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Volume 42 (2011)
- Issue 6 Pages 355-
- Issue 5 Pages 297-
- Issue 4 Pages 205-
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- Issue 2 Pages 33-
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Volume 42, Issue 5
Displaying 1-7 of 7 articles from this issue
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Feature Articles: Topic of New Anticoagulants. The Role of New Anticoagulants in the Prevention of Thromboembolism in Patients with Atrial Fibrillation
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Tsuyoshi SHIGA2011 Volume 42 Issue 5 Pages 297-298
Published: 2011
Released on J-STAGE: December 08, 2011
JOURNAL RESTRICTED ACCESSDownload PDF (138K) -
Kagari MURASAKI2011 Volume 42 Issue 5 Pages 299-303
Published: 2011
Released on J-STAGE: December 08, 2011
JOURNAL RESTRICTED ACCESSAtrial fibrillation (AF) is the most common cardiac arrhythmia, and its prevalence increases with age. AF is strongly associated with increased risk of vascular events, especially stroke due to thromboembolism. Warfarin is highly effective in preventing thromboembolism clinically, not only ischemic stroke but also systemic thromboembolism. Nonetheless, warfarin increases the risk of major hemorrhage and is very burdensome in practice to maintain the optimal level of anticoagulant intensity for both physicians and patients.
The limitations of warfarin highlight the unmet need for new anticoagulants in the prevention of stroke in patients with AF. Therefore, new anticoagulants have been developed as a result of tireless pursuit for an ideal anticoagulant for long-term use in AF. These novel anticoagulant agents selectively inhibit the active form of a single factor in the coagulation cascade. Among the numerous classes of new drugs, direct thrombin inhibitors and Xa inhibitors have been most successful in the prevention of thromboembolism in patients with AF.
Old and current evidence suggests that formation of thrombi is the result of three components known as“Virchow's triad” (i.e., hypercoagulable state, an abnormal blood flow, and endothelial dysfunction). These components are all present in patients at high risk of AF. Anticoagulant therapy has been shown to be an effective countermeasure against a hypercoagulable state. Normalization of blood flow by rhythm control or atrial appendage closure is the second strategy for prevention of thromboembolism. However, the third factor in Virchow's triad, endothelial dysfunction, has not yet been studied specifically as a therapeutic target. Inflammation plays a role in endothelial dysfunction. Inflammation and thrombogenesis in patients with AF should be discussed.View full abstractDownload PDF (397K) -
Masayuki HASHIGUCHI, Mayumi MOCHIZUKI2011 Volume 42 Issue 5 Pages 305-313
Published: 2011
Released on J-STAGE: December 08, 2011
JOURNAL RESTRICTED ACCESSVitamin K antagonists (VKA) such as warfarin are highly effective in preventing recurrent ischemic stroke of cardiac origin due to atrial fibrillation. During the last five decades, little progress has been made in the development of oral anticoagulants, and warfarin is the only oral anticoagulant currently recommended for the prevention of stroke in patients with moderate to high risk of stroke. Although effective, VKA have unpredictable pharmacologic effects, requiring regular coagulation monitoring and dose adjustment to maintain effects within the therapeutic range. These limitations increase the complexity of VKA use in the clinical setting, creating a burden for patients, physicians, and pharmacists. Therefore, the current focus of clinical development is on new oral anticoagulants that directly target thrombin or activated factor X(FXa). These new anticoagulants are more convenient than VKA, with predictable anticoagulant response, low potential of drug-drug interactions, and using fixed doses without coagulation monitoring. Recently, some of these drugs have been approved in the EU, Canada, and Japan for the prevention of thromboembolism in patients undergoing hip- and knee-replacement surgery, prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation, or prevention of cardiac events in patients with acute coronary syndromes. This review summarizes the pharmacokinetic properties and drug interactions of new anticoagulants (dabigatran etexilate, edoxaban, rivaroxaban, apixaban, idrabiotaparinux).View full abstractDownload PDF (410K) -
Yukihiro KORETSUNE2011 Volume 42 Issue 5 Pages 315-319
Published: 2011
Released on J-STAGE: December 08, 2011
JOURNAL RESTRICTED ACCESSAtrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and occurs in 1-2% of the general population. This arrhythmia is the greatest risk factor of cardiogenic embolism that has poor prognosis. Therefore anticoagulation medication is widely used for stroke prevention in atrial fibrillation (SPAF).
Warfarin (WF), which is the only oral anticoagulant, has been used for more than half a century as a SPAF medication. As meta-analysis showed that WF reduced strokes in AF patients by 64%, WF has been highly recommended for stroke prevention in moderate- to high-risk AF patients.
However WF is reported to be under-used. The reasons are significant management challenges including the necessities for frequent monitoring of the international normalized ratio (INR) and dose adjustment to maintain the INR within a narrow therapeutic window (2 to 3 for most indications).
Today, not only in Japan but also in other regions, a new oral anticoagulant (NOAC) dabigatran, which is a thrombin inhibitor, has been approved as the first NOAC with an indication of SPAF, and an FXa inhibitor with AF indication will be marketed in the near future. Anticoagulant therapy using NOACs for SPAF is in the spotlight around the world since the RE-LY (dabigatran) and ROCKET (rivaroxaban) studies were published and substantiated either superiority or equality in efficacy and safety versus WF.
In this paper, the past and current status of anticoagulant therapy in patients with atrial fibrillation will be described. Important points to note when using the new anticoagulants will also be discussed.View full abstractDownload PDF (477K) -
Yoshio UETSUKA2011 Volume 42 Issue 5 Pages 321-332
Published: 2011
Released on J-STAGE: December 08, 2011
JOURNAL RESTRICTED ACCESSOral anticoagulant reduces the risk of ischemic stroke in patients with atrial fibrillation (AF), but increases the risk of bleeding. The use of oral anticoagulant adds to the cost of existing therapy, but if the benefit of the reduction in incidence of ischemic stroke exceeds the incremental cost of additional oral anticoagulant, the total health expenditure of the country will decrease. The first part of this article explains the method used for calculating the incremental cost-effectiveness ratio (ICER), the theory of quality-adjusted life year (QALY) and Makov cycles. The latter part describes the application of ICER in patients with AF receiving warfarin (warfarin vs. aspirin vs. no antithrombotic agents) in computer simulations followed by the introduction of recently published articles regarding the ICER of dabigatran vs. warfarin. Any health intervention which has an incremental cost of more than US$50,000 per additional QALY gained is likely to be rejected by the healthcare administration of the country. Warfarin vs. aspirin or dabigatran vs. warfarin was well within such a range and regarded as cost-effective. The sensitivity test revealed that the merit depends heavily on the price of dabigatran.View full abstractDownload PDF (922K)
Original
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Hajime NAKASHIMA, Jun MIURA, Tsukasa UNO, Terufumi MATSUNAGA, Tomonori ...2011 Volume 42 Issue 5 Pages 333-340
Published: 2011
Released on J-STAGE: December 08, 2011
JOURNAL RESTRICTED ACCESSThe influence of genetic polymorphisms and non-genetic factors upon warfarin maintenance dose was investigated in elderly Japanese patients. Blood sample were collected and demographic and clinical data including age, sex, weight, height, warfarin dose, and prothrombin time expressed as the international normalized ratio (INR) were obtained from 104 unrelated Japanese patients aged from 44 to 94 years. Plasma concentration of S-warfarin was quantified and genetic polymorphisms of VKORC1, CYP2C9 and CYP2C19 were determined. The warfarin dose was significantly higher in men than in women (2.7 vs 2.3mg/d, respectively) although INR was not different significantly. The dose correlated inversely with age and positively with height, weight and body surface area (BSA). Thus, the dose per BSA was not different between males and females, indicating that the gender difference in warfarin dose might be attributed to difference in body size. Both the VKORC1 and CYP2C9 genotypes significantly influenced the dose per BSA. The dose per BSA was higher in patients with the VKORC1-1639GA (n=17) than those with the-1639AA genotype (n=87). The dose per BSA was lower in patients with CYP2C9*1/*3 (n=9) than in those with CYP2C9*1/*1 (n=95), but was not influenced by the CYP2C19 genotype. Warfarin dose per BSA, INR and plasma concentration of S-warfarin correlated significantly with one another. Step-wise regression model for the warfarin maintenance dose indicated significant contributions from the VKORC1 genotype, age and weight. In conclusion, warfarin dose should be adjusted according to the VKORC1 genotype, age and weight to improve safety and efficacy of treatment.View full abstractDownload PDF (176K)
Case Report
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Mikako HIROTA, Tosifusa TODA, Hiraku MORISAWA, Satoru MINESHITA2011 Volume 42 Issue 5 Pages 341-343
Published: 2011
Released on J-STAGE: December 08, 2011
JOURNAL RESTRICTED ACCESSAmong 30 elderly patients who received ivermectin for the treatment of scabies, we observed a case of possible ivermectin-induced liver dysfunction in an 85 year-old patient. He developed liver dysfunction after the second dose of the drug. While elevated serum ALT and AST subsided to normal levels 2 months after discontinuation of the drug, increased serum ALP and γ-GPT persisted. Ivermectin was effective in all patients for the eradication of scabies.View full abstractDownload PDF (122K)
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