Are proton pump inhibitors an effective and safe drug not only in the prophylaxis of gastrointestinal bleeding in antithrombotic treatment?

Česká verzia

Authors: Jan Bultas
Authors place of work: Ústav farmakologie 3. LF UK Praha
Published in the journal: Vnitř Lék 2020; 66(3): 169-179
Category: Main Topic

Summary

Proton pump inhibitors (PPIs) are popular and widely used “gastroprotectives”. More than 10% of our population is treated. In addition to classical indications such as gastroduodenal peptic disease or gastroesophageal reflux disease, they are indicated for the reduction of hemorrhagic complications in the digestive tract during antithrombotic treatment. The effect of PPIs on reducing upper gastrointestinal bleeding in antithrombotic treatment (rivaroxaban, acetylsalicylic acid or a combination) was called into question by a recently published randomised mega-study – COMPASS pantoprazole. Treatment of PPIs is accompanied by a number of significant drug interactions, in particular a severe reduction in the bioactivation of clopidogrel and a reduction in the absorption of acetylsalicylic acid or dabigatran. As a result, the effect of these antithrombotics is reduced. A number of observational studies – in the indication of PPIs in the treatment of gastroduodenal or gastrooesophageal disease or when used in the treatment of PPIs in antithrombotic treatment – found a greater incidence of major vascular events and an increase in mortality. So are PPIs effective in protecting gastrointestinal bleeding and are they safe?

Keywords:

clopidogrel – antithrombotics – atherothrombotic diseases – proton pump inhibitors – H2 receptor blockers – acetylsalicylic acid – overview

Zdroje

1. Moayyedi P, Eikelboom JW, Bosch J et al. Pantoprazole to Prevents Gastroduodenal Events in Patients Receiving Rivaroxaban and.or Aspirin in a Randomized, Double‑blind, Placebo‑controlled Trial, Gastroenterology 2019, DOI https:..doi.org.10.1053.j. gastro.2019. 04. 041

2. Hussaarts GAM, Marijn Veerman GD, Jansman FGA et al, Clinically relevant drug interactions with multikinase inhibitors: a review. Ther Adv Med Oncol 2019, 11: 1–34.

3. Makunts T, Cohen IV, Awdishu L Analysis of postmarketing safety data for proton‑pump inhibitors reveals increased propensity for renal injury, electrolyte abnormalities, and nephrolithiasis, Scientific Reports 2019; 9: 2282.

4. https: doi.org.10.1038.s41598-019-39335-7

5. Wedemeyer RS, Blume H Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf 2014; 37: 201–211.

6. Strand DS, Kim D, Peura DA 25 Years of Proton Pump Inhibitors: A Comprehensive Review. Gut Liver. 2017; 11(1): 27–37.

7. Zvyaga T, Chang SY, Chen C et al. Evaluation of Six Proton Pump Inhibitors As Inhibitors of Various Human Cytochromes P450: Focus on Cytochrome P450 2C19. Drug Metabolism and Disposition 2012; 40: 1698–1711.

8. Li L, Geraghty OC, Mehta Z et al, Age‑specific risks, severity, time course, and outcome of bleeding on long‑term antiplatelet treatment after vascular events: a population‑based cohort study. Lancet 2017; 390: 490–499.

9. Kuwayama T, Osanai H, Ajioka M et al. Influence of proton pump inhibitors on blood dabigatran concentrations in Japanese patients with non‑valvular atrial fibrillation. J Arrhythm 2017; 33: 619–623.

10. Stangier J, Stähle H, Rathgen K et al. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet 2008; 47: 47–59.

11. Bolek T, Samoš M, Stančiaková L et al. The Impact of Proton Pump Inhibition on Da‑ bigatran Levels in Patients With Atrial Fibrillation. Am J Ther 2017; Apr 25. doi: 10.1097. MJT.0000000000000599https: ..www.ema.europa.eu.documents.product‑information. pradaxa‑epar‑product‑information_cs.pdf

12. Connolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139–1151.

13. Bultas J Kyselina acetylsalicylová - stále neotřesitelné postavení i v roce 2018? Remedia 2018; 28: 127–136.

14. Bultas J, Karetová D Enterosolventní forma kyseliny acetylsalicylové - ano, či ne? Remedia 2017; 27: 145–151.

15. Charlot M, Grove EL, Hansen PR et al. 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 2011; 342: d2690.

16. Bhatt DL, Cryer BL, Contant CF et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010; 363: 1909–1917.

17. Demcsak A, Lantos T, Balint ER et al. PPIs Are Not Responsible for Elevating Cardiovascular Risk in Patients on Clopidogrel - A Systematic Review and Meta‑Analysis. Front Physiol 2018; 9: 1550.