Fixed Dose Combination of Aspirin and Pantoprazole: Results of a Multicenter, Comparative, Randomized, Double-blind, Double Dummy, Phase III Study in Indian Patients

Overview

Journal Indian Heart J

Publisher Elsevier

Specialty Cardiology & Vascular Diseases

Date 2024 Jul 15

PMID 39009075

Authors

Rahul Choudhary

Mohd Aziz Khan

Rupal Dosi

Sachin Choudhari

Dattatray Pawar

Vinayak Shahavi

Akhilesh Sharma

Affiliations

Soon will be listed here.

Abstract

Objective: To compare the efficacy and safety of a fixed-dose combination of aspirin and pantoprazole with that of aspirin alone for the prevention of gastro duodenal mucosal damage in patients taking aspirin for secondary prevention of cardiovascular disease or cerebrovascular disease.

Methods: This was a comparative, double-blind, double-dummy, randomized, multicenter, phase III study conducted in patients taking aspirin ≤150 mg daily for ≥3 to ≤6 months and expected to require daily aspirin therapy for at least 6 months for the secondary prevention of cardiovascular disease or cerebrovascular disease.

Results: A total of 240 patients were randomized to receive either a fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg or aspirin 150 mg alone in a 2:1 ratio. The proportion of non-responders (patients experiencing gastroduodenal events) was 9.7 % in the test group (fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg) compared to 19.7 % in the comparator group (aspirin 150 mg) at week 12, while the proportions were 11.0 % in the test group and 22.4 % in the comparator group at the end of 24 weeks of treatment (p-value was <0.05 at week 12 and 24). GI injuries were significantly less in test group as compared to comparator group. Both drugs were well tolerated by all patients.

Conclusion: The fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg was found to be more efficacious and safer compared to aspirin 150 mg alone for the prevention of gastroduodenal mucosal damage in patients receiving aspirin.

References

Scheiman J, Devereaux P, Herlitz J, Katelaris P, Lanas A, Veldhuyzen Van Zanten S . Prevention of peptic ulcers with esomeprazole in patients at risk of ulcer development treated with low-dose acetylsalicylic acid: a randomised, controlled trial (OBERON). Heart. 2011; 97(10):797-802. PMC: 3088470. DOI: 10.1136/hrt.2010.217547. View

Abraham N, Hlatky M, Antman E, Bhatt D, Bjorkman D, Clark C . ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and.... Am J Gastroenterol. 2010; 105(12):2533-49. DOI: 10.1038/ajg.2010.445. View

Hennekens C, DYKEN M, Fuster V . Aspirin as a therapeutic agent in cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1997; 96(8):2751-3. DOI: 10.1161/01.cir.96.8.2751. View

Bhatt D, Cryer B, Contant C, Cohen M, Lanas A, Schnitzer T . Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010; 363(20):1909-17. DOI: 10.1056/NEJMoa1007964. View

Williams C, Chan A, Elman M, Kristensen A, Miser W, Pignone M . Aspirin use among adults in the U.S.: results of a national survey. Am J Prev Med. 2015; 48(5):501-8. DOI: 10.1016/j.amepre.2014.11.005. View

Rahme E, Nedjar H, Bizzi A, Morin S . Hospitalization for gastrointestinal adverse events attributable to the use of low-dose aspirin among patients 50 years or older also using non-steroidal anti-inflammatory drugs: a retrospective cohort study. Aliment Pharmacol Ther. 2007; 26(10):1387-98. DOI: 10.1111/j.1365-2036.2007.03523.x. View

Annibale B, Capurso G, Chistolini A, DAmbra G, DiGiulio E, Monarca B . Gastrointestinal causes of refractory iron deficiency anemia in patients without gastrointestinal symptoms. Am J Med. 2001; 111(6):439-45. DOI: 10.1016/s0002-9343(01)00883-x. View

Goswami N, Gandhi A, Patel P, Dikshit R . An evaluation of knowledge, attitude and practices about prescribing fixed dose combinations among resident doctors. Perspect Clin Res. 2013; 4(2):130-5. PMC: 3700327. DOI: 10.4103/2229-3485.111797. View

Moore A, Bjarnason I, Cryer B, Garcia-Rodriguez L, Goldkind L, Lanas A . Evidence for endoscopic ulcers as meaningful surrogate endpoint for clinically significant upper gastrointestinal harm. Clin Gastroenterol Hepatol. 2009; 7(11):1156-63. DOI: 10.1016/j.cgh.2009.03.032. View

10.

Nikolsky E, Stone G, Kirtane A, Dangas G, Lansky A, McLaurin B . Gastrointestinal bleeding in patients with acute coronary syndromes: incidence, predictors, and clinical implications: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. J Am Coll Cardiol. 2009; 54(14):1293-302. DOI: 10.1016/j.jacc.2009.07.019. View

11.

Prabhakaran D, Jeemon P, Roy A . Cardiovascular Diseases in India: Current Epidemiology and Future Directions. Circulation. 2016; 133(16):1605-20. DOI: 10.1161/CIRCULATIONAHA.114.008729. View

12.

Scally B, Emberson J, Spata E, Reith C, Davies K, Halls H . Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol. 2018; 3(4):231-241. PMC: 5842491. DOI: 10.1016/S2468-1253(18)30037-2. View

13.

Anker S, Voors A, Okonko D, Clark A, James M, von Haehling S . Prevalence, incidence, and prognostic value of anaemia in patients after an acute myocardial infarction: data from the OPTIMAAL trial. Eur Heart J. 2009; 30(11):1331-9. DOI: 10.1093/eurheartj/ehp116. View

14.

Lai K, Lam S, Chu K, Wong B, Hui W, Hu W . Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med. 2002; 346(26):2033-8. DOI: 10.1056/NEJMoa012877. View

15.

Holster I, Valkhoff V, Kuipers E, Tjwa E . New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology. 2013; 145(1):105-112.e15. DOI: 10.1053/j.gastro.2013.02.041. View

16.

Ruhil R . India has Reached on the Descending Limb of Tobacco Epidemic. Indian J Community Med. 2018; 43(3):153-156. PMC: 6166507. DOI: 10.4103/ijcm.IJCM_213_17. View

17.

Garcia Rodriguez L, Barreales Tolosa L . Risk of upper gastrointestinal complications among users of traditional NSAIDs and COXIBs in the general population. Gastroenterology. 2007; 132(2):498-506. DOI: 10.1053/j.gastro.2006.12.007. View

18.

Yeomans N, Lanas A, Labenz J, Veldhuyzen Van Zanten S, Van Rensburg C, Racz I . Efficacy of esomeprazole (20 mg once daily) for reducing the risk of gastroduodenal ulcers associated with continuous use of low-dose aspirin. Am J Gastroenterol. 2008; 103(10):2465-73. DOI: 10.1111/j.1572-0241.2008.01995.x. View

19.

Chan F, Ching J, Hung L, Wong V, Leung V, Kung N . Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med. 2005; 352(3):238-44. DOI: 10.1056/NEJMoa042087. View

20.

Bhatt D, Scheiman J, Abraham N, Antman E, Chan F, Furberg C . ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2008; 52(18):1502-17. DOI: 10.1016/j.jacc.2008.08.002. View