Download PDF
CC BY-NC-ND 4.0 · Endosc Int Open 2020; 08(04): E481-E487
DOI: 10.1055/a-1067-4380
Original article
Owner and Copyright © Georg Thieme Verlag KG 2020

Efficacy of vonoprazan for the prevention of bleeding after gastric endoscopic submucosal dissection with continuous use of antiplatelet agents

Shunsuke Yoshii
 1   Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Takuya Yamada
 2   Department of Gastroenterology, Osaka Rosai Hospital, Osaka, Japan
 3   Department of Gastroenterology, National Hospital Organization Osaka National Hospital, Osaka, Japan
,
Shinjiro Yamaguchi
 4   Department of Gastroenterology, Kansai Rosai Hospital, Osaka, Japan
,
Yoshito Hayashi
 1   Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Masanori Nakahara
 5   Department of Gastroenterology, Ikeda Municipal Hospital, Osaka, Japan
,
Narihiro Shibukawa
 6   Department of Gastroenterology, NTT West Osaka Hospital, Osaka, Japan
,
Masashi Yamamoto
 7   Department of Gastroenterology, Toyonaka Municipal Hospital, Osaka, Japan
,
Ryu Ishihara
 8   Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
,
Kazuo Kinoshita
 9   Department of Gastroenterology, Otemae Hospital, Osaka, Japan
,
Satoshi Egawa
10   Department of Gastroenterology, Osaka Police Hospital, Osaka, Japan
,
Yoshiki Tsujii
 1   Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Hideki Iijima
 1   Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
,
Tetsuo Takehara
 1   Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
› Author AffiliationsTRIAL REGISTRATION: multicenter, single-arm, prospective, interventional trial UMIN000020174 at umin.ac.jp
Further Information

Publication History

submitted 19 July 2019

accepted after revision 15 October 2019

Publication Date:
23 March 2020 (online)

Also available at
   Permissions and Reprints

Abstract

Background Post-procedural bleeding, after gastric endoscopic submucosal dissection (ESD) for high risk thromboembolic cases that require continuous antiplatelet therapy, is challenging. Its incidence rate is > 20 % among those using conventional antacids. We evaluated the efficacy of perioperative management with vonoprazan to prevent post-ESD bleeding.

Materials and methods This was a multicenter prospective interventional trial conducted at 10 Japanese referral centers. Patients who regularly used antiplatelet agents (aspirin or thienopyridine derivatives, etc.) and who required continuous antithrombotic medication due to high thromboembolic risk were enrolled. They underwent gastric ESD with continuous aspirin therapy. Oral administration of vonoprazan (20 mg daily) was started from the day of ESD and continued for 28 days. The primary end point was the incidence of post-ESD bleeding. The sample size was 50 patients, and vonoprazan was considered to be effective when the upper threshold of the 95 % confidence interval (CI) for post-ESD bleeding did not exceed 20 %.

Results Although 50 patients were enrolled, one patient withdrew consent. Therefore, 49 patients were included in the analysis. One patient who used aspirin and clopidogrel experienced bleeding 11 days after ESD. The overall post-ESD bleeding rate was 2.0 % (1/49; 95 %CI 0.4–10.7 %). Thromboembolic events were not observed. One case of ESD-associated adverse events (perforation) and one case of drug-associated adverse events (drug eruption, possibly due to vonoprazan) were observed.

Conclusions Vonoprazan may be efficacious for preventing post-ESD bleeding in patients using continuous antiplatelet therapy, warranting further comparative study to definitively test the effectiveness of the drug.

 

  • References

  • 1 Akasaka T, Nishida T, Tsutsui S. et al. Short-term outcomes of endoscopic submucosal dissection (ESD) for early gastric neoplasm: multicenter survey by Osaka University ESD study group. Dig Endosc 2011; 23: 73-77
    CrossrefPubMedSearch in Google Scholar
  • 2 Kato M, Nishida T, Hamasaki T. et al. Outcomes of ESD for patients with early gastric cancer and comorbid liver cirrhosis: a propensity score analysis. Surg Endosc 2015; 29: 1560-1566
    CrossrefPubMedSearch in Google Scholar
  • 3 Yoshioka T, Nishida T, Tsujii M. et al. Renal dysfunction is an independent risk factor for bleeding after gastric ESD. Endosc Int Open 2015; 3: E39-E45
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Nishida T, Kato M, Yoshio T. et al. Endoscopic submucosal dissection in early gastric cancer in elderly patients and comorbid conditions. World J Gastrointest Endosc 2015; 7: 524-531
    CrossrefPubMedSearch in Google Scholar
  • 5 Fujimoto K, Fujishiro M, Kato M. et al. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig Endosc 2014; 26: 1-14
    PubMedSearch in Google Scholar
  • 6 Ono S, Fujishiro M, Yoshida N. et al. Thienopyridine derivatives as risk factors for bleeding following high risk endoscopic treatments: Safe Treatment on Antiplatelets (STRAP) study. Endoscopy 2015; 47: 632-637
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Cho SJ, Choi IJ, Kim CG. et al. Aspirin use and bleeding risk after endoscopic submucosal dissection in patients with gastric neoplasms. Endoscopy 2012; 44: 114-121
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Tounou S, Morita Y. Gastric and duodenal endoscopic submucosal dissection in patients on aspirin therapy has increased risk of hemorrhage but is feasible. Gastroenterol Endosc 2011; 53: 3326-3335
    PubMedSearch in Google Scholar
  • 9 Takizawa K, Oda I, Gotoda T. et al. Routine coagulation of visible vessels may prevent delayed bleeding after endoscopic submucosal dissection--an analysis of risk factors. Endoscopy 2008; 40: 179-183
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Okada K, Yamamoto Y, Kasuga A. et al. Risk factors for delayed bleeding after endoscopic submucosal dissection for gastric neoplasm. Surg Endosc 2011; 25: 98-107
    CrossrefPubMedSearch in Google Scholar
  • 11 Suzuki H, Takizawa K, Hirasawa T. et al. Short-term outcomes of multicenter prospective cohort study of gastric endoscopic resection: ‘Real-world evidence’ in Japan. Dig Endosc 2019; 31: 30-39
    CrossrefPubMedSearch in Google Scholar
  • 12 Uedo N, Takeuchi Y, Yamada T. et al. Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer: a prospective randomized controlled trial. Am J Gastroenterol 2007; 102: 1610-1616
    CrossrefPubMedSearch in Google Scholar
  • 13 Hershcovici T, Fass R. Management of gastroesophageal reflux disease that does not respond well to proton pump inhibitors. Curr Opin Gastroenterol 2010; 26: 367-378
    CrossrefPubMedSearch in Google Scholar
  • 14 Li XQ, Andersson TB, Ahlstrom M. et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 2004; 32: 821-827
    CrossrefPubMedSearch in Google Scholar
  • 15 Katsuki H, Nakamura C, Arimori K. et al. Genetic polymorphism of CYP2C19 and lansoprazole pharmacokinetics in Japanese subjects. Eur J Clin Pharmacol 1997; 52: 391-396
    CrossrefPubMedSearch in Google Scholar
  • 16 Suri A, Bramer SL. Effect of omeprazole on the metabolism of cilostazol. Clin Pharmacokinet 1999; 37 (Suppl. 02) 53-59
    CrossrefPubMedSearch in Google Scholar
  • 17 Malhotra K, Katsanos AH, Bilal M. et al. Cerebrovascular outcomes with proton pump inhibitors and thienopyridines: A systematic review and meta-analysis. Stroke 2018; 49: 312-318
    CrossrefPubMedSearch in Google Scholar
  • 18 Ho PM, Maddox TM, Wang L. et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009; 301: 937-944
    CrossrefPubMedSearch in Google Scholar
  • 19 Sakurai Y, Mori Y, Okamoto H. et al. Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or rabeprazole 10 mg in healthy adult male subjects – a randomised open-label cross-over study. Aliment Pharmacol Ther 2015; 42: 719-730
    CrossrefPubMedSearch in Google Scholar
  • 20 Jenkins H, Sakurai Y, Nishimura A. et al. Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of TAK-438 (vonoprazan), a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther 2015; 41: 636-648
    CrossrefPubMedSearch in Google Scholar
  • 21 Echizen H. The first-in-class potassium-competitive acid blocker, vonoprazan fumarate: Pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet 2016; 55: 409-418
    CrossrefPubMedSearch in Google Scholar
  • 22 Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer 2017; 20: 1-19
    PubMedSearch in Google Scholar
  • 23 Maekawa S, Nomura R, Murase T. et al. Complete closure of artificial gastric ulcer after endoscopic submucosal dissection by combined use of a single over-the-scope clip and through-the-scope clips (with videos). Surg Endosc 2015; 29: 500-504
    CrossrefPubMedSearch in Google Scholar
  • 24 Tsuji Y, Fujishiro M, Kodashima S. et al. Polyglycolic acid sheets and fibrin glue decrease the risk of bleeding after endoscopic submucosal dissection of gastric neoplasms (with video). Gastrointest Endosc 2015; 81: 906-912
    CrossrefPubMedSearch in Google Scholar
  • 25 Tounou S, Morita Y, Hosono T. Continuous aspirin use does not increase post-endoscopic dissection bleeding risk for gastric neoplasms in patients on antiplatelet therapy. Endosc Int Open 2015; 3: E31-E38
    Thieme ConnectPubMedSearch in Google Scholar
  • 26 Lim JH, Kim SG, Kim JW. et al. Do antiplatelets increase the risk of bleeding after endoscopic submucosal dissection of gastric neoplasms?. Gastrointest Endosc 2012; 75: 719-727
    CrossrefPubMedSearch in Google Scholar
  • 27 Sanomura Y, Oka S, Tanaka S. et al. Continued use of low-dose aspirin does not increase the risk of bleeding during or after endoscopic submucosal dissection for early gastric cancer. Gastric Cancer 2014; 17: 489-496
    CrossrefPubMedSearch in Google Scholar
  • 28 Kataoka Y, Tsuji Y, Hirasawa K. et al. Endoscopic tissue shielding to prevent bleeding after endoscopic submucosal dissection: a prospective multicenter randomized controlled trial. Endoscopy 2019; 51: 619-627
    PubMedSearch in Google Scholar
  • 29 Green Jr. FW, Kaplan MM, Curtis LE. et al. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978; 74: 38-43
    CrossrefPubMedSearch in Google Scholar
  • 30 Kagawa T, Iwamuro M, Ishikawa S. et al. Vonoprazan prevents bleeding from endoscopic submucosal dissection-induced gastric ulcers. Aliment Pharmacol Ther 2016; 44: 583-591
    CrossrefPubMedSearch in Google Scholar
  • 31 Hamada K, Uedo N, Tonai Y. et al. Efficacy of vonoprazan in prevention of bleeding from endoscopic submucosal dissection-induced gastric ulcers: A prospective randomized phase II study. J Gastroenterol 2019; 54: 122-130
    CrossrefPubMedSearch in Google Scholar
  • 32 Horikawa Y, Mizutamari H, Mimori N. et al. Short-term efficacy of potassium-competitive acid blocker following gastric endoscopic submucosal dissection: a propensity score analysis. Scand J Gastroenterol 2018; 53: 243-251
    CrossrefPubMedSearch in Google Scholar
  • 33 Tsuchiya I, Kato Y, Tanida E. et al. Effect of vonoprazan on the treatment of artificial gastric ulcers after endoscopic submucosal dissection: Prospective randomized controlled trial. Dig Endosc 2017; 29: 576-583
    CrossrefPubMedSearch in Google Scholar
  • 34 Maruoka D, Arai M, Kasamatsu S. et al. Vonoprazan is superior to proton pump inhibitors in healing artificial ulcers of the stomach post-endoscopic submucosal dissection: A propensity score-matching analysis. Dig Endosc 2017; 29: 57-64
    CrossrefPubMedSearch in Google Scholar
  • 35 Yamasaki A, Yoshio T, Muramatsu Y. et al. Vonoprazan is superior to rabeprazole for healing endoscopic submucosal dissection: Induced ulcers. Digestion 2018; 97: 170-176
    CrossrefPubMedSearch in Google Scholar
  • 36 Hirai A, Takeuchi T, Takahashi Y. et al. Comparison of the effects of vonoprazan and lansoprazole for treating endoscopic submucosal dissection-induced artificial ulcers. Dig Dis Sci 2018; 63: 974-981
    CrossrefPubMedSearch in Google Scholar
  • 37 Ishii Y, Yamada H, Sato T. et al. Effects of vonoprazan compared with esomeprazole on the healing of artificial postendoscopic submucosal dissection ulcers: A prospective, multicenter, two-arm, randomized controlled trial. Gastroenterol Res Pract 2018; 2018: 1615092
    PubMedSearch in Google Scholar
  • 38 Jaruvongvanich V, Poonsombudlert K, Ungprasert P. Vonoprazan versus proton-pump inhibitors for gastric endoscopic submucosal dissection-induced ulcers: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2018; 30: 1416-1421
    CrossrefPubMedSearch in Google Scholar
  • 39 Mochizuki S, Uedo N, Oda I. et al. Scheduled second-look endoscopy is not recommended after endoscopic submucosal dissection for gastric neoplasms (the SAFE trial): a multicentre prospective randomised controlled non-inferiority trial. Gut 2015; 64: 397-405
    CrossrefPubMedSearch in Google Scholar