Drug Interaction Between Clopidogrel and Ranitidine or Omeprazole in Stable Coronary Artery Disease: A Double-Blind, Double Dummy, Randomized Study.
BACKGROUND
Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine.


OBJECTIVE
Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine.


METHODS
We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12™ (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA).


RESULTS
We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] -1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04).


CONCLUSIONS
Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel.


BACKGROUND
NCT01896557.
Heart Institute, University of São Paulo Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo, 05403-000, Brazil. remo_holanda@hotmail.com.
Remo Holanda de Mendonça
RHM
Furtado
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Robert Patrick
RP
Giugliano
Heart Institute, University of São Paulo Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo, 05403-000, Brazil.
Celia Maria Cassaro
CMC
Strunz
Heart Institute, University of São Paulo Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo, 05403-000, Brazil.
Cyrillo Cavalheiro
CC
Filho
Heart Institute, University of São Paulo Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo, 05403-000, Brazil.
José Antonio Franchini
JAF
Ramires
Heart Institute, University of São Paulo Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo, 05403-000, Brazil.
Roberto Kalil
RK
Filho
Heart Institute, University of São Paulo Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo, 05403-000, Brazil.
Pedro Alves Lemos
PAL
Neto
Heart Institute, University of São Paulo Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo, 05403-000, Brazil.
Alexandre Costa
AC
Pereira
Clinics Hospital, University of São Paulo Medical School, São Paulo, Brazil.
Tânia Rúbia
TR
Rocha
Heart Institute, University of São Paulo Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo, 05403-000, Brazil.
Beatriz Tonon
BT
Freire
Clinics Hospital, University of São Paulo Medical School, São Paulo, Brazil.
Elbio Antonio
EA
D'Amico
Heart Institute, University of São Paulo Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo, 05403-000, Brazil.
José Carlos
JC
Nicolau
D000368:Aged; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D010979:Platelet Function Tests / Q000379:methods; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D011899:Ranitidine / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D011899:Ranitidine; D000077144:Clopidogrel; D009853:Omeprazole; D013988:Ticlopidine