The Scottish Heart and Arterial Risk Prevention (SHARP) survey of cardiovascular risk: regional differences.

The objective was to explore variation in cardiovascular risk profiles within the Scottish workforce over different regions of Scotland by a planned review of survey data of workplaces throughout Scotland, surveyed between December 1991 and March 1996. The subjects sampled were 19,400 men and women aged between 18 and 70, who were in work and apparently healthy at the time of screening. The results showed that the regions of Scotland may be distinguished through particular risk factors and also by using a single summary score (the SHARP risk score). Overall the Perth and Kinross region tops the league for cardiovascular risk (with the main contributing factors being smoking and high blood pressure); regions of least risk are Inverness-shire and Edinburgh. There are statistically significant differences to be discerned in the regional distribution of cardiovascular risk within the working population of Scotland.

Results of a survey of cardiovascular risk factor prevalence amongst health care workers. The Executive Committee of SHARP--(Scottish Heart and Arterial Risk Prevention).

Summary analyses of screening data were used to ascertain the cardiovascular risk profile in a sample of health care workers in Scotland. A sample of NHS staff (298 women and 78 men) were screened during visits to Perth Royal Infirmary (PRI) in 1996 and 1997. Comparisons were made within subsets and with previous screening studies. Health care workers have been a neglected component of the workforce for receiving education about risk factors. The high prevalence of smokers found in this sample should be a cause for concern.

A mobile screening unit, practicalities and problems.

The need for a mobile screening unit to travel throughout Scotland to measure and modify cardiovascular risk factors in the apparently healthy working population was fulfilled by the conversion of a double-decker bus. The aim of the project was to assess the incidence of risk factors in healthy individuals and to modify their risk factors by individual counselling. Many unforeseen practical problems were encountered and overcome during the planning stage and during the project. The team of specially trained staff spent three and a half years screening more than 20,000 people throughout Scotland. This project provides a model for other screening projects involving a multicentre/scattered cohort.

Clopidogrel compatibility with concomitant cardiac co-medications: a study of its interactions with a beta-blocker and a calcium uptake antagonist.

The safety and pharmacodynamic compatibility of clopidogrel with medications commonly used in patients with atherosclerosis, such as, a beta-adrenergic receptor antagonist (atenolol) and a calcium uptake inhibitor (nifedipine) were assessed. Atenolol and nifedipine interactions with clopidogrel were studied in patients with peripheral arterial obstructive disease taking a well-established regimen of nifedipine (N group of 6 patients) and in patients with coronary artery disease taking a well-established regimen of either atenolol (A group of 8 patients) or of atenolol and nifedipine (AN group of 8 patients). The study was conducted as a double-blind, randomized, crossover comparison of clopidogrel, 75 mg once daily, and placebo treatment for 7 days, with a 14-day washout between treatments. Pharmacodynamic interactions between atenolol and nifedipine, either alone or in combination, and clopidogrel were assessed primarily on the clinical control of angina or hypertension and, secondarily, by comparing the extent of inhibition of ADP (5 microM)-induced platelet aggregation achieved between the 3 groups. The mean number of anginal episodes per patient during the placebo week was 1.50, 9.0 and 11.5 in the A, N and AN groups, respectively; during the week of clopidogrel treatment, it was 1.39, 7.3 and 9.0, respectively, indicating no change in occurrence. Likewise, review of the use of nitrates (long or short acting) did not suggest any major change in usage during any period of the study. ECGs did not change between the three recording times (at screening and at the end of each treatment period). Vital signs were also unchanged throughout. Percent inhibition of platelet aggregation on day 7 was 31% in the N group, 39% in the A group, 28% in the AN group, and 33% overall. In conclusion, the coadministration of clopidogrel did not interfere with the clinical control of hypertension or angina established with atenolol or nifedipine, or both. Clopidogrel retained its full antiplatelet effect, and there were no safety problems caused by the coadministration.

Antiplatelet therapy for secondary stroke prevention.

The precise role of antiplatelet therapy in secondary stroke prevention remains a matter of some debate. Although specific antiplatelet agents (notably aspirin, ticlopidine, dipyridamole, and clopidogrel) have been shown to be active in the prevention of secondary stroke, questions remain about the effective dose of these agents and their potential efficacy in combined therapeutic regimens. In addition, haematological and gastrointestinal side-effects of antiplatelet agents remain a significant clinical concern for patients and prescribing physicians. This review article examines research on both monotherapy and combination antiplatelet therapy for secondary stroke prevention, with an emphasis on lessons learned about dosage schedules, treatment protocols, and side-effect profiles.

Secondary stroke prevention with low-dose aspirin, sustained release dipyridamole alone and in combination. ESPS Investigators. European Stroke Prevention Study.

Patients who had survived a stroke or transient ischaemic attacks (TIA) were admitted to a trial of low-dose aspirin (50 mg) alone, sustained release dipyridamole (400 mg/day) alone, or a combination of the two agents, and results compared with a placebo over 24 months. This low-dose aspirin regimen produced in pairwise comparisons a significant risk reduction of 18% for stroke, 13% for stroke and/or death but no reduction in all cause mortality. The sustained release dipyridamole produced a significant risk reduction of 16% for stroke, 15% for stroke and/or death but no significant reduction of mortality. In combination, aspirin and dipyridamole produced a risk reduction of 37% in stroke, 24% in stroke and/or death, and no reduction in mortality. Similar findings were found in TIA, which was a secondary endpoint. These results are highly significant in comparison with placebo. As expected, there were enhanced reports of alimentary side-effects in the aspirin groups and also enhanced bleeding. Dipyridamole was associated with a slight increase in headache, which resolved in most patients if therapy was continued. The conclusions are that 50 mg/day of aspirin alone or 400 mg/day of sustained release dipyridamole alone are equally effective in stroke and TIA prevention. When used in combination the effects were additive and were significantly more effective than the single agents.

Secondary prevention of stroke--an update.

Stroke disease remains a national priority due to the high morbidity and mortality. Good clinical practice dictates that risk factors are identified and corrected. Various therapeutic regimens have been tested in trials of sufficient strength to give answers. In the second European Stroke Prevention Study (ESPSZ), low dose aspirin (50 mg/d), sustained release dipyridamole (200 mg/d) were shown to reduce recurrence of stroke and TIA. The combination was twice as effective. Also in the Clopidogrel/aspirin Prevention of Recurrence of Ischaemic Events (CAPRIE) trial clopidogrel was shown to be superior to aspirin. In clinical practice patients with stroke or TIA should be investigated rapidly, their risk factors corrected and appropriate drug regimens implemented.

Are safety committees really safe?

In an increasing number of recent major clinical trials, independent safety committees or safety monitors have been involved. Their role and function is not yet defined and continues to evolve. The aim of this paper is to discuss the role and tasks of safety committees as a result of our collective experience as members of three safety committees of studies evaluating antithrombotic prophylaxis against postoperative deep vein thrombosis. We believe that the type of pharmacological intervention used is of less importance than the general experiences gained, which can be extrapolated to other studies and should stimulate a more general debate.

Heart and arterial disease risk factors measured in an office workforce: changes from 1993 to 1996. The Scottish Heart and Arterial Risk Prevention Group (SHARP).

Screening for cardiovascular risk factor prevalence was arranged in an office workforce in Scotland with two screenings taking place three years apart, in order to measure and attempt to modify individual risk factor profiles, and in order to explore the nature and extent of any changes. There were some increases over time for both sexes, with increased tobacco usage for men, significant increases in diastolic blood pressure for both sexes and a significant increase in mean cholesterol levels for women. A separate analysis was restricted to those individuals screened on both occasions and sought to explore the effect of personal counselling and advice: in fact there were significant increases in tobacco usage for women, with more starting smoking than stopping, and for both sexes there were significant rises in cholesterol levels and increases in body mass index for many individuals. There was significantly increased use of wine and spirits by both sexes.

Recurrence-free long-term survival after liver transplantation for hepatitis B using interferon-alpha pretransplant and hepatitis B immune globulin posttransplant.

OBJECTIVE: The authors determined whether pretransplant reduction of hepatitis B virus (HBV) load using alpha-interferon-2b (IFN) and passive immunoprophylaxis using hepatitis B immunoglobulin (HBIg) posttransplantation can prevent HBV recurrence in patients undergoing liver transplantation (LT) for HBV cirrhosis. SUMMARY BACKGROUND DATA: Liver transplantation in patients with HBV cirrhosis is associated with a high rate of recurrence and reduced survival. In patients with evidence of replicating virus (HBV-DNA or hepatitis B e antigen [HBeAg]-positive serum or both), recurrence is nearly universal. Passive immunoprophylaxis with HBIg alone is not effective in preventing HBV recurrence posttransplant, especially in patients with evidence of active viral replication pretransplant. Higher doses of HBIg posttransplant has reduced recurrence rates to 30% to 50%. Lamivudine, a nucleoside analogue that has shown early promise, also is associated with significant HBV recurrence. The authors report a reliable method of preventing viral recurrence in patients even with evidence for active HBV replication pretransplant. METHODS: Pretransplant patients with evidence of replicating HBV were given IFN starting at 1 million IU 3 times per week subcutaneously. This dose was increased to 2 and then 3 million IU 3 times per week when patient's side effects permitted and was maintained until the patient underwent a LT. All patients were tested every 4 weeks for hepatitis B surface antigen (HBsAg), HBeAg, and HBV-DNA. When patients became negative for HBeAg and HBV-DNA, they were listed for LT. Patients that were only HBsAg positive were listed immediately and received a LT without prior IFN treatment. Post-LT, all patients began receiving HBIg 2000 IU (10 mL) daily from days 1 to 20 and then weekly for the first 2 years. After 2 years, all patients received 2000 IU (10 mL) monthly. Additional HBIg immunoprophylaxis was given during intense immunosuppression for rejection. Posttransplant serum was tested for HBsAg, HBeAg, and HBV-DNA in all patients 1 week, 1 month, and every 3 months thereafter. Liver biopsies were done at least yearly and when liver enzymes were abnormal and were always tested for HBsAg and HBcAg by immunoperoxidase. RESULTS: Thirteen patients with decompensated HBV cirrhosis were transplanted. Pretransplant, eight patients had evidence of active viral replication at the initial assessment (HBeAg or HBV-DNA-positive serum or both). All eight were successfully treated with IFN (median duration, 24 weeks; range, 8-53) and converted to a negative status before transplantation. Side effects from IFN were minimal and well tolerated, except in one patient who required 6 million IU to convert to a nonreplicating status. The five patients that were only HBsAg positive were not treated with IFN pretransplant. After surgery, HBIg given as described achieved consistently serum levels greater than 1000 IU/L. Twelve of the 13 patients are alive with normal liver function and without serologic evidence of HBV recurrence at a median follow-up of 32 months (range, 9-56 months). None have evidence of HBV recurrence as measured by serum HBsAg/HBeAg/HBV-DNA at recent follow-up. The sera of the seven longest survivors has tested negative for HBV-DNA using the polymerase chain reaction method. In addition, a liver biopsy was obtained in six of these patients, the results of which also tested negative for HBV-DNA using polymerase chain reaction. Liver biopsy specimens have been negative for the presence of HBsAg and HBcAg by immunoperoxidase staining in all 12 patients. CONCLUSION: A reduction of viral load pretransplant with IFN and posttransplant HBIg prevents recurrence of hepatitis B and permits LT for HBV cirrhosis, even in patients with evidence of replicating virus. The IFN pretransplant was well tolerated, and the small frequent dosing of HBIg posttransplant did not cause side effects while achieving serum levels > 1000 IU/L.

European stroke prevention study 2: dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.

In 1988, an optimal antiplatelet regimen for secondary stroke prevention remained to be defined. We undertook a randomised, placebo-controlled, double-blind trial to investigate the safely and efficacy of low-dose acetylsalicylic acid (ASA), modified-release dipyridamole, and the two agents in combination. Patients with prior stroke or transient ischaemic attack (TIA) were randomised to treatment with ASA alone (50 mg daily), modified-release dipyridamole alone (400 mg daily), the two agents in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death. TIA and other vascular events were secondary endpoints. Patients were followed on treatment for two years. We concluded that dipyridamole, in a modified-release form, at a dose of 200 mg b.d. and ASA 25 mg b.d., have been shown to be equally effective in the secondary prevention of ischaemic stroke and TIA; that when co-prescribed, the protective effects are additive, the combination being significantly more effective than each agent prescribed singly; and that low-dose ASA does not eliminate the propensity for induced bleeding.

Heart and arterial disease risk factor levels in the Scottish workforce: cross-sectional study of risk factor levels. The SHARP Committee. Scottish Heart and Arterial Disease Risk Prevention.

Between 1991-93 a specially trained team of nurses screened 19,435 subjects from various workforces in different regions of Scotland to identify cardiovascular disease risk factor levels in the Scottish working population. The regions visited provided a wide geographical spread. Name, age, occupation, social class, personal and family history of cardiovascular disease were recorded along with consumption of tobacco, alcohol and salt. Height and weight were measured and Body Mass Index (BMI) calculated; systolic (SBP) and diastolic (DBP) blood pressure, blood glucose and blood cholesterol were also measured. The proportion of social class I-IV in men studied was 49, 22, 22, and 7% respectively and in women 28, 29, 39 and 5%. Fifty two per cent of men and 61% of women had never smoked and 24% of men and 17% of women had previously stopped smoking. Twenty one per cent of both sexes were still smoking. Eighteen per cent of men drank more than 21 units of alcohol per week and 3.4% of women drank more than 14 units per week. Mean values of SBP and DBP increased with age and the percentage with hypertension (> or = 148/90 mm Hg) in men and women was 5% and 24% respectively. Mean BMI was slightly higher in men than women (25.3 & 24.5 respectively) and there was a significant (p < 0.01) rise in BMI with age in both sexes. Forty six per cent of men and 32% of women were classified as overweight (BMI > 25) while 9% of men and 9% of women were classified as obese (BMI > 30).(ABSTRACT TRUNCATED AT 250 WORDS)