Correspondence

Platelet Inhibition with Cangrelor

N Engl J Med 2010; 362:1048-1049March 18, 2010

Article

To the Editor:

Harrington et al.1 and Bhatt et al.2 (Dec. 10 issue) describe the results of studies of platelet inhibition with intravenous cangrelor in patients undergoing percutaneous coronary intervention (PCI). In the study by Harrington et al., 996 patients with myocardial infarction with ST-segment elevation were enrolled. In this select group of patients, the administration of oral antiplatelet agents is not always an option. In our institution, such drugs could not be administered to 2% of patients presenting with ST-segment–elevation myocardial infarction who underwent primary PCI. Such patients include those who have undergone intubation after cardiac arrest or who have intractable emesis in the emergency department. Although cangrelor may not have shown superiority over clopidogrel in all patients with acute coronary syndromes with respect to the end points outlined in this study, a substantial minority would benefit from the use of this intravenous agent, which would reduce the risk of complications (e.g., acute stent thrombosis), as compared with no antiplatelet therapy.

Neil Ruparelia, M.B., B.S.
Nicos Spyrou, M.D.
Royal Berkshire Hospital, Reading, United Kingdom
neilruparelia@doctors.org.uk

No potential conflict of interest relevant to this letter was reported.

2 References

1. 1

   Harrington RA, Stone GW, McNulty S, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009;361:2318-2329
   Full Text | Web of Science | Medline

2. 2

   Bhatt DL, Lincoff AM, Gibson CM, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009;361:2330-2341
   Full Text | Web of Science | Medline

To the Editor:

Several studies have shown that there is considerable variation in the response of patients to antiplatelet drugs.1 Previous studies have reported that 20 to 40% of patients with coronary artery disease who underwent elective PCI did not have a response to clopidogrel, even when the drug was administered with aspirin.2,3 Similar results were obtained with the use of other blockers of platelet adenosine diphosphate receptor P2Y₁₂, such as cangrelor.3 Harrington et al. and Bhatt et al. conclude that cangrelor does not provide additional advantages to those achieved with clopidogrel. Nevertheless, the patients who received either clopidogrel or cangrelor were not stratified according to their response to either drug at baseline. Such stratification before randomization might have had an effect on the study's end points, because hyporesponsiveness to antiplatelet drugs is frequently associated with a poorer clinical outcome.

Giuseppe Lippi, M.D.
Massimo Franchini, M.D.
Azienda Ospedaliero–Universitaria di Parma, Parma, Italy
ulippi@tin.it

Emmanuel J. Favaloro, Ph.D.
Westmead Hospital, Westmead, NSW, Australia

No potential conflict of interest relevant to this letter was reported.

3 References

1. 1

   Lippi G, Favaloro EJ, Salvagno GL, Franchini M. Laboratory assessment and perioperative management of patients on antiplatelet therapy: from the bench to the bedside. Clin Chim Acta 2009;405:8-16
   CrossRef | Web of Science | Medline

2. 2

   Lepantolo A, Virtanen KS, Heikkila J, Wartiovaara U, Lassila R. Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions. Eur Heart J 2004;25:476-483
   CrossRef | Web of Science | Medline

3. 3

   Lepantolo A, Virtanen KS, Resendiz JC, et al. Antiplatelet effect of clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions -- limited inhibition of the P2Y12 receptor. Thromb Res 2009;124:193-198
   CrossRef | Web of Science | Medline

Author/Editor Response

Ruparelia and Spyrou raise an important practical point, since not all patients can take oral antiplatelet therapy in the emergency setting. Examples include intubated patients, nauseated patients, and heavily sedated patients. Absorption and metabolism of oral antiplatelet drugs may also be impaired in patients in shock.1 We agree that a potent, rapid-acting, intravenous antiplatelet agent that is reversible would fulfill a vital role in such high-risk patients by reducing ischemic outcomes, such as stent thrombosis. Potentially, cangrelor could provide that sort of clinical protection, but its availability for use will depend on further investigation.

Lippi et al. discuss the possible implications of variability in response to antiplatelet medications. There is inherent biologic variability in all drugs, but it does seem that this variability in response to antiplatelet therapy may be associated with ischemic outcomes. We did not define responsiveness to clopidogrel at the time of entry into either of the two trials. However, point-of-care assays of platelet function or pharmacogenomic analyses might be useful in deciding which patients would be best served by various antiplatelet regimens. However, this logical concept needs to be validated prospectively in randomized clinical trials.2

Deepak L. Bhatt, M.D., M.P.H.
Veterans Affairs Boston Healthcare System, Boston, MA
dlbhattmd@post.harvard.edu

Robert A. Harrington, M.D.
Duke Clinical Research Institute, Durham, NC

Since publication of their articles, the authors report no further potential conflicts of interest.

2 References

1. 1

   Osmancik P, Jirmar R, Hulikova K, et al. A comparison of the VASP index between patients with hemodynamically complicated and uncomplicated acute myocardial infarction. Catheter Cardiovasc Interv 2010;75:158-166
   CrossRef | Web of Science | Medline

2. 2

   Bhatt DL. Tailoring antiplatelet therapy based on pharmacogenomics: how well do the data fit? JAMA 2009;302:896-897
   CrossRef | Web of Science | Medline