Background 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. Design 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. Summary 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.
Objectives The aim of this study was to determine if rivaroxaban is associated with a reduction in stent thrombosis among patients with acute coronary syndromes (ACS) in the ATLAS-ACS 2 TIMI 51 ...(Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome—Thrombolysis in Myocardial Infarction 51) trial. Background Dual antiplatelet therapy (DAPT) has been the mainstay of efforts to prevent stent thrombosis. Because 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 The ATLAS-ACS 2 TIMI 51 study was a placebo-controlled trial that randomly assigned 15,526 patients with recent ACS 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 patients who had a stent placed before or at the time of the index event, rivaroxaban significantly reduced independently adjudicated Academic Research Consortium definite and probable stent thrombosis in the pooled (1.9% vs. 1.5%; hazard ratio HR: 0.65; p = 0.017) and the 2.5 mg twice-daily (1.9% vs. 1.5%; HR: 0.61; p = 0.023) treatment groups when compared with placebo, with a trend toward a reduction in the 5 mg twice-daily treatment group (1.9% vs. 1.5%; HR: 0.70; p = 0.089). Among patients who received both aspirin and a thienopyridine (stratum 2), the benefit of rivaroxaban emerged during the period of active treatment with DAPT (HR: 0.68; 95% CI: 0.50 to 0.92, combined rivaroxaban group vs. placebo). Among stented patients who were treated with dual antiplatelet therapy, there was a mortality reduction among those treated with twice-daily rivaroxaban 2.5 mg (HR: 0.56; 95% CI: 0.35 to 0.89; p = 0.014). Conclusions Among stented patients with ACS treated with DAPT, the administration of twice-daily rivaroxaban 2.5 mg was associated with a reduction in stent thrombosis and mortality. (An Efficacy and Safety Study for Rivaroxaban in Patients With Acute Coronary Syndrome; NCT00809965 )
Background Antiplatelet therapy with clopidogrel and acetylsalicylic acid (ASA) reduces major cardiovascular events in patients with ST and non–ST-segment-elevation acute coronary syndromes (ACS). ...Recent mechanistic and clinical data suggest that higher loading and maintenance doses of clopidogrel may achieve a more rapid and greater degree of platelet inhibition that translates into improved clinical outcomes, but this is yet to be formally evaluated in an adequately powered randomized trial. Objectives To evaluate the efficacy and safety of (1) a higher loading and initial maintenance dose of clopidogrel compared with the standard-dose regimen and (2) high-dose ASA compared with low-dose ASA in patients with ST or non–ST-segment-elevation ACS managed with an early invasive strategy. Design Multicenter, international, randomized, 2×2 factorial design trial evaluating a clopidogrel high-dose regimen (600 mg loading dose on day 1 followed by 150 mg once daily on days 2 to 7, followed by 75 mg once daily on days 8-30) compared with the standard-dose regimen (300 mg loading dose on day 1, followed by 75 mg once daily on days 2-30) and high-dose ASA (300-325 mg daily) versus low-dose ASA (75-100 mg daily) in patients with ST or non–ST-segment-elevation ACS managed with an early invasive strategy. The clopidogrel dose comparison is double-blind and the ASA dose comparison is open-label. The primary outcome is the composite of death from cardiovascular causes, myocardial (re)infarction or stroke up to day 30. The primary safety outcome is major bleeding. The sample size is 18,000 to 20,000 patients. Conclusions The CURRENT-OASIS 7 trial will help to define optimal dosing regimens for clopidogrel and ASA in patients with ST and non–ST-segment-elevation ACS treated with an early invasive strategy.
The greater mortality observed in women compared to men after acute myocardial infarction remains unexplained. Using an analysis of pairs, matched on a conditional probability of being male ...(propensity score), we assessed the effect of the baseline characteristics and management on 30-day mortality. Consecutive patients were included from January 2006 to December 2007. Two propensity scores (for being male) were calculated, 1 from the baseline characteristics and 1 from both the baseline characteristics and treatment. Two matched cohorts were composed using 1:1 matching and computed using the best 8 digits of the propensity score. Paired analyses were performed using conditional regression analysis. During the study period, 3,510 patients were included in the registry; 1,119 (32%) were women. Compared to the men, the women were 10 years older, had more co-morbidities, less often underwent angiography and reperfusion, and received less medical treatment. The 30-day mortality rate was 12.3% (130 of 1,060) for the women and 7.2% (167 of 2,324) for the men (p <0.001). The 2 matched populations represented 1,298 and 1,168 patients. After matching using the baseline characteristics, the only difference in treatment was a lower rate of angiography and reperfusion, with a trend toward greater 30-day mortality in women. After matching using both baseline characteristics and treatment, the 30-day mortality was similar for the men and women, suggesting that the increased use of invasive procedures in women could potentially be beneficial. In conclusion, compared to men, the 30-day mortality is greater in women and explained primarily by differences in baseline characteristics and to a lesser degree by differences in management. The difference in the use of invasive procedures persisted after matching by characteristics. In contrast, after matching using the baseline characteristics and treatment, the 30-day mortality was comparable across the genders.
In patients admitted with acute coronary syndromes, those with anemia are at higher risk. However, current risk score systems do not take into account the presence of anemia. The impact of anemia on ...mortality was studied, and its incremental predictive value was evaluated. Demographic, clinical, and biologic characteristics at admission, as well as treatments and mortality, were recorded for 1,410 consecutive patients with acute coronary syndromes. The incremental value of adding anemia information to risk score evaluation was determined using changes in the appropriateness of Cox models when anemia was added. Anemia was detected in 381 patients (27%). They were older, had more co-morbidities, had higher Global Registry of Acute Coronary Events (GRACE) risk scores, received fewer guideline-recommended treatments, and, as a result, had 4-fold higher mortality. When included in a prediction model based on the GRACE risk score, anemia remained an independent predictor of mortality. The addition of anemia improved both the discriminatory capacity and calibration of the models. According to the GRACE risk score, the population was divided into 4 groups of different risk levels of <1%, 1% to <5%, 5% to <10%, and ≥10%. The addition of anemia to the model made it possible to reclassify 9%, 43%, 47%, and 23% of patients into the different risk categories, respectively. In conclusion, our data confirmed that anemia was an independent predictive factor of mortality and had incremental predictive value to the GRACE score system for early clinical outcomes.
Rationale An increase in albuminuria occurs in the early days after acute myocardial infarction. The aim of this study was to assess the relation between albuminuria and 30-day mortality, as well as ...its incremental predictive value, on top of established prognostic parameters. Methods and results Demographic, clinical, and biological characteristics at admission, as well as in-hospital treatments and 1-month survival, were recorded in 1,211 consecutive patients admitted for acute myocardial infarction. Albuminuria was assessed from an 8-hour overnight urine collection within the first 2 days using immunonephelemetry. The population was categorized into 3 groups according to albuminuria levels (<20, 20-200, and >200 μg/min). Among survivors on day 2, 52% (625/1,211) of patients had an albuminuria level <20 μg/min, 39% (477) between 20 and 200 μg/min, and 9% (109) >200 μg/min. High levels of albuminuria were associated with older age, peripheral vessel disease, systolic blood pressure, glucose, creatinine, troponin, B-type natriuretic peptide, and high-sensitivity C reactive protein levels, as well as use of angiography, angiotensin-converting enzyme inhibitors, and β blockers. At 1 month, there was a significantly higher mortality rate in groups with higher albuminuria. After adjustment for baseline characteristics, patients with albuminuria level of >20 μg/min had a 2.7-fold higher 30-day mortality, and those with >200 μg/min had an almost 4-fold higher 30-day mortality compared to those with albuminuria level of <20 μg/min. The addition of albuminuria information improved the discrimination capacity of the model and the global risk prediction. Conclusions Albuminuria level, taken as a quantitative or categorical variable, is an independent and powerful predictor of mortality after acute myocardial infarction.
Background The OASIS-5 (Organization to Assess Strategies in Ischemic Syndromes-5) trial demonstrated that fondaparinux was noninferior to enoxaparin while reducing the risk of bleeding by 50%. The ...objectives of our study were to assess the effects of fondaparinux compared to enoxaparin in patients stratified by their Global Registry of Acute Coronary Events (GRACE) score and to examine the ability of the GRACE score to predict bleeding in patients with acute coronary syndromes (ACS). Methods We analyzed efficacy and safety according to the GRACE admission risk score. Results The impact of fondaparinux versus enoxaparin on the primary outcome of death, myocardial infarction, and refractory ischemia at 180 days was similar in the low-, intermediate-, and high-risk groups: 7.0% versus 7.7% (hazard ratio HR 0.90, 95% confidence interval CI 0.75-1.08), 10.2% versus 11.3% (HR 0.89, 95% CI 0.77-1.03), and 20.1% versus 21.1% (HR 0.95, 95% CI 0.85-1.06). Major bleeding rates were higher with increasing GRACE risk scores: 2.2%, 3.2%, and 4.1% in the low, intermediate, and high-risk groups. Six-month mortality was 2.2%, 4.2%, and 12.3% in the 3 groups. The risk of major bleeding was substantially lower with fondaparinux in all groups: 1.6% versus 2.9% (HR 0.55, 95% CI 0.39-0.77), 2.2% versus 4.1% (HR 0.53, 95% CI 0.40-0.70), 2.8% versus 5.5% (HR 0.50, 95% CI 0.38-0.64). Conclusion The GRACE score predicted both bleeding and mortality in patients with ACS. The efficacy and safety of fondaparinux were consistent in all risk groups supporting its use in a broad range of ACS patients.
Background Fondaparinux has recently been approved in patients with acute coronary syndromes. The primary aim of this study was to describe the changes in use of anticoagulants between January 2006 ...and December 2007. The secondary aim was to compare 30-day mortality and rate of a combined end point (30-day death or major bleeding) according to the initial and final anticoagulant agent used. Methods The rates of use of unfractionated heparin (UFH), enoxaparin, and fondaparinux were compared by periods of 1 month in a multicenter registry. The initial anticoagulant (first used at admission), the final anticoagulant (last used during hospitalization), and switches in anticoagulation were recorded. Temporal trends in monthly use of each anticoagulant were assessed; 30-day mortality rates and the combined end point were compared according to initial and final anticoagulant. Results Among 2,874 patients included, the first anticoagulant used was UFH in 26%, enoxaparin in 59%, and fondaparinux in 15%. Respective figures for final anticoagulant were 17%, 56%, and 27%. Although 3 centers did not use fondaparinux (community centers with catheterization laboratory), the overall rate of use of fondaparinux, as initial and final anticoagulant, increased at the expense of the use of enoxaparin. We observed a growing proportion of patients with a switch from UFH to either enoxaparin or fondaparinux, ranging from 5% at the beginning to 25% at the end of the study. Patients treated with UFH were older, had more comorbidities, were at higher risk, and received fewer guidelines-recommended treatments. In patients submitted to angioplasty and treated with fondaparinux, a bolus of 60 IU/kg of UFH was added. After adjustment, 30-day mortality and combined end point rates were higher in patients treated with UFH. Irrespective of the type of acute coronary syndromes, patients treated with enoxaparin or fondaparinux had similar outcomes. Conclusions Between 2006 and 2007, the use of fondaparinux in patients with acute coronary syndromes increased considerably, either because it was used instead of enoxaparin or because of a switch from UFH. Adjusted mortality in patients treated with fondaparinux was lower than with UFH and similar to enoxaparin.
The effects of balloon angioplasty (BA) on plaque distribution remain incompletely documented. In 20 patients with unstable angina pectoris, intravascular ultrasound gray scale and radiofrequency ...analyses were performed before and after BA. Composition of the plaque was 61% fibrotic tissue, 15% fibrofatty tissue, 15% necrotic tissue, and 7% dense calcium tissue. After BA, 35% of lumen enlargement was due to an increase in total vessel area and 65% to a significant decrease in plaque area. This resulted from a longitudinal redistribution of the tissue toward the reference segments. Radiofrequency analysis showed that the fibrous and fibrofatty tissues were able to redistribute longitudinally, whereas calcium remained at the same level. A third of necrotic tissue was lost after BA. In conclusion, in unstable plaques, BA resulted in a longitudinal redistribution of fibrotic and fibrofatty tissues and disappearance of 1/3 of necrotic tissue.
Objectives The purpose of this study is to evaluate the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome undergoing coronary artery bypass graft surgery ...(CABG), as a post-randomization strategy. Background Ticagrelor is a novel, reversibly binding, oral, direct-acting P2Y12 -receptor antagonist. In the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized 18,624 patients with acute coronary syndromes, ticagrelor compared with clopidogrel significantly reduced the risk of the primary composite end point of cardiovascular (CV) death, myocardial infarction, or stroke (hazard ratio HR: 0.84; 95% confidence interval CI: 0.77 to 0.92; p < 0.001). This report investigated the outcomes of patients treated with CABG during the trial. Methods In total, 1,899 patients underwent CABG post-randomization. The protocol recommended ticagrelor/placebo to be withheld for 24 to 72 h and clopidogrel/placebo for 5 days preoperatively. In all, 1,261 patients underwent CABG and were receiving study drug treatment <7 days before surgery. The statistical analysis was based on events occurring from the CABG procedure until the end of the study, excluding 3 patients with CABG after study end. Results In the 1,261 patient cohort, the relative reduction of primary composite end point at 12 months (10.6% 66 of 629 with ticagrelor versus 13.1% 79 of 629 with clopidogrel; HR: 0.84; 95% CI: 0.60 to 1.16; p = 0.29) was consistent with the results of the whole trial. Total mortality was reduced from 9.7% (58 of 629) to 4.7% (29 of 629; HR: 0.49; 95% CI: 0.32 to 0.77; p < 0.01), CV death from 7.9% (47 of 629) to 4.1% (25 of 629; HR: 0.52; 95% CI: 0.32 to 0.85; p < 0.01), and non-CV death numerically from 2.0% to 0.7% (p = 0.07). There was no significant difference in CABG-related major bleeding between the randomized treatments. Conclusions In the subgroup of patients undergoing CABG within 7 days after the last study drug intake, ticagrelor compared with clopidogrel was associated with a substantial reduction in total and CV mortality without excess risk of CABG-related bleeding.
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