Outcomes and drivers of inappropriate dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a systematic review and meta-analysis

Objective: There has been limited systematic evaluation of outcomes and drivers of inappropriate non-vitamin K antagonist oral anticoagulants (NOACs) dosing among patients with atrial fibrillation (AF). This review identified and systematically evaluated literature on clinical and economic outcomes of inappropriate NOAC dosing and associated patient characteristics. Methods: MEDLINE, Embase, Cochrane Library, International Pharmaceutical Abstracts, Econlit, PubMed and NHS EEDs databases were searched for English language observational studies from all geographies published between 2008 and 2020, examining outcomes of, or factors associated with, inappropriate NOAC dosing in adult patients with AF. Results: One hundred and six studies were included in the analysis. Meta-analysis showed that compared with recommended NOAC dosing, off-label underdosing was associated with a null effect on stroke outcomes (ischaemic stroke and stroke/transient ischaemic attack (TIA), stroke/systemic embolism (SE) and stroke/SE/TIA). Meta-analysis of 15 studies examining clinical outcomes of inappropriate NOAC dosing found a null effect of underdosing on bleeding outcomes (major bleeding HR=1.04, 95% CI 0.90 to 1.19; p=0.625) but an increased risk of all-cause mortality (HR=1.28, 95% CI 1.10 to 1.49; p=0.006). Overdosing was associated with an increased risk of major bleeding (HR=1.41, 95% CI 1.07 to 1.85; p=0.013). No studies were found examining economic outcomes of inappropriate NOAC dosing. Narrative synthesis of 12 studies examining drivers of inappropriate NOAC dosing found that increased age, history of minor bleeds, hypertension, congestive heart failure and low creatine clearance (CrCl) were associated with an increased risk of underdosing. There was insufficient evidence to assess drivers of overdosing. Conclusions: Our analysis suggests that off-label underdosing of NOACs does not reduce bleeding outcomes. Patients prescribed off-label NOAC doses are at an increased risk of all-cause mortality. These data underscore the importance of prescriber adherence to NOAC dosing guidelines to achieve optimal clinical outcomes for patients with AF

Non-embolic outcomes in patients with cardiovascular disease and atrial fibrillation treated with rivaroxaban

Aim: It is not well known how comorbidities may change the prognosis of atrial fibrillation (AF) patients. This study was aimed to analyze the impact of cardiovascular disease on this population. Materials & methods: EMIR was a multicenter, prospective study, including 1433 AF patients taking rivaroxaban for ≥6 months. Data were analyzed according to the presence of vascular disease. Results: Coronary artery disease was detected in 16.4%, peripheral artery disease/aortic plaque in 6.7%, vascular disease in 28.3%. Patients with coronary artery disease had higher rates (per 100 patient-years) of major adverse cardiovascular events (2.98 vs 0.71; p < 0.001) and cardiovascular death (1.79 vs 0.41; p = 0.004). Those with vascular disease had higher rates of thromboembolic events (1.47 vs 0.44; p = 0.007), major adverse cardiovascular events (2.03 vs 0.70; p = 0.004), and cardiovascular death (1.24 vs 0.39; p = 0.025). Patients with peripheral artery disease/aortic plaque had similar rates. Conclusion: AF patients with vascular disease have a higher risk of non-embolic outcomes

Observation of Bs0→D‾∗0ϕB_s^0 \to \overline{D}^{*0} \phi and search for B0→D‾0ϕB^0 \to \overline{D}^0 \phi decays

International audienceThe first observation of the Bs0→D¯*0ϕ decay is reported, with a significance of more than seven standard deviations, from an analysis of pp collision data corresponding to an integrated luminosity of 3  fb-1, collected with the LHCb detector at center-of-mass energies of 7 and 8 TeV. The branching fraction is measured relative to that of the topologically similar decay B0→D¯0π+π- and is found to be B(Bs0→D¯*0ϕ)=(3.7±0.5±0.3±0.2)×10-5, where the first uncertainty is statistical, the second systematic, and the third from the branching fraction of the B0→D¯0π+π- decay. The fraction of longitudinal polarization in this decay is measured to be fL=(73±15±4)%. The most precise determination of the branching fraction for the Bs0→D¯0ϕ decay is also obtained, B(Bs0→D¯0ϕ)=(3.0±0.3±0.2±0.2)×10-5. An upper limit, B(B0→D¯0ϕ)<2.0 (2.3)×10-6 at 90% (95%) confidence level is set. A constraint on the ω-ϕ mixing angle δ is set at |δ|<5.2° (5.5°) at 90% (95%) confidence level

Observation of the decay Bs0→D‾0K+K−B_s^0 \to \overline{D}^0 K^+ K^-

International audienceThe first observation of the Bs0→D¯0K+K- decay is reported, together with the most precise branching fraction measurement of the mode B0→D¯0K+K-. The results are obtained from an analysis of pp collision data corresponding to an integrated luminosity of 3.0  fb-1. The data were collected with the LHCb detector at center-of-mass energies of 7 and 8 TeV. The branching fraction of the B0→D¯0K+K- decay is measured relative to that of the decay B0→D¯0π+π- to be B(B0→D¯0K+K-)B(B0→D¯0π+π-)=(6.9±0.4±0.3)%, where the first uncertainty is statistical and the second is systematic. The measured branching fraction of the Bs0→D¯0K+K- decay mode relative to that of the corresponding B0 decay is B(Bs0→D¯0K+K-)B(B0→D¯0K+K-)=(93.0±8.9±6.9)%. Using the known branching fraction of B0→D¯0π+π-, the values of B(B0→D¯0K+K-)=(6.1±0.4±0.3±0.3)×10-5 and B(Bs0→D¯0K+K-)=(5.7±0.5±0.4±0.5)×10-5 are obtained, where the third uncertainties arise from the branching fraction of the decay modes B0→D¯0π+π- and B0→D¯0K+K-, respectively

Observation of a new Ξb−\Xi_b^- resonance

International audienceFrom samples of pp collision data collected by the LHCb experiment at s=7, 8 and 13 TeV, corresponding to integrated luminosities of 1.0, 2.0 and 1.5  fb-1, respectively, a peak in both the Λb0K- and Ξb0π- invariant mass spectra is observed. In the quark model, radially and orbitally excited Ξb- resonances with quark content bds are expected. Referring to this peak as Ξb(6227)-, the mass and natural width are measured to be mΞb(6227)-=6226.9±2.0±0.3±0.2  MeV/c2 and ΓΞb(6227)-=18.1±5.4±1.8  MeV/c2, where the first uncertainty is statistical, the second is systematic, and the third, on mΞb(6227)-, is due to the knowledge of the Λb0 baryon mass. Relative production rates of the Ξb(6227)-→Λb0K- and Ξb(6227)-→Ξb0π- decays are also reported

Observation of Bs0→Dˉ∗0ϕB_s^0 \to \bar{D}^{*0} \phi and search for B0→Dˉ0ϕB^0 \to \bar{D}^0 \phi decays

The first observation of the $B^0_s → \bar{D}^{*0}ϕ$ decay is reported, with a significance of more than seven standard deviations, from an analysis of pp collision data corresponding to an integrated luminosity of 3  fb$^{−1}$, collected with the LHCb detector at center-of-mass energies of 7 and 8 TeV. The branching fraction is measured relative to that of the topologically similar decay $B^0 → \bar{D}^0 π^+ π^−$ and is found to be $\mathcal{B}(B^0_s → \bar{D}^{*0}ϕ)=(3.7±0.5±0.3±0.2) × 10^{−5}$, where the first uncertainty is statistical, the second systematic, and the third from the branching fraction of the $B^0 → \bar{D}^0 π^+ π^−$ decay. The fraction of longitudinal polarization in this decay is measured to be $f_L = (73±15±4)\%$. The most precise determination of the branching fraction for the $B^0_s → \bar{D}^{0}ϕ$ decay is also obtained, $\mathcal{B}(B^0_s → \bar{D}^0 ϕ)=(3.0±0.3±0.2±0.2) × 10^{−5}$. An upper limit,$\mathcal{B}(B^0 → \bar{D}^0 ϕ) < 2.0 (2.3) × 10^{−6}$ at 90% (95%) confidence level is set. A constraint on the $ω−ϕ$ mixing angle $δ$ is set at $|δ| < 5.2°$ (5.5°) at 90% (95%) confidence level

Measurement of the CKM angle γ\gamma using B±→DK±B^\pm\to DK^\pm with D→KS0π+π−D\to K_\text{S}^0\pi^+\pi^-, KS0K+K−K_\text{S}^0K^+K^- decays

International audienceA binned Dalitz plot analysis of B$^{±}$ → DK$^{±}$ decays, with D → K$_{S}^{0}$ π$^{+}$π$^{−}$ and D → K$_{S}^{0}$ K$^{+}$K$^{−}$, is used to perform a measurement of the CP-violating observables x$_{±}$ and y$_{±}$, which are sensitive to the Cabibbo-Kobayashi-Maskawa angle γ. The analysis is performed without assuming any D decay model, through the use of information on the strong-phase variation over the Dalitz plot from the CLEO collaboration. Using a sample of proton-proton collision data collected with the LHCb experiment in 2015 and 2016, and corresponding to an integrated luminosity of 2.0 fb$^{−1}$, the values of the CP violation parameters are found to be x$_{−}$ = (9.0 ± 1.7 ± 0.7 ± 0.4) × 10$^{−2}$, y$_{−}$ = (2.1 ± 2.2 ± 0.5 ± 1.1) × 10$^{−2}$, x$_{+}$ = (−7.7 ± 1.9 ± 0.7 ± 0.4) × 10$^{−2}$, and y$_{+}$ = (−1.0 ± 1.9 ± 0.4 ± 0.9) × 10$^{−2}$. The first uncertainty is statistical, the second is systematic, and the third is due to the uncertainty (on the strong-phase measurements. These values are used to obtain γ = (87$_{− 12}^{+ 11}$ )$^{∘}$, r$_{B}$ = 0.086$_{− 0.014}^{+ 0.013}$ , and δ$_{B}$ = (101±11)°, where r$_{B}$ is the ratio between the suppressed and favoured B-decay amplitudes and δ$_{B}$ is the corresponding strong-interaction phase difference. This measurement is combined with the result obtained using 2011 and 2012 data collected with the LHCb experiment, to give γ = (80$_{− 9}^{+ 10}$ )$^{∘}$, r$_{B}$ = 0.080 ± 0.011, and δ$_{B}$ = (110 ± 10)°

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes

Physics case for an LHCb Upgrade II - Opportunities in flavour physics, and beyond, in the HL-LHC era

The LHCb Upgrade II will fully exploit the flavour-physics opportunities of the HL-LHC, and study additional physics topics that take advantage of the forward acceptance of the LHCb spectrometer. The LHCb Upgrade I will begin operation in 2020. Consolidation will occur, and modest enhancements of the Upgrade I detector will be installed, in Long Shutdown 3 of the LHC (2025) and these are discussed here. The main Upgrade II detector will be installed in long shutdown 4 of the LHC (2030) and will build on the strengths of the current LHCb experiment and the Upgrade I. It will operate at a luminosity up to $2 \times 10^{34} \rm cm^{-2}s^{-1}$, ten times that of the Upgrade I detector. New detector components will improve the intrinsic performance of the experiment in certain key areas. An Expression Of Interest proposing Upgrade II was submitted in February 2017. The physics case for the Upgrade II is presented here in more depth. $CP$-violating phases will be measured with precisions unattainable at any other envisaged facility. The experiment will probe $b\to s \ell^+\ell^-$ and $b\to d \ell^+\ell^-$ transitions in both muon and electron decays in modes not accessible at Upgrade I. Minimal flavour violation will be tested with a precision measurement of the ratio of $B(B^0\to\mu^+\mu^-)/B(B_s^0\to \mu^+\mu^-)$. Probing charm $CP$ violation at the $10^{-5}$ level may result in its long sought discovery. Major advances in hadron spectroscopy will be possible, which will be powerful probes of low energy QCD. Upgrade II potentially will have the highest sensitivity of all the LHC experiments on the Higgs to charm-quark couplings. Generically, the new physics mass scale probed, for fixed couplings, will almost double compared with the pre-HL-LHC era; this extended reach for flavour physics is similar to that which would be achieved by the HE-LHC proposal for the energy frontier

Observation of the decay B‾s0→χc2K+K− {\overline{B}}_s^0\to {\chi}_{c2}{K}^{+}{K}^{-} in the ϕ\phi mass region

The $\overline{B_s^0} \rightarrow \chi_{c2} K^+ K^-$ decay mode is observed and its branching fraction relative to the corresponding $\chi_{c1}$ decay mode, in a $\pm 15 \textrm{MeV}/c^2$ window around the $\phi$ mass, is found to be $\frac{\mathcal{B}(\overline{B_s^0} \rightarrow \chi_{c2} K^+ K^-) }{ \mathcal{B}(\overline{B_s^0} \rightarrow \chi_{c1} K^+ K^-)} = (17.1 \pm 3.1 \pm 0.4 \pm 0.9)\%,$ where the first uncertainty is statistical, the second systematic and the third due to the knowledge of the branching fractions of radiative $\chi_c$ decays. The decay mode $\overline{B_s^0} \rightarrow \chi_{c1} K^+ K^-$ allows the $B_s^0$ mass to be measured as $m(B_s^0) = 5366.83 \pm 0.25 \pm 0.27 \, \textrm{MeV}/c^2,$ where the first uncertainty is statistical and the second systematic. A combination of this result with other LHCb determinations of the $B_s^0$ mass is made