Author + information
- Received February 2, 2018
- Revision received February 22, 2018
- Accepted February 22, 2018
- Published online March 11, 2018.
- Francesca Maria Notarangelo, MDa,
- Giuseppe Maglietta, MScb,c,
- Paola Bevilacqua, MSca,
- Marco Cereda, PhDd,
- Piera Angelica Merlini, MDe,
- Giovanni Quinto Villani, MDf,
- Paolo Moruzzi, MDg,
- Giampiero Patrizi, MDh,
- Guidantonio Malagoli Tagliazucchi, PhDa,b,
- Antonio Crocamo, MDa,
- Angela Guidorossi, MDa,
- Filippo Pigazzani, MD, PhDa,
- Elisa Nicosia, MSca,
- Giorgia Paoli, MDa,
- Marco Bianchessi, PhDd,
- Mario Angelo Comelli, MSci,
- Caterina Caminiti, MScb and
- Diego Ardissino, MDa,∗ ()
- aDivision of Cardiology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- bDivision of Research and Innovation, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
- cDepartment of Statistics, Computer Science, Applications, Università di Firenze, Florence, Italy
- dST Microelectronics S.R.L., Agrate Brianza, Monza Brianza, Italy
- eDivision of Cardiology, Azienda Ospedaliera, Ospedale Niguarda Cà Granda, Milano, Italy
- fDivision of Cardiology, Azienda Territoriale di Piacenza, Piacenza, Italy
- gDivision of Cardiology, Azienda Territoriale di Parma, Fidenza, Italy
- hDivision of Cardiology, Azienda Territoriale di Modena, Carpi, Italy
- iDepartment of Brain and Behavioural Science, Università di Pavia, Pavia, Italy
- ↵∗Address for correspondence: Diego Ardissino, MD Unità Operativa di Cardiologia, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43126 Parma, Italy Telephone: +39 0521 702070 Fax +39 0521 702189.
Background Clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), but its efficacy is hampered by interpatient response variability, due to genetic polymorphisms associated with clopidogrel metabolism.
Objective To evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel or ticagrelor) on the basis of a patient’s genetic and clinical characteristics leads to better clinical outcomes in comparison with the standard of care, which bases the selection on clinical characteristics alone
Methods Patients hospitalised for ACS were randomly assigned to standard of care or pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, CYP2C19*17 using an ST Q3 system that provide the data within 70 minutes at each patient’s bedside. The patients were followed up for 12 ± 1 months for the primary composite endpoint of cardiovascular death and the first occurrence of non-fatal myocardial infarction, non-fatal stroke andBARC 3 to 5-defined major bleeding.
Results After enrolling 888 patients, the study was prematurely stopped. Clopidogrel was used more frequently in the standard of care arm (50.7% vs 43.3%), ticagrelor in the pharmacogenomic arm (42.6% vs 32.7%; P=0.02), and prasugrel was equally used in both arms. The primary endpoint occurred in 71 patients (15.9%) in thepharmacogenomicarm and in 114 (25.9%) in the standard of care arm (hazard ratio 0.58; 95% confidence interval [CI] 0.43 to 0.78; P<0.001).
Conclusion A personalised approach to selecting antiplatelet therapy for ACS patients may reduce ischemic and bleeding events (PHARMCLO - NCT03347435).
Funding: This scientific project was approved by the Health Authority of Regione Emilia Romagna and was supported by “Programma di Ricerca Regione – Università, Regione Emilia Romagna, bando 2010–2012– Area 2 Ricerca per il Governo clinico” (Project Identification Number and title: PRUa2-2010-010 “Pharmacogenetics of clopidogrel in patients with acute coronary syndromes (PHARMCLO)”.
All authors have no relationships relevant to the contents of this paper to disclose.
- Received February 2, 2018.
- Revision received February 22, 2018.
- Accepted February 22, 2018.
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