Prescribing patterns of oral antiplatelets in Wales: evolving trends from 2005 to 2016.

AIM: Antiplatelets have been used for decades to prevent atherothrombotic disease, but there is limited 'real-life' prescribing data. We hereby report the prescribing patterns for oral antiplatelets in Wales, UK. METHODS/RESULTS: Retrospective analysis of anonymized data in Wales from 2005 to 2016 revealed differences in prescribing patterns of oral antiplatelets. Aspirin and dipyridamole use declined with a corresponding increase in clopidogrel prescription. Costs declined with a sharp decrease coinciding with clopidogrel coming off patent. Prasugrel and ticagrelor have shown significant cost contribution (29% of total) despite only forming 1% of total items prescribed in 2016. CONCLUSION: This first-look analysis of real-life antiplatelet data demonstrates a decrease in the overall prescribing costs with varying patterns. This may aid policy-makers in reviewing funding strategies.

Regadenoson versus Dipyridamole: A Comparison of the Frequency of Adverse Events in Patients Undergoing Myocardial Perfusion Imaging.

STUDY OBJECTIVE: To compare the frequency of adverse events in patients undergoing myocardial perfusion imaging (MPI) with either regadenoson or dipyridamole. DESIGN: Single-center, retrospective cohort study. SETTING: Large community teaching hospital. PATIENTS: A total of 568 adults who underwent single-photon emission tomography MPI with either regadenoson (284 patients) or dipyridamole (284 patients) as a vasodilator agent, following an institution conversion from regadenoson to dipyridamole in the MPI protocol on July 15, 2013, for cost-saving purposes. MEASUREMENTS AND MAIN RESULTS: Data were collected from the patients' electronic medical records. The primary endpoint was the composite occurrence of any documented adverse event in each group. Secondary endpoints were individual components of the primary endpoint, reason for termination of the MPI examination (protocol completion or premature end due to an adverse event), use of an interventional agent to an treat adverse event, and cost-related outcomes. A higher proportion of patients in the regadenoson group experienced an adverse event than those who received dipyridamole (84.9% vs 56.7%, p<0.0001). None of the patients in either group required early MPI study termination due to an adverse event. No significant differences were noted between groups regarding use of aminophylline or other interventions to treat adverse events. The overall drug cost savings in the postconversion dipyridamole group was $51,526. CONCLUSION: Dipyridamole was associated with fewer adverse events than regadenoson in patients undergoing MPI. Dipyridamole offers a safe and cost-effective alternative to regadenoson for cardiac imaging studies.

Antiplatelet therapies for secondary stroke prevention: an update on clinical and cost-effectiveness.

Stroke exacts a huge toll physically, mentally and economically. Antiplatelet therapy is the cornerstone of secondary stroke prevention, and proven drugs available to successfully realize this therapeutic strategy for the long term include aspirin, dipyridamole plus aspirin and clopidogrel. However, government agencies, corporations, health plans and patients desire more information about the clinical- and cost-effectiveness of these established therapies in real-world settings. This paper provides an update on evidence-based secondary stroke prevention with antiplatelet medications, discusses cost-related issues and offers perspective about the future.

Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events (review of Technology Appraisal No. 90): a systematic review and economic analysis.

BACKGROUND: Occlusive vascular events such as myocardial infarction (MI), ischaemic stroke and transient ischaemic attack (TIA) are the result of a reduction in blood flow associated with an artery becoming narrow or blocked through atherosclerosis and atherothrombosis. Peripheral arterial disease is the result of narrowing of the arteries that supply blood to the muscles and other tissues, usually in the lower extremities. The primary objective in the treatment of all patients with a history of occlusive vascular events and peripheral arterial disease is to prevent the occurrence of new occlusive vascular events. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of clopidogrel and modified-release dipyridamole (MRD) alone or with aspirin (ASA) compared with ASA (and each other where appropriate) in the prevention of occlusive vascular events in patients with a history of MI, ischaemic stroke/TIA or established peripheral arterial disease. To consider the clinical effectiveness and cost-effectiveness of clopidogrel in patients with multivascular disease. This review is an update of the evidence base for the National Institute for Health and Clinical Excellence (NICE) guidance Technology Appraisal No. 90 (TA90) entitled Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events (2005). DATA SOURCES: Four electronic databases (EMBASE, MEDLINE, Web of Science and The Cochrane Library) were searched for randomised controlled trials (RCTs) and economic evaluations. Submissions to NICE by the manufacturers of the interventions were also considered. REVIEW METHODS: A systematic review of clinical effectiveness and cost-effectiveness was conducted. To manage heterogeneity between trials, indirect analysis (using a mixed-treatment methodology) was performed on selected clinical outcomes. A new economic model was developed to assess incremental costs per life-year gained [quality-adjusted life-years (QALYs)]. RESULTS: For evidence of clinical effectiveness, four RCTs were identified: CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events), ESPRIT (European/Australasian Stroke Prevention in Reversible Ischaemia Trial), PRoFESS (Prevention Regimen For Effectively avoiding Second Strokes) and ESPS-2 (Second European Stroke Prevention Study). In CAPRIE (patients with MI, ischaemic stroke or peripheral arterial disease), statistically significant outcomes in favour of clopidogrel were noted for the primary outcome (first occurrence of ischaemic stroke, MI or vascular death) compared with ASA [relative risk reduction 8.7%; 95% confidence interval (CI) 0.3% to 16.5%; p = 0.043]. In ESPRIT (patients with ischaemic stroke/TIA) for the primary outcome (first occurrence of death from all vascular causes, non-fatal stroke, non-fatal MI or major bleeding complication), the risk of event occurrence was statistically significantly lower in the MRD + ASA arm than in the ASA arm [hazard ratio (HR) 0.80; 95% CI 0.66 to 0.98], with no statistically significant difference in bleeding events between the two arms. In PRoFESS (patients with ischaemic stroke) the rate of recurrent stroke of any type (primary outcome) was similar in the MRD + ASA and clopidogrel groups, and the null hypothesis (that MRD + ASA was inferior to clopidogrel) could not be rejected. In ESPS-2 (patients with ischaemic stroke/TIA), on the primary outcome of stroke, statistically significant differences in favour of MRD + ASA were observed compared with ASA and MRD alone (relative risk 0.76; 95% CI 0.63 to 0.93). The outcomes addressed in the mixed-treatment comparisons (limited by the available data) for the ischaemic stroke/TIA population confirmed the results of the direct comparisons. The 11 economic evaluations included in the review of cost-effectiveness indicated that for patients with previous peripheral arterial disease, ischaemic stroke or MI, clopidogrel is cost-effective compared with ASA, and for patients with previous ischaemic stroke/TIA, treatment with MRD + ASA is cost-effective compared with any other treatment in patients in the secondary prevention of occlusive vascular events. The relevance of the review was limited as the economic evaluations were not based on the most current clinical data. Cost-effectiveness results generated from the Assessment Group's de novo economic model suggested that the most cost-effective approach for patients with ischaemic stroke/TIA is clopidogrel followed by MRD + ASA then ASA. For patients with MI, the most cost-effective approach is ASA followed by clopidogrel. For patients with established peripheral arterial disease, the most cost-effective approach is clopidogrel followed by ASA. For patients with multivascular disease, clopidogrel followed by ASA is the most cost-effective approach. Incremental cost-effectiveness ratios (ICERs) were also calculated for patients who are intolerant to ASA. Assuming that the branded price for clopidogrel is used and TA90 guidance is not applied, all of the ICERs range between £2189 and £13,558 per QALY gained. Probabilistic sensitivity analyses were fully consistent with these findings. CONCLUSIONS: The evidence suggests that the most cost-effective treatment for patients with ischaemic stroke/TIA is clopidogrel followed by MRD + ASA followed by ASA; for patients with MI, ASA followed by clopidogrel; and for patients with established peripheral arterial disease or multivascular disease, clopidogrel followed by ASA. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

[Incremental cost-effectiveness of dipyridamole + acetylsalicylic acid in secondary prevention of ischemic noncardioembolic stroke]. / Inkrementelle Kosteneffektivität von Dipyridamol + Acetylsalicylsäure in der Sekundärprävention bei ischämischem nichtkardioembolischem Schlaganfall.

BACKGROUND AND PURPOSE: The aim of secondary prevention in stroke is to avoid restrokes. The current standard treatment in Germany is a lifelong therapy with low-dose acetylsalicylic acid (ASA). As the incidence of restrokes remains relatively high from a health-care payer's perspective, the question arises, whether the combination of dipyridamole + acetylsalicylic acid (Dip + ASA) is cost-effective in comparison with a therapy based on ASA only. METHODS: A decision-analytic cross-sectional epidemiologic steady-state model of the German population compares the effects of two strategies of secondary prevention with Dip + ASA (12 months vs. open end) and with ASA monotherapy. RESULTS: The model predicts the following estimates: the annual incidence of initial ischemic strokes in Germany is estimated at 130,000 plus an extra 34,000 restrokes (base year 2005). Additionally, there are 580,000 people that experienced a stroke > 12 months earlier, of whom 135,000 had a restroke. Every year, nearly 89,000 Germans die of the consequences of an ischemic stroke. If Dip + ASA would have been the standard therapy in secondary prevention of ischemic stroke, an additional 7,500 persons could have been saved in 2005. Statutory health insurance would have to spend 33,000 Euro for every additional life year gained with Dip + ASA as secondary prevention strategy. If secondary prevention with Dip + ASA would be limited to the first 12 months after an initial stroke, which is the time of the highest risk for a restroke, the incremental cost-effectiveness ratio is about 7,000 Euro per life year gained. The results proved to be robust in sensitivity analyses. CONCLUSION: Secondary prevention with Dip + ASA is cost-effective in comparison to treatment with ASA in monotherapy, because its incremental cost-effectiveness ratio is within common ranges of social willingness to pay. From the standpoint of the patient as well as the health-care payer, focusing on the first 12 months after the initial incident for intensified preventive drug treatment with Dip + ASA should be valuable from a medical as well as a health-economic perspective.

Prevention of secondary stroke and transient ischaemic attack with antiplatelet therapy: the role of the primary care physician [corrected].

BACKGROUND: Stroke risk is heightened among patients who have had a primary stroke or transient ischaemic attack (TIA). The primary care physician is in the best position to monitor these patients for stroke recurrence. Because stroke recurrence can occur shortly after the primary event, guidelines recommend initiating antiplatelet therapy as soon as possible. Aspirin, with or without extended-release dipyridamole (ER-DP), and clopidogrel are options for such patients. Low-dose aspirin (75-150 mg/day) has the same efficacy as higher doses but with less gastrointestinal bleeding. Clopidogrel remains an option for prevention of secondary events and may benefit patients with symptomatic atherothrombosis, but its combined use with aspirin can harm patients with multiple risk factors and no history of symptomatic cerebrovascular, cardiovascular or peripheral vascular disease. RESULTS: Low dose aspirin is effective in secondary stroke prevention. Trials assessing aspirin plus ER-DP have shown that the combination is more effective than aspirin monotherapy in preventing stroke, with efficacy increasing among higher risk patients, notably those with prior stroke/TIA. Clopidogrel does not appear to have as much advantage over aspirin in secondary stroke prevention as aspirin plus ER-DP. Smoking cessation and cholesterol, blood glucose and blood pressure control are also important concerns in preventing recurrent stroke. In choosing pharmacological therapy, the physician must consider the individual patient's risk factors and tolerance, as well as other issues, such as use of aspirin among patients with ulcers. CONCLUSION: Antiplatelet therapy is effective in secondary stroke prevention. Low dose aspirin can be used first-line, but aspirin plus ER-DP improves efficacy. Clopidogrel is another option in secondary stroke prevention, especially for aspirin-intolerant patients, but it appears to have less advantage over aspirin than aspirin plus ER-DP, and its combined use with aspirin has only marginally better efficacy and increased bleeding risk.

Cost-effectiveness of antiplatelet agents in secondary stroke prevention: the limits of certainty.

UNLABELLED: Which of the available antiplatelet therapies should be preferred for secondary prevention of recurrent ischemic stroke has been contentious. OBJECTIVE: We applied the Duke Stroke Policy Model (DSPM) to reconsider this issue, paying particular attention to the degree of uncertainty in the estimates of their efficacy. The DSPM is a continuous-time simulation model of stroke development and outcome. METHODS: We modified the inputs to reflect the cost of the drugs aspirin (ASA), extended release dipyridamole/aspirin (DP/A) and clopidogrel (CLO), as well as their relative risk in preventing subsequent ischemic stroke in comparison with placebo (PBO). These relative risks were derived from published reports from the second European Stroke Prevention Study (ESPS-2) and Clopidogrel Versus Aspiring in Patients at Risk of Ischemic Events studies. Precision was addressed by applying bootstrapping to the above estimates of relative risk. The target population was 70-year-old men with nondisabling stroke. The outcome measures were quality-adjusted life-years (QALYs), costs, and costs per QALY. RESULTS: Results of Base Case Analysis: In large part because of its modest drug cost, ASA was cost-effective in comparison with PBO. DP/A tended to have improved outcomes, but at increased costs. CLO was dominated in the base case. RESULTS OF SENSITIVITY ANALYSIS: ASA and DP/A cannot be differentiated on a statistical basis alone. In probabilistic sensitivity analysis, CLO was rarely preferred. CONCLUSIONS: Either DP/A or ASA appear to be a good value in comparison with no treatment, but there is no clear winner between the two. In the absence of a definitive randomized trial, simulation modeling can help clarify the trade-offs between the various antiplatelet agents, but not beyond the constraints imposed by the imprecision in the estimates that can be obtained from the current evidence base.

Clinical effectiveness and cost-effectiveness of clopidogrel and modified-release dipyridamole in the secondary prevention of occlusive vascular events: a systematic review and economic evaluation.

OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of two alternative antiplatelet agents, clopidogrel and modified-release (MR)-dipyridamole, relative to prophylactic doses of aspirin for the secondary prevention of occlusive vascular events. DATA SOURCES: Electronic databases. REVIEW METHODS: A total of 2906 titles and abstracts were rigorously screened and 441 studies were assessed in detail. Two RCTs were identified. For the assessment of cost-effectiveness, eight reviews were identified. The results were presented in structured tables and as a narrative summary. No additional clinical effectiveness data were presented in either of two company submissions. All economic evaluations (including accompanying models) included in the company submissions were assessed. Following this analysis, if the existing models (company or published) were not sufficient, a de novo model or modified versions of the models were developed. RESULTS: In the CAPRIE trial the point estimate for the primary outcome, i.e. ischaemic stroke, myocardial infarction (MI) or vascular death, favoured clopidogrel over aspirin, but the boundaries of the confidence intervals raise the possibility that clopidogrel is not more beneficial than aspirin. In terms of the secondary outcomes reported, there was a non-significant trend in favour of clopidogrel over aspirin but the boundaries of the confidence intervals on the relative risks all crossed unity. There was no difference in the number of patients ever reporting any bleeding disorder in the clopidogrel group compared with the aspirin group. The incidences of rash and diarrhoea were statistically significantly higher in the clopidogrel group than the aspirin group. Patients in the aspirin group had a higher incidence of indigestion/nausea/vomiting than patients in the clopidogrel group. Haematological adverse events were rare in both the clopidogrel and aspirin groups. No cases of thrombotic thrombocytopenic purpura were reported in either group. Treatment with MR-dipyridamole alone did not significantly reduce the risk of any of the primary outcomes reported in ESPS-2 compared with treatment with aspirin. ASA-MR-dipyridamole was significantly more effective than aspirin alone in patients with stroke or transient ischaemic attacks (TIAs) at reducing the outcome of stroke and marginally more effective at reducing stroke and/or death. Treatment with ASA-MR-dipyridamole did not statistically significantly reduce the risk of death compared to treatment with aspirin. The number of strokes was statistically significantly reduced in the ASA-MR-dipyridamole group compared with the MR-dipyridamole group. In terms of the other primary outcomes, stroke and/or death and death, the results favoured treatment with ASA-MR-dipyridamole but the findings were not statistically significant. There was no difference in the number of bleeding complications between the ASA-MR-dipyridamole and aspirin groups. The incidence of bleeding complications was significantly lower in the MR-dipyridamole treatment group. More patients in the MR-dipyridamole treatment groups experienced headaches compared to patients receiving treatment with aspirin alone. The York model assessed the cost-effectiveness of differing combinations of treatment strategies in four patient subgroups, under a number of different scenarios. The results of the model were sensitive to the assumptions made in the alternative scenarios, in particular the impact of therapy on non-vascular deaths. CONCLUSIONS: Clopidogrel was marginally more effective than aspirin at reducing the risk of ischaemic stroke, MI or vascular death in patients with atherosclerotic vascular disease, however, it did not statistically significantly reduce the risk of vascular death or death from any cause compared with aspirin. There was no statistically significant difference in the number of bleeding complications experienced in the clopidogrel and aspirin groups. MR-dipyridamole in combination with aspirin was superior to aspirin alone at reducing the risk of stroke and marginally more effective at reducing the risk of stroke and/or death. Compared with treatment with MR-dipyridamole alone, MR-dipyridamole in combination with aspirin significantly reduced the risk of stroke. Treatment with MR-dipyridamole in combination with aspirin did not statistically significantly reduce the risk of death compared with aspirin. Compared with treatment with MR-dipyridamole alone, bleeding complications were statistically significantly higher in patients treated with aspirin and MR-dipyridamole in combination with aspirin. Due to the assumptions that have to be made, no conclusions could be drawn about the relative effectiveness of MR-dipyridamole, alone or in combination with aspirin, and clopidogrel from the adjusted indirect comparison. The following would apply for a cost of up to GBP20,000-40,000 per additional quality-adjusted life-year. For the stroke and TIA subgroups, ASA-MR-dipyridamole would be the most cost-effective therapy given a 2-year treatment duration as long as all patients were not left disabled by their initial (qualifying) stroke. For a lifetime treatment duration, ASA-MR-dipyridamole would be considered more cost-effective than aspirin as long as treatment effects on non-vascular deaths are not considered and all patients were not left disabled by their initial stroke. In patients left disabled by their initial stroke, aspirin is the most cost-effective therapy. Clopidogrel and MR-dipyridamole alone would not be considered cost-effective under any scenario. For the MI and peripheral arterial disease subgroups, clopidogrel would be considered cost-effective for a treatment duration of 2 years. For a lifetime treatment duration, clopidogrel would be considered more cost-effective than aspirin as long as treatment effects on non-vascular deaths are not considered. It is suggested that the combination of clopidogrel and aspirin should be evaluated for the secondary prevention of occlusive vascular events. Also randomised, direct comparisons of clopidogrel and MR-dipyridamole in combination with aspirin are required to inform the treatment of patients with a history of stroke and TIA, plus trials that compare treatment with clopidogrel and MR-dipyridamole for the secondary prevention of vascular events in patients who demonstrate a genuine intolerance to aspirin.

Economic assessment of the secondary prevention of ischaemic stroke with dipyridamole plus aspirin (Aggrenox/Asasantin) in France.

OBJECTIVE: To assess the cost effectiveness of aspirin 25 mg plus dipyridamole 200 mg twice daily in the secondary prevention of ischaemic stroke, according to the French social security perspective, using efficacy data from the second European Stroke Prevention Study (ESPS-2). The ESPS-2 was a double-blind, placebo-controlled clinical trial which assessed the efficacy of four secondary prevention strategies: (i) placebo; (ii) aspirin (acetylsalicylic acid) 25 mg twice daily; (iii) dipyridamole 200 mg twice daily; and (iv) aspirin 25 mg plus dipyridamole 200 mg twice daily. METHOD: We performed a cost-effectiveness analysis with Monte Carlo simulations to compute confidence intervals. We combined data from various sources including the Dijon Stroke Registry, Institut National de la Statistique et des Etudes Economiques, Etude du Coût de l'Infarctus Cérébral (Study of the Cost of Cerebral Infarction [ECIC]) study and the ESPS-2 trial. RESULTS: According to our findings, a preventive strategy with aspirin 25 mg plus dipyridamole 200 mg twice daily is associated with net benefits per avoided stroke recurrence amounting to USD 23,932 (95% CI -USD 32,609, USD 35,772) compared with aspirin 25 mg twice daily alone, and USD 31,555 (95% CI USD 4921, USD 74,515) compared with dipyridamole alone (1997 values). Sensitivity analysis demonstrated that dipyridamole plus aspirin was still cost effective when the average cost of adverse effects per episode (ignored in the original estimation of the cost-effectiveness ratios due to a lack of data) was assumed to be USD 8600 (50,000 French francs); this cost is unlikely as most of the adverse effects associated with aspirin plus dipyridamole are only slight to moderate in severity. CONCLUSIONS: In the secondary prevention of stroke in France, this study suggests, given its underlying assumptions and data, that aspirin 25 mg plus dipyridamole 200 mg twice daily is likely to be a cost-effective strategy from the social security perspective, when compared with other relevant strategies that were evaluated in the ESPS-2 trial.

Aggrenox((R)) versus other pharmacotherapy in preventing recurrent stroke.

Stroke is the third leading cause of death in the US with recurrent events a high likelihood in those who survive an initial event. The long-term goal of therapy is to prevent the recurrence of stroke and other atherosclerotic events. Aspirin has been the first-line agent for stroke prevention for a long time. As new antiplatelet agents have been introduced, their role in the secondary prevention of stroke remains to be defined. In particular, the role of the combination of aspirin and modified-release dipyridamole (Aggrenox, Boehringer Ingelheim Corp.), the newest product, in the secondary prevention of stroke, remains unknown. The purpose of this manuscript is to review the evidence of these antiplatelet agents in the secondary prevention of stroke and arrive at a conclusion specifically regarding the role of Aggrenox. Clinical studies which examined stroke as a single primary outcome or as one event in a combined primary outcome will be reviewed.

[Epidemiologic and economic efficacy of massive prophylaxis of influenza and other acute respiratory viral infections using curantil in Moscow enterprises]. / Epidemiologicheskaia i ékonomicheskaia éffektivnost' massovoi profilaktiki grippa i drugikh ostrykh respiratorno-virusnykh infekstii na Moskovskikh predpriiatiiakh s pomoshch'iu kurantila.

AIM: To evaluate epidemiological and cost-effect value of curantil in "in-office" prophylaxis of influenza and acute respiratory diseases (ARD) in Moscow. MATERIAL AND METHODS: Curantil was given once a week for 4-5 weeks in a dose 50 mg with 2-3-week intervals in autumn peaks of ARD and influenza epidemics. Participation of the population was 50-70% maximum. Prevailing influenza viruses causing epidemic in 1990-1991, 1991-1992 were A(H3N2) and B, respectively; ARD were caused by parainfluenza viruses, PC, P, mycoplasma etc. Efficiency index and rate were calculated: EI = a/b; ER = (a-b)/a x 100 where a--morbidity in the test group, b--in the control. Cost effectiveness was estimated by sick leaves pays for workers equal to the number protected by curantil and wages for those who worked instead of the ill workers or by the cost of the saved production. RESULTS: Epidemiological efficiency at enterprise 1 in autumn 1990 was the following (70% covarage): EI = 4.4, ER = 77.2%; in winter epidemic EI = 2.7, ER = 62.4% (covarage 50%). Close results were obtained in the next epidemiological season. In autumn in the enterprise 2 EI = 3.9; ER = 74.3%. Curantil prophylaxis at enterprise 1 protected 53 workers and saved 11278.88 roubles. CONCLUSION: Curantil effectiveness, wide spectrum of action, safety in oral administration 50 mg once a week make curantil convenient for mass prevention of influenza and ARD.

Aggrenox: an aspirin and extended-release dipyridamole combination.

Stroke is one of the leading causes of death in the United States. The risk of experiencing a recurrent stroke remains elevated for several years after an initial stroke or a transient ischemic attack (TIA), therefore secondary prevention is crucial in reducing the risk of stroke and the complications and costs associated with stroke. Aggrenox, a combination of low-dose aspirin and extended-release dipyridamole, is a new agent that is effective in the secondary prevention of stroke and transient ischemia of the brain. The clinical effect of its two antiplatelet agents are additive and significantly better than either aspirin or dipyridamole alone, although it has not been shown to be more effective than aspirin alone in preventing death. Aggrenox is much more expensive than aspirin alone but has been shown to be more cost-effective. At this point, much of the pharmacologic information concerning this combination agent is based on previous data about aspirin and immediate-release dipyridamole. This combination of aspirin and extended-release dipyridamole may play a significant role in secondary stroke and TIA prevention.

[Calculation of costs of stroke, cost effectiveness of stroke units and secondary prevention in patients after a stroke, as recommended by revised CBO practice guideline 'Stroke']. / Berekening van kosten na een beroerte en kosteneffectiviteit van 'stroke units' en van secundaire preventie, zoals aanbevolen in de herziene CBO-richtlijn 'Beroerte'.

OBJECTIVE: Economic analyses have been part of the revision of the Dutch multi-disciplinary stroke guidelines. We evaluated the recommendations on stroke units and prevention of stroke recurrencies in terms of medical costs and health effects among stroke patients. DESIGN: Cost calculation. METHOD: Mathematical modelling of medical costs per patient and costs per life year gained without severe stroke (Rankin score (> 3)), by age and sex for each guideline. RESULTS: Lifetime costs of stroke depended on age and sex and vary between 84,000 and 292,000 Dutch guilders (HFL). The cost-effectiveness of stroke units decreases with age and varies between HFL 37,000 and HFL 60,200 with a large uncertainty range. Four of seven options in secondary prevention were cost-effective by previously established criteria (< HFL 40,000 per year gained without severe disease). Acetylsalicylic acid remained the drug of choice for monotherapy with dipyridamol as a second choice in patients without atrial fibrillation. Clopidogrel was not cost-effective at the current cost level. Anticoagulation after stroke in case of atrial fibrillation was cost-effective. CONCLUSIONS: Given a short hospital stay stroke units can be as affective as other hospital interventions. Acetylsalicylic acid is the most cost effective monotherapy for secondary prevention.

Cost-effectiveness of new antiplatelet regimens used as secondary prevention of stroke or transient ischemic attack.

BACKGROUND: Compared with aspirin alone, use of the new antiplatelet regimens, including aspirin combined with dipyridamole and clopidogrel bisulfate, has been found to further reduce the risk of stroke and other vascular events in patients who have experienced stroke or transient ischemic attack. However, their cost-effectiveness ratios relative to aspirin alone have not been estimated. METHODS: We developed a Markov model to measure the clinical benefits and the economic consequences of the following strategies to treat high-risk patients aged 65 years or older: (1) aspirin, 325 mg/d; (2) aspirin, 50 mg/d, and dipyridamole, 400 mg/d; and (3) clopidogrel bisulfate, 75 mg/d. Input data were obtained by literature review. Outcomes were expressed as US dollars per quality-adjusted life-year (QALY). RESULTS: The use of aspirin combined with dipyridamole was more effective and less costly compared with the use of aspirin alone, providing a gain of 0.3 QALY for a 65-year-old patient. This regimen remained cost-effective despite wide sensitivity analyses. Clopidogrel was more effective and more costly compared with aspirin alone, yielding a gain of 0.2 QALY with a marginal cost-effectiveness ratio of $26,580 per each additional QALY (patient aged 65 years). Sensitivity analyses demonstrated that the efficacy of clopidogrel and its cost were key factors in determining its cost-effectiveness ratio compared with aspirin, which exceeded $50,000 when its efficacy decreased by half or its cost doubled. CONCLUSION: To prevent stroke in high-risk patients, dipyridamole combined with aspirin was more effective and less costly than aspirin alone, and clopidogrel was cost-effective compared with current standards of medical practice, except in extreme scenarios.

Antiplatelet drugs in cardiovascular prevention: take adverse effects and costs into account.

(1) Several antiplatelet drugs have proven preventive efficacy, including aspirin, aspirin + dipyridamole, clopidogrel, ticlopidine and flurbiprofen. They differ mainly in their adverse effects and costs. (2) Aspirin has essentially gastrointestinal adverse effects, whose incidence can be limited by prescribing a daily dose below 350 mg. (3) The addition of dipyridamole to aspirin can cause headache and diarrhoea. (4) Ticlopidine should be avoided because of the risk of agranulocytosis. (5) Adverse effects are less frequent and less severe with clopidogrel than with ticlopidine. (6) Like other nonsteroidal antiinflammatory drugs, flurbiprofen has mainly gastrointestinal adverse effects. (7) Treatment is least costly with low-dose aspirin and most costly with clopidogrel.

Aspirin plus extended-release dipyridamole or clopidogrel compared with aspirin monotherapy for the prevention of recurrent ischemic stroke: a cost-effectiveness analysis.

OBJECTIVE: The goal of this health economic analysis was to asses the cost-effectiveness of a fixed combination of aspirin plus extended-release dipyridamole (ASA/ER-DP) or clopidogrel compared with ASA monotherapy for prevention of recurrent ischemic stroke. BACKGROUND: The second European Stroke Prevention Study (ASA/ESPS-2), a large-scale clinical trial, demonstrated that a new therapy--a fixed combination of ASA/ER-DP--is more effective than ASA monotherapy for the prevention of recurrent ischemic stroke. METHODS: We used data from ESPS-2 to create a health economic model that estimates the incremental cost and cost-effectiveness of ASA/ER-DP during the 2-year time frame after an ischemic stroke. The model was developed from a payor perspective. The analysis used direct cost estimates for stroke from a Medicare claims database analysis. Efficacy data were obtained from clinical trials to determine the incremental cost per stroke averted for ASA/ER-DP or clopidogrel versus ASA. Sensitivity analyses also were conducted to test the reliability and robustness of the model. RESULTS: The results of the analysis demonstrated that ASA/ER-DP was cost-effective compared with ASA monotherapy for the secondary prevention of stroke, with a cost-effectiveness ratio of $28,472. The model remained robust over a range of assumptions and cost estimates. Clopidogrel, however, was not cost-effective compared with ASA (cost per stroke averted, $161,316) in either the base-case analysis or any of the sensitivity analyses. CONCLUSION: ASA/ER-DP thus offers a cost-effective alternative to ASA monotherapy for the prevention of recurrent ischemic stroke.

Cost-effectiveness analysis of antiplatelet therapy in the prevention of recurrent stroke in the UK. Aspirin, dipyridamole and aspirin-dipyridamole.

OBJECTIVES: To evaluate the cost effectiveness from a UK health and social services perspective of antiplatelet therapies tested in the Second European Stroke Prevention Study (ESPS-2) in preventing recurrent stroke. To demonstrate the value of modelling studies in this area. DESIGN AND SETTING: A decision-analytic model was developed to evaluate health outcomes and associated costs. Sources of data for efficacy, adverse events, background event risks, disability and mortality were ESPS-2, the Oxfordshire Community Stroke Project and UK national statistics. Published national unit costs were applied to clinician panel estimates of resource use for acute stroke, rehabilitation and long term care. Outcome measures were strokes or disabled life-years averted, and disability-free, stroke-free or quality-adjusted life-years gained. PATIENTS AND INTERVENTIONS: 30-day survivors of ischaemic stroke treated with low dose aspirin, modified-release dipyridamole; the coformulation of low dose aspirin plus modified-release dipyridamole, or no antiplatelet therapy. MAIN OUTCOME MEASURES AND RESULTS: The model predicted that over 5 years the coformulation prevented 29 more strokes than aspirin alone per 1000 patients, at an additional cost of 1900 Pounds per stroke averted (1996 values). Over 5 years, each antiplatelet therapy was cost saving compared with no therapy. Results were sensitive to the cost of acute care, the cost of long term care of disabled stroke survivors, the effectiveness of therapy and the background risk of recurrent stroke. In sensitivity analyses, the cost effectiveness did not exceed 7000 Pounds per stroke averted or 11,000 Pounds per quality-adjusted life-year (QALY) gained, except when varying the effectiveness parameter. CONCLUSIONS: Application of a decision-analytic model to the results of ESPS-2 indicated that first-line therapy with the coformulation of modified-release dipyridamole and low dose aspirin to patients with a previous ischaemic stroke is likely to generate significant health benefits at modest extra costs to health and social services. The extra costs of treatment are balanced by the savings in future costs of acute care and long term care of the disabled. Future economic evaluations in this area should pay particular attention to the cost perspective, the duration of analysis, the selection of trials from which effectiveness data are derived, and the impact of the pooling of outcome events with potentially different economic consequences.