Clinical relevance of clopidogrel-proton pump inhibitors interaction

Table 1 Major observational studies that evaluated the effects of coadministration of clopidogrel and proton pump inhibitors on cardiovascular events

Ref.	Population	n	Hazard ratio in patients who received clopidogrel and proton pump inhibitors vs patients treated with clopidogrel alone
[10]	Patients hospitalized for ACS or coronary revascularization	20596	0.99 (95%CI: 0.82-1.19, P = NS)
[11]	Patients hospitalized for ACS	8205	1.25 (95%CI: 1.11-1.41, P = NR)
[12]	Patients hospitalized for ACS	56406	0.98 (95%CI: 0.88-1.10, P = NS)
[26]	Patients hospitalized for ACS or coronary stent placement	2066	1.64 (95%CI: 1.16-2.32, P = 0.005)
[27]	Patients hospitalized for ACS or coronary stent placement	18565	1.22 (95%CI: 0.99-1.51 P = NS)
[28]	Patients hospitalized for ACS	13636	1.27 (95%CI: 1.03-1.57, P = NR)
[29]	Patients hospitalized for ACS	24471	0.75 (95%CI: 0.55-1.01, P = NS)
[30]	Patients who underwent coronary stent placement	13001	1.20 (95%CI: 0.91-1.58, P = NS)
[31]	Patients with ACS undergoing coronary stent placement	6795	0.94 (95%CI: 0.80-1.11, P = NS)

ACS: Acute coronary syndrome; NS: Non-significant; NR: Not reported.

Table 2 Polymorphisms that potentially affect the antiplatelet effect of clopidogrel

Polymorphism	Mechanism of reduced antiplatelet effect of clopidogrel
CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5, CYP2C19*6, CYP2C19*7, CYP2C19*8	Reduced metabolism of clopidogrel to its active metabolite
C3435T polymorphism of the ABCB1 gene	Overexpression of the drug efflux pump P-glycoprotein leading to reduced intestinal absorption of clopidogrel
Q192R polymorphism of the paraoxonase-1 gene	Reduced metabolism of clopidogrel to its active metabolite