Jeroen Jaspers Focks

Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial

Objective To determine whether the treatment effect of apixaban versus warfarin differs with increasing numbers of concomitant drugs used by patients with atrial fibrillation. Design Post hoc analysis performed in 2015 of results from ARISTOTLE (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation)—a multicentre, double blind, double dummy trial that started in 2006 and ended in 2011. Participants 18 201 ARISTOTLE trial participants. Interventions In the ARISTOTLE trial, patients were randomised to either 5 mg apixaban twice daily (n=9120) or warfarin (target international normalised ratio range 2.0-3.0; n=9081). In the post hoc analysis, patients were divided into groups according to the number of concomitant drug treatments used at baseline (0-5, 6-8, ≥9 drugs) with a median follow-up of 1.8 years. Main outcome measures Clinical outcomes and treatment effects of apixaban versus warfarin (adjusted for age, sex, and country). Results Each patient used a median of six drugs (interquartile range 5-9); polypharmacy (≥5 drugs) was seen in 13 932 (76.5%) patients. Greater numbers of concomitant drugs were used in older patients, women, and patients in the United States. The number of comorbidities increased across groups of increasing numbers of drugs (0-5, 6-8, ≥9 drugs), as did the proportions of patients treated with drugs that interact with warfarin or apixaban. Mortality also rose significantly with the number of drug treatments (P<0.001), as did rates of stroke or systemic embolism (1.29, 1.48, and 1.57 per 100 patient years, for 0-5, 6-8, and ≥9 drugs, respectively) and major bleeding (1.91, 2.46, and 3.88 per 100 patient years, respectively). Relative risk reductions in stroke or systemic embolism for apixaban versus warfarin were consistent, regardless of the number of concomitant drugs (Pinteraction=0.82). A smaller reduction in major bleeding was seen with apixaban versus warfarin with increasing numbers of concomitant drugs (Pinteraction=0.017). Patients with interacting (potentiating) drugs for warfarin or apixaban had similar outcomes and consistent treatment effects of apixaban versus warfarin. Conclusions In the ARISTOTLE trial, three quarters of patients had polypharmacy; this subgroup had an increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic and bleeding complications. In terms of a potential differential response to anticoagulation therapy in patients with atrial fibrillation and polypharmacy, apixaban was more effective than warfarin, and is at least just as safe. Trial registration ARISTOTLE trial, ClinicalTrials.gov NCT00412984.

Su1642 Over a Quarter of the General Adult Population Experiences Gastrointestinal Symptoms Influencing Health-Related Quality of Life: Results of 50,000 Questionnaires

BACKGROUND: Esophago-gastrointestinal (EGI) symptoms are frequently reported by patients with eating disorders (ED), who tend to use somatic disturbances to justify modifications of alimentary behaviour. It is not clear if referred symptoms are real, whether they ameliorate after controlled diet or if there are related to psychopathogical traits. AIM: (i) to analyze the prevalence of moderate-severe EGI symptoms, either individual or pooled, and of Minnesota Multiphasic Personality Inventory (MMPI-2 or MMPI-A) scales in hospitalized ED patients and symptoms modifications after 6 months of follow-up; (ii) to correlate EGI symptoms and sds-body mass index (sdsBMI) changes with MMPI scales. METHODS: We enrolled 48 consecutive patients (41 F, median age 15) hospitalized with a diagnosis of ED. Thirty-nine patients (81%) were classified as AN and 9 (19%) as BN. At admission (T1) all patients completed MMPI-2 or MMPI-A and the italian version of a validated questionnaire on gastroesophageal (E) and gastrointestinal (GI) symptoms. EGI questionnaire was then completed at discharge (T2), at 1 month of follow up (T3) and after 6 months (T4). RESULTS: (i) the most frequently reported symptoms classified as moderate-severe were postprandial fullness (70%) and abdominal distention (57%). The most prevalent pychopathological trait with abnormal MMPI score (>55) was depression (67%). During observational period of 6 months (T1-T4), E and GI symptoms significantly decreased (IR 3-19 and 0.5-6.5, IR 1444 and 4-28, p<0.05 and p<0.0001, respectively), as well as sdsBMI (-3.4 -1.7 e -1.5 -0.4; p<0.001). Patients with abnormal scores of Hypochondriasis (HS) had significantly more severe abdominal distention and pooled GI symptoms than patients with normal HS scores (p<0.05 and p<0.005, respectively). (ii) sdsBMI change did not correlate with EGI symptoms improvement (p=NS). Normal HS, Hysteria (HY), Psychoastenia (PT), Schizophrenia (SC) scores were significantly correlated with reduction of postprandial fullness compared to abnormal scores (p<0.05). Abdominal distention improved in all patients, irrespectively of MMPI scores (p<0.05). Pooled E symptoms significantly diminished in patients with normal HY scores vs abnormal (p<0.05), whereas pooled GI symptoms improved irrespectively of high HS and HY scores (p<0.05). All patients showed a reduction in sdsBMI, irrespectively of MMPI scores (p<0.05). CONCLUSIONS: Postprandial fullness and abdominal distention are the most prevalent digestive complaints reported by ED patients. An improvement of sdsBMI is observed in controlled ED patients as well as EGI symptoms. Abnormal MMPI traits may interfere with amelioration of postprandial fullness, but has no influence on abdominal distention, nor on sdsBMI.