PLAVIX (clopidogrel) - Atherothrombotic events

The clinical benefit of PLAVIX 75 mg and 300 mg (clopidogrel) film-coated tablets is moderate in the MA indication extension considered.

Considering:

• the absence of studies specifically assessing clopidogrel conducted in STEMI patients managed by primary PCI, and, in particular, versus clinically relevant comparators;
• a low quality of evidence in view of the major methodological limitations of the comparative data versus placebo submitted by the pharmaceutical company (PCI-CLARITY analysis and CREDO trial), due, in particular, to:
  • the poor match between the population included and that of the indication sought: STEMI patients only managed by delayed PCI (post fibrinolysis) in the PCI-CLARITY analysis, reflecting a clear temporal bias linked to changes in treatment practices, and non-inclusion of STEMI patients in the CREDO trial;
  • the post-hoc, open-label design of the PCI-CLARITY analysis, performed on subgroups, the results of which can only be considered to be exploratory for the assessment at 28 days;
  • purely exploratory results for the composite secondary endpoint (death from any cause, Q-wave +/- MI, and stroke) at 1 year in the CREDO study, and non-significant results for the primary endpoint at 28 days and on the key composite secondary endpoint at 1 year as defined by the CSR;
• a modest body of evidence assessing the loading dose of 600 mg clopidogrel in the indication considered;
• safety data in favour of clopidogrel in certain populations with a bleeding risk, to be considered based on the individual risk-benefit assessment;
• the medical need partially met by the available alternatives;

the Committee deems that PLAVIX 75 mg and 300 mg (clopidogrel) film-coated tablets provide no clinical added value (CAV V) in the current care pathway for the treatment of ST segment elevation acute myocardial infarction, in combination with acetylsalicylic acid (ASA) in adult patients undergoing percutaneous coronary intervention (including patients
undergoing a stent placement), which includes relevant comparators: generics of PLAVIX 75 mg (clopidogrel), BRILIQUE 90 mg (ticagrelor), EFIENT (prasugrel).