Citation

Angiolillo DJ, Datto C, Raines S, Yeomans ND. J. Thromb. Thrombolysis 2014; 38(1): 11-23.

Copyright

(Copyright © 2014, Springer)

DOI

10.1007/s11239-013-1035-4

PMID

unavailable

Abstract

Patients receiving chronic nonsteroidal anti-inflammatory drugs (NSAIDs) and concomitant low-dose aspirin (LDA) are at increased risk of gastrointestinal (GI) toxicity. A fixed-dose combination of enteric-coated (EC) naproxen and immediate-release esomeprazole magnesium (NAP/ESO) has been designed to deliver a proton-pump inhibitor followed by an NSAID in a single tablet. To examine safety data from 5 Phase III studies of NAP/ESO in LDA users (≤325 mg daily, administered at any time during the study), and LDA non-users, data were analyzed from 6-month studies assessing NAP/ESO versus EC naproxen in patients with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis (n = 2), 3-month studies assessing NAP/ESO vs celecoxib or placebo in patients with knee osteoarthritis (n = 2), and a 12-month, open-label, safety study of NAP/ESO (n = 1). In an analysis of two studies, incidences of endoscopically confirmed gastric ulcers (GUs) and duodenal ulcers (DUs) were summarized by LDA subgroups. In the pooled analysis from all five studies, incidences of treatment-emergent adverse events (AEs) (including prespecified NSAID-associated upper GI AEs and cardiovascular AEs), serious AEs, and AE-related discontinuations were stratified by LDA subgroups. Overall, 2,317 patients received treatment; 1,157 patients received NAP/ESO and, of these, 298 received LDA. The cumulative incidence of GUs and DUs in the two studies with 6-month follow-up was lower for NAP/ESO vs EC naproxen in both LDA subgroups [GUs: 3.0 vs 27.9 %, respectively, for LDA users, 6.4 vs 22.4 %, respectively, for LDA non-users (both P < 0.001); DUs: 1.0 vs 5.8 % for LDA users, 0.6 vs 5.3 % for LDA non-users]. The incidence of erosive gastritis was lower in NAP/ESO- vs EC naproxen-treated patients for both LDA users [18.2 vs 36.5 %, respectively (P = 0.004)] and LDA non-users [19.8 vs 38.5 %, respectively (P < 0.001)]. Among LDA users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 16.1 %; EC naproxen, 31.7 %; celecoxib, 22.1 %; placebo, 23.2 %. Among LDA non-users, incidences of NSAID-associated upper GI AEs were: NAP/ESO, 20.3 %; EC naproxen, 36.6 %; celecoxib, 18.5 %; placebo, 18.9 %. For LDA users, incidences of cardiovascular AEs were: NAP/ESO, 3.0 %; EC naproxen, 1.0 %; celecoxib, 0 %; placebo, 0 %. For LDA non-users, incidences of cardiovascular AEs were: NAP/ESO, 1.0 %; EC naproxen, 0.6 %; celecoxib, 0.3 %; placebo, 0 %. NAP/ESO appears to be well-tolerated in patients receiving concomitant LDA. For LDA users, AE incidence was less than that observed for EC naproxen. For most AE categories, incidences were similar among NAP/ESO, celecoxib and placebo groups. The safety of NAP/ESO appeared similar regardless of LDA use. © 2013 Springer Science+Business Media.

Language: en

Keywords

Humans; adolescent; Adult; Female; Male; Middle Aged; adult; human; Adolescent; female; male; incidence; Gastrointestinal Diseases; Double-Blind Method; abdominal pain; randomized controlled trial; suicide attempt; clinical trial; Aspirin; Naproxen; Tolerability; Delayed-Action Preparations; article; major clinical study; vomiting; controlled study; priority journal; double blind procedure; headache; phase 3 clinical trial; middle aged; gangrene; heart infarction; acetylsalicylic acid; drug safety; placebo; Arthritis, Rheumatoid; rheumatoid arthritis; backache; nonsteroid antiinflammatory agent; drug efficacy; drug tolerability; nausea; multicenter study; naproxen; coronary artery disease; cerebrovascular disease; esophagus hemorrhage; coughing; esophagitis; drug indication; thorax pain; gastrointestinal hemorrhage; dyspepsia; pneumonia; celecoxib; drug hypersensitivity; gastrointestinal toxicity; transient ischemic attack; treatment response; hip fracture; acute pancreatitis; drug exposure; esophagus ulcer; urinary tract infection; unstable angina pectoris; antiulcer agent; atrioventricular block; abdominal discomfort; gastritis; gastroesophageal reflux; outcome assessment; Anti-Inflammatory Agents, Non-Steroidal; esophagus stenosis; coronary artery obstruction; anaphylaxis; colitis; upper respiratory tract infection; chemically induced; delayed release formulation; osteoarthritis; esophagus disease; creatinine clearance; incisional hernia; Staphylococcus infection; stomach hemorrhage; stomach mucosa lesion; hematemesis; lower abdominal pain; heart atrium flutter; esomeprazole; ankylosing spondylitis; upper abdominal pain; stomach discomfort; swelling; musculoskeletal pain; abdominal tenderness; esophagus varices; necrotizing fasciitis; epigastric discomfort; duodenum bleeding; Esomeprazole; limb fracture; Anti-Ulcer Agents; appendix perforation; duodenal scarring; duodenitis; duodenum disease; esomeprazole plus naproxen; hyperchlorhydria; Low-dose aspirin; Naproxen/esomeprazole magnesium; NSAID; Osteoarthritis; reflux esophagitis; Safety profile