Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial

Muthiah Vaduganathan, Christopher P. Cannon, Byron L. Cryer, Yuyin Liu, Wen Hua Hsieh, Gheorghe Doros, Marc Cohen, Angel Lanas, Thomas J. Schnitzer, Thomas L. Shook, Pablo Lapuerta, Mark A. Goldsmith, Loren Laine, Deepak L. Bhatt

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background Proton-pump inhibitors (PPIs) have been demonstrated to reduce rates of gastrointestinal events in patients requiring dual antiplatelet therapy (DAPT). Data are limited regarding the efficacy and safety of PPIs in high-risk cardiovascular subsets after acute coronary syndrome or percutaneous coronary intervention. Methods All patients enrolled in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) were initiated on DAPT (with aspirin and clopidogrel) for various indications within the prior 21 days. These post hoc analyses of the COGENT trial evaluated the efficacy and safety of omeprazole compared with placebo in subsets of patients requiring DAPT for the 2 most frequent indications: 1) patients undergoing percutaneous coronary intervention (for any indication) within 14 days of randomization (n = 2676; 71.2%); and 2) patients presenting with acute coronary syndrome managed with or without percutaneous coronary intervention (n = 1573; 41.8%). Unadjusted Cox proportional hazards models were used to estimate effect sizes through final follow-up. Results Median follow-up duration was 110 days (interquartile range 55-167). In percutaneous coronary intervention-treated patients, omeprazole significantly reduced rates of composite gastrointestinal events at 180 days (1.2% vs 2.7%; hazard ratio [HR] 0.43; 95% confidence interval [CI], 0.22-0.85; P =.02) without increasing composite cardiovascular events (5.4% vs 6.3%; HR 1.00; 95% CI, 0.67-1.50; P = 1.00). Similarly, omeprazole lowered risk of the primary gastrointestinal endpoint at 180 days in patients presenting with acute coronary syndrome (1.1% vs 2.7%; HR 0.37; 95% CI, 0.13-1.01; P =.05) without a significant excess in cardiovascular events (5.6% vs 4.5%; HR 1.40; 95% CI, 0.77-2.53; P =.27). Conclusions PPI therapy attenuates gastrointestinal bleeding risk without significant excess in major cardiovascular events in high-risk cardiovascular subsets, regardless of indication for DAPT. Future studies will be needed to clarify optimal gastroprotective strategies for higher-intensity and longer durations of DAPT.

Original languageEnglish (US)
Pages (from-to)1002-1005
Number of pages4
JournalAmerican Journal of Medicine
Volume129
Issue number9
DOIs
StatePublished - Sep 1 2016

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clopidogrel
Proton Pump Inhibitors
Safety
Percutaneous Coronary Intervention
Omeprazole
Acute Coronary Syndrome
Confidence Intervals
Therapeutics
Random Allocation
Proportional Hazards Models
Aspirin

Keywords

  • Acute coronary syndrome
  • Bleeding
  • Clinical outcomes
  • Clinical trials
  • Coronary artery disease
  • Percutaneous coronary intervention
  • Proton-pump inhibitors

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial. / Vaduganathan, Muthiah; Cannon, Christopher P.; Cryer, Byron L.; Liu, Yuyin; Hsieh, Wen Hua; Doros, Gheorghe; Cohen, Marc; Lanas, Angel; Schnitzer, Thomas J.; Shook, Thomas L.; Lapuerta, Pablo; Goldsmith, Mark A.; Laine, Loren; Bhatt, Deepak L.

In: American Journal of Medicine, Vol. 129, No. 9, 01.09.2016, p. 1002-1005.

Research output: Contribution to journalArticle

Vaduganathan, M, Cannon, CP, Cryer, BL, Liu, Y, Hsieh, WH, Doros, G, Cohen, M, Lanas, A, Schnitzer, TJ, Shook, TL, Lapuerta, P, Goldsmith, MA, Laine, L & Bhatt, DL 2016, 'Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial', American Journal of Medicine, vol. 129, no. 9, pp. 1002-1005. https://doi.org/10.1016/j.amjmed.2016.03.042
Vaduganathan, Muthiah ; Cannon, Christopher P. ; Cryer, Byron L. ; Liu, Yuyin ; Hsieh, Wen Hua ; Doros, Gheorghe ; Cohen, Marc ; Lanas, Angel ; Schnitzer, Thomas J. ; Shook, Thomas L. ; Lapuerta, Pablo ; Goldsmith, Mark A. ; Laine, Loren ; Bhatt, Deepak L. / Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial. In: American Journal of Medicine. 2016 ; Vol. 129, No. 9. pp. 1002-1005.
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abstract = "Background Proton-pump inhibitors (PPIs) have been demonstrated to reduce rates of gastrointestinal events in patients requiring dual antiplatelet therapy (DAPT). Data are limited regarding the efficacy and safety of PPIs in high-risk cardiovascular subsets after acute coronary syndrome or percutaneous coronary intervention. Methods All patients enrolled in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) were initiated on DAPT (with aspirin and clopidogrel) for various indications within the prior 21 days. These post hoc analyses of the COGENT trial evaluated the efficacy and safety of omeprazole compared with placebo in subsets of patients requiring DAPT for the 2 most frequent indications: 1) patients undergoing percutaneous coronary intervention (for any indication) within 14 days of randomization (n = 2676; 71.2{\%}); and 2) patients presenting with acute coronary syndrome managed with or without percutaneous coronary intervention (n = 1573; 41.8{\%}). Unadjusted Cox proportional hazards models were used to estimate effect sizes through final follow-up. Results Median follow-up duration was 110 days (interquartile range 55-167). In percutaneous coronary intervention-treated patients, omeprazole significantly reduced rates of composite gastrointestinal events at 180 days (1.2{\%} vs 2.7{\%}; hazard ratio [HR] 0.43; 95{\%} confidence interval [CI], 0.22-0.85; P =.02) without increasing composite cardiovascular events (5.4{\%} vs 6.3{\%}; HR 1.00; 95{\%} CI, 0.67-1.50; P = 1.00). Similarly, omeprazole lowered risk of the primary gastrointestinal endpoint at 180 days in patients presenting with acute coronary syndrome (1.1{\%} vs 2.7{\%}; HR 0.37; 95{\%} CI, 0.13-1.01; P =.05) without a significant excess in cardiovascular events (5.6{\%} vs 4.5{\%}; HR 1.40; 95{\%} CI, 0.77-2.53; P =.27). Conclusions PPI therapy attenuates gastrointestinal bleeding risk without significant excess in major cardiovascular events in high-risk cardiovascular subsets, regardless of indication for DAPT. Future studies will be needed to clarify optimal gastroprotective strategies for higher-intensity and longer durations of DAPT.",
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T1 - Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial

AU - Vaduganathan, Muthiah

AU - Cannon, Christopher P.

AU - Cryer, Byron L.

AU - Liu, Yuyin

AU - Hsieh, Wen Hua

AU - Doros, Gheorghe

AU - Cohen, Marc

AU - Lanas, Angel

AU - Schnitzer, Thomas J.

AU - Shook, Thomas L.

AU - Lapuerta, Pablo

AU - Goldsmith, Mark A.

AU - Laine, Loren

AU - Bhatt, Deepak L.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background Proton-pump inhibitors (PPIs) have been demonstrated to reduce rates of gastrointestinal events in patients requiring dual antiplatelet therapy (DAPT). Data are limited regarding the efficacy and safety of PPIs in high-risk cardiovascular subsets after acute coronary syndrome or percutaneous coronary intervention. Methods All patients enrolled in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) were initiated on DAPT (with aspirin and clopidogrel) for various indications within the prior 21 days. These post hoc analyses of the COGENT trial evaluated the efficacy and safety of omeprazole compared with placebo in subsets of patients requiring DAPT for the 2 most frequent indications: 1) patients undergoing percutaneous coronary intervention (for any indication) within 14 days of randomization (n = 2676; 71.2%); and 2) patients presenting with acute coronary syndrome managed with or without percutaneous coronary intervention (n = 1573; 41.8%). Unadjusted Cox proportional hazards models were used to estimate effect sizes through final follow-up. Results Median follow-up duration was 110 days (interquartile range 55-167). In percutaneous coronary intervention-treated patients, omeprazole significantly reduced rates of composite gastrointestinal events at 180 days (1.2% vs 2.7%; hazard ratio [HR] 0.43; 95% confidence interval [CI], 0.22-0.85; P =.02) without increasing composite cardiovascular events (5.4% vs 6.3%; HR 1.00; 95% CI, 0.67-1.50; P = 1.00). Similarly, omeprazole lowered risk of the primary gastrointestinal endpoint at 180 days in patients presenting with acute coronary syndrome (1.1% vs 2.7%; HR 0.37; 95% CI, 0.13-1.01; P =.05) without a significant excess in cardiovascular events (5.6% vs 4.5%; HR 1.40; 95% CI, 0.77-2.53; P =.27). Conclusions PPI therapy attenuates gastrointestinal bleeding risk without significant excess in major cardiovascular events in high-risk cardiovascular subsets, regardless of indication for DAPT. Future studies will be needed to clarify optimal gastroprotective strategies for higher-intensity and longer durations of DAPT.

AB - Background Proton-pump inhibitors (PPIs) have been demonstrated to reduce rates of gastrointestinal events in patients requiring dual antiplatelet therapy (DAPT). Data are limited regarding the efficacy and safety of PPIs in high-risk cardiovascular subsets after acute coronary syndrome or percutaneous coronary intervention. Methods All patients enrolled in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) were initiated on DAPT (with aspirin and clopidogrel) for various indications within the prior 21 days. These post hoc analyses of the COGENT trial evaluated the efficacy and safety of omeprazole compared with placebo in subsets of patients requiring DAPT for the 2 most frequent indications: 1) patients undergoing percutaneous coronary intervention (for any indication) within 14 days of randomization (n = 2676; 71.2%); and 2) patients presenting with acute coronary syndrome managed with or without percutaneous coronary intervention (n = 1573; 41.8%). Unadjusted Cox proportional hazards models were used to estimate effect sizes through final follow-up. Results Median follow-up duration was 110 days (interquartile range 55-167). In percutaneous coronary intervention-treated patients, omeprazole significantly reduced rates of composite gastrointestinal events at 180 days (1.2% vs 2.7%; hazard ratio [HR] 0.43; 95% confidence interval [CI], 0.22-0.85; P =.02) without increasing composite cardiovascular events (5.4% vs 6.3%; HR 1.00; 95% CI, 0.67-1.50; P = 1.00). Similarly, omeprazole lowered risk of the primary gastrointestinal endpoint at 180 days in patients presenting with acute coronary syndrome (1.1% vs 2.7%; HR 0.37; 95% CI, 0.13-1.01; P =.05) without a significant excess in cardiovascular events (5.6% vs 4.5%; HR 1.40; 95% CI, 0.77-2.53; P =.27). Conclusions PPI therapy attenuates gastrointestinal bleeding risk without significant excess in major cardiovascular events in high-risk cardiovascular subsets, regardless of indication for DAPT. Future studies will be needed to clarify optimal gastroprotective strategies for higher-intensity and longer durations of DAPT.

KW - Acute coronary syndrome

KW - Bleeding

KW - Clinical outcomes

KW - Clinical trials

KW - Coronary artery disease

KW - Percutaneous coronary intervention

KW - Proton-pump inhibitors

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