Efficacy Of Oral Anticoagulant Therapy Research Articles

Bleeding risk and major adverse events in patients with cancer on oral anticoagulation therapy

BackgroundThe efficacy of oral anticoagulation therapy (OAT) has not been revealed in atrial fibrillation (AF) patients with newly diagnosed cancers. This study evaluated the thromboembolic and bleeding events in AF patients with malignancies according to OAT. Methods and resultsIn 2168 consecutive non-valvular AF patients with newly diagnosed malignancies, we analyzed the composite endpoints including major adverse cardiac events (MACEs) and major bleeding. Based on a propensity score matching, two groups with 690 matched pairs were created.Patient baseline characteristics were comparable between the matched groups. During a follow-up period of 3.9±2.8years, 72 (10%) and 65 (9%) patients had MACEs in the propensity score-matched OAT+ and OAT− groups, respectively (p=0.461). There was no significant difference in the major bleeding (10% vs. 8%, p=0.300) and composite endpoints (18% vs. 16%, p=0.181) between OAT+ and OAT− patients. During the first year after the cancer diagnosis, 66 (48%) MACEs, 52 (41%) major bleedings, and 116 (49%) composite end points of all events occurred. The optimal international normalized ratio (2.0 to 3.0) level was achieved in only 85 (12%) patients. However, 1year after cancer diagnosis, OAT+ patients with the target therapeutic range of ≥60% demonstrated better cumulative survival free of composite end point than OAT− patients (p=0.026). ConclusionDuring the first year after the cancer diagnosis, OAT did not improve the composite end point because of poor INR control caused by cancer treatment. However, after 1year after diagnosis of cancer, optimal anticoagulation significantly reduced the composite end point.

Safety and efficacy of oral anticoagulation therapy in Chinese patients with concomitant atrial fibrillation and hypertension

Limited evidence is available on the safety and efficacy of anticoagulants in non-valvular atrial fibrillation (AF) patients with concomitant hypertension. We investigated the safety and efficacy of 476 consecutive anticoagulated Chinese outpatients with non-valvular AF and hypertension. Occurrence of ischaemic stroke and major bleeding, and international normalized ratio (INR) values during these events were recorded. There was no significant difference in anticoagulation control between patients with or without hypertension. INR-specific incidence rates of the events were calculated, which showed no excessive risk for ischaemic stroke (2.5 vs 1.6% per year, P=0.22) or major bleeding (3.9 vs 3.2% per year, P=0.29) in non-valvular AF patients with or without hypertension. In multivariate analysis, congestive heart failure, smoking and high CHADS2 score were independent predictors for ischaemic stroke, whereas use of antiplatelet agents was an independent predictor for bleeding. It can be noted that hypertension was not associated with ischaemic stroke or major bleeding. Hypertensive patients who achieved target blood pressure control (<130/80 mm Hg) had a lower ischaemic stroke (0.9 vs 3.1% per year, P=0.01), but similar bleeding risk compared with those not achieving target blood pressure. Our findings demonstrate the effects of hypertension on the outcomes of warfarin therapy; further investigation is needed to clarify whether more aggressive antihypertensive therapy could result in better outcomes in hypertensive patients with non-valvular AF.

The genetic interaction between VKORC1 c1173t and calumenin a29809g modulates the anticoagulant response of acenocoumarol.

The efficacy of oral anticoagulant therapy is largely conditioned by both environmental and genetic factors. To attempt to define the genetic profile involved in the response to this treatment. We selected 100 men younger than 75 years, with non-valvular atrial fibrillation, who started anticoagulation with acenocoumarol following the same protocol: 3 mg for three consecutive days. Then, doses were individually adjusted to achieve a steady International Normalized Ratio (INR). The basal plasma level and the level after 3 days were obtained, and the INR was determined. We studied five functional polymorphisms: FVII -323 Del/Ins, CYP2C*9, VKORC1 c1173t, calumenin (CALU) R4Q and CALU a29809g. The dose required for a steady INR was also recorded. Only the VKORC1 genotype had significant impact on the efficacy of therapy. Carriers of the 1173t allele were significantly more sensitive to therapy for 3 days [INR 2.07 (1.59-2.87) vs. 1.74 (1.30-2.09); P = 0.015] and they needed lower acenocoumarol doses to stabilize their INR (15.8 +/- 5.6 vs. 19.5 +/- 6.0 mg week(-1); P = 0.004). Its effect was exacerbated by combination with the CALU a29809g polymorphism. Carriers of both variants (27% of the sample) achieved the highest INR [2.26 (1.70-3.32)] and required the lowest dose (14.1 +/- 5.1 mg week(-1)). This genetic profile was particularly relevant in patients with INR >or= 3.5 at the start of therapy (P = 0.005; odds ratio = 6.67, 95% confidence interval = 1.32-37.43). Our results suggest that CALU a29809g might be a new genetic factor involved in the pharmacogenetics of anticoagulant therapy, and confirm that specific genetic profiles defined by different polymorphisms will determine the initial response and dose required to achieve a stable and safe INR.

Anticoagulation therapy for the prevention of hemodialysis tunneled cuffed catheter (TCC) thrombosis

Chronic oral anticoagulation is currently used to avoid thrombosis and the malfunction of tunneled cuffed catheters (TCCs) for hemodialysis (HD). The aim of the study was to assess the efficacy of early warfarin administration, after TCC placement, in comparison to its administration after the first thrombosis or malfunction event of the TCC. One hundred and forty-four chronic dialysis patients, who underwent TCC placement between June 2001 and June 2005, were randomized into two groups: 81 patients, group A, started oral anticoagulation 12 hr after the TCC placement (target international normalized ratio (INR) 1.8-2.5), in association with ticlopidine 250 mg/die; 63 patients, group B, started warfarin after the first thrombosis/malfunction episode (target INR 1.8-2.5) in association with ticlopidine 250 mg/die. The efficacy of oral anticoagulation therapy in preventing TCC thrombotic complications was evaluated in a 12-month follow-up period, after TCC placement, in terms of: a) the number of patients with thrombotic-malfunction events; b) the number of thrombotic-malfunction events with urokinase infusion (events/patient/year); c) intradialytic blood flow rate (BFR, ml/min); d) negative blood pressure (BP) from the arterial line of the TCC (AP, mmHg); e) positive BP, in the extracorporeal circuit from the venous line (VP, mmHg); and f) bleeding complications. Ten patients (12%) in group A showed TCC thrombosis/malfunction vs. 33 patients (52%) in group B (p < 0.01). In group A, 0.16 events of thrombosis/malfunction per patient/year vs. 1.65 in group B (p < 0.001) were ob-served. BFR was respectively 305 +/- 34 vs. 246 +/- 42 ml/min (p < 0.001). AP was -124 +/- 13 in group A vs. -174 +/- 21 mmHg in group B (p < 0.05). VP was 112 +/- 28 in group A vs. 168 +/- 41 mmHg in group B (p < 0.05). No patient showed any bleeding events. Early warfarin therapy allows a significant reduction in TCC thrombotic complications and an improvement in both arterial and venous fluxes in comparison with the same therapy administered after the first TCC thrombotic/malfunction event. This therapy did not induce any bleeding complications in the patients included in the study.

Optimal Oral Anticoagulant Therapy in Patients with Nonrheumatic Atrial Fibrillation and Recent Cerebral Ischemia

A number of studies have demonstrated the efficacy of oral anticoagulant therapy in reducing the risk of stroke and systemic embolism in patients with nonrheumatic atrial fibrillation. However, both the targeted and the actual levels of anticoagulation differed widely among the studies, and a number of studies failed to report standardized prothrombin-time ratios as international normalized ratios (INRs). We therefore performed an analysis to determine the intensity of oral anticoagulant therapy in nonrheumatic atrial fibrillation that provides the best balance between the prevention of thromboembolism and the occurrence of bleeding complications. We calculated INR-specific incidence rates for both ischemic and major hemorrhagic events occurring in 214 patients who received anticoagulant therapy in the European Atrial Fibrillation Trial, a secondary-prevention trial in patients with nonrheumatic atrial fibrillation and a recent episode of minor cerebral ischemia. The optimal intensity of anticoagulation was found to lie between an INR of 2.0 and an INR of 3.9. No treatment effect was apparent with anticoagulation below an INR of 2.0. The rate of thromboembolic events was lowest at INRs from 2.0 to 3.9, and most major bleeding complications occurred with treatment at intensities with INRs of 5.0 or above. To achieve optimal levels of anticoagulation with the lowest risk in patients with atrial fibrillation and a recent episode of cerebral ischemia, the target value for the INR should be set at 3.0, and values below 2.0 and above 5.0 should be avoided.

Nonvalvular Atrial Fibrillation and Primary Stroke Prevention from a Geriatric Point of View

Cerebrovascular disease constitutes one of the major causes of death. Patients with atrial fibrillation are known to be at high risk for stroke. The efficacy of oral anticoagulant therapy in the primary prevention of stroke in individuals with nonvalvular atrial fibrillation has been demonstrated in several large randomized trials. However, many geriatricians remain reluctant to prescribe anticoagulants. This article focuses on the risks and benefits of stroke prophylaxis with anticoagulant therapy in elderly patients with nonvalvular atrial fibrillation.

Oral Anticoagulant Therapy and its Control: An International Survey

A survey for the International Study Group for Anticoagulant Control has been conducted in which a questionnaire was sent to members in 39 countries. Information based on 37 replies obtained indicated that the most widely used test in oral anticoagulant therapy is the Quick one stage prothrombin estimation. There is a great diversity in the method of reporting prothrombin time results. Percentage activity of normal on the basis of saline dilution curves is the most popular. Only six countries have national or regional systems for anticoagulant control. Recommendations for the therapeutic range of dosage vary widely. The upper limit in one country may be the lower limit in another. In many centres doses of anticoagulant drugs are advocated which elsewhere are considered either inadequate anticoagulation or dangerous overdosages. The variation of therapeutic range may still be considerable even when a standard thromboplastin is available. Data collected from the survey indicates the need for urgent measures to provide a uniform of laboratory control of clinical dosage of anticoagulant drugs. Until such measures are implemented it is meaningless to try to compare the efficacy of oral anticoagulant therapy from country to country or even to attempt multicentre trials within national boundaries.