From: The potential interaction between clopidogrel and proton pump inhibitors: a systematic review
Study | Population (special conditions) | PPIs studied | Propensity for bias* | Procedures to minimize bias** | Study quality*** | Primary outcome/Results (all PPIs combined) | Secondary analyses according to specific PPIs | Authors' conclusions about clopidogrel-PPI interaction |
---|---|---|---|---|---|---|---|---|
Ho et al. [11] | 8,205 ACS (VA patients) | L, O, P, R | Moderate | Yes | Low | 3-year mortality or ACS OR: 1.25; 95% CI: 1.11-1.41 | O = OR: 1.24; 95% CI: 1.08-1.41 R = OR, 2.83; 95% CI: 1.96-4.09 L NR P NR | "Concomitant use after hospital discharge for ACS was associated with increased risk of adverse outcomes." |
Juurlink et al. [12] | 13,636 ACS (age ≥66) | L, O, P, R | Moderate | Yes | Low | 90-day nonfatal MI OR: 1.27; 95% CI: 1.03-1.57 | P = OR 1.02, 95% CI 0.70-1.47 Non P = OR 1.40 (1.10-1.77) | "Concomitant therapy with PPIs other than pantoprazole was associated with loss of beneficial effects of clopidogrel." |
Aubert et al. [23] | 14,383 PCI | NR | Uncertain | Uncertain | Low | 1-year combined stroke, MI, angina or CABG OR:1.79; 95% CI 1.62-1.97 | NR | "The drug interaction between PPIs and clopidogrel may result in serious adverse outcomes within one year of therapy initiation." |
Banerjee et al. [24] | 534 PCI | NR | Uncertain | Uncertain | Low | Mortality, MI, repeat revascularization and stroke OR 1.54 no CI P < 0.006 (557-615 days) | NR | "PPI(s) with clopidogrel is associated with an increased risk." |
Bhatt et al. [25] | 3,267 ACS PCI | O | Low | Yes | High | 130-day CD, nonfatal MI, revascularization or ischemic stroke HR: 1.02; 95% CI = 0.70-1.51 | Only O studied | "No apparent cardiovascular interaction between clopidogrel and omeprazole" |
Dunn et al. [26] | 1,053 PCI | NR | Uncertain | No | Low | 1-year death, MI or stroke OR: 1.63; 95% CI, 1.02-2.62 | NR | "PPI use was associated with an increased cardiovascular risk." |
Gaspar et al. [27] | 922 ACS | O, L, R | Uncertain | Uncertain | Low | 6-month death, MI or UA 8.8% vs. 8.4%, P = NS | NR | "Was not associated with a worse prognosis in patients with ACS" |
Gupta et al. [28] | 315 PCI (VA patients) | L, O, R | Moderate | No | Low | 4-year death, MI or TVF OR: 1.95; 95% CI: 1.09-3.49 | NR | "PPIs may attenuate clopidogrel's beneficial antiplatelet effect." |
Huang et al. [29] | 3,278 PCI (Taiwan) | NR | Moderate | No | Low | 5-year all-cause mortality HR: 1.65; 95% CI, 1.35-2.01 | NR | "Concomitant use should be done with care to avoid adverse outcomes." |
O'Donoghue et al. [30] | 6,795 ACS (age ≥60) | E, L, O, P, R | Low | Yes | Moderate | 1-year CD, MI or stroke OR: 0.94; 95% CI: 0.80-1.11 | No specific data reported "Regardless of PPI type (including omeprazole alone or the exclusion of pantoprazole), no independent association existed" | "No clinically relevant adverse cardiovascular interaction between clopidogrel and PPIs." |
Pezalla et al. [31] | 1,010 ACS (age <65) | NR | Uncertain | No | Low | 1-year adjusted MI OR 4.3; 95% CI 2.2-8.4# | NR | "Evidence is pointing toward a potentially significant interaction." |
Ramirez et al. [32] | 534 PCI | NR | Uncertain | Uncertain | Low | 1-year mortality/MI OR NA P = 0.32 | NR | "Concomitant use of PPI's did not result in adverse cardiovascular outcomes at one year." |
Rassen et al. [33] | 18,565 ACS PCI (age ≥65) | E, L, O, P, R | Low | Yes | Moderate | 180-day death or MI OR: 1.22; 95% CI: 0.99-1.51 | O = RR 1.17; 95% CI: 0.68-2.01 P = RR 1.26; 95% CI: 0.93-1.71 | "We did not observe conclusive evidence of a clopidogrel/PPI interaction." |
Ray et al. [34] | 20,596 ACS PCI (age ≥30) | E, L, O, P, R | Low | Yes | Moderate | 1-year MI, CD or stroke HR: 0.99; 95% CI, 0.82-1.19 | E = HR 0.71; 95% CI 0.48-1.06 L = HR 1.06; 95% CI 0.77-1.45 O = HR 0.79;95% CI 0.54-1.15 P = HR 1.08; 95% CI 0.88-1.32 R = HR 0.54; 95% CI 0.30-0.97 | "Concurrent use of a PPI was not associated with a statistically significant increased risk for serious cardiovascular disease." |
Sarafoff et al. [35] | 2,025 PCI | NR | Uncertain | Uncertain | Low | 30-day stent thrombosis OR NR, P = 0.002 death OR NR, P = 0.04 | NR | "A PPI is associated with higher rates of stent thrombosis and an increased mortality." |
Stockl et al. [36] | 2,066 ACS PCI (age 18-84) | E, L, O, P, R | Moderate | Yes | Low | 1-year nonfatal MI HR: 1.93; 95% CI: 1.05-3.54 | P = HR 2.18; 95% CI 0.88-5.39 | "Patients who received clopidogrel plus a PPI had a significantly higher risk." |
Tsiaousis et al. [37] | 612 PCI | NR | Uncertain | Uncertain | Low | 1-year death HR: 1.1; 95% CI: 0.7-1.4 1-year MI HR: 1.0; 95% CI: 0.8-1.3 | NR | "PPIs drug therapy does not have any impact on the effectiveness." |
Charlot et al. [38] | 56,408 AMI | E, L, O, P | Low | Yes | Moderate | 1-year death, MI, stroke HR: 0.98; 95% CI, 0.88-1.10 | "No difference in risk associated with the type of PPI" | "No statistically significant interaction occurred between a PPI and clopidogrel." |