Clinical evidence of interaction between clopidogrel and proton pump inhibitors

Table 2 Clinical evidences against interaction between clopidogrel and proton pump inhibitors

Study design	Follow-up	Number of patients on clopidogrel with/without PPI	End point	Results	Ref.
Cohort study	12 yr	PPI: 83; no PPI: 176	MI, CV death, urgent revascularization	No significant effect of use of PPIs	Collet et al[43]
Retrospective cohort study	180 d	PPI: 3996; no PPI: 14 569	MI, death or coronary revascularization	Adjusted RR for MI or death: 1.22 (95% CI: 0.99-1.51); for revascularization, 0.97 (95% CI: 0.79-1.21)	Rassen et al[47]
Retrospective cohort study	1-yr	PPI: 397; no PPI: 138	MI, death, CABG or repeat PCI	Death, MI events with PPI vs non-PPI groups: 6.7% vs 9.6% (P = 0.32); CABG with PPI vs non-PPI groups: 3.1% vs 4.1% (P = 0.53); revascularization with PPI vs non-PPI groups: 15.8% vs 14.2% (P = 0.65)	Ramirez et al[51]
Prospective, double-blind placebo- controlled multicentre RCT	Median of 133 d	PPI: 1801; no PPI: 1826	Cardiovascular events (death, non-fatal MI, CABG or PCI, or ischemic stroke)	Cardiovascular events: HR: 1.02, 95% CI: 0.70-1.51	Bhatt et al[53]
Double-blind randomized trial	6 mo	PPI: 2257; no PPI: 4538	MACE (CV death, MI, stroke)	MACE in PPI vs no PPI groups after adjustment for potential confounders: 11.8% vs 12.2%, adjusted HR: 0.94 (95% CI: 0.80-1.11, P = 0.46)	O’Donoghue et al[26]
Retrospective cohort study (FAST-MI Registry)	1 yr	PPI: 1453; no PPI: 900	Death, MI, or stroke	No in-hospital difference in death, reinfarction, or major bleeding in PPI vs no PPI groups; Death, MI, or stroke at 1 yr in PPI. no PPI groups: 12% vs 14% (P = 0.72), adjusted OR: 0.98 (95% CI: 0.90-1.08)	Simon et al[54]

PPI: Proton pump inhibitor; PCI: Percutaneous coronary intervention; MI: Myocardial infarction; RR: Relative risk; CV: Cardiovascular.