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Once-Daily Esomeprazole 20 mg Prevents Recurrence of Peptic Ulcer
in East Asian Low-Dose Aspirin Users at Gastrointestinal Risk: the LAVENDER Study
Shinya Goto1, Yasushi Okada2, Myung-Gyu Choi3, Jaw-Town Lin4, Yoshikazu Kinoshita5, Hiroto Miwa6, Chern-En Chiang7, Kentaro Sugano8
1Tokai University School of Medicine, Kanagawa, Japan; 2National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; 3The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, Korea; 4E-Da Hospital, Kaohsiung & Fu Jen Catholic University, Taipei, Taiwan; 5Shimane University School of Medicine, Shimane, Japan; 6Hyogo College of Medicine, Hyogo, Japan; 7Taipei Veterans General Hospital & National Yang-Ming University, Taipei, Taiwan; 8Jichi Medical University, Tochigi, Japan Assessments and statistical analysis
Ulcer recurrence
Table 2. Estimated ulcer-free rates by subgroup (48-week full analysis set)
Table 4. Number (%) of patients with at least one serious adverse event (SAE)
CONCLUSION
other than death (safety analysis set)
• Each patient underwent planned endoscopy at 12-week intervals up to
• The time to ulcer recurrence was significantly longer in the esomeprazole
Esomeprazole 20 mg
study end or upon early withdrawal (eg, because of GI bleeding). The Esomeprazole 20 mg
group compared with placebo by week 48 (hazard ratio, 0.09; 96.65% • Daily esomeprazole 20 mg is efficacious and well tolerated for
primary end point was the time to ulcer recurrence, based on the 48-week confidence interval [CI]: 0.02–0.41; p<0.001) (Figure).
Subgroup
Ulcer-free rate
Ulcer-free rate
reducing the recurrence of peptic ulcer in East Asian patients who
interim analysis for the full analysis set (FAS; all randomized patients have a history of peptic ulcers and are taking low-dose aspirin
who received ≥1 dose of study medication and who had no active ulcer Patients who remained free of ulcers
(ASA) for cardioprotection.
– Data were analyzed by the Kaplan-Meier method and displayed
Esomeprazole
as time-to-event curves; the log-rank test was used for statistical INTRODUCTION
• Clinical practice guidelines recommend the use of ASA (75–325 mg
• Secondary end points include estimated ulcer-free rates along with
daily) for prevention of cardiovascular (CV) events in patients who have descriptive assessment of mucosal lesion(s) by modified LANZA score, and the incidence/severity of reflux esophagitis and GI symptoms. However, continuous long-term use of ASA has been associated with A Cox proportional hazard model was used to evaluate the effect of Time from randomization (weeks)
gastrointestinal (GI) problems such as upper GI symptoms3 and peptic subgroups (gender, age, Helicobacter pylori status, cytochrome P450 [CYP] 2C19 genotype, and ASA treatment) on the estimated ulcer-free rate.
ulcers4 that, in turn, may decrease patient adherence to cardiopreventive therapy.5 Gastroprotection with a proton pump inhibitor is therefore • Safety end points included adverse events, clinical laboratory data, and
recommended for ASA users who are at increased GI risk.6 Figure. Kaplan-Meier curves of ulcer-free rates (48-week full analysis set).
vital signs; findings are presented for the whole treatment period.
CI, confidence interval.
• In two randomized controlled studies, esomeprazole proved efficacious
• Estimated ulcer-free rates in the FAS at week 12 were 99.3% for
and well tolerated at preventing the development of peptic ulcers in Injury, poisoning, and procedural complications esomeprazole and 89.0% for placebo. Rates were high and remained Western patients taking ASA and at high GI risk.7,8 However, data in • A total of 364 patients comprised the 48-week FAS (esomeprazole,
steady in esomeprazole-treated patients only through week 48 (98.3% a comparable population of East Asian patients are scant.
n=182; placebo, n=182) (Table 1). Patients were mostly men (81%), with a mean age of 67 years. The majority of patients were treated with ASA 100 mg daily (82%), and had received such treatment (mainly for • Sub-analysis showed superior ulcer-free rates for esomeprazole compared
secondary prevention) for >4 weeks before enrollment (89%).
• To assess the potential effects of esomeprazole in prevention of recurrent
Table 1. Baseline demographics (48-week full analysis set)
– Among placebo recipients, the estimated ulcer-free rate for patients
peptic (gastric and/or duodenal) ulcer in East Asian patients taking ASA aged ≤64 years (75.9%) was lower than those for other age categories Esomeprazole 20 mg
(65–74 years, 88.2%; ≥75 years, 80.2%) despite advanced age being a recognized risk factor for peptic ulcer. Age did not impact ulcer-free Study design and patients
– In the placebo group, the estimated ulcer-free rate was lower for ASA
Abbreviations: ASA, low-dose aspirin; CI, confidence interval; EM, extensive metabolizer.
81mg compared with the subset of patients who received the 100 mg • The LAVENDER (Low-dose Aspirin-related ulcer recurrence preVENtion
dosage (71.9% and 83.2%, respectively). Esomeprazole protected against unDER esomeprazole 20 mg treatment) study§ was a randomized,
ulcer recurrence irrespective of ASA dose.
Table 3. Shift analysis of modified LANZA score (48-week full analysis seta)
double-blind, placebo-controlled, multicenter study in East Asian (Japan, Korea, and Taiwan) patients taking prescribed ASA (81–324 mg – Regardless of reason for ASA treatment, the estimated ulcer-free rates
Esomeprazole 20 mg (n=144)
Placebo (n=145)
were lower in the placebo group compared with esomeprazole.
REFERENCES
Baseline
Baseline
1. Perk J et al. Eur Heart J 2012;33:1635–701.
Multivariate Cox regression analysis showed that gender (p=0.026) and Enrolled patients were aged ≥20 years. All participants underwent 2. Smith SC Jr et al. Circulation 2011;124:2458–73.
esomeprazole treatment (p<0.001) were the only factors significantly endoscopy at the time of enrollment, and were eligible for inclusion if 3. Pratt S et al. Am J Cardiovasc Drugs 2010;10:281–8.
predictive of the time to ulcer recurrence in the FAS.
gastric and/or duodenal ulcer scarring was visually verified. In addition 4. Yeomans ND et al. Aliment Pharmacol Ther 2005;22:795–801.
to prescribed ASA, patients were randomized (1:1) to esomeprazole 20 mg 5. Cayla G et al. Int J Cardiol 2012;156:69–75.
LANZA score, reflux esophagitis, and GI symptoms
daily or placebo for a maximum period of 72 weeks. All patients received 6. Abraham NS et al. Am J Gastroenterol 2010;105:2533–49.
7. Yeomans N et al. Am J Gastroenterol 2008;103:2465–73.
gefarnate 50 mg twice daily for mucosal protection. Concomitant use of • More esomeprazole-treated patients (32%, 46/144) in the 48-week FAS
8. Scheiman JM et al. Heart 2011;97:797–802.
nonsteroidal anti-inflammatory drugs was not permitted.
showed improvement in mucosal lesions by modified LANZA score NOTE: The data in this poster differ slightly from those in the published abstract owing to
compared with placebo (18%, 26/145), while a smaller proportion of further refinement of the analysis.
• Patients with an active peptic ulcer, uncontrolled diabetes, unstable
patients had a worsening of scores with esomeprazole (14%, 20/144) hypertension, serious heart failure, or history of acute coronary ACKNOWLEDGEMENTS
Patients with baseline plus ≥1 subsequent measurement. Shading indicates improvement in score compared with placebo (41%, 60/145) (Table 3).
This study was funded by AstraZeneca, Osaka, Japan. We thank Robert Schupp and Steve Winter of inScience Communications, syndromes/stroke (within the past 3 months) were excluded from Springer Healthcare who provided medical writing support funded by AstraZeneca.
• Fewer esomeprazole-treated patients than placebo recipients had
CONFLICTS OF INTERESTS
Safety findings
endoscopic evidence of reflux esophagitis at weeks 12 (0% vs 6.5%), 24 Shinya Goto: grant/research support – Boehringer Ingelheim, Eisai, Otsuka, and Sanofi; speaker fees – Eisai, Otsuka, and Sanofi; consultancy and/or advisory board member – Bayer, MSD, and Pfizer; honoraria – Bayer and Bristol-Myers Squibb.
As defined by the protocol, the study design incorporated an interim (1.0% vs 6.8%), and 36 (0% vs 6.7%), with no cases reported at week 48.
• Treatment with esomeprazole 20 mg daily was well tolerated through the
Yasushi Okada: no conflicts to declare.
analysis to assess the superiority of esomeprazole relative to placebo whole treatment period. The number of patients who had serious adverse Myung-Gyu Choi: grant/research support – AstraZeneca.
Jaw-Town Lin: grant/research support – AstraZeneca.
when a minimum of 18 ulcer events had occurred in the overall patient Values are n (%) unless otherwise stated.
• At baseline, the majority of patients in both treatment groups did not
events, including CV events, was similar in the two treatment groups (Table 4).
Yoshikazu Kinoshita: grant/research support and honoraria – AstraZeneca and Daiichi Sankyo.
population, and >250 patients had been randomized to treatment. An aData missing for 7 patients (esomeprazole, n=3; placebo, n=4).
report GI symptoms. More placebo-treated patients without symptoms at Hiroto Miwa: grant/research support – AstraZenenca, Chugai, Dainippon Sumitomo, Eisai, Takeda, and Yakult; consultancy and/or advisory board member – AstraZeneca, Daiichi Sankyo, and Eisai; directorships – AstraZeneca and Takeda.
independent Data Monitoring Committee decided that the corresponding bA total of 4 patients received ASA for other reasons (esomeprazole, n=2; placebo, n=2).
baseline developed mild-to-severe GI symptoms by study end compared • No clinically significant changes were noted for laboratory tests and vital
Chern-En Chiang: grant/research support – AstraZeneca.
cut-off date for this analysis was 48 weeks.
Kentaro Sugano: grant/research support – Astellas, AstraZeneca, Daiichi Sankyo, Eisai, Otsuka, and Takeda; consultancy and/or Abbreviations: ASA, low-dose aspirin; EM, extensive metabolizer; SD, standard deviation.
with esomeprazole recipients (data not shown).
signs in either treatment group, and there were no new safety concerns.
advisory board member – AstraZeneca and Takeda; honoraria – Takeda.
§ ClinicalTrials.gov identifier: NCT01069939; study code: D961PC00001
Supported by AstraZeneca, Osaka, Japan

Source: http://clinicaltrialresults.org/Slides/AHA%202012/Goto_AHA%202012%20LAVENDER%20poster%2023%20Oct%202012-5.pdf