Antiplatelet effect of 50-mg maintenance dose of clopidogrel compared to 200 mg ticlopidine: a preliminary study.

In the United States and Europe, patients with coronary stents are maintained on 75 mg clopidogrel. Because the maintenance dose of ticlopidine in patients with coronary stents is 100 mg twice daily in Japan and 250 mg twice daily in the United States and Europe, in Japanese patients a lower dose of clopidogrel may achieve an antiplatelet effect comparable to 200 mg ticlopidine. Platelet aggregation was evaluated in 104 consecutive patients on 50 mg clopidogrel plus aspirin (n = 54) and 200 mg ticlopidine plus aspirin (n = 50). Platelets were stimulated with adenosine diphosphate (5 and 20 mumol/l) and aggregation was assessed by optical aggregometry. There was no significant difference in platelet aggregation induced with 5 (37% +/- 11% vs 38% +/- 15%, not significant) and 20 mumol/l adenosine diphosphate (48% +/- 13% vs 51% +/- 12%, not significant) between 50 mg clopidogrel and 200 mg ticlopidine. In Japanese patients, there is the possibility that a maintenance dose of 50 mg clopidogrel on platelet inhibition is comparable to 200 mg ticlopidine.

Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia.

BACKGROUND: Injection of bone marrow mononuclear cells has been reported to promote neovascularization of ischemic tissues effectively. We found that peripheral blood mononuclear cells were as efficient as bone marrow mononuclear cells for the treatment of limb ischemia in animals and showed that this treatment was feasible and safe in no-option patients with limb ischemia. However, the long-term outcome of such therapy has not been investigated. METHODS AND RESULTS: We retrospectively analyzed the data for 42 patients who were treated between July 2002 and December 2005 by using the log-rank test, the Kaplan-Meier method, and the Cox proportional hazard model. Improvement of ischemic symptoms was observed in 60% to 70% of the patients. The annual rate of major amputation was decreased markedly by treatment. Improvement of ischemic symptoms was less marked in arteriosclerosis obliterans (ASO) patients on dialysis compared with nonhemodialysis ASO or thromboangiitis obliterans patients. Indeed, the survival rate of these patients was lower than that of nonhemodialysis ASO or thromboangiitis obliterans patients. Major adverse events such as death, major amputation, and cardiovascular events occurred mostly in ASO patients, and most of them were on dialysis. There was no significant difference in the cardiovascular event-free rate between responders and nonresponders. The survival rate of younger responders was better than that of nonresponders. CONCLUSIONS: Although this study was not placebo-controlled and these initial results were from a retrospective analysis, injection of peripheral blood mononuclear cells might be safe and potentially effective for the treatment of limb ischemia, but caution is needed when managing ASO patients on dialysis.

Quantitative gated single-photon emission computed tomography with (99m)Tc sestamibi predicts major cardiac events in elderly patients with known or suspected coronary artery disease: the QGS-Prognostic Value in the Elderly (Q-PROVE) Study.

BACKGROUND: Although electrocardiogram-gated single-photon emission computed tomography (SPECT) may be useful in risk stratification of elderly patients with coronary artery disease (CAD), few studies have prospectively evaluated its prognostic value in this patient population. METHODS AND RESULTS: A total of 175 patients aged 75 years or more with known or suspected CAD were prospectively evaluated by stress gated SPECT using a 20-segment model and an automatic functional analysis. Patients with acute coronary syndrome within the previous 3 months, and those who underwent coronary revascularization within 3 months after the SPECT study were excluded. Outcome assessment included prespecified cardiac events and noncardiac deaths. During a mean follow-up of 3.4 years, there were 18 cardiac events: 2 cardiac deaths, 1 nonfatal myocardial infarction, 3 coronary artery bypass grafting, 5 percutaneous coronary interventions, 1 unstable angina, 4 heart failures, and 2 malignant arrhythmias. Kaplan-Meier survival estimation indicated an event-free survival rate of 98.1% at 3 years in patients without myocardial ischemia, but 79.9% in those with ischemia as documented by gated SPECT (p=0.0001). Multivariate analysis using the Cox proportional hazard model demonstrated that stress-induced myocardial ischemia was the only independent predictor for subsequent cardiac events (p<0.01). CONCLUSIONS: Stress gated SPECT predicts cardiac events in patients aged 75 years or more with known or suspected CAD and may have a role in risk stratification of this patient population.

Critical roles of muscle-secreted angiogenic factors in therapeutic neovascularization.

The discovery of bone marrow-derived endothelial progenitors in the peripheral blood has promoted intensive studies on the potential of cell therapy for various human diseases. Accumulating evidence has suggested that implantation of bone marrow mononuclear cells effectively promotes neovascularization in ischemic tissues. It has also been reported that the implanted cells are incorporated not only into the newly formed vessels but also secrete angiogenic factors. However, the mechanism by which cell therapy improves tissue ischemia remains obscure. We enrolled 29 "no-option" patients with critical limb ischemia and treated ischemic limbs by implantation of peripheral mononuclear cells. Cell therapy using peripheral mononuclear cells was very effective for the treatment of limb ischemia, and its efficacy was associated with increases in the plasma levels of angiogenic factors, in particular interleukin-1beta (IL-1beta). We then examined an experimental model of limb ischemia using IL-1beta-deficient mice. Implantation of IL-1beta-deficient mononuclear cells improved tissue ischemia as efficiently as that of wild-type cells. Both wild-type and IL-1beta-deficient mononuclear cells increased expression of IL-1beta and thus induced angiogenic factors in muscle cells of ischemic limbs to a similar extent. In contrast, inability of muscle cells to secrete IL-1beta markedly reduces induction of angiogenic factors and impairs neovascularization by cell implantation. Implanted cells do not secret angiogenic factors sufficient for neovascularization but, instead, stimulate muscle cells to produce angiogenic factors, thereby promoting neovascularization in ischemic tissues. Further studies will allow us to develop more effective treatments for ischemic vascular disease.

Assessment of myocardial perfusion and fatty acid metabolism in a patient with Churg-Strauss syndrome associated with eosinophilic heart disease.

Churg-Strauss syndrome is characterized by asthma, eosinophilia and systemic necrotizing vasculitis; cardiac involvement (ie, eosinophilic heart disease) is the major cause of morbidity and mortality, although there are no reports of an association between left ventricular dysfunction because of eosinophilic heart disease and myocardial blood flow or myocardial fatty acid metabolism. A patient presented with Churg-Strauss syndrome associated with eosinophilic heart disease that had progressed to dilated cardiomyopathy. Coronary angiography, thallium-201 ((201)Tl) and iodine-123 beta-methyl-iodophenyl pentadecanoic acid ((123)I BMIPP) myocardial single photon emission computed tomography (SPECT) were performed to evaluate left ventricular dysfunction. Although coronary angiography was normal and (201)Tl SPECT showed no apparent image defect, (123)I BMIPP SPECT showed diffuse decreased accumulation, excepting the apex. The left ventricular dysfunction in patients with eosinophilic heart disease is associated with impaired myocardial fatty acid metabolism rather than with impaired myocardial blood flow.