Comparative effectiveness of novel oral anticoagulants for atrial fibrillation: evidence from pair-wise and warfarin-controlled network meta-analyses.

INTRODUCTION: Novel oral anticoagulants have been tested against warfarin for atrial fibrillation, yet no direct comparison is available. We thus aimed to perform pair-wise (direct) and warfarin-adjusted network (i.e. indirect) meta-analyses of novel oral anticoagulants for atrial fibrillation. METHODS: Databases were searched for randomized warfarin-controlled trials of novel anticoagulants for non-valvular atrial fibrillation. The primary end-point was long-term stroke/systemic embolism. Odds ratios (95% intervals) were computed with RevMan and WinBUGS. RESULTS: Seven trials (52701 patients) were included, focusing on apixaban, dabigatran, edoxaban and rivaroxaban. Pair-wise meta-analysis showed that after a weighted average of 23 months these novel anticoagulants lead to significant reductions in the risk of stroke/systemic embolism (odds ratio=0.81 [0.71-0.92], I2=23%) and all cause death (odds ratio=0.88 [0.82-0.95], I2=0%) in comparison to warfarin. Network meta-analysis showed that apixaban and dabigatran proved similarly superior to warfarin in preventing stroke/systemic embolism (odds ratio=0.78 [0.62-0.96] for apixaban vs warfarin; odds ratio=0.66 [0.52-0.84] for high-dose dabigatran vs warfarin; odds ratio for apixaban vs high-dose dabigatran=1.17 [0.85-1.63]), but apixaban was associated with fewer major bleedings (odds ratio=0.73 [0.57-0.93]) and drug discontinuations (odds ratio=0.64 [0.52-0.78]) than dabigatran. Rivaroxaban did not reduce stroke/systemic embolism (odds ratio=0.87 [0.71-1.07]) or major bleedings in comparison to warfarin (odds ratio=0.87 [0.71-1.07]) and was associated with more major bleedings in comparison to apixaban (odds ratio=1.52 [1.19-1.92]). Data for edoxaban were inconclusive. CONCLUSIONS: Novel oral anticoagulants appear as a very promising treatment option for atrial fibrillation.

Management of syncope referred urgently to general hospitals with and without syncope units.

OBJECTIVE: We tested the hypothesis that management of patients with syncope admitted urgently to a general hospital may be influenced by the presence of an in-hospital structured syncope unit. BACKGROUND: The management of syncope is not standardized. Methods We compared six hospitals equipped with a syncope unit organized inside the department of cardiology with six matched hospitals without such facilities. The study enroled all consecutive patients referred to the emergency room from 5 November 2001 to 7 December 2001 who were affected by transient loss of consciousness as their principal symptom. RESULTS: There were 279 patients in the syncope unit hospitals and 274 in the control hospitals. In the study group, 30 (11%) patients were referred to the syncope unit for evaluation. In the study group, 12% fewer patients were hospitalized (43 vs 49%, not significant) and 8% fewer tests were performed (3.3+/-2.2 vs 3.6+/-2.2 per patient, not significant). In particular, the study group patients underwent fewer basic laboratory tests (75 vs 86%, P=0.002), fewer brain-imaging examinations (17 vs 24%, P=0.05), fewer echocardiograms (11 vs 16%, P=0.04), more carotid sinus massage (13 vs 8%, P=0.03) and more tilt testing (8 vs 1%, P=0.000). In the study group, there was a +56% rate of final diagnosis of neurally mediated syncope (56 vs 36%, P=0.000). CONCLUSION: Although only a minority of patients admitted as an emergency are referred to the syncope unit, overall management is substantially affected. It is speculated that the use of a standardized approach, such as that typically adopted in the syncope unit, is able to influence overall practice in the hospital.

Double-blind, multicenter, randomized trial to compare the effect of two doses of adrenocorticotropic hormone versus placebo in controlling delayed emesis after high-dose cisplatin in adult patients with cancer.

PURPOSE: To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation of adrenocorticotropic hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND METHODS: One hundred fifty-two patients were enrolled onto the study. On day 1, all patients received cisplatin (60 to 120 mg/m2) and a combination of dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis. On day 2 (24 hours after cisplatin administration), patients were randomized to receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse effects were recorded daily for every 24-hour period from day 2 to day 6. In a subset of patients, serum cortisol levels were measured between 20 and 72 hours after cisplatin administration. RESULTS: One hundred fifty patients were assessable. Over the 5 days of the study, delayed vomiting occurred less frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant differences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH injection, but was suppressed for approximately 44 hours in the placebo group. Toxicity was mild and transient in all groups. CONCLUSION: ACTH reduces the incidence and severity of delayed vomiting and nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than one of 1 mg. Whether the activity of ACTH is mediated only by adrenal corticosteroids needs to be verified.

[Current approaches in the medical treatment of advanced ovarian carcinoma]. / Attuali orientamenti nella terapia medica del carcinoma ovarico in fase avanzata.

Ovarian cancer is most frequently diagnosed at an advanced stage. In recent years there has been intense interest in the chemotherapy of this disease. About cisplatin, the most active agent in the treatment of advanced ovarian cancer, some questions are only partially answered, as the optimal dose, the duration of treatment, the role of ciplatin-based two-, three-, or four-drug regimens, the role of intraperitoneal therapy, the use of old and new drugs in cisplatin-resistant patients. Carboplatin is currently the most important cisplatin analogue with a toxicity pattern very different from that of the parent compound, but, up to date, the combination of these two drugs does not seem to be any better than standard chemotherapy. Among new drugs, three deserve particular attention: taxol, a natural produce from the bark of the Pacific yew Taxus brevifolia, taxotere, a taxoid obtained by semisynthesis from the needles of the European yew Taxus baccata and gemcitabine, a cytostatic agent with a close resemblance to cytosine-arabinoside. Anyway, new approaches must continue to be sought too: among these, probably gene therapy may offer the best mechanism to overcome both intrinsic and acquired drug resistance.

Hyperglycemia and prognosis of acute myocardial infarction in patients without diabetes mellitus.

The present study assessed the prognostic value of hyperglycemia--a common feature in the early phase of acute myocardial infarction (AMI)--in 330 nondiabetic patients. Seventy-nine known diabetics and 10 (3%) unknown diabetics--diagnosed before discharge by stable glycosylated hemoglobin greater than 6.9% and by oral glucose tolerance testing--were excluded. Thirty-three (10%) patients died. The mortality rate was higher in women, in patients with anterior AMI, in older patients (greater than 65 years) and in the presence of heart failure. It was highest in patients with cardiogenic shock (24/36 vs 9/294; p less than 0.0001). Admission plasma glucose was significantly higher in nonsurvivors than in survivors (163 +/- 60 vs 114 +/- 36 mg/dl; p less than 0.0001). Mortality rate increased with increasing admission plasma glucose: 3% in normoglycemic patients (less than or equal to 120 mg/dl) versus 15% in patients with borderline plasma glucose (121 to 180 mg/dl) versus 43% in hyperglycemic patients (greater than 180 mg/dl) (p less than 0.0001). Multiple regression (stepwise) analysis identified cardiogenic shock, infarct site and age as the major determinants of mortality, while admission plasma glucose failed to reach full statistical significance (p = 0.067). Hyperglycemia was related to all 3 of these independent prognostic factors; when age and infarct site were accounted for, hyperglycemia was significantly associated with heart failure only and this association was characterized by a remarkable mortality rate. In nondiabetic patients with AMI, hyperglycemia is a correlate of heart failure and, therefore, an important factor of prognosis.