Cecilia Bahit

A clustered randomized trial to IMProve treatment with AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AF): design and rationale

Atrial fibrillation (AF) is common, increasing as the population ages, and a major cause of embolic stroke. While oral anticoagulation (OAC) is highly effective at preventing stroke in patients with AF, it continues to be underused in eligible patients worldwide. The objective of this prospective, cluster randomized controlled trial (IMPACT-AF; ClinicalTrials.gov #NCT02082548) is to determine whether a comprehensive customized intervention will increase the rate and persistence of use of OAC in patients with AF. IMPACT-AF will be conducted in approximately 50 centers in 5 low- to middle-income countries. Before randomization, sites within countries will be paired to match in size, practice type and baseline rate of OAC use. Site pairs will be randomized to intervention versus control. In total, 40 to 70 patients with AF and at least 2 CHA2DS2-VASc risk factors will be enrolled at each site using a consecutive enrollment strategy, with the goal of capturing actual practice patterns. We aim for patients with a new diagnosis of AF to comprise at least 30% of the study cohort. Assuming an average baseline OAC use of 60% and a post-intervention use of 70% with a post-control rate of 60%, there will be roughly 94-98% power with 25 clusters per group (intracluster correlation coefficient of 0.02). While this trial focuses on improving treatment use and reducing preventable strokes, we also aim to better understand the reasons for OAC underuse. This will improve the intervention with the goal of creating educational recommendations to improve care for patients with AF.

Regional differences in presentation and antithrombotic treatment of patients with atrial fibrillation: Baseline characteristics from a clustered randomized trial to IMProve treatment with AntiCoagulanTs in patients with atrial fibrillation (IMPACT-AF)

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. However, there are few contemporary comparative data on AF from middle-income countries. METHODS Baseline characteristics of the IMPACT-AF trial were analyzed to assess regional differences in presentation and antithrombotic treatment of AF from 5 middle-income countries (Argentina, Brazil, China, India, and Romania) and factors associated with antithrombotic treatment prescription. RESULTS IMPACT-AF enrolled 2281 patients (69 ± 11 years, 47% women) at 48 sites. Overall, 66% of patients were on anticoagulation at baseline, ranging from 38% in China to 91% in Brazil. The top 3 reasons for not prescribing an anticoagulant were patient preference/refusal (26%); concomitant antiplatelet therapy (15%); and risks outweighing the benefits, as assessed by the physician (13%). In a multivariable model, the most significant factors associated with prescription of oral anticoagulants were no prior major bleeding (odds ratio [OR] = 4.34; 95% CI = 2.22-8.33), no alcohol abuse (OR = 2.27; 95% CI = 1.12-4.55), and history of rheumatic valvular heart disease (OR = 2.10; 95% CI = 1.36-3.26), with a strong predictive accuracy (c statistic = 0.85), whereas the most significant factors associated with prescription of a combination of oral anticoagulants and antiplatelet drugs were prior coronary revascularization (OR = 5.10; 95% CI = 2.88-9.05), prior myocardial infarction (OR = 2.24; 95% CI = 1.38-3.63), and no alcohol abuse (OR = 2.22; 95% CI = 1.11-4.55), with a good predictive accuracy (c statistic = 0.76). CONCLUSIONS IMPACT-AF provides contemporary data from 5 middle-income countries regarding antithrombotic treatment of AF. Lack of prior major bleeding and coronary revascularization were the most important factors associated with prescription of oral anticoagulants and their combination with antiplatelet drugs, respectively.

Cardiovascular clinical research in South America

In recent years, international clinical trials have increasingly included large numbers of patients and research sites from developing countries. In South America particularly, enrollment in randomized clinical trials has increased substantially. Despite this significant growth of late, there has been little systematic assessment of the role of this region in cardiovascular clinical trials. South America has several strengths with respect to conducting and participating in clinical trials. These include a large population, a high prevalence of cardiovascular diseases, reliable quality of data, a track record of important contributions to previous clinical trials, and good patient adherence and retention in trials. Labor costs also tend to be lower than those in high-income countries. On the other hand, clinical research in this region of the world faces limitations posed by a relatively small clinical trials network with limited operations expertise, as well as prolonged regulatory approval timelines, diversity in health care systems, limited training opportunities in clinical research, and a low patient level of education. Thus, there are many opportunities to improve the conduct of clinical research in South America, but strategies and systems must be developed to overcome barriers in this economically growing region and to establish a robust infrastructure for clinical trials, including high-quality investigator networks.

An international cluster randomized quality-improvement trial to increase the adherence to evidence-based therapies for acute ischemic stroke and transient ischemic attack patients: Rationale and design of the BRIDGE STROKE trial

Background Translating evidence into clinical practice in the management of acute ischemic stroke (AIS) and transient ischemic attack (TIA) is challenging especially in low‐ and middle‐income countries. Objectives The aim of this study is to assess the effect of a multifaceted quality improvement intervention on adherence to evidence‐based therapies for AIS and TIA patients care. Design We designed a pragmatic, 2‐arm cluster‐randomized trial involving 36 clusters and 1624 patients from Brazil, Argentina, and Peru. Hospitals are randomized to receive a multifaceted quality improvement intervention (intervention group) or to routine care (control group). The BRIDGE Stroke multifaceted quality improvement intervention includes case management, reminders, health care providers’ educational materials (including treatment algorithms), interactive workshops, and audit and feedback reports. Primary outcome is a composite adherence score to AIS and TIA performance measures. Secondary outcomes include an “all or none” composite end point to performance measures, the individual components of the composite end points, and clinical outcomes at 90 days following admission (stroke recurrence, death, and disability measured by the modified Rankin scale). Summary The BRIDGE Stroke Trial is an international pragmatic evaluation of a multifaceted quality improvement intervention. If effective, this intervention could be potentially extended widely to improve the quality of care and outcomes of patients with AIS or TIA.