Background Using data from the GARFIELD ‐ AF (Global Anticoagulant Registry in the FIELD –Atrial Fibrillation), we evaluated the impact of chronic kidney disease ( CKD ) stage on clinical outcomes in patients with newly diagnosed atrial fibrillation ( AF ). Methods and Results GARFIELD ‐ AF is a prospective registry of patients from 35 countries, including patients from Asia (China, India, Japan, Singapore, South Korea, and Thailand). Consecutive patients enrolled (2013–2016) were classified with no, mild, or moderate‐to‐severe CKD , based on the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative guidelines. Data on CKD status and outcomes were available for 33 024 of 34 854 patients (including 9491 patients from Asia); 10.9% (n=3613) had moderate‐to‐severe CKD , 16.9% (n=5595) mild CKD , and 72.1% (n=23 816) no CKD . The use of oral anticoagulants was influenced by stroke risk (ie, post hoc assessment of CHA 2 DS 2 ‐ VAS c score), but not by CKD stage. The quality of anticoagulant control with vitamin K antagonists did not differ with CKD stage. After adjusting for baseline characteristics and antithrombotic use, both mild and moderate‐to‐severe CKD were independent risk factors for all‐cause mortality. Moderate‐to‐severe CKD was independently associated with a higher risk of stroke/systemic embolism, major bleeding, new‐onset acute coronary syndrome, and new or worsening heart failure. The impact of moderate‐to‐severe CKD on mortality was significantly greater in patients from Asia than the rest of the world ( P =0.001). Conclusions In GARFIELD ‐ AF , moderate‐to‐severe CKD was independently associated with stroke/systemic embolism, major bleeding, and mortality. The effect of moderate‐to‐severe CKD on mortality was even greater in patients from Asia than the rest of the world. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01090362.
AF is the most common sustained cardiac rhythm disorder and an established risk factor for ischemic stroke. Ischemic strokes which occur in patients with AF are particularly severe and disabling. In addition, stroke recurrence is more common in patients with AF compared with those without it. Previous cerebrovascular events, age, hypertension, diabetes, and heart failure are risk factors for stroke in patients with AF. Various risk stratification schemes have been developed to quantify the risk for stroke in patients with AF. Currently, the most frequently used schemes to assess stroke risk in patients with AF are CHADS
Summary K2tu-PA is a hybrid plasminogen activator linking the kringle 2 domain of tissue-type plasminogen activator (t-PA) to the catalytic protease domain of single-chain urokinase-type plasminogen activator (scu-PA). K2tu-PA, as t-PA has high affinity for fibrin and is activated by fibrin but has a longer plasma half-life (over 30 min). The aim of this study was to compare the effects of bolus doses of recombinant t-PA (rt-PA) and K2tu-PA, on: 1) lysis of preformed thrombi (fibrinolysis), 2) accretion of new fibrin on pre-existing thrombi during fibrinolysis (thrombus growth), 3) thrombolysis as assessed by reduction of thrombus weight and 4) systemic plasma proteolysis and blood loss from a standard wound. A jugular vein thrombosis model and an ear bleeding model were adopted in rabbits. Saline produced 11 ± 2% fibrinolysis. rt-PA, 0.2 mg/kg, 0.4 mg and 0.8 mg/kg produced 35 ± 4%, 54 ± 4% and 78 ± 6% fibrinolysis, respectively. K2tu-PA, at the same doses, produced 39 ± 5%, 57 ± 6% and 83 ± 6% fibrinolysis, respectively. Thus, no differences in the fibrinolytic activity of rt-PA and K2tu-PA were observed. Injection of saline was followed by an accretion of 56.4 ± 5.9 μg of radioactive new fibrin on the thrombi. The injection of the three increasing doses of rt-PA was followed by an accretion of 54.9 ± 5.3 μg, 49.1 ± 6.1 μg and 47.2 ± 4.8 μg. The injection of three increasing doses of K2tu-PA was followed by an accretion of 38.1 ± 3.4 μg, 29.6 ± 2.5 μg and 17.1 ± 3.4 μg. At each of the three doses, K2tu-PA was more effective than rt-PA in reducing the accretion of new fibrin on the thrombi (p <0.01) and, as a consequence, in reducing thrombus weight (p <0.01). The two lower doses of rt-PA and K2tu-PA did not produce systemic proteolysis and bleeding. The highest dose of K2tu-PA produced a statistically significant more intense systemic proteolysis and bleeding than the highest dose of rt-PA. This study demonstrates that bolus doses of K2tu-PA and rt-PA produce a similar degree of fibrinolysis. Due to its longer half-life K2tu-PA is more efficient than rt-PA in inhibiting accretion of new fibrin on the thrombi during thrombolysis so that the thrombus size is more efficiently reduced. As a consequence the concomitant use of heparin might not be necessary. The potential increased risk of bleeding with bolus of high doses of K2tu-PA has to be seen in view of the advantage of avoiding the concomitant use of heparin.
In the last 10 years the introduction of the direct oral anticoagulants (DOACs) has revolutionized the anticoagulant treatment, one of the cornerstones of the therapy for cardiovascular diseases. Thanks to their efficacy at least not inferior compared to vitamin K antagonists and their better safety profile, particularly with regard to intracranial bleeding, DOACs are now the first choice for the prevention of cardioembolism in patients with non-valvular atrial fibrillation and for the treatment of venous thromboembolism (VTE). Other areas of clinical use for DOACs include the prevention of VTE in orthopedic and oncology surgery and in outpatient cancer patients treated with anticancer therapy, or the use of low-dose in association with aspirin in patients with coronary or peripheral artery disease.An increased risk of gastrointestinal bleeding has been reported for some DOACs. In addition, DOACs have also experienced some failures including stroke prevention in patients with mechanical prosthetic valves or rheumatic diseases and VTE therapy in patients with antiphospholipid antibody syndrome. Also, no data are available on DOACs in some particular areas, including severe renal impairment and thrombocytopenia.In recent years, the clinical use of factor XI and factor XII inhibitors has been proposed. Currently, factor XI inhibitors have more clinical data than factor XII inhibitors. This article will report the rationale for the clinical use and the main evidences currently available on factor XI inhibitors.
