To evaluate the effect of Oral-Anticoagulants in Non-Valvular Atrial Fibrillation(NVAF) to control the occurrence of stroke and to assess the mortalityrate, hospital-readmissions, duration of hospital-stay associated with its use in South-Indian population. Methods: This retrospective, comparative hospital-based study conducted in a tertiary-care hospital, Kerala. In this study, NVAF patients with more than eighteen years who were initiated with Newer-Oral-Anticoagulants(NOACs) or Warfarin during the period from January-2016 to January-2018 were selected. Patients with Valvular-Heart-Disease, Transient-Ischemic-Attack, Deep-Vein-Thrombosis, Pulmonary-Embolism, End-Stage-Renal-Disease and those who contraindicated to these drugs were excluded. The patients were followed-up for a period of 1year. The effect of drugs in controlling the occurrence of stroke, stroke-free period, hospital-readmissions, length of hospital-stay and allcause mortality were compared and analyzed among the groups. Analysis of Variance test(ANOVA) were used to compare the baseline parameters and Student's t test, used to compare categorical variables. Results: A total of 133 patients (51warfarin and 82NOAC-group) were enrolled. The number of patients on NOACs had a clinical benefit over warfarin in controlling stroke (78.04% vs 70.58%),(P=0.22). Stroke was not reported in 7.47% of NOAC users during the entire study-period. They were associated with lesser cardiac complications(36.5%), readmissions(15.85%; P=0.07); and had higher risk-reduction in readmissions (41.7%; Relative-Risk-Reduction=0.417) and mortality (12.91%; RRR=0.1291). Mean duration of hospital stay was equally-likely in both groups (Warfarin7;NOACs6). Warfarin-users experienced higher incidence of mortality within first six-months of initiation though mortalityrate similar in both groups during entire study-period (19.6% vs 17.1% for warfarin vs NOAC),[P=0.71]. Hazard ratio were assessed in terms of stroke [0.49 (CI:0.15-1.57);P=0.24), mortality [0.28(CI:0.06-1.19); P=0.71] and major-bleeding [0.844(CI:0.34-2.07);P=0.08] between both drugs, indicating NOACs were associated with lower-risk and had higher safety profile. Conclusions: NOACs were found to be a better alternative for NVAF patients, due to its higher risk-reduction, improved health outcomes and clinical benefits over warfarin under routine clinical settings in South-India.

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The treatment of spinal muscular atrophy (SMA) is undergoing a period of important advances: in the last few years innovative treatments have emerged and are being evaluated by regulators, payers, and Health Technology Assessment bodies across the globe. None of the novel treatments were directly compared through head-to-head trials. The objective of this study is to perform indirect treatment comparisons (ITCs) to evaluate relative efficacy of risdiplam against novel therapies (nusinersen and AVXS-101) and best supportive care (BSC). Methods: Comparator studies that formed the evidence base were identified through a systematic literature review, data was extracted and/or digitized. Baseline prognostic and predictive factors (age, duration/onset of symptoms, baseline CHOP intend score) were compared. As appropriate, unadjusted and matching-adjusted indirect comparison (MAIC) estimates of relative efficacy were calculated. Confidence intervals were estimated using bootstrap resampling methods. Results: Comparative efficacy relative to BSC and nusinersen was evaluated against the ENDEAR study. FIREFISH and ENDEAR populations were found to be comparable in terms of prognostic and predictive factors. The matching-adjusted indirect treatment comparison suggests that risdiplam may significantly reduce the number of deaths and permanent ventilations as compared to BSC and nusinersen. The hazard ratios for Event-Free Survival were respectively 0.11 (95%CI:0.00;0.35) and 0.23 (95%CI:0.00;0.68). Unadjusted ITC analyses yielded similar results. Comparative efficacy relative to AVXS-101 was evaluated against the CL-101 trial. The FIREFISH and CL-101 populations differed in terms of prognostic and predictive factors. Due to the lack of overlap in population characteristics it was not possible to perform matchingadjusted analyses. Conclusions: Preliminary results based on the Part 1 results of the FIREFISH study suggest that treatment of infantile onset SMA with risdiplam may yield better results than nusinersen. An unbiased estimate of relative efficacy of risdiplam against AVXS-101 would require a comparison of treatments in similar patient populations.

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