Antiplatelet cilostazol is beneficial in diabetic and/or hypertensive ischemic stroke patients. Subgroup analysis of the cilostazol stroke prevention study.

BACKGROUND AND PURPOSE: Although antiplatelets are known to be effective for secondary prevention of cerebral infarction, the number needed to treat is rather large and the effects in stroke patients with complications such as hypertension or diabetes are inadequately defined. This study was conducted to examine the effect of such complications on recurrence of cerebral infarction, and to assess the effect of cilostazol, an antiplatelet agent, in these high-risk subjects. METHODS: A post hoc subgroup analysis of the already reported Cilostazol Stroke Prevention Study, which was a placebo-controlled double-blind trial, has been carried out to clarify the influence of various complications on recurrence in the placebo group and the effects of cilostazol in 1,095 patients with noncardioembolic ischemic cerebrovascular disease. Treatment continued for an average of 1.8 +/- 1.3 years (maximum 4.8 years). RESULTS: The recurrence rate of the diabetic stroke patients was significantly higher compared with the nondiabetics in the placebo group (9.4 vs. 4.7%/year, p = 0.01). Furthermore, our study showed that the relative risk reduction (RRR) for recurrence of infarction was 41.7% with cilostazol. This treatment provided a significant benefit in patients with lacunar infarction (RRR 43.4%, p = 0.04), with diabetes (RRR 64.4%, p = 0.008), or with hypertension (RRR 58.0%, p = 0.003). CONCLUSIONS: Diabetic patients are particularly at risk for recurrence of cerebral infarction. Cilostazol is useful for the prevention of the recurrence of vascular events in patients with lacunar infarction, and is probably effective in high-risk patients with diabetes and/or hypertension.

Long-term results of a multicenter randomized, comparative trial of modified CHOP versus THP-COP versus THP-COPE regimens in elderly patients with non-Hodgkin's lymphoma.

In treating elderly non-Hodgkin's lymphoma (NHL) patients, it is particularly important to use drugs that have a low incidence of adverse events and high efficacy. In this multicenter study, THP (pirarubicin)-COP (cyclophosphamide, vincristine, and prednisolone) was compared to two thirds dosage of full CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen with regard to both adverse events and efficacy. For a third group, etoposide (E) was added to the THP-COP regimen (THP-COPE) in order to achieve high dose-intensity. Subjects were 486 previously untreated patients, aged 65 or older (range, 65-92 years; median, 74 years), with NHL. Subjects were randomly assigned to receive THP-COP, two thirds CHOP, or THP-COPE. Four hundred and forty-three patients were assessed for response and followed for 8 years after the last subject registered. The complete remission rates for the THP-COP, CHOP, and THP-COPE groups were 42.5%, 41.4%, and 48.0%, respectively. There was no difference in overall survival or progression-free survival among these 3 groups. In aggressive lymphoma, there was also no difference in complete response (CR) rate (45.3% in THP-COP, 44.9% in CHOP, 48.0% in THP-COPE), overall survival, and progression-free survival among these groups. The 5- and 8-year survival rates for all patients were 29.4% and 18.7%, respectively. The 5- and 8-year survival rates for patients with aggressive lymphoma were 27.4% and 17.4%, respectively. Although long-term survival for patients with aggressive lymphoma on our regimens was not worse compared to previous reports, the CR rate was lower. Because severe adverse events were not observed, higher dose chemotherapy may be directed to achieve better CR rates. In patients with T-cell-type lymphoma, the CR rate was greater after treatment with THP-COP (51.4%) or THP-COPE (57.7%) compared to treatment with CHOP (19.4%). Pirarubicin may be more useful for T-cell lymphoma than doxorubicin. Because adverse cardiac events were reported only in CHOP, adverse cardiac events might be low in the THP group.

Atorvastatin reduces plasma levels of factor VII activity and factor VII antigen in patients with hyperlipidemia.

Atorvastatin is a powerful new synthetic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor currently in clinical use. Its effects on plasma levels of factor VII were examined in 30 hyperlipidemic patients. After 12 weeks of atorvastatin treatment, factor VII activity (FVIIc) and factor VII antigen (FVIIag) levels had decreased by 13% (p < 0.0001) and 12% (p < 0.0001), respectively. The decreased concentrations of serum triglycerides correlated with decreases in FVIIc levels (r = 0.54, p = 0.0023) and FVIIag levels (r = 0.59, p = 0.0006) at 12 weeks of treatment with atorvastatin. No significant changes were seen in activated factor VII (FVIIa) levels. Plasma concentrations of fibrinogen were slightly, but not significantly, increased at 12 weeks. No significant changes were seen in plasminogen activator inhibitor-1 levels. The effects of atorvastatin on FVII may contribute to a decreased thrombotic potential, resulting in fewer thromboembolic events, including a reduction in coronary heart disease.

A comparative double-blind randomized trial of activated protein C and unfractionated heparin in the treatment of disseminated intravascular coagulation.

A randomized prospective double-blind trial was performed to compare the safety and efficacy of human activated protein C (APC) and unfractionated heparin for the treatment of disseminated intravascular coagulation (DIC). One hundred thirty-two patients with DIC were enrolled in this study: 63 patients received APC (12.5 U [2.5 microg]/kg body wt per hour) and 69 patients received heparin (8 U/kg body wt per hour) by intravenous infusion for 6 days. Forty-nine APC-treated patients and 55 heparin-treated patients were evaluated for efficacy, and 52 APC-treated patients and 55 heparin-treated patients were evaluated for safety. The 2 groups were similar with respect to sex, age, body weight, underlying diseases, and coagulation/fibrinolysis parameters before treatment. Aggravation of bleeding was seen after treatment in 8 patients receiving heparin, but in none of the patients receiving APC. The number of patients who showed alleviation of bleeding was significantly higher in the APC group than the heparin group (P = .009). The effects on DIC-related organ dysfunction were not significantly different between the 2 groups. Fibrinogen-fibrin degradation products, D-dimer, thrombin-antithrombin complex (TAT), and plasmin-plasmin inhibitor complex (PIC) were all significantly decreased by treatment in both groups. Fibrinogen, protein C, and antithrombin were significantly increased in the APC group, whereas only protein C was significantly increased in the heparin group. Platelet count in the nonleukemic group was significantly increased in those patients receiving APC but not increased in those patients receiving heparin. Improvement of coagulation/fibrinolysis was assessed by scoring 4 parameters (soluble fibrin monomers, D-dimer, TAT, and PIC), and the results indicated that the APC group showed significantly greater improvement than the heparin group (P = .046). There was, however, no significant difference in the rate of complete recovery from DIC between the 2 groups. The rate of death from any cause within 28 days after treatment was 20.4% in the APC group, significantly lower than the 40% death rate observed in the heparin group (P < .05). There were no severe adverse events in either group. These results suggest that APC in a relatively small dosage can improve DIC more efficiently than can heparin, without increasing bleeding, and may be a better alternative.

Efficacy of granulocyte colony-stimulating factor in the treatment of acute myelogenous leukaemia: a multicentre randomized study.

To investigate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in patients with acute myelogenous leukaemia, a multicentre randomized study was performed. From October 1993 to September 1996, 270 patients with newly diagnosed acute myelogenous leukaemia were randomized to G-CSF or control groups after remission induction therapy. The G-CSF group received G-CSF (Filgrastim) from 48 h after the completing chemotherapy until the absolute neutrophil count exceeded 1.5 x 10(9)/l. The control group did not receive G-CSF unless severe infection occurred. There were 245 evaluable patients (120 and 125 in the G-CSF and control groups respectively). The complete remission rate was similar in the G-CSF and control groups (80.8% versus 76.8%), as was the 5-year probability of disease-free survival (34.5% versus 33.6%) and overall survival (42.7% versus 35.6%). Neutrophil recovery was significantly faster in the G-CSF group than in the control group (12 d versus 18 d, P = 0.0001). The median duration of febrile neutropenia was significantly shorter in the G-CSF group than in the control group (3 d versus 4 d, P = 0.0001). In conclusion, prophylactic administration of G-CSF after remission induction therapy for acute myelogenous leukaemia is safe and useful even in patients without infection on completing chemotherapy.