[Show abstract][Hide abstract] ABSTRACT: Background—Among patients with atrial fibrillation (AF), women are at higher risk of stroke than men. Using prospective cohort data from a large global population of patients with nonvalvular AF, we sought to identify any differences in the use of anticoagulants for stroke prevention in women and men.
Methods and Results—This was a prospective multicenter observational registry with 858 randomly selected sites in 30 countries. A total of 17 184 patients with newly diagnosed (≤6 weeks) nonvalvular AF and ≥1 additional investigator-defined stroke risk factor(s) were recruited (March 2010 to June 2013). The main outcome measure was the use of anticoagulants (vitamin K antagonists, factor Xa inhibitors, and direct thrombin inhibitors) for stroke prevention at AF diagnosis. Of 17 184 patients enrolled, 43.8% were women. More women than men were at moderate-to-high risk of stroke (CHADS2 score ≥2: 65.1% versus 54.7%). Rates of anticoagulant use were not different overall (60.9% of men versus 60.8% of women) and in patients with a CHADS2 score ≥2 (adjusted odds ratio for women versus men, 1.00; 95% confidence interval, 0.92–1.09). In patients at low risk (CHA2DS2-VASc of 0 in men and 1 in women), 41.8% of men and 41.1% of women received an anticoagulant. In patients at high risk (CHA2DS2-VASc score ≥2), 35.4% of men and 38.4% of women did not receive an anticoagulant.
Conclusions—These contemporary global data show that anticoagulant use for stroke prevention is no different in men and women with nonvalvular AF. Thromboprophylaxis was, however, suboptimal in substantial proportions of men and women, with underuse in those at moderate-to-high risk of stroke and overuse in those at low risk.
[Show abstract][Hide abstract] ABSTRACT: In recent years, it has become evident that the level of guideline adherence in patients presenting with acute coronary syndrome (ACS) is highly correlated with patient outcomes. Unfortunately, guideline adherence is low in some geographic areas and especially in those patients at high-risk. Regional networks including ambulance systems and hospitals with catheterization laboratories are able to increase guideline adherence and patient outcomes by streamlining the critical pre- and intra-hospital processes as well as improving timely access to invasive procedures and recommended medication. Successful organization of an ACS network requires engagement of multiple stakeholders to create effective solutions for the specific local setting. There is no 'one-size-fits all' strategy to set-up and successfully run an ACS network. We present a framework for how to set up and organize an effective ACS network, delivering guideline-based care to improve patient outcomes.
Acute Cardiac Care 03/2014; 16(2). DOI:10.3109/17482941.2014.881502
[Show abstract][Hide abstract] ABSTRACT: Despite widespread adoption of acetylsalicylic acid and P2Y12 receptor inhibitor therapy as the standard of care for secondary event prevention in patients with acute coronary syndrome (ACS), the rate of cardiovascular death or myocardial infarction following discharge is approximately 24-31% over five years, indicating an important unmet need to reduce further the risk of recurrent ACS events. Because thrombin has a role in arterial thrombus generation, a mechanistic rationale exists for adding an anticoagulant to dual antiplatelet therapy to reduce cardiovascular event rates and mortality. The direct thrombin inhibitor dabigatran and the direct Factor Xa inhibitors rivaroxaban and apixaban have been investigated for this application, with only rivaroxaban successfully completing a phase III trial. These results suggest that dose selection is of paramount importance in this indication, with lower anticoagulant doses (relative to those used in other indications, such as stroke prevention in atrial fibrillation) plus low-dose acetylsalicylic acid potentially improving cardiovascular outcomes. This article reviews clinical trial data of anticoagulants for secondary event prevention in patients with ACS; it also discusses the mechanistic reasons that may underlie these observations and looks towards the potential impact of findings from the ATLAS ACS 2 TIMI 51 trial on clinical practice.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 03/2014; 9(11):1333-41. DOI:10.4244/EIJV9I11A224 · 3.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dual antiplatelet therapy in older vs. younger patients with acute coronary syndromes (ACS) is under-studied. Low-dose prasugrel (5mg/d) is recommended for younger, lower-body-weight ACS patients and elderly ACS patients to mitigate bleeding risk of standard-dose prasugrel (10mg/d).
9326 medically managed ACS patients from the TRILOGY trial (7243 <75y; 2083 ≥75y) were randomized to prasugrel (10mg/d; 5mg/d for those ≥75y or <75y and <60kg) or clopidogrel (75mg/d), plus aspirin, for ≤30 months. A total of 515 participants ≥75y (25% of total elderly population) had serial platelet reactivity unit (PRU) measurements in a platelet-function substudy (PFS). Cumulative risks of the primary endpoint (cardiovascular death/myocardial infarction/stroke) and TIMI major bleeding increased progressively with age and were ≥twofold higher in older participants. Among those ≥75y, TIMI-major bleeding (4.1% vs. 3.4%, HR=1.09, 95%CI: 0.57-2.08) and primary endpoint rates were similar with reduced-dose prasugrel vs. clopidogrel. Despite a correlation between lower 30-day on-treatment PRU values and lower weight only in the prasugrel group, there was a nonsignificant treatment-by-weight interaction for PRU values among participants ≥75y in the PFS (P=0.06). No differences in weight were seen in all participants ≥75y with vs. without TIMI-major/minor bleeding in both treatment groups.
Older age is associated with substantially increased long-term cardiovascular risk and bleeding among medically managed ACS patients, with no differences in ischemic or bleeding outcomes with reduced-dose prasugrel vs. clopidogrel in elderly patients. No significant interaction among weight, pharmacodynamic response, and bleeding risk was observed between reduced-dose prasugrel vs. clopidogrel in elderly patients.
http://clinicaltrials.gov/ct2/home. Identifier: NCT0069999.
[Show abstract][Hide abstract] ABSTRACT: Background
Limited data are available on the characteristics, clinical management, and outcomes of patients with atrial fibrillation at risk of stroke, from a worldwide perspective. The aim of this study was to describe the baseline characteristics and initial therapeutic management of patients with non-valvular atrial fibrillation across the spectrum of sites at which these patients are treated.
Methods and Findings
The Global Anticoagulant Registry in the FIELD (GARFIELD) is an observational study of patients newly diagnosed with non-valvular atrial fibrillation. Enrollment into Cohort 1 (of 5) took place between December 2009 and October 2011 at 540 sites in 19 countries in Europe, Asia-Pacific, Central/South America, and Canada. Investigator sites are representative of the distribution of atrial fibrillation care settings in each country. Cohort 1 comprised 10,614 adults (≥18 years) diagnosed with non-valvular atrial fibrillation within the previous 6 weeks, with ≥1 investigator-defined stroke risk factor (not limited to those in existing risk-stratification schemes), and regardless of therapy. Data collected at baseline included demographics, medical history, care setting, nature of atrial fibrillation, and treatments initiated at diagnosis. The mean (SD) age of the population was 70.2 (11.2) years; 43.2% were women. Mean±SD CHADS2 score was 1.9±1.2, and 57.2% had a score ≥2. Mean CHA2DS2-VASc score was 3.2±1.6, and 8,957 (84.4%) had a score ≥2. Overall, 38.0% of patients with a CHADS2 score ≥2 did not receive anticoagulant therapy, whereas 42.5% of those at low risk (score 0) received anticoagulant therapy.
These contemporary observational worldwide data on non-valvular atrial fibrillation, collected at the end of the vitamin K antagonist-only era, indicate that these drugs are frequently not being used according to stroke risk scores and guidelines, with overuse in patients at low risk and underuse in those at high risk of stroke.
PLoS ONE 05/2013; 8(5):e63479. DOI:10.1371/journal.pone.0063479 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: To determine if rivaroxaban is associated with a reduction in stent thrombosis among ACS subjects in the ATLAS ACS 2-TIMI 51 trial. BACKGROUND: Dual antiplatelet therapy has been the mainstay of efforts to prevent stent thrombosis. Since thrombin is a potent stimulant of platelet activation, we hypothesized that inhibition of thrombin generation via factor Xa inhibition may further reduce the risk of stent thrombosis. METHODS: ATLAS ACS 2-TIMI 51 was a placebo-controlled trial that randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. RESULTS: Among subjects who had a stent placed prior to or at the time of the index event, rivaroxaban significantly reduced independently adjudicated Academic Research Consortium (ARC) definite and probable stent thrombosis in the pooled (1.9% vs. 1.5%, HR 0.65, p=0.017) and the 2.5 mg BID (1.9% vs. 1.5%, HR 0.61, p=0.023) treatment groups when compared to placebo, with a trend toward a reduction in the 5 mg BID treatment group (1.9% vs. 1.5%, HR 0.70, p=0.089). Among subjects who received both aspirin and a thienopyridine (Stratum 2), the benefit of rivaroxaban emerged during the period of active treatment with dual antiplatelet therapy (HR 0.68, 95% CI 0.50-0.92, combined rivaroxaban group vs. placebo). Among stented subjects who were treated with dual antiplatelet therapy, there was a mortality reduction among those treated with 2.5 mg BID of rivaroxaban (HR 0.56, 95% CI 0.35-0.89, p=0.014). CONCLUSIONS: Among stented ACS patients treated with dual antiplatelet therapy, the administration of 2.5 mg BID of rivaroxaban is associated with a reduction in stent thrombosis and mortality. CLINICAL TRIAL ID: NCT00809965.
Journal of the American College of Cardiology 04/2013; 62(4). DOI:10.1016/j.jacc.2013.03.041 · 16.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atrial fibrillation (AF) is strongly associated with cardioembolic stroke, and thromboprophylaxis is an established means of reducing stroke risk in patients with AF. Oral vitamin K antagonists such as warfarin have been the mainstay of therapy for stroke prevention in patients with AF. However, they are associated with a number of limitations, including excessive bleeding when not adequately controlled. Antiplatelet agents do not match vitamin K antagonists in terms of their preventive efficacy. Dual-antiplatelet therapy (clopidogrel and acetylsalicylic acid) or combined antiplatelet-vitamin K antagonist therapy in AF has also failed to provide convincing evidence of their additional benefit over vitamin K antagonists alone. Novel oral anticoagulants, including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban, apixaban, and edoxaban, have now been approved or are currently in late-stage clinical development in AF. These newer agents may provide a breakthrough in the optimal management of stroke risk.
[Show abstract][Hide abstract] ABSTRACT: Atrial fibrillation (AF) is associated with high rates of morbidity and mortality. Patients with AF carry a fivefold increased risk of stroke and the risk of death from AF-related stroke is doubled. Current management is often inadequate, leaving patients at risk for a potentially fatal or disabling event. The purpose of the GARFIELD registry is to evaluate the management and outcomes of patients with newly diagnosed non-valvular AF at risk for stroke.
The GARFIELD registry is an observational, multicenter, prospective study of patients with newly diagnosed AF and one or more additional risk factors for stroke. The aim is to enroll 55,000 patients at >1,000 centers in 50 countries. Enrollment will take place in five independent, sequential, prospective cohorts. An additional retrospective validation cohort of 5,000 patients with established AF and at least one additional risk factor for stroke will be conducted in parallel with cohort one. The study started in December 2009, with a planned recruitment period of 4 years and a minimum of 2-year follow-up for each patient.
The GARFIELD registry will provide valuable insights into the clinical management and related outcomes of AF patients throughout many regions of the world and across the spectrum of healthcare systems. By capturing data from unselected patients treated in everyday practice, the registry has the potential to identify best practices as well as deficiencies in available treatment options for specific patient populations and to describe how therapeutic strategies, patient care, and outcomes will evolve over time.
American heart journal 01/2012; 163(1):13-19.e1. DOI:10.1016/j.ahj.2011.09.011 · 4.46 Impact Factor