Ticlopidine versus oral anticoagulation for coronary stenting.

BACKGROUND: A 2-4 week course of ticlopidine plus aspirin following coronary stenting is considered effective in preventing thrombotic occlusion of the stented vessel and safe in regards to bleeding and peripheral vascular complications. However, rare, although potentially life-threatening haematological complications have been reported with this drug regimen. OBJECTIVES: To evaluate the efficacy and safety of ticlopidine plus aspirin versus oral anticoagulants after coronary stenting SEARCH STRATEGY: Electronic search of the Cochrane Library, Medline, Embase from 1991 to June 1999; references from trials and experts. SELECTION CRITERIA: Randomised controlled trials comparing ticlopidine plus aspirin versus oral anticoagulants (either with or without aspirin) after elective or bail out coronary stenting. DATA COLLECTION AND ANALYSIS: Three reviewers assessed trial quality and compiled data on outcomes including: total mortality, non fatal myocardial infarction and revascularization occurring within the first 30 days after hospitalization, stent thrombosis on angiography, major and minor bleeding, neutropenia, thrombocytopenia, thrombotic thrombocytopenic purpura. MAIN RESULTS: Four trials (n=2436 patients) were included. Ticlopidine plus aspirin compared to oral anticoagulants significantly reduced the risk of non-fatal acute myocardial infarction and revascularization at 30 days, combined negative events (mortality, myocardial infarction, revascularization at 30 days) (RR: 0.41; 95% CI: 0.25-0.69; NNT for 30 days: 22; 95% CI: 14-45), and major bleeding (RR in high quality studies: 0.24; 95% CI: 0.07-0.79). Ticlopidine plus aspirin compared to oral anticoagulants significantly increased the risk of eutropenia, thrombocytopenia and neutropenia (RR 5; 95% CI: 1.08-13.07; NNT for 30 days: 142; 95% CI: 76-1000). Ticlopidine plus aspirin vs oral anticoagulation did not affect all cause mortality. Ticlopidine plus aspirin significantly reduced the risk of stent thrombosis (angiography) which was seen only on studies with blinded outcome assessment (RR: 0.14; 95% CI: 0.03-0.60; NNT for 30 days: 33; 95% CI:16-166). Minor bleeding was reported only in one study and no studies recorded thrombotic thrombocytopenic purpura (TTP). REVIEWER'S CONCLUSIONS: Ticlopidine plus aspirin after coronary stenting is effective in reducing the risk of the revascularization, non fatal myocardial infarction and bleeding complications when compared with oral anticoagulants. No effect is observed on total mortality. However, the haematological side effects of ticlopidine are still a matter of concern, and strict monitoring of blood-cell counts is recommended. Physicians should also be aware of the possibility of rare although potentially life-threatening complications such as TTP

The therapeutic course as a measure complementary to defined daily doses when studying exposure to antibacterial agents.

OBJECTIVE: The defined daily dose (DDD) method may not provide accurate information about exposure to antibacterial agents, owing to their short-term use and the consequently high turnover of subjects. This study was addressed to evaluate whether the number of "therapeutic courses" could offer additional information. METHODS: Prescription data of antibacterial agents (ATC J01) in Ravenna, Italy (350,000 inhabitants), were studied in 1998. All the prescriptions issued within 10 days were considered as belonging to one therapeutic course (TC). The following measures were compared: DDD/1000 inhabitants/year, number of exposed subjects/1000 inhabitants/year and number of TC/1000 inhabitants/year. In order to compare the number of 10-day TCs with the number of DDDs, the latter was divided by 10 (DDD10). The intensity of drug treatment was also evaluated as the average number of DDDs per TC (therapeutic intensity). RESULTS: Sixty-one percent of the subjects received only one prescription in 1998. Among the second prescriptions, 69% were issued after a time interval greater than 21 days. The overall prevalence of use was 329 per 1000 inhabitants, the TCs were 525 per 1000 inhabitants and DDD10/1000 inhabitants/year were 470. The therapeutic intensity varied with the age classes (being lowest in the elderly) and with the individual antibiotics used. Two or more antibacterials were used within the same TC in 7% of the cases. CONCLUSION: The measures considered in this study provided different estimates of exposure to antimicrobial agents. The combined analysis of DDDs and TCs may offer a more reliable information about exposure to antimicrobial agents.

Pattern of antibiotic use in primary health care in Italy.

OBJECTIVE: The overuse and misuse of antibiotics have been related to the growing emergence of bacterial resistance. The aim of the present study was to assess the pattern of antibiotic use by Italian general practitioners (GPs) in the treatment of the most frequent infectious problems. METHODS: The study was performed with 131 GPs recruited on a voluntary basis from among the 181 GPs contacted in two Italian regions, Emilia Romagna and Umbria. GPs were requested to report all the infectious events encountered during six sample weeks on a special form, whether an antibiotic was administered or not. RESULTS: The GPs reported 7095 infectious cases, of which 5036 (77%) were respiratory-tract infections (RTIs) and 749 (11%) were urinary-tract infections (UTIs). Antibiotics were prescribed in 71% of the cases. The proportion of antibiotic-treated cases was highest in UTIs (97%), followed by lower respiratory-tract infections (LRTIs; 93%) and upper respiratory-tract infections (URTIs; 54%). Drugs belonging to 16 Anatomical Therapeutical Chemical groups (fourth level) were used. Wide-spectrum penicillins and macrolides ranked first (23%), followed by penicillins plus beta-lactamase inhibitors (15%), cephalosporins (15%) and fluoroquinolones (10%). The most prescribed antibiotics for the major disease groups were wide-spectrum penicillins for URTIs (36%), macrolides and cephalosporins for LRTIs (27% each) and fluoroquinolones for UTIs (46%). CONCLUSIONS: The present survey showed a high level of inappropriate use. In fact, a large number of infectious diseases, including infections commonly caused by viral agents, were treated with an anti-bacterial drug. Italian GPs had a tendency to preferentially prescribe wide-spectrum antibiotics and to use, in many cases, antibiotics that are rarely of choice in primary health care, such as cephalosporins and fluoroquinolones. In order to attain a more evidence-based prescription, local guidelines shared by specialists and GPs should be implemented.

[Pharmaco economics aspects of antibiotic therapy for AIDS patients in department of infectious disease]. / La spesa per la terapia antibiotica e chemioterapica in un reparto di malattie infettive per i malati con infezione HIV.

The financial budget for public health care in Italy has been more and more restricted in the last few years, but, on the other hand, the care of AIDS patients is still very expensive and antibiotic therapy plays an important role in the management and cost of these patients. The antibiotic therapies and related costs have been evaluated in 99 patients affected by AIDS (59 pts), ARC (28 pts) or HIV serum positive (12 pts), all hospitalized or treated in Day Hospital for different bacterial infections in 1995 at the Department of Infectious Diseases, Ospedale Maggiore, Bologna, for a total of 7733 days of antibiotic therapy. The average cost for antibiotic therapy was about 400,000 Italian Lira, with no significant difference depending on the stage of HIV related disease. The crude cost for antibiotic treatment was not particularly high, but the high frequency of adverse events, registered in these patients, required additional medical support and/or a prolonged hospital stay, which increased substantially the total cost of management of bacterial infections.