Drug Saf

INTRODUCTION: Non-steroidal anti-inflammatory drugs are associated with a dose and duration-dependent coronary risk. There is little information concerning analgesic-dose ibuprofen, among the most widely used drugs worldwide. OBJECTIVE: Our objective was to measure the risks of acute coronary syndrome (ACS) after dispensing of ibuprofen, versus paracetamol. METHODS: Propensity score 1:2-matched cohorts of ibuprofen or paracetamol treatment episodes (TEs) in Echantillon Generaliste de Beneficiaires (EGB), the 1/97 sample of Systeme National des Donnees de Sante (SNDS), the French nationwide claims database, from 2009 to 2014, were compared. Outcomes were hospital admissions for ACS during the 3 months after the dispensing of ibuprofen or paracetamol. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated overall and stratified on low-dose aspirin dispensing. RESULTS: A total of 315,269 ibuprofen TEs in 168,400 persons were matched to 630,457 paracetamol TEs in 395,952 patients. Event rates were 50-100 times higher in low-dose aspirin users (27 vs 0.28 per 1000 patient years). Overall there was no difference in risk of ACS at 3 months (HR 0.94, 95% CI 0.74-1.20) despite a transient increase in the first 2 weeks in ibuprofen users (HR 1.70, 95% CI 1.11-2.59). In the stratified analysis, this short-term risk was only found in aspirin users (5% of population, HR 1.84, 95% CI 1.24-3.24), but not in non-aspirin users (HR 1.09, 95% CI 0.40-2.94). CONCLUSIONS: There was no evidence for an increased risk of ACS in patients dispensed ibuprofen compared to paracetamol

Am J Cardiovasc Drugs

Background Clinical trials have indicated that the direct-acting oral anticoagulants dabigatran and rivaroxaban have better risk/benefit profiles than do vitamin K antagonists (VKAs) for stroke prevention in non-valvular atrial fibrillation (NVAF). Objective Our objective was to compare the 1-year real-life risk of major clinical events with dabigatran or rivaroxaban versus VKAs for NVAF. Methods This was a high-dimensional propensity score (hdPS)-matched cohort study of new users of dabigatran, rivaroxaban or VKAs for NVAF in the French national healthcare systems database in 2013 followed-up for 1 year [22]. Hazard ratios (HRs) with 95% confidence intervals (CIs) for clinical events and death were determined during exposure. Results In 2013, a total of 103,101 new anticoagulant users had definite NVAF: 44,653 VKA, 27,060 dabigatran, and 31,388 rivaroxaban. In matched populations, HRs were as follows for dabigatran versus VKAs (20,489 per group): stroke and systemic embolism (SSE) 0.75 (95% CI 0.63–0.88), clinically relevant bleeding (CRB) 0.58 (95% CI 0.51–0.66), hemorrhagic stroke (HS) 0.22 (95% CI 0.14–0.36), gastrointestinal bleeding (GIB) 0.98 (95% CI 0.80–1.19), acute coronary syndrome (ACS) 0.79 (95% CI 0.65–0.95), death 0.74 (95% CI 0.67–0.82), composite (any of the above) 0.71 (95% CI 0.66–0.76). For matched rivaroxaban versus VKA (23,053 per group) HRs were as follows: SSE 0.98 (95% CI 0.85–1.14), CRB 0.83 (95% CI 0.75–0.92), HS 0.65 (95% CI 0.49–0.87), GIB 1.08 (95% CI 0.90–1.30), ACS 0.84 (95% CI 0.71–1.00), death 0.77 (95% CI 0.71–0.84), composite 0.84 (95% CI 0.79–0.89). Numbers needed to treat to observe one fewer death were 49 ± 0.05 with dabigatran or rivaroxaban versus VKAs. Conclusion Consistent with results from clinical trials and other observational studies, dabigatran and rivaroxaban were at least as effective and safer than VKAs for the prevention of thromboembolic events in NVAF over 1 year in the French population

Br J Clin Pharmacol

BACKGROUND: We compared the 1-year safety and effectiveness of dabigatran 110 mg (D110) or 150 mg (D150) to vitamin K antagonists (VKA) in patients with non-valvular atrial fibrillation (NVAF), METHODS: New user cohort study of patients dispensed D110 or D150 vs. VKA in 2013 for NVAF, followed 1 year in the French Systeme National des Donnees de Sante (SNDS, 66 million persons). D110 and D150 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing, and high-dimensional propensity score (hdPS). Hazard ratios (HR [95% confidence intervals]) for stroke and systemic embolism (SSE), major bleeding (MB), and death were computed using Cox proportional hazards or Fine and Gray models during exposure. RESULTS: In 14,442 matched D110 and VKA patients, mean age 79, 49% male, 91% with CHA2 DS2 -VASc >/=2 and 8% with HAS-BLED >3, incidence rates of SSE were 1.9% and 2.6% person-years (HR 0.69 [0.56-0.84]), MB 1.8% and 2.9% (0.62 [0.51-0.76]), death 7.2% and 8.6% (0.84 [0.76-0.94]). In 8,389 matched D150 and VKA patients, mean age 67, 67% male, 65% with CHA2 DS2 -VASC >/= 2; 3, incidence rates were for SSE 1.4% and 1.9% (0.76 [0.56-1.04]), MB 0.6 % and 1.9% (0.30 [0.20-0.46]), death 1.6% and 3.6% (0.46 [0.35-0.59]). Numbers needed to treat to observe one fewer death were 78 for D110, 88 for D150 CONCLUSION: In real life D110 and D150 were at least as effective and safer than VKA

Clin Pharmacol Ther

Dabigatran and rivaroxaban at standard (SD) or reduced doses (RD) have been compared to warfarin in non-valvular atrial fibrillation (NVAF), but not to each other. This was a new user study of SD and RD dabigatran or rivaroxaban for NVAF in the French healthcare database, matched on gender, age, date of first dispensing, and high-dimensional propensity score, followed 2 years. Hazard ratios [95% Confidence Intervals] of stroke or systemic embolism (SSE), major bleeding (MB) or death, were computed. In matched SD patients (8,290 per arm), mean age 67, HR for dabigatran vs. rivaroxaban were SSE 0.92 [0.67-1.26], MB 0.59 [0.39-0.90], death 0.84 [0.65-1.11]. In RD patients (7639 per arm), mean age 80, HR for dabigatran vs. rivaroxaban were SSE 0.73 [0.59-0.94], MB 0.74 [0.57-0.96], death 0.95 [0.83-1.09]. In conclusion, at either dose dabigatran had similar or better effectiveness than rivaroxaban, but lower bleeding risk. Death rates were not different. This article is protected by copyright. All rights reserved