PMID- 24368727
OWN - NLM
STAT- MEDLINE
DCOM- 20150212
LR  - 20211021
IS  - 1573-742X (Electronic)
IS  - 0929-5305 (Linking)
VI  - 38
IP  - 1
DP  - 2014 Jul
TI  - Impact of concomitant low-dose aspirin on the safety and tolerability of naproxen 
      and esomeprazole magnesium delayed-release tablets in patients requiring chronic 
      nonsteroidal anti-inflammatory drug therapy: an analysis from 5 Phase III 
      studies.
PG  - 11-23
LID - 10.1007/s11239-013-1035-4 [doi]
AB  - 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. %; 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.
FAU - Angiolillo, Dominick J
AU  - Angiolillo DJ
AD  - Division of Cardiology, University of Florida College of Medicine-Jacksonville, 
      ACC Building 5th Floor, 655 West 8th Street, Jacksonville, FL, 32209, USA, 
      dominick.angiolillo@jax.ufl.edu.
FAU - Datto, Catherine
AU  - Datto C
FAU - Raines, Shane
AU  - Raines S
FAU - Yeomans, Neville D
AU  - Yeomans ND
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Thromb Thrombolysis
JT  - Journal of thrombosis and thrombolysis
JID - 9502018
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Anti-Ulcer Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - 57Y76R9ATQ (Naproxen)
RN  - N3PA6559FT (Esomeprazole)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage
MH  - Anti-Ulcer Agents/*administration & dosage/adverse effects
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Aspirin/*administration & dosage/adverse effects
MH  - Delayed-Action Preparations
MH  - Double-Blind Method
MH  - Esomeprazole/*administration & dosage/adverse effects
MH  - Female
MH  - Gastrointestinal Diseases/chemically induced/prevention & control
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Naproxen/*administration & dosage/adverse effects
MH  - Osteoarthritis/*drug therapy
EDAT- 2013/12/26 06:00
MHDA- 2015/02/13 06:00
CRDT- 2013/12/26 06:00
PHST- 2013/12/26 06:00 [entrez]
PHST- 2013/12/26 06:00 [pubmed]
PHST- 2015/02/13 06:00 [medline]
AID - 10.1007/s11239-013-1035-4 [doi]
PST - ppublish
SO  - J Thromb Thrombolysis. 2014 Jul;38(1):11-23. doi: 10.1007/s11239-013-1035-4.