Complement Therapeutics in Autoimmune Disease.

Many autoimmune diseases are characterized by generation of autoantibodies that bind to host proteins or deposit within tissues as a component of immune complexes. The autoantibodies can activate the complement system, which can mediate tissue damage and trigger systemic inflammation. Complement inhibitory drugs may, therefore, be beneficial across a large number of different autoimmune diseases. Many new anti-complement drugs that target specific activation mechanisms or downstream activation fragments are in development. Based on the shared pathophysiology of autoimmune diseases, some of these complement inhibitory drugs may provide benefit across multiple different diseases. In some antibody-mediated autoimmune diseases, however, unique features of the autoantibodies, the target antigens, or the affected tissues may make it advantageous to block individual components or pathways of the complement system. This paper reviews the evidence that complement is involved in various autoimmune diseases, as well as the studies that have examined whether or not complement inhibitors are effective for treating these diseases.

Interventions for Preventing Thromboembolic Events in Patients With Atrial Fibrillation: A Systematic Review.

Background: The comparative safety and effectiveness of treatments to prevent thromboembolic complications in atrial fibrillation (AF) remain uncertain. Purpose: To compare the effectiveness of medical and procedural therapies in preventing thromboembolic events and bleeding complications in adults with nonvalvular AF. Data Sources: English-language studies in several databases from 1 January 2000 to 14 February 2018. Study Selection: Two reviewers independently screened citations to identify comparative studies of treatments to prevent stroke in adults with nonvalvular AF who reported thromboembolic or bleeding complications. Data Extraction: Two reviewers independently abstracted data, assessed study quality and applicability, and rated strength of evidence. Data Synthesis: Data from 220 articles were included. Dabigatran and apixaban were superior and rivaroxaban and edoxaban were similar to warfarin in preventing stroke or systemic embolism. Apixaban and edoxaban were superior and rivaroxaban and dabigatran were similar to warfarin in reducing the risk for major bleeding. Treatment effects with dabigatran were similar in patients with renal dysfunction (interaction P > 0.05), and patients younger than 75 years had lower bleeding rates with dabigatran (interaction P < 0.001). The benefit of treatment with apixaban was consistent in many subgroups, including those with renal impairment, diabetes, and prior stroke (interaction P > 0.05 for all). The greatest bleeding risk reduction was observed in patients with a glomerular filtration rate less than 50 mL/min/1.73 m2 (P = 0.003). Similar treatment effects were observed for rivaroxaban and edoxaban in patients with prior stroke, diabetes, or heart failure (interaction P > 0.05 for all). Limitation: Heterogeneous study populations, interventions, and outcomes. Conclusion: The available direct-acting oral anticoagulants (DOACs) are at least as effective and safe as warfarin for patients with nonvalvular AF. The DOACs had similar benefits across several patient subgroups and seemed safe and efficacious for a wide range of patients with nonvalvular AF. Primary Funding Source: Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42017069999).

Predicting Thromboembolic and Bleeding Event Risk in Patients with Non-Valvular Atrial Fibrillation: A Systematic Review.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of stroke. Medical therapy for decreasing stroke risk involves anticoagulation, which may increase bleeding risk for certain patients. In determining the optimal therapy for stroke prevention for patients with AF, clinicians use tools with various clinical, imaging and patient characteristics to weigh stroke risk against therapy-associated bleeding risk. AIM: This article reviews published literature and summarizes available risk stratification tools for stroke and bleeding prediction in patients with AF. METHODS: We searched for English-language studies in PubMed, Embase and the Cochrane Database of Systematic Reviews published between 1 January 2000 and 14 February 2018. Two reviewers screened citations for studies that examined tools for predicting thromboembolic and bleeding risks in patients with AF. Data regarding study design, patient characteristics, interventions, outcomes, quality, and applicability were extracted. RESULTS: Sixty-one studies were relevant to predicting thromboembolic risk and 38 to predicting bleeding risk. Data suggest that CHADS2, CHA2DS2-VASc and the age, biomarkers, and clinical history (ABC) risk scores have the best evidence for predicting thromboembolic risk (moderate strength of evidence for limited prediction ability of each score) and that HAS-BLED has the best evidence for predicting bleeding risk (moderate strength of evidence). LIMITATIONS: Studies were heterogeneous in methodology and populations of interest, setting, interventions and outcomes analysed. CONCLUSION: CHADS2, CHA2DS2-VASc and ABC scores have the best prediction for stroke events, and HAS-BLED provides the best prediction for bleeding risk. Future studies should define the role of imaging tools and biomarkers in enhancing the accuracy of risk prediction tools. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute (PROSPERO #CRD42017069999).

Diagnostic Accuracy of Screening Tests and Treatment for Post-Acute Coronary Syndrome Depression: A Systematic Review.

BACKGROUND: Patients who have had an acute coronary syndrome (ACS) event have an increased risk for depression. PURPOSE: To evaluate the diagnostic accuracy of depression screening instruments and to compare safety and effectiveness of depression treatments in adults within 3 months of an ACS event. DATA SOURCES: MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane Database of Systematic Reviews from January 2003 to August 2017, and a manual search of citations from key primary and review articles. STUDY SELECTION: English-language studies of post-ACS patients that evaluated the diagnostic accuracy of depression screening tools or compared the safety and effectiveness of a broad range of pharmacologic and nonpharmacologic depression treatments. DATA EXTRACTION: 2 investigators independently screened each article for inclusion; abstracted the data; and rated the quality, applicability, and strength of evidence. DATA SYNTHESIS: Evidence from 6 of the 10 included studies showed that a range of depression screening instruments produces acceptable levels of diagnostic sensitivity, specificity, and negative predictive values (70% to 100%) but low positive predictive values (below 50%). The Beck Depression Inventory-II was the most studied tool. A large study found that a combination of cognitive behavioral therapy (CBT) and antidepressant medication improved depression symptoms, mental health-related function, and overall life satisfaction more than usual care. LIMITATION: Few studies, no evaluation of the influence of screening on clinical outcomes, and no studies addressing several clinical interventions of interest. CONCLUSION: Depression screening instruments produce diagnostic accuracy metrics that are similar in post-ACS patients and other clinical populations. Depression interventions have an uncertain effect on cardiovascular outcomes, but CBT combined with antidepressant medication produces modest improvement in psychosocial outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality (PROSPERO: CRD42016047032).