Joji Morii

Evaluation of the Antithrombotic Effects of Rivaroxaban and Apixaban Using the Total Thrombus-Formation Analysis System®: In Vitro and Ex Vivo Studies

Background The usefulness of the Total Thrombus-Formation Analysis System® (T-TAS®) for monitoring the anticoagulant effects of non-vitamin K oral anticoagulants (NOACs) in clinical practice has been poorly addressed. Methods NOACs (rivaroxaban and apixaban) were added to whole blood from healthy subjects in an in vitro study, and their effects on thrombus formation were evaluated by the T-TAS®. We also evaluated antithrombotic effects using ex vivo samples of whole blood from patients given rivaroxaban or apixaban at the respective trough and peak drug concentrations. Results T-TAS® could determine anticoagulant effects in whole blood treated with rivaroxaban or apixaban in vitro. The increases in the anticoagulant effects of rivaroxaban and apixaban from the trough to peak concentrations in whole blood were successfully monitored by the T-TAS® using ex vivo samples. The antithrombotic effects of rivaroxaban and apixaban (in terms of factor Xa inhibition) at the peak were strongly linked to those at the trough. Conclusion T-TAS® could be a clinically useful tool for monitoring the anticoagulant effects of factor Xa inhibitors, and may represent an accurate quantitative analysis.

Efficacy and safety of a single-pill fixed-dose combination of high-dose telmisartan/hydrochlorothiazide in patients with uncontrolled hypertension

Objective: Many patients still have high blood pressure (BP) after treatment with high-dose angiotensin II type 1 receptor blockers (ARBs) or Preminent® (medium-dose of losartan (50 mg/day)/hydrochlorothiazide (HCTZ) (12.5 mg/day)). Therefore, we analyzed whether Micombi®BP (high-dose telmisartan (80 mg/day)/HCTZ (12.5 mg/day)) could provide better results with regard to efficacy and safety for patients with uncontrolled hypertension. Methods: In total, 44 hypertensive patients (22 males, age 71±14 years) who showed uncontrolled BP despite the use of high-dose ARBs or Preminent® were enrolled in this study. We used a changeover design in which the patients were switched from high-dose ARBs or Preminent® to Micombi®BP. We analyzed BP, heart rate (HR), and biochemical parameters before and after treatment for 3 months. Results: Systolic BP and diastolic BP significantly decreased (125±15/69±11 mmHg) and 85% of the patients achieved their target BP at 3 months after changeover. Patients who switched from ARBs and those who switched from Preminent® showed similar BP-lowering effects. In addition, the reductions in BP after 3 months in patients with or without chronic kidney disease and in those with or without metabolic syndrome (MetS) were also similar. There were no significant changes in HR during the study period. Although blood levels of potassium, hemoglobin A1c and uric acid (UA) significantly increased after 3 months for all of the patients, none of the patients showed serious adverse effects. Conclusion: High-dose telmisartan/HCTZ therapy was associated with a significant reduction in BP and helped patients achieve their target BP.

Comparison of the Efficacy and Safety of Irbesartan and Olmesartan in Patients With Hypertension (EARTH Study)

Fifty-four patients were randomly divided into irbesartan and olmesartan groups. Blood pressure (BP) was significantly decreased in all patients at 12 weeks. In particular, BP in patients who initially received irbesartan showed significant reductions. The equality of variance of BP in the irbesartan group was significantly smaller than that in the olmesartan group at 12 weeks. Blood concentrations of adiponectin were significantly increased in the irbesartan group at 12 weeks. Log [pentraxin-3] in the irbesartan group were significantly decreased. In conclusion, the ability of irbesartan to reduce BP is comparable to that of olmesartan with equivalent safety.

Determination of the cut-off plasma adiponectin level associated with a lower risk of restenosis in patients with stable angina.

ObjectiveHypoadiponectinemia is an independent predictor for the progression of coronary artery disease (CAD); however, the importance of plasma adiponectin levels in the midterm clinical outcome in patients with CAD who underwent percutaneous coronary intervention (PCI) has not been fully elucidated. The purpose of this study was to investigate the association between plasma adiponectin levels and midterm clinical outcome in patients with CAD who underwent PCI. Materials and methodsA total of 112 patients (120 lesions) with stable angina who underwent PCI under intravascular ultrasound guidance, and who underwent follow-up coronary angiography about 8 months after PCI from August 2004 to December 2009 were enrolled in this study. ResultsPlasma adiponectin levels were significantly lower in the group with restenosis (n=13) than in the group without restenosis (n=107) (4.2±1.5 vs. 6.8±4.9 &mgr;g/ml, P<0.0001). A two-graph receiver operating characteristic curve analysis indicated that the cut-off point of adiponectin was 6.0 &mgr;g/ml. Although plasma adiponectin levels were independent of well-known risk factors of CAD, a multivariate logistic regression analysis indicated that the higher adiponectin group (patients with hyperadiponectinemia) was independently associated with lower risk of restenosis (odds ratio=0.21, 95% confidence interval=0.03–0.82). ConclusionHyperadiponectinemia (plasma adiponectin levels ≥6.0 &mgr;g/ml) is independently associated with a lower risk of restenosis. Thus, the plasma adiponectin level may be useful as a marker of restenosis independent of preinterventional intravascular ultrasound variables.

A case of coronary artery disease with antiphospholipid syndrome that showed repeated stent thrombosis

A 55-year-old man with severe chest pain was hospitalized for acute coronary syndrome. Coronary angiography revealed total occlusion of his left anterior descending coronary artery, which was successfully recanalized by percutaneous coronary intervention (PCI). However, the patient subsequently experienced subacute stent thrombosis, restenosis in the stent, and frequent thrombosis in PCI toward restenosis. Primary antiphospholipid syndrome should be considered as a possible cause of repeated stent thrombosis, and, if salvage by PCI is impossible, salvage by coronary artery bypass graft should be considered.

Effects of Tolvaptan With or Without the Pre-Administration of Renin-Angiotensin System Blockers in Hospitalized Patients With Acute Decompensated Heart Failure

We examined whether tolvaptan combined with an angiotensin II receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACE-I) is more effective than tolvaptan alone in the treatment of patients with heart failure (HF). Sixty-five hospitalized patients with acute decompensated HF were included in this study. They were divided into 2 groups; an ARB/ACE-I group (n = 44, who received ARB or ACE-I before the use of tolvaptan) and a non-ARB/ACE-I group (n = 21). There were no significant differences in patient characteristics including medications at baseline between the non-ARB/ACE-I and ARB/ACE-I groups with the exception of the percentages of hypertension and ischemic heart disease. Urinary volume (UV) at baseline in the ARB/ACE-I group was slightly higher than that in the non-ARB/ACE-I group. The increase in UV after the use of tolvaptan in the non-ARB/ACE-I group was significantly higher than that in the ARB/ACE-I group. The cardiothoracic ratio and the reduction in body weight were similar between the groups after tolvaptan use. Finally, in a logistic regression analysis, a response to the use of tolvaptan was independently associated with the non-use of ARB/ACE-I, but not with age, gender, body mass index, loop diuretic, or human arterial natriuretic peptide. In conclusion, tolvaptan alone might induce an increase in UV in decompensated HF patients without ARB/ ACE-I, although the treatment of HF with ARB/ACE-I is the first choice strategy.

Circadian variations in laboratory measurements of coagulation assays after administration of rivaroxaban or warfarin in patients with nonvalvular atrial fibrillation

BACKGROUND Although rivaroxaban has a relatively shorter half-life and peak and trough plasma concentrations throughout the day than warfarin, rivaroxaban has been found to be non-inferior to warfarin in preventing thromboembolic events in patients with nonvalvular atrial fibrillation (NVAF). We measured circadian variations in laboratory measurements of coagulation assays for chronic treatment with rivaroxaban or warfarin in patients with NVAF. METHODS We included 28 consecutive patients with NVAF who were treated with rivaroxaban (n=13) or warfarin (n=15). Blood samples were collected at 6 AM, 11 AM, and 3 PM on the same day and on the next morning at 6 AM. Prothrombin time (PT), international normalized ratio of the PT (PT-INR), activated partial thromboplastin time (APTT), prothrombin fragment 1+2 (F1+2), and protein C level/activity were measured in each patient. RESULTS PT and PT-INR were significantly and consistently lower, and the F1+2 and protein C level/activity were significantly and consistently higher throughout the day in rivaroxaban-treated patients than in warfarin-treated patients. Significant increases in PT and PT-INR were observed 3h after oral administration in the patients taking rivaroxaban in the morning, whereas, significant increases in the protein C level/activity were observed 3h after oral administration in the patients taking warfarin in the morning. CONCLUSIONS The protein C level/activity was significantly and consistently higher in the rivaroxaban-treated patients than in the warfarin-treated patients throughout the day, which was in contrast to the findings for other coagulation assays. These findings may partly explain the specific persistent anticoagulant effects of rivaroxaban even during the trough phase of the plasma concentration.

Efficacy and Safety of Combination Therapy Consisting of Angiotensin II Type 1 Receptor Blocker, Calcium Channel Blocker and Hydrochlorothiazide in Patients With Hypertension

Background Many patients continue to have high blood pressure (BP) even after treatment with high-dose (H)-angiotensin II type 1 receptor blocker (ARB)/calcium channel blocker (CCB) or middle-dose (M)-ARB/CCB/hydrochlorothiazide (HCTZ). Methods Thirty-two hypertensive patients who had the use of H-ARB/CCB or M-ARB/CCB/HCTZ were enrolled in this study. We applied a changeover with a switch to H-ARB (telmisartan 80 mg/day)/CCB (amlodipine 5 mg/day or nifedipine CR 40 mg/day)/HCTZ (12.5 mg/day). Results Systolic BP (SBP) and diastolic BP (DBP) were significantly decreased in all patients and in the H-ARB/CCB and M-ARB/CCB/HCTZ groups after 3 months. Percentage (%) of patients who reached the target BP after 3 months (72%) in all patients was significantly higher than that at 0 months (19%). There were no serious adverse effects in any of the patients. Conclusions Combination therapy with H-ARB/CCB/HCTZ was associated with a significant reduction of BP.

Recent Patient Characteristics and Medications at Admission and Discharge in Hospitalized Patients With Heart Failure

Background To improve the clinical outcome of heart failure (HF), it is important to evaluate the etiology and comorbidities of HF. We previously reported the baseline clinical characteristics and medications in hospitalized patients with HF in years 2000 - 2002 (group 2000) and 2007 - 2009 (group 2008). Methods We conducted a retrospective study of 158 patients who were hospitalized due to HF between 2012 and 2014 (group 2013) in the Department of Cardiology, Fukuoka University Hospital. We analyzed the clinical characteristics and medications at admission and discharge, and compared the findings in group 2013 to those in group 2000 and group 2008. Results The major causes of HF were ischemic heart disease, hypertensive cardiomyopathy, valvular heart disease, and dilated cardiomyopathy. The New York Heart Association classification in group 2013 was significantly higher than those in group 2000 and group 2008. There was no difference in the level of brain natriuretic peptide at admission between group 2008 and group 2013. Tolvaptan began to be administered in group 2013. The median dose of furosemide just before the use of tolvaptan was 40 mg/day. At discharge, group 2013 showed higher rates of β-blocker and aldosterone antagonist. There was no difference in the frequency of loop diuretics. The dose of carvedilol at discharge was only 6.2 ± 4.0 mg/day. Antiarrhythmic drugs and β-blocker were used more frequently in HF with reduced ejection fraction (EF) than in HF with preserved EF. Conclusions We may be able to improve the clinical outcome of HF by examining the differences in the clinical characteristics and medications at admission and discharge in hospitalized patients with HF.

Acute Myocardial Infarction in a 26-Year-Old Patient With Familial Hypercholesteremia

A 26-year-old male suffered sustained chest pain. Electrocardiogram showed ST-segment elevation in the anteroseptal wall and reciprocal ST-segment change in the inferior wall. The troponin-I level and the white blood cell count were elevated. We gave a diagnosis of acute myocardial infarction. He underwent urgent coronary angiography, which revealed 90% diffuse stenosis in the middle right coronary artery and total occlusion in the proximal left anterior descending coronary artery (LAD). Since the electrocardiogram indicated that the culprit lesion was in the proximal LAD, we performed percutaneous coronary intervention. The coronary flow in the LAD was classified as thrombolysis in myocardial infarction trial 3. His coronary risk factors were obesity, smoking, family history, hypertension and diabetes, in addition to heterozygous familial hypercholesteremia (FH). Herein, we describe the case of a young patient with acute anteroseptal myocardial infarction and discuss the potential importance of controlling cholesterol levels in FH.