to clopidogrel alone, one (3%) was hypo-responsive to aspirin alone and 10 (26%) were hypo-responsive to both aspirin and clopidogrel. Following treatment modification, an adequate response to aspirin and P2Y12 agent was achieved in 10 (91%) and 22 (85%) patients, respectively. None has presented with a further ST episode.
There is a high prevalence of hypo-responsiveness to APT in patients with ST. Improved APT efficacy can be achieved by tailored therapy. Short TEG is a plausible platelet function test that can be used to deliver point of care personalised APT.
Perspective – Clinical impact
As the authors point out, these data from this ‘real world’ registry raise four important questions with regard to clinical practice that warrant further investigation.
1) There is a high prevalence of hypo-responsiveness to APT, particularly clopidogrel (67%). The results of this investigation suggest that ST patients may possess a pro-thrombotic tendency, consistent with the significant proportion found to have high on-treatment platelet reactivity.
2) The majority of cases (82%) were very late ST and, as a result, 29 (74%) patients were not on clopidogrel at the time of their ST presentation.
3) The majority of aspirin hypo-responders in this registry were also hypo-responsive to clopidogrel (91%). This is clearly important as dual APT hypo-responsiveness has been shown to be an independent predictor of ST and cardiac death.
4) The current observational data support the notion that hypo-responsiveness to APT can be overcome with tailored therapy by way of dose or agent adjustment.
We can draw the following conclusions:
This study corroborates previous observations of a high prevalence of hypo-responsiveness to APT, in particular clopidogrel, in patients with ST. Demonstrates the feasibility of providing tailored APT using a novel near-patient platelet function test. Demonstrates that improved APT efficacy can be achieved by tailored therapy. Raises further questions with regards to (a) the mechanism(s) of very late ST, and (b) whether responses to APT are dynamic and vary significantly over time.
Corresponding author from original article : Nick Curzen Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK; firstname.lastname@example.org.