Therapeutic Research
Volume 32, Issue 8, 2011
Volumes & issues:
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今月の話題:J-CLEAR特別シンポジウムXa阻害薬の登場とAblation 普及で脳卒中は激減するか?
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Review
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GLP-1 受容体作動薬リラグルチドの臨床使用―リラグルチドのベネフィットの最大化に向けて―
32巻8号(2011);View Description Hide DescriptionBackground:In recent years, the glucagon-like peptide-1 receptor agonist liraglutidehas become available for clinical use and appears to hold promise as a novel therapeutic optionthat offers potent glucose lowering without causing significant weight gain or hypoglycemia,with additional potential to arrest the progressive deterioration of pancreatic β-cell function,unlike conventional anti-diabetic therapy, in type 2 diabetic patients.Methods:The results of clinical trials of liraglutide conducted to date in Japanesepatients were reviewed, and clinical settings were explored in which the benefit of liraglutidecould be maximized.Results:Data from clinical trials suggested that obese patients with early-stage type 2diabetes might benefit most from the use of liraglutide through reductions in both HbA1c andbody weight. Consistent with the trial results, subsequent clinical experience suggested anumber of potential clinical settings in which the benefit of liraglutide could be maximized:liraglutide monotherapy may represent a frontline option for obese patients with early-stagetype 2 diabetes requiring long-term therapy, a safe and effective alternative to combinationtherapy with multiple OADs associated with weight gain and hypoglycemia, and an alternativecombination therapy with multiple OADs to promote better QOL.Conclusions:Liraglutide monotherapy may represent a frontline option in patients withearly-stage type 2 diabetes, particularly those with obesity, as well as a safe and effective alternativefor combination therapy employing multiple anti-diabetic drugs even in those with goodglycemic control. Further clinical experience will help clarify the role of liraglutide in a realworldsetting.
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原著
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スタチンによる脂質改善効果と心血管イベント抑制の関係―CIRCLE Study サブ解析―
32巻8号(2011);View Description Hide DescriptionBackground:Statins vary in their effectiveness in lowering low-density lipoproteincholesterol(LDL-C)and increasing high-density lipoprotein cholesterol(HDL-C)levels.We documented that the degree of these changes can explain cardiac risk reduction in theCIRCLE Study. To compare efficacy of the most potent statin, pitavastatin, with no statingroup, especially in diabetic patients, we conducted subanalysis of the CIRCLE Study.Methods and Results:The 431 consecutive patients who underwent PCI from 2001 to2008 were retrospectively investigated. Treatment with pitavastatin significantly reducedLDL-C and increased HDL-C compared with no statin. Pitavatatin significantly preventedmajor adverse cardiac events(MACE)compared with no statin in patients with or withoutdiabetes. Multivariate-adjusted analysis revealed that percent changes of both LDL-C andHDL-C independently predicted the incidence of MACE(hazard ratio[HR]:1.14;95%confidence interval[CI]:1.07-1.21, HR:0.88;95%CI:0.80-0.98, in each 10% change,respectively).Conclusions:The extent of changes in LDL-C and HDL-C with statin treatment wouldindependently alter the risk of cardiac events. Pitavastatin potently decrease LDL-C andsignificantly increase HDL-C might provide good prognosis in patients after PCI with orwithout diabetes. -
保存期慢性腎臓病患者におけるDarbepoetin 月 1 回投与の有効性と安全性
32巻8号(2011);View Description Hide DescriptionBackground and aim:Recombinant human erythropoietin(rHuEPO)was used widely totreat renal anemia, but patients had to have weekly or biweekly medical examinations to beadministrated rHuEPO, and it was still difficult to achieve recommended hemoglobin level.Recently, Darbepoetin (DA), a long-acting erythropoiesis stimulating agent (ESA) wasapproved in Japan for renal anemia patients with chronic kidney disease not on dialysis(CKDND),and it enabled to extend ESA dosing interval to once a month in hemoglobin maintenancephase. We conducted a clinical study to determine the efficacy and safety of monthly DA administration in CKD-ND patients.Patients and methods:CKD-ND outpatients with renal anemia, but without a history ofcardiovascular diseases were included. Patients changed ESA from rHuEPO to monthly DAtreatment(n=50, group C), ESA naïve patients newly starting with monthly DA treatment(n=30, group D)and historical control patients(n=30, group E)were followed. ESA(DAor rHuEPO)dosage was adjusted to maintain hemoglobin level at 11.0~13.0 g/dL. Primaryendpoint was deterioration rate of estimated glomerular filtration ratio(ΔeGFR, mL/min/1.73 m2/year).Results:No deaths or cardiovascular events were occurred. Ten patients in group Cwas inducted to hemodialysis. ΔeGFR was improved from -2.53 to -1.25 by the treatmentchange in group C but not significantly(p=0.81). ΔeGFR in group D(-0.07)was smallerthan that in group E(-1.70, p=0.78). The hemoglobin increasing rate by DA was less than0.5 g/dL/week, satisfying the level recommended by the guideline.Conclusion:The present study suggests the effectiveness of a monthly administrationof DA for improving anemia and preventing CKD progression. It also suggests the safety ofmonthly administration of DA. -
Efficacy and Safety of Long-term and High-dose Treatment with Ropinirole(ROP)in Japanese Patients withParkinson’s Disease:LEAD-PD Study
32巻8号(2011);View Description Hide DescriptionAn open-label, non-randomized, multicenter clinical study was conducted to evaluatethe efficacy and safety of long-term, high-dose treatment(10.5 to 15 mg/day)with ropinirole(ROP)in Japanese patients with Parkinson’s disease(PD)who were receiving concomitantL-dopa or not receiving concomitant L-dopa. In PD patients receiving treatment withother dopamine agonists, ROP was alternatively introduced and used for up to 1 year whilethe need for dose increase was considered to assess the Japanese Unified Parkinson’sDisease Rating Scale(UPDRS)score, off time, and safety. A total of 123 patients(adjunctto L-dopa group, 65 patients;monotherapy group, 58 patients)received ROP. In 93 of the123 patients who received treatment for 1 year, the UPDRS part I I I total score decreased inboth adjunct to L-dopa group(20.5 to 12.7)and monotherapy group(19.8 to 13.1), indicatingthat the efficacy was maintained for 1 year. Higher doses of ROP further improvedmotor symptoms and tended to reduce the symptoms in more patients. The reportedadverse events were similar to those caused by other dopamine agonists, and there wereno specific adverse events that were markedly more often observed at increased doses orafter longer duration of treatment. Although the study was designed an open-label, nonrandomized,it suggests that long-term and high-dose(more than 10.5 mg/day)treatmentwith ROP may be useful in Japanese PD patients. -
Effect of Hemoglobin Concentration on I-ECOH in Hemodialysis Patients
32巻8号(2011);View Description Hide DescriptionThe purpose of this study is to examine to what extent an increase in the hemoglobin(Hb)concentration affects the inclination of the exponential curve-fitting model for oxygenuptake and heart rate during graded exercise(I-ECOH)in hemodialysis(HD)patients. Fivepatients who had received regular HD for 1.4±1.3 years were recruited(mean age:28.4±9.4years). Three units of red cell concentrate(RCC)were transfused into 4 patientsthrough blood tubing for purification. As one patient had a high hemoglobin(Hb)level(7g/dL), he received 2 units of RCC. Before and after the transfusion, cardiopulmonary exercisetests were performed on a non-HD day according to the modified Bruce protocol. Thefollowing equation was used to determine the relationship between oxygen uptake(V O2)and heart rate(HR)from rest to the end of the exercise:HR=A・expB・VO2 where“B”was defined as I-ECOH. The mean exercise duration, VO2 peak, and HR peak increasedsignificantly after the transfusion(p<0.01), whereas the I-ECOH decreased significantlyafter the transfusion(p<0.01). The VO2 peak before and after the transfusion was correlatedwith the Hb level(r=0.71, p<0.05), whereas the I-ECOH was not correlated withthe Hb concentration. These results suggest that the increase in Hb improve I-ECOH,however the effect is weaker than that on VO2 peak in HD patients. -
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特発性レストレスレッグズ症候群におけるPramipexoleの早期効果
32巻8号(2011);View Description Hide Description特発性レストレスレッグズ症候群(iRLS:idiopathic restless legs syndrome)の病因の一つにドパミン神経系異常がある。その治療としてドパミンD2/3受容体アゴニストがよく使われているが,その効果発現時期についてこれまでに十分には検討されていない。今回われわれは,ドパミンD2/3受容体アゴニストであるpramipexole を未治療のiRLS患者に投与して,効果発現時期についての検討を行った。患者の臨床症状は国際レストレスレッグズ症候群評価尺度(IRLS:InternationalRestless Legs Syndrome Rating Scale),エップワース眠気尺度,ピッツバーグ睡眠質問票,患者による全般的印象度,医師による全般的印象度を用いて,投与前と投与後2 週間の変化を検討した。その結果,投与直後にIRLS合計スコアが有意に低下し,2 週間漸減する変化を示した。その他のスコアでは数日遅れて有意に改善することがわかった。本研究の結果は,pramipexole が投与直後からRLS症状に対する改善効果を発揮する可能性を示唆しており,ドパミンD2/3受容体アゴニストをiRLS治療の第一選択とする考えを支持した。
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