Impact of Proton Pump Inhibitor Use on Efficacy of Dual Antiplatelet Therapy in Post-PCI Patients: A Meta-Analysis of Randomized Controlled Trials
DOI:
https://doi.org/10.70749/ijbr.v3i3.926Keywords:
Dual Antiplatelet Therapy, Proton Pump Inhibitors, Clopidogrel, Gastrointestinal Bleeding, Cardiovascular Events, Meta-analysisAbstract
Background: Dual antiplatelet therapy (DAPT) is a standard treatment following percutaneous coronary intervention (PCI), significantly reducing ischemic events but increasing gastrointestinal (GI) bleeding risk. Proton pump inhibitors (PPIs) are frequently co-prescribed to mitigate this risk, yet concerns persist regarding potential interactions with P2Y12 inhibitors—particularly clopidogrel—that may compromise cardiovascular outcomes. Objective: The objective of this meta-analysis is to assess the impact of proton pump inhibitor (PPI) use on the efficacy and safety of dual antiplatelet therapy (DAPT) in patients who have undergone percutaneous coronary intervention (PCI). By analyzing data from randomized controlled trials (RCTs), this study aims to determine whether concurrent PPI therapy alters cardiovascular outcomes or provides gastrointestinal protection without compromising antiplatelet effectiveness. Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science identified RCTs comparing DAPT with and without concurrent PPI use in PCI patients. Five RCTs met the inclusion criteria. Primary outcomes included major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, and GI events. Data were synthesized using a random-effects model, and heterogeneity was assessed via the I² statistic. Results: PPI use was associated with a significantly increased risk of MACE (OR: 1.12; 95% CI: 1.04–1.21), MI (OR: 1.20; 95% CI: 1.10–1.31), and stroke (OR: 1.15; 95% CI: 1.02–1.29), while significantly reducing GI events (OR: 0.75; 95% CI: 0.68–0.83). Subgroup analyses indicated heightened cardiovascular risk in high-risk patients and those on prolonged DAPT or omeprazole. Heterogeneity was low to moderate across outcomes. Conclusion: While PPIs offer substantial GI protection in patients on DAPT post-PCI, their use may elevate cardiovascular risk, particularly with clopidogrel and long-term therapy. These findings support personalized risk-benefit assessment and the cautious selection of PPIs in this patient population.
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Bhatt, D. L., Cryer, B. L., Contant, C. F., Cohen, M., Lanas, A., Schnitzer, T. J., Shook, T. L., Lapuerta, P., Goldsmith, M. A., Laine, L., Scirica, B. M., Murphy, S. A., & Cannon, C. P. (2010). Clopidogrel with or without Omeprazole in Coronary Artery Disease. New England Journal of Medicine, 363(20), 1909–1917. https://doi.org/10.1056/nejmoa1007964
Moayyedi, P., Eikelboom, J. W., Bosch, J., Connolly, S. J., Dyal, L., Shestakovska, O., Leong, D., Anand, S. S., Störk, S., Branch, K. R., Bhatt, D. L., Verhamme, P. B., O’Donnell, M., Maggioni, A. P., Lonn, E. M., Piegas, L. S., Ertl, G., Keltai, M., Bruns, N. C., . . . Yusuf, S. (2019). Pantoprazole to prevent gastroduodenal events in patients receiving rivaroxaban and/or aspirin in a randomized, Double-Blind, Placebo-Controlled trial. Gastroenterology, 157(2), 403-412.e5. https://doi.org/10.1053/j.gastro.2019.04.041
Gilard, M., Arnaud, B., Cornily, J., Gal, G. L., Lacut, K., Calvez, G. L., Mansourati, J., Mottier, D., Abgrall, J., & Boschat, J. (2008). Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin. Journal of the American College of Cardiology, 51(3), 256–260. https://doi.org/10.1016/j.jacc.2007.06.064
O’Donoghue, M. L., Braunwald, E., Antman, E. M., Murphy, S. A., Bates, E. R., Rozenman, Y., Michelson, A. D., Hautvast, R. W., Lee, P. N. V., Close, S. L., Shen, L., Mega, J. L., Sabatine, M. S., & Wiviott, S. D. (2009). Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. The Lancet, 374(9694), 989–997. https://doi.org/10.1016/s0140-6736(09)61525-7
Goodman, S. G., Clare, R., Pieper, K. S., Nicolau, J. C., Storey, R. F., Cantor, W. J., Mahaffey, K. W., Angiolillo, D. J., Husted, S., Cannon, C. P., James, S. K., Kilhamn, J., Steg, P. G., Harrington, R. A., & Wallentin, L. (2012). Association of proton pump inhibitor use on cardiovascular outcomes with Clopidogrel and Ticagrelor. Circulation, 125(8), 978-986. https://doi.org/10.1161/circulationaha.111.032912
Zhong, P., Shang, Y., Bai, N., Ma, Y., Niu, Y., & Wang, Z. (2021). Efficacy and Safety of Very Short-Term Dual Antiplatelet therapy After Drug-Eluting Stents Implantation for Acute Coronary Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Frontiers in Cardiovascular Medicine, 8. https://doi.org/10.3389/fcvm.2021.660360
Bundhun, P. K., Teeluck, A. R., Bhurtu, A., & Huang, W. (2017). Is the concomitant use of clopidogrel and Proton Pump Inhibitors still associated with increased adverse cardiovascular outcomes following coronary angioplasty?: a systematic review and meta-analysis of recently published studies (2012 – 2016). BMC Cardiovascular Disorders, 17(1). https://doi.org/10.1186/s12872-016-0453-6
Sehested, T. S. G., Gerds, T. A., Fosbøl, E. L., Hansen, P. W., Charlot, M. G., Carlson, N., Hlatky, M. A., Torp‐Pedersen, C., & Gislason, G. H. (2017b). Long‐term use of proton pump inhibitors, dose–response relationship and associated risk of ischemic stroke and myocardial infarction. Journal of Internal Medicine, 283(3), 268–281. https://doi.org/10.1111/joim.12698
Sehested, T. S. G., Carlson, N., Hansen, P. W., Gerds, T. A., Charlot, M. G., Torp-Pedersen, C., Køber, L., Gislason, G. H., Hlatky, M. A., & Fosbøl, E. L. (2019). Reduced risk of gastrointestinal bleeding associated with proton pump inhibitor therapy in patients treated with dual antiplatelet therapy after myocardial infarction. European Heart Journal, 40(24), 1963–1970. https://doi.org/10.1093/eurheartj/ehz104
Sherwood, M. W., Melloni, C., Jones, W. S., Washam, J. B., Hasselblad, V., & Dolor, R. J. (2015). Individual proton pump inhibitors and Outcomes in patients with coronary artery Disease on dual antiplatelet therapy: a systematic review. Journal of the American Heart Association, 4(11). https://doi.org/10.1161/jaha.115.002245
Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study – American College of Cardiology. (2014, May 6). American College of Cardiology. https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2014/05/06/23/12/PRODIGY
Bhatt, D. L., Cryer, B. L., Contant, C. F., Cohen, M., Lanas, A., Schnitzer, T. J., Shook, T. L., Lapuerta, P., Goldsmith, M. A., Laine, L., Scirica, B. M., Murphy, S. A., & Cannon, C. P. (2010). Clopidogrel with or without Omeprazole in Coronary Artery Disease. New England Journal of Medicine, 363(20), 1909–1917. https://doi.org/10.1056/nejmoa1007964
Moayyedi, P., Eikelboom, J. W., Bosch, J., Connolly, S. J., Dyal, L., Shestakovska, O., Leong, D., Anand, S. S., Störk, S., Branch, K. R., Bhatt, D. L., Verhamme, P. B., O’Donnell, M., Maggioni, A. P., Lonn, E. M., Piegas, L. S., Ertl, G., Keltai, M., Bruns, N. C., . . . Yusuf, S. (2019). Pantoprazole to prevent gastroduodenal events in patients receiving rivaroxaban and/or aspirin in a randomized, Double-Blind, Placebo-Controlled trial. Gastroenterology, 157(2), 403-412.e5. https://doi.org/10.1053/j.gastro.2019.04.041
O’Donoghue, M. L., Braunwald, E., Antman, E. M., Murphy, S. A., Bates, E. R., Rozenman, Y., Michelson, A. D., Hautvast, R. W., Lee, P. N. V., Close, S. L., Shen, L., Mega, J. L., Sabatine, M. S., & Wiviott, S. D. (2009). Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. The Lancet, 374(9694), 989–997. https://doi.org/10.1016/s0140-6736(09)61525-7
Charlot, M., Grove, E. L., Hansen, P. R., Olesen, J. B., Ahlehoff, O., Selmer, C., Lindhardsen, J., Madsen, J. K., Kober, L., Torp-Pedersen, C., & Gislason, G. H. (2011). Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study. BMJ, 342(may11 1), d2690. https://doi.org/10.1136/bmj.d2690
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