New oral anticoagulants - a practical guide.

Oral direct inhibitors of thrombin and activated factor Xa are approved as new anticoagulant drugs. In contrast to vitamin K antagonists (VKA) and heparins, the new agents have single targets in the coagulation cascade and more predictable pharmacokinetics, but they lack validated and available antidotes. Unlike VKA, they do not require routine monitoring of coagulation. However, the measurement of their pharmacologic effects might be of value in selected patients. They interfere with the routine coagulation tests, which should be interpreted with caution. Specific tests exist and can be used in case of emergencies. Adequate supportive care and temporary removal of all antithrombotic agents constitute the basis for management of serious bleeding complications. The administration of coagulation factors, such as fresh frozen plasma, prothrombin complex concentrates or recombinant activated FVII, can benefit in life-threatening bleeding or emergency surgery. Specific antidotes for non-vitamin K oral anticoagulants are in clinical development. This review aims at answering in a brief and simplified manner some clinical questions.

Factors affecting the quality of anticoagulation with warfarin: experience of one cardiac centre.

INTRODUCTION: The risk of complications in anticoagulation therapy can be reduced by maximising the percentage of time spent by the patient in the optimal therapeutic range (TTR). However, little is known about the predictors of anticoagulation control. The aim of this paper was to assess the quality of anticoagulant therapy in patients on warfarin and to identify the factors affecting its deterioration. MATERIAL AND METHODS: We studied 149 patients who required anticoagulant therapy with warfarin due to non-valvular atrial fibrillation and/or venous thromboembolism. Each patient underwent proper training regarding the implemented treatment and remained under constant medical care. RESULTS: The mean age of the patients was 68.8 ± 12.6 years, and 59% were male. A total of 2460 international normalised ratio (INR) measurements were collected during the 18-month period. The mean TTR in the studied cohort was 76 ± 21%, and the median was 80%. The level at which high-quality anticoagulation was recorded for this study was based on TTR values above 80%. Seventy-five patients with TTR ≥ 80% were included in the stable anticoagulation group (TTR ≥ 80%); the remaining 74 patients constituted the unstable anticoagulation group (TTR < 80%). According to multivariate stepwise regression analysis, the independent variables increasing the risk of deterioration of anticoagulation quality were: arterial hypertension (OR 2.74 [CI 95%: 1.06-7.10]; p = 0.038), amiodarone therapy (OR 4.22 [CI 95%: 1.30-13.70]; p = 0.017), and obesity (OR 1.11 [CI 95%: 1.02-1.21]; p = 0.013). CONCLUSIONS: The presence of obesity, hypertension, or amiodarone therapy decreases the quality of anticoagulation with warfarin. High quality of anticoagulation can be achieved through proper monitoring and education of patients.

Single sST2 protein measurement predicts adverse outcomes at 1-year follow-up in patients with chronic heart failure.

INTRODUCTION: sST2 protein is a new biomarker. Its prognostic value in chronic heart failure (CHF) is still unclear. OBJECTIVES: The aim of the study was to evaluate the value of sST2 protein in patients with CHF during 1-year follow-up after hospitalization for prediction of adverse events: cardiovascular death, rehospitalization, an increase in diuretic doses, and/or worsening of the New York Heart Association functional class, defined as the composite endpoint. PATIENTS AND METHODS: The study involved 145 consecutive patients (mean age, 62.16 ±11.25 y; men, 82.76%) with left ventricular (LV) ejection fraction of 30% or less and symptomatic CHF. We analyzed clinical and biochemical data along with the serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and sST2. The optimal cut-off points for significant predictors of the composite endpoint were determined using receiver operating characteristi c curves. RESULTS: Patients with elevated levels of sST2 and NT-proBNP had more than a 4-fold higher risk of composite endpoint (odds ratio [OR], 4.033; 95%CI, 1.540-10.559) compared with patients in whom both biomarkers were below the cut-off points. The C-statistic for predicting the composite endpoint was improved when both biomarkers were incorporated into the model (C-statistic, 0.692; P = 0.0001) compared with an individual analysis for NT-proBNP (C-statistic, 0.606; P = 0.009) and sST2 (C-statistic, 0.613; P = 0.003). Moreover, after the addition of sST2 to NT-proBNP, the continuous net reclassification improvement index (OR, 0.256; 95% CI, 0.090-0.401; P = 0.007) and the integrated discrimination improvement index (OR, 0.104; 95% CI 0.011-0.221; P = 0.007) significantly improved. CONCLUSIONS: A single measurement of sST2 levels on admission in patients with poor LV systolic function and stable CHF is useful in short-term risk stratification and, in combination with NT-proBNP, it could be more useful in identifying patients with unfavorable c ourse of CHF.

Truly low and high thromboembolic risk - impact of risk scores in real life.

BACKGROUND: Anticoagulation therapy is followed by analysis of factors used in the CHA2DS2-VASc score and assessing the risk of bleeding (HAS-BLED). THE AIM OF THE STUDY: The aim of the study was to evaluate in 'real life' risk stratification scores in nonvalvular atrial fibrillation (AF). MATERIAL AND METHODS: From 81 consecutive patients who had not yet received anticoagulation, 68 were finally enrolled after exclusion criteria. Patients were analyzed related to risk scores: CHADS2 ≥ 2 (group I) vs. CHADS2 < 2 and CHA2DS2-VASc score ≥ 2 (group II) and gender. Patients at high thromboembolic risk were treated with warfarin, after consideration of the patient's decision. RESULTS: At high risk of thromboembolic complications were 61 patients (90%). In 26 subjects (43%, 15 women - 57%) indication for anticoagulation was established by CHA2DS2-VASc. When compared to CHADS2 ≥ 2, these patients were younger (72 ±10 years vs. 63 ±10 years, p = 0.0002), less frequently burdened with arterial hypertension (p = 0.03) and had lower risk in HAS-BLED (1.23 ±0.65 vs. 0.81 ±0.49, p = 0.03). Seven patients (10%) did not require anticoagulation (CHA2DS2-VASc = 0). Compared to men, women more often had ischemic stroke (2 vs. 18%, p = 0.03), but less coronary artery disease (58 vs. 25%, p = 0.005). During 18 months on warfarin, bleeding occurred in 9 patients (13%, 6 women). On dual antiplatelet therapy were 11 patients (16%). No thromboembolic complications were recorded. CONCLUSIONS: CHA2DS2-VASc and HAS-BLED schemata easily identify real low and high thromboembolic risk patients and bleeding risk. It seems that women present higher risk of bleeding, but less frequent use of antiplatelet therapy.

The impact of chronic kidney disease on the annual prognosis in patients 80+ years old suffering from chronic heart failure.

INTRODUCTION: It is well known that the function of kidneys is impaired with age. AIM: The purpose of the study was to evaluate whether chronic kidney disease (CKD) is a predictor for 1-year follow-up mortality among hospitalized chronic heart failure (CHF) patients aged 80+. MATERIAL AND METHODS: The study included 141 consecutive patients aged 80-92 (mean: 82.4 years, 44.7% men). The prospective analysis contains 61 variables with glomerular filtration rate (GFR) and the occurrence of death at the 1-year follow-up. Patients were divided and analyzed depending on GFR. RESULTS: Chronic kidney disease defined as estimated GFR < 60 ml/min/1.73 m(2) was recorded in 93 patients (66%). A relationship with GFR < 60 was found for older age (p = 0.0001), lower body mass index - BMI (p = 0.003), more advanced NYHA class III (p = 0.007), higher concentrations of N-terminal probrain natriuretic peptide - NT-proBNP (p = 0.023), lower hemoglobin (p = 0.0004) and LVEF (p = 0.005), longer hospitalization (p = 0.005), more frequent ventricular blocks in ECG (p = 0.017) and rarely performed coronary angiography (p = 0.021). In turn, GFR < 30 ml/min/1.73 m(2) was recorded in 14 patients (9.9%). Similar relationships as in GFR < 60 were found for GFR < 30 and additionally higher concentrations of high-sensitivity C-reactive protein (hsCRP) (p = 0.003), D-dimer (p = 0.002) and more frequent dyslipidemia (p = 0.004) and left main coronary artery disease (p = 0.007). Annual mortality for the total population was 14.2% (n = 20) and was higher (16.1%) if GFR was < 60 and even more (21.4%) in GFR < 30. However, the relationship between deaths and GFR was not statistically significant (for GFR < 60, p = 0.505 and GFR < 30, p = 0.547). CONCLUSIONS: Annual mortality in the patients 80+ who suffered from CHF was high but not statistically significantly associated with CKD.