Christine Teutsch

Antithrombotic Treatment Patterns in Patients with Newly Diagnosed Nonvalvular Atrial Fibrillation: The GLORIA-AF Registry, Phase II

BACKGROUND The Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) was designed to provide prospectively collected information on patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke, with the aim of addressing treatment patterns and questions of effectiveness and safety. METHODS AND RESULTS In this predefined analysis from GLORIA-AF, the baseline characteristics and initial antithrombotic management of the first 10,000 patients in Phase II of this large Registry Program are presented. Overall, 32.3% of patients received vitamin K antagonists (VKAs) and 47.7% received non-VKA oral anticoagulants (NOACs), while 12.3% received antiplatelet treatment and 7.6% did not receive any antithrombotic treatment. Among patients with CHA2DS2-VASc score ≥2, 6.7% received no antithrombotic treatment and 10.0% received aspirin. In Europe, treatment with dabigatran was as common as treatment with VKAs (38.8% and 37.8%, respectively). More than half of the patients were treated with NOACs (52.4%), while antiplatelet treatment was given to 5.7%, and 4.1% did not receive any antithrombotic treatment. In North America, treatment with dabigatran (25.0%) was as common as with VKAs (26.1%), but overall NOAC use was more common (52.1%) than with VKAs (26.1%); however, 14.1% received antiplatelet treatment, while 7.6% received no antithrombotic treatment. In Asia, treatment with VKAs (31.9%) was more prevalent than NOACs (25.5%), but antiplatelet treatment was given to 25.8%, and 16.9% did not receive any antithrombotic treatment. In Asia, only 60.7% of patients with high stroke risk received oral anticoagulants (OACs). Paroxysmal atrial fibrillation and minimally symptomatic (or asymptomatic) patients were often undertreated with OACs. CONCLUSION In this analysis, OAC use was high in Europe and North America, with overall NOAC use higher than VKA use. A considerable percentage of high-risk patients in North America still received antiplatelet treatment or were untreated, while Asian patients had a high proportion of aspirin use and nontreatment.

Design and rationale of Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation: A global registry program on long-term oral antithrombotic treatment in patients with atrial fibrillation

BACKGROUND Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting 1% to 2% of the population and raising the risk of stroke 5-fold. Until recently, the only treatment choices for stroke prevention in patients with AF have been vitamin K antagonists (VKA) or antiplatelet drugs. With approval of novel oral anticoagulants (NOACs) antithrombotic treatment, patterns are changing. The Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation is designed to investigate patient characteristics influencing choice of antithrombotic treatment of stroke prevention in patients with nonvalvular AF and to collect data on outcomes of antithrombotic therapy in clinical practice. METHODS The GLORIA-AF is a large, international, observational registry involving patients with newly diagnosed nonvalvular AF at risk for stroke, enrolling up to 56,000 patients in nearly 50 countries. We will collect and analyze data from routine care using an inception cohort design. Phase I includes patients before approval of NOACs. Phase II, beginning early after approval of dabigatran, monitors dabigatran safety and addresses potential channeling across treatment options based on propensity scoring to assess comparability of baseline characteristics of patients treated with dabigatran or VKA. Phase III entails analysis of large treatment groups, adjusting for differences in propensity score, to provide information about the relative effectiveness and safety of NOACs and VKA in routine clinical care. CONCLUSIONS Novel features of this registry program will add data from clinical practice to those from randomized trials to expand knowledge of antithrombotic treatment in patients with AF.

Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort

Aims The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice. Methods and results In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME. Conclusion Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment.

Regional Differences in Antithrombotic Treatment for Atrial Fibrillation: Insights from the GLORIA-AF Phase II Registry

Introduction  Although guideline-adherent antithrombotic therapy (ATT) for stroke prevention in atrial fibrillation (AF) is associated with lower mortality and thromboembolism, ATT uptake shows geographic variation worldwide. We aimed to assess thromboembolic risk and baseline ATT by geographic region and identify factors associated with prescription of ATT in a large, truly global registry of patients with recently diagnosed AF. Methods and Results  Our analysis comprises 15,092 patients newly diagnosed with non-valvular AF at risk for stroke, enrolled in Phase II of Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF). Global oral anticoagulation (OAC) use was 79.9%, being highest in Europe (90.1%), followed by Africa/Middle East (87.4%) and Latin America (85.3%), North America (78.3%) and Asia (55.2%). Among OAC users, vitamin K antagonists (VKAs) have been replaced by non-VKA OACs (NOACs) as the more prevalent OAC option in all regions, with highest use in North America (66.5%) and lowest in Asia (50.2%). In Asia, OAC was 80.4% in community hospitals but only 49.8% in university hospitals and 42.6% in specialist offices, and varied from 21.0% in China to 89.7% in Japan (NOACs at 5.8% in China and 83.3% in Japan). Globally, 76.5% of low-risk patients were prescribed ATT (46.1% OAC), whereas 17.7% high-risk patients were not anticoagulated (Europe 8.8%; North America 18.9%; Asia 42.4%). Conclusion  Substantial inter- and intra-regional differences in ATT for stroke prevention in AF are evident in this global registry. While guideline-adherent ATT can be further improved, NOACs are the main contributor to high OAC use worldwide.

Telmisartan regresses left ventricular hypertrophy in caveolin-1-deficient mice

The role of angiotensin II (Ang II) in promoting cardiac hypertrophy is well known; however, its role in a spontaneous model of hypertrophy in mice lacking the protein caveolin-1 (Cav-1 KO) has not been explored. In this study, WT and Cav-1 KO mice were treated with angiotensin receptor blocker (ARB), telmisartan (Telm), and cardiac function was assessed by echocardiography. Treatment of Cav-1 KO mice with Telm significantly improved cardiac function compared with age-matched vehicle-treated Cav-1 KO mice, whereas Telm did not affect cardiac function in WT mice. Both left ventricular (LV) weight to body weight ratios and LV to tibial length ratios were also reverted by Telm in Cav-1 KO but not in WT mice. LV hypertrophy was associated with increased expression of natriuretic peptides A and B, β-myosin heavy chain and TGF-β, and Telm treatment normalized the expression of these genes. Telm reduced the expression of collagen genes (Col1A and Col3A) and associated perivascular fibrosis in intramyocardial vessels in Cav-1 KO mice. In conclusion, Telm treatment reduces indexes of cardiac hypertrophy in this unique genetic model of spontaneous LV hypertrophy.

Two-year follow-up of patients treated with dabigatran for stroke prevention in atrial fibrillation: Global Registry on Long-Term Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry

Background and purpose GLORIA‐AF is a large, global, prospective registry program of newly diagnosed atrial fibrillation (AF) patients with ≥1 stroke risk factors. We describe the effectiveness and safety of dabigatran etexilate over 2 years from routine clinical practice in nearly 3000 patients from GLORIA‐AF who are newly diagnosed with non‐valvular AF and at risk of stroke. Methods Consecutive enrollment into phase II of GLORIA‐AF was initiated following approval of dabigatran for stroke prevention in non‐valvular AF. Within this Phase II, 2937 dabigatran patients completed 2‐year follow‐up by May 2016 and were eligible for analysis. Patients who took at least 1 dose of dabigatran (n = 2932) were used to estimate incidence rates. Results Overall incidence rates per 100 person‐years of 0.63 (95% confidence interval [CI], 0.42‐0.92) for stroke, 1.12 (0.83‐1.49) for major bleeding, 0.47 (0.29‐0.72) for myocardial infarction, and 2.69 (2.22‐3.23) for all‐cause death were observed. For patients taking 150 mg dabigatran twice daily (BID), corresponding rates (95% CI) were 0.56 (0.30‐0.94), 1.00 (0.64‐1.47), 0.48 (0.25‐0.83), and 2.07 (1.55‐2.72), respectively. For patients taking 110 mg dabigatran BID, event rates (95% CI) were 0.67 (0.33‐1.20), 1.16 (0.70‐1.80), 0.43 (0.17‐0.88), and 3.16 (2.36‐4.15). Conclusions These global data confirm the sustained safety and effectiveness of dabigatran over 2 years of follow‐up, consistent with the results from clinical trials as well as contemporary real‐world studies. What is known • Non–vitamin K antagonist (VKA) anticoagulants (NOACs) are the preferred therapy for prevention of ischemic stroke based on phase 3 trials, but there is insufficient information on their efficacy and safety in daily practice, based on prospectively collected data. What is new • This study shows that in non‐valvular AF patient population, with up to 2 years of follow‐up, the use of dabigatran led to a low incidence of ischemic stroke, major bleeding, and myocardial infarction in routine clinical care, confirming the sustained safety and effectiveness of dabigatran in clinical practice over 2 years of follow‐up.

INCREASED RATE OF PREVIOUS STROKE IN ASYMPTOMATIC/MINIMALLY SYMPTOMATIC VERSUS SYMPTOMATIC PATIENTS WITH NEWLY DETECTED ATRIAL FIBRILLATION WORLDWIDE: RESULTS FROM THE GLORIA-AF REGISTRY

Background: GLORIA-AF is a global, observational, registry program involving up to 56,000 patients (pts.) with newly diagnosed, non-valvular atrial fibrillation (NVAF) at risk for stroke in 44 countries worldwide. The aim of this sub-analysis was to compare patient characteristics between

Clinical InvestigationsTwo-year follow-up of patients treated with dabigatran for stroke prevention in atrial fibrillation: GLORIA-AF Registry☆

Background and purpose GLORIA‐AF is a large, global, prospective registry program of newly diagnosed atrial fibrillation (AF) patients with ≥1 stroke risk factors. We describe the effectiveness and safety of dabigatran etexilate over 2 years from routine clinical practice in nearly 3000 patients from GLORIA‐AF who are newly diagnosed with non‐valvular AF and at risk of stroke. Methods Consecutive enrollment into phase II of GLORIA‐AF was initiated following approval of dabigatran for stroke prevention in non‐valvular AF. Within this Phase II, 2937 dabigatran patients completed 2‐year follow‐up by May 2016 and were eligible for analysis. Patients who took at least 1 dose of dabigatran (n = 2932) were used to estimate incidence rates. Results Overall incidence rates per 100 person‐years of 0.63 (95% confidence interval [CI], 0.42‐0.92) for stroke, 1.12 (0.83‐1.49) for major bleeding, 0.47 (0.29‐0.72) for myocardial infarction, and 2.69 (2.22‐3.23) for all‐cause death were observed. For patients taking 150 mg dabigatran twice daily (BID), corresponding rates (95% CI) were 0.56 (0.30‐0.94), 1.00 (0.64‐1.47), 0.48 (0.25‐0.83), and 2.07 (1.55‐2.72), respectively. For patients taking 110 mg dabigatran BID, event rates (95% CI) were 0.67 (0.33‐1.20), 1.16 (0.70‐1.80), 0.43 (0.17‐0.88), and 3.16 (2.36‐4.15). Conclusions These global data confirm the sustained safety and effectiveness of dabigatran over 2 years of follow‐up, consistent with the results from clinical trials as well as contemporary real‐world studies. What is known • Non–vitamin K antagonist (VKA) anticoagulants (NOACs) are the preferred therapy for prevention of ischemic stroke based on phase 3 trials, but there is insufficient information on their efficacy and safety in daily practice, based on prospectively collected data. What is new • This study shows that in non‐valvular AF patient population, with up to 2 years of follow‐up, the use of dabigatran led to a low incidence of ischemic stroke, major bleeding, and myocardial infarction in routine clinical care, confirming the sustained safety and effectiveness of dabigatran in clinical practice over 2 years of follow‐up.

Two-year follow-up of patients treated with dabigatran for stroke prevention in atrial fibrillation: GLORIA-AF Registry

Background and purpose GLORIA‐AF is a large, global, prospective registry program of newly diagnosed atrial fibrillation (AF) patients with ≥1 stroke risk factors. We describe the effectiveness and safety of dabigatran etexilate over 2 years from routine clinical practice in nearly 3000 patients from GLORIA‐AF who are newly diagnosed with non‐valvular AF and at risk of stroke. Methods Consecutive enrollment into phase II of GLORIA‐AF was initiated following approval of dabigatran for stroke prevention in non‐valvular AF. Within this Phase II, 2937 dabigatran patients completed 2‐year follow‐up by May 2016 and were eligible for analysis. Patients who took at least 1 dose of dabigatran (n = 2932) were used to estimate incidence rates. Results Overall incidence rates per 100 person‐years of 0.63 (95% confidence interval [CI], 0.42‐0.92) for stroke, 1.12 (0.83‐1.49) for major bleeding, 0.47 (0.29‐0.72) for myocardial infarction, and 2.69 (2.22‐3.23) for all‐cause death were observed. For patients taking 150 mg dabigatran twice daily (BID), corresponding rates (95% CI) were 0.56 (0.30‐0.94), 1.00 (0.64‐1.47), 0.48 (0.25‐0.83), and 2.07 (1.55‐2.72), respectively. For patients taking 110 mg dabigatran BID, event rates (95% CI) were 0.67 (0.33‐1.20), 1.16 (0.70‐1.80), 0.43 (0.17‐0.88), and 3.16 (2.36‐4.15). Conclusions These global data confirm the sustained safety and effectiveness of dabigatran over 2 years of follow‐up, consistent with the results from clinical trials as well as contemporary real‐world studies. What is known • Non–vitamin K antagonist (VKA) anticoagulants (NOACs) are the preferred therapy for prevention of ischemic stroke based on phase 3 trials, but there is insufficient information on their efficacy and safety in daily practice, based on prospectively collected data. What is new • This study shows that in non‐valvular AF patient population, with up to 2 years of follow‐up, the use of dabigatran led to a low incidence of ischemic stroke, major bleeding, and myocardial infarction in routine clinical care, confirming the sustained safety and effectiveness of dabigatran in clinical practice over 2 years of follow‐up.