The value of a simplified approach to end-systolic volume measurement for assessment of left ventricular contractile reserve during stress-echocardiography.

The peak stress/rest ratio of left ventricular (LV) elastance, or LV force, is a load-independent index of left ventricular contractile reserve (LVCR) with stress echo (SE). To assess the accuracy of LVCR calculated during SE with approaches of different complexity. Two-hundred-forty patients were referred to SE for known or suspected coronary artery disease or heart failure and, of those, 200 patients, age 61 ± 15, 99 females, with interpretable volumetric SE were enrolled. All readers had passed the upstream quality control reading for regional wall motion abnormality (RWMA) and end-systolic volume (ESV) measurement. The employed stress was dipyridamole (0.84 mg, 6 min) in 86 (43%) and dobutamine (up to 40 mcg/kg/min) in 114 (57%) patients. All underwent SE with evaluation of RWMA and simultaneous LVCR assessment with stress/rest ratio of LV force (systolic blood pressure by cuff sphygmomanometer/ESV). ESV was calculated in each patient by two of three methods: biplane Simpson rule (S, in 100 patients), single plane area-length (AL, apical four-chamber area and length, in 100 patients), and Teichholz rule (T, from parasternal long axis and/or short axis view, in 200 patients). RMWA were observed in 54 patients. Success rate for ESV measurement was 76% (100/131) for S, 92% (100/109) for AL, and 100% (240/240) for T. There were 100 paired measurements (rest and stress) with S versus T, and 100 with AL versus T. The analysis time was the shortest for T (33 ± 8 s at rest, 34 ± 7 s at stress), intermediate for AL (70 ± 22 s at rest 67 ± 21 s at stress), and the longest for S (136 ± 24 at rest 129 ± 27 s at stress, p < 0.05 vs. T and AL). ESV absolute values were moderately correlated: T versus S (r rest = 0.746, p < 0.01, n = 100; r stress = 0.794, p < 0.01, n = 100); T vs. AL (r = 0.603 p < 0.01, n = 100, at rest and r = 0.820 p < 0.01 n = 100 at peak stress). LVCR values were tightly correlated independently of the method employed: T versus S (r = 0.899, p < 0.01, n = 100), and T versus AL (r = 0.845, p < 0.01, n = 100). LVCR can be accurately determined with all three methods used to extract the raw values of ESV necessary to generate the calculation of Force. Although S is known to be more precise in determining absolute ESV values, the relative (rest-stress) changes can be assessed, with comparable accuracy, with simpler and more feasible T and AL methods, characterized by higher success rate, shorter imaging and analysis time.

Non-contrast assessment of microvascular integrity using arterial spin labeled cardiovascular magnetic resonance in a porcine model of acute myocardial infarction.

BACKGROUND: Following acute myocardial infarction (AMI), microvascular integrity and function may be compromised as a result of microvascular obstruction (MVO) and vasodilator dysfunction. It has been observed that both infarcted and remote myocardial territories may exhibit impaired myocardial blood flow (MBF) patterns associated with an abnormal vasodilator response. Arterial spin labeled (ASL) CMR is a novel non-contrast technique that can quantitatively measure MBF. This study investigates the feasibility of ASL-CMR to assess MVO and vasodilator response in swine. METHODS: Thirty-one swine were included in this study. Resting ASL-CMR was performed on 24 healthy swine (baseline group). A subset of 13 swine from the baseline group underwent stress ASL-CMR to assess vasodilator response. Fifteen swine were subjected to a 90-min left anterior descending (LAD) coronary artery occlusion followed by reperfusion. Resting ASL-CMR was performed post-AMI at 1-2 days (N = 9, of which 6 were from the baseline group), 1-2 weeks (N = 8, of which 4 were from the day 1-2 group), and 4 weeks (N = 4, of which 2 were from the week 1-2 group). Resting first-pass CMR and late gadolinium enhancement (LGE) were performed post-AMI for reference. RESULTS: At rest, regional MBF and physiological noise measured from ASL-CMR were 1.08 ± 0.62 and 0.15 ± 0.10 ml/g/min, respectively. Regional MBF increased to 1.47 ± 0.62 ml/g/min with dipyridamole vasodilation (P < 0.001). Significant reduction in MBF was found in the infarcted region 1-2 days, 1-2 weeks, and 4 weeks post-AMI compared to baseline (P < 0.03). This was consistent with perfusion deficit seen on first-pass CMR and with MVO seen on LGE. There were no significant differences between measured MBF in the remote regions pre and post-AMI (P > 0.60). CONCLUSIONS: ASL-CMR can assess vasodilator response in healthy swine and detect significant reduction in regional MBF at rest following AMI. ASL-CMR is an alternative to gadolinium-based techniques for assessment of MVO and microvascular integrity within infarcted, as well as salvageable and remote myocardium. This has the potential to provide early indications of adverse remodeling processes post-ischemia.

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial.

BACKGROUND: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. METHODS: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. FINDINGS: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67-1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05-3·16, p<0·0001). INTERPRETATION: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice. FUNDING: National Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.

Secondary stroke prevention: misguided by guidelines?

OBJECTIVES: Despite large clinical trials, there is no consensus about the best antithrombotic strategy for the secondary prevention of non-cardioembolic ischaemic stroke.This retrospective study is the first to combine the results of the most important trials and to integrate data on study validity, effectiveness, adverse events, risk of non-compliance, and cost. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Database (1996 to July 2011) and selected long-term secondary prevention trials with treatment with aspirin, dipyridamole, clopidogrel, aspirin plus dipyridamole, or aspirin plus clopidogrel. Subgroup analyses were included to explain differences in interpretations that could have led to the differences in guidelines. RESULTS: Two trials showed a small but significant reduction with aspirin plus dipyridamole compared to aspirin (ARR 1.5%, P < 0.05 and ARR 1.0%, P < 0.05). There was no effect on vascular death. One trial showed a small but statistical significant reduction with clopidogrel compared to aspirin (ARR 0.5%, P < 0.05). The association of clopidogrel with aspirin could not show any significant benefit compared to clopidogrel monotherapy, nor compared to aspirin monotherapy, but showed higher rates of adverse events. Significantly more patients discontinued treatment with aspirin plus dipyridamole compared to aspirin monotherapy (34.5% versus 13.4% and 29.0% versus 22.2%, P < 0.001) and clopidogrel monotherapy (29.1% versus 22.6%, P < 0.001). Transposition of statistical significant reductions in stroke recurrence into clinical significance could not be supported. CONCLUSIONS: Despite changes in international guidelines, aspirin monotherapy should retain its position as the main antiplatelet agent for secondary prevention of non-cardioembolic ischaemic stroke.

Stress-only Tc-99m myocardial perfusion imaging in an emergency department chest pain unit.

BACKGROUND: Stress-only myocardial perfusion imaging (MPI) saves time by eliminating rest imaging, which is important for emergency department (ED) throughput but has not been studied in an ED population. STUDY OBJECTIVE: To determine the prognosis of a normal stress-only MPI study compared to a normal rest-stress MPI and establish its effectiveness in an ED setting. METHODS: All patients evaluated in the ED over 6.5 years who underwent a stress-only technetium-99m gated MPI were compared to those who had a rest-stress study. All-cause mortality was determined using the Social Security Death Index. Survival was analyzed in patients with normal and abnormal MPI results. RESULTS: A total of 4145 studies (2340 stress-only, 1805 rest-stress) were performed. Patients' average age was 57.9 years, 38.5% were male, and most had an intermediate or low pretest risk of coronary artery disease (87.7%). Average follow-up was 35.9 ± 20.9 months. In patients with normal perfusion, at 1 year of follow-up there were 11 deaths in the stress-only group (0.5% 1-year mortality), and 13 deaths in the rest-stress cohort (1.1% 1-year mortality). At the end of follow-up, the stress-only group had a lower all-cause mortality (p < 0.0001) and similar risk adjusted all-cause mortality (p = 0.10) than the rest-stress cohort. Patients with abnormal perfusion demonstrated the expected differential prognosis based on total perfusion deficits in both groups. CONCLUSIONS: A normal stress-only MPI study has a benign 1-year prognosis similar to a rest-stress study when performed in the ED. The ability to triage patients more rapidly and reduce radiation exposure represents an attractive alternative for low-risk patients.

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.

Effect of intravenous dipyridamole on coronary flow parameters in patients with isolated coronary artery ectasia: assessment by transesophageal echocardiography.

BACKGROUND: In a prospective study design, we sought to assess the effect of dipyridamole on coronary flow parameters in patients with isolated coronary artery ectasia (CAE) as compared to subjects with normal coronaries. METHODS: We enrolled 30 patients with ectasia of the left anterior descending (LAD) artery (study group), and 10 subjects with normal coronaries (control group). All subjects underwent transesophageal echocardiography to record flow velocities in the proximal LAD coronary artery, and velocity time integrals were calculated. The diameter of the proximal LAD coronary artery was measured and flow was calculated. Dipyridamole (0.56 mg/kg) was administered intravenously and measurements were repeated 5 minutes later. RESULTS: At baseline, systolic and diastolic velocities, systolic, diastolic, and total velocity time integrals were significantly higher in the control group (P < 0.05 for all), yet, systolic, diastolic, and total coronary flow were significantly higher in the study group (P < 0.05 for all). Following dipyridamole administration, systolic, diastolic, and total coronary flow were still significantly higher in the study group (P < 0.05 for all), yet, there was no significant difference between the two groups regarding the other parameters, and regarding coronary reserve values (P > 0.05 for all). CONCLUSIONS: We concluded that patients with isolated CAE have a higher resting coronary flow as compared to control subjects with normal coronaries. Intravenous dipyridamole administration in these patients maintained a significantly higher coronary flow, with a coronary flow reserve similar to controls.

Assessment of tailor-made HPMC-based matrix minitablets comprising a weakly basic drug compound.

Tailor-made, pH-controlled matrix minitablets based on different HPMC types were developed comprising the weakly basic drug dipyridamole. The incorporation of pH modifiers, i.e., fumaric and succinic acid, enhanced the drug release at pH 6.8. Assessing the drug release, acid release, and the microenvironmental pH (pHM) provided detailed understanding of pH-controlled mini-matrices. The extent and duration of pHM alteration was more pronounced in presence of fumaric acid. Minitablets based on the fast dissolving Methocel K100LV (< or = 100 cps) showed simultaneous release rates of dipyridamole and fumaric acid with a constant low average pHM.

Superior efficacy of clopidogrel plus acetylsalicylic acid compared with extended-release dipyridamole plus acetylsalicylic acid in preventing arterial thrombogenesis in healthy volunteers.

INTRODUCTION: Recent ex vivo platelet aggregometry data indicate that clopidogrel 75 mg/day plus acetylsalicylic acid (ASA) 75 mg/day is a more potent antiplatelet regimen than the marketed combination of dipyridamole+ASA. The present study was designed to assess the antithrombotic effect of both dual antiplatelet regimens using a human ex vivo model of arterial thrombosis. MATERIALS AND METHODS: This was a randomized, double-blind, placebo-controlled, crossover study. During two 10-day treatment periods separated by a 14-day washout period, 23 healthy male volunteers received once-daily clopidogrel 75 mg plus acetylsalicylic acid 75 mg, or twice-daily extended-release dipyridamole 200 mg plus acetylsalicylic acid 25 mg. Assessments were made at baseline and on Day 10 of each period. Arterial thrombus formation was induced ex vivo by exposing a collagen-coated surface in a parallel-plate perfusion chamber to native blood for 3 min (arterial wall shear rate 2600 s(-1)). Total platelet and fibrin deposition was determined by immunoenzymatic methods. RESULTS: Compared with baseline values, the mean inhibition of total platelet deposition was 63.9+/-5.9% with clopidogrel plus acetylsalicylic acid, compared with 18.4+/-5.6% for extended-release dipyridamole plus acetylsalicylic acid (67% reduction; 95% CI, 49-79%; p<0.0001). Corresponding figures for fibrin deposition were 64.9+/-4.8% and 18.3+/-9.7%, respectively (58% reduction; 95% CI, 45-67%; p<0.0001). Both treatments were well tolerated. CONCLUSIONS: Clopidogrel plus acetylsalicylic acid showed significantly superior antithrombotic efficacy compared with extended-release dipyridamole plus acetylsalicylic acid in preventing arterial thrombogenesis in humans.

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.

Antiplatelet agents for secondary prevention of ischemic stroke.

OBJECTIVE: To review and summarize the efficacy, mechanisms of action, and cost of the options available when choosing antiplatelet agents for secondary stroke prevention. DATA SOURCES: This article is based on a review of the literature found with MEDLINE, CINAHL, and Cochrane Reviews (1980-June 2000) and abstracts from relevant international scientific meetings. We searched for the terms aspirin, ticlopidine, dipyridamole, antiplatelet, and clopidogrel. STUDY SELECTION: English-language articles, both reviews and original studies, were evaluated, and all information considered relevant was included in this review. In addition, guidelines from the American Heart Association are included. DATA SYNTHESIS: Aspirin is a relatively inexpensive and effective agent for secondary stroke prevention, and lower doses of aspirin appear as effective as higher doses. Ticlopidine has been used alone or in combination with aspirin, but serious adverse effects have limited its use. Clopidogrel has emerged as a safe and effective alternative to ticlopidine and lacks some of the serious adverse effects associated with ticlopicine, but is not superior to aspirin in secondary stroke prevention. Unlike previous studies, one recent trial showed that dipyridamole in combination with aspirin is superior to aspirin alone. CONCLUSIONS: Antiplatelet therapy is a key component of secondary prevention strategies in ischemic stroke. While aspirin has been the cornerstone in the management of stroke, other classes of antiplatelet drugs present new opportunities to optimize antiplatelet therapy.

Antithrombotic drugs for secondary stroke prophylaxis.

Stroke is the third most common cause of adult mortality in the United States. Antithrombotic agents form the mainstay of stroke prevention. Aspirin produces a modest reduction in the risk of second stroke and is widely recommended for initial therapy. The thienopyridines ticlopidine and clopidogrel are alternatives for secondary prevention in patients who do not respond to or cannot take aspirin. They are no more effective than aspirin and have been associated with thrombotic thrombocytopenic purpura. The combination of aspirin and extended-release dipyridamole has several mechanisms of action and an additive effect on reducing stroke risk compared with either agent alone. A 2-fold increase in risk reduction and favorable safety profile suggest that the combination can serve as first-line prophylaxis against a second stroke.

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: stroke: acute phase and secondary prevention.

(1) In the acute phase of ischaemic stroke in patients free of thrombogenic heart disease, combined treatment with aspirin + moderate-dose unfractionated heparin reduces the risk of relapse and death. Unfractionated heparin at higher anticoagulant doses has an unfavourable risk-benefit ratio. Treatment is controversial in patients with events associated with atrial fibrillation. (2) After ischaemic stroke in patients free of thrombogenic heart disease, aspirin reduces the risk of relapse and death. Other antiplatelet drugs, the aspirin + dipyridamole combination, ticlopidine and clopidogrel have similar efficacy to aspirin. (3) The risk-benefit ratio of oral anticoagulant is favourable after ischaemic stroke associated with atrial fibrillation; but it is unfavourable after stroke without thrombogenic heart disease.

Noninvasive assessment of left and right internal mammary artery graft patency with high-frequency transthoracic echocardiography.

OBJECTIVES: The aim of this study was (1) to visualize internal mammary artery grafts (IMAG) on coronary artery by transthoracic echocardiography and (2) to assess the patency of the grafts. METHODS: Twenty-three patients (21 men, 56 +/- 6 years) with previous coronary artery bypass grafting were studied at baseline and after they underwent low-dose dipyridamole infusion. The parameters obtained were systolic (SPV) and diastolic (DPV) peak velocities and their ratio (DPV/SPV); the dipyridamole infusion to baseline ratio of DPV was an index of IMAG blood flow reserve (FR). Two groups of patients were selected at baseline: group A, (n = 12) with a DPV/SPV >1, and group B (n = 11), with a DPV/SPV <1. RESULTS: The IMAG was identified in all patients. Intraluminal flow signals obtained with pulsed wave Doppler showed a biphasic pattern (1 systolic and 1 diastolic wave). After dipyridamole infusion was administered, flow velocities increased in 11 of 12 patients in group A and in 5 of 11 patients in group B. In group A the DPV/SPV increased from 1.79 +/- 0.47 to 1.8 +/- 0.43 (P = not significant), and the FR was 1.8 +/- 0.4. In group B the DPV/SPV increased from 0. 46 +/- 0.05 to 0.5 +/- 0.09 (P = not significant), and the FR was 1. 3 +/- 0.41. Coronary angiography showed the graft patency in all patients in group A and in 5 patients in group B with increased flow velocity after dipyridamole infusion. In the identification of graft stenosis at baseline, DPV/SPV showed 100% sensibility and 58% specificity, and FR showed 92% sensibility and 84% specificity. CONCLUSION: Doppler echocardiographic evaluation of the IMAG is a simple noninvasive method to assess the functional impairment of the vessel.

Assessment of flow mismatch with pharmacologic stress test on myocardial contrast echocardiography in a model of critical stenosis: adenosine triphosphate and dipyridamole.

Although adenosine triphosphate (ATP) is a favorable vasodilator because of its short-acting duration, the agent's effectiveness in facilitating the diagnosis of myocardial ischemia with myocardial contrast echocardiography (MCE) is not fully understood. The goal of this study was to examine the efficacy of intravenous ATP administration (0.15 to 0.30 mg/kg/min for 5 minutes) in diagnosing the flow mismatch with MCE. To achieve this, a critical stenosis was produced in the left circumflex artery in 10 anesthetized dogs. The peak intensity ratio of risk area to control area was reduced by ATP from 0.51 +/- 0.19 to 0.31 +/- 0.12 (P <.05). Systolic wall thickening of the risk area did not change significantly (32.8% +/- 9.8% to 27.5% +/- 12.8%). These changes did not differ from those obtained after dipyridamole. We conclude that MCE with intravenous ATP administration is as useful as the dipyridamole method for diagnosing critical coronary stenosis.

Determinación de la reserva coronaria mediante el eco-Doppler transesofágico / Assessment of coronary flow reserve by transesophageal Doppler echocardiography

Las mediciones e índices del flujo coronario basal y posvasodilatación obtenidos con eco-Doppler transesofágico en el territorio proximal de la arteria descendente anterior se correlacionaron con los resultados de la cinecoronariografía. Los pacientes sin lesión significativa de la descendente anterior presentaron una velocidad sistólica y diastólica basal más baja con un incremento mayor posadenosina o dipiridamol y en consecuencia una reserva coronaria más elevada que los portadores de obstrucción severa. Se registró una reserva coronaria diastólica mayor o igual 2,3 en 20/20 pacientes con coronaria normal (especificidad 100 por ciento) y menor o igual 1,4 en 9/10 pacientes con lesión severa (sensibilidad 90 por ciento). En conclusión, se demuestra que el método resultó ser de suma utilidad para la evaluación no invasiva de la arteria descendente anterior

Morphologic and functional assessment of coronary aneurysm after Kawasaki disease by repeated dipyridamole-loading coronary angiography.

The long-term outcome of coronary aneurysm after Kawasaki disease was investigated using dipyridamole-loading angiography in 33 children with coronary aneurysms after Kawasaki disease. Morphologic regression may not accompany functional improvement in the dilated coronary arteries.

[An acetylsalicylic acid-dypiridamole combination (Asasantine) in the prevention of the recurrence of cerebrovascular accidents (a cost-effectiveness analysis)]. / Association AAS-dypiridamole (Asasantine) dans la prévention des récidives d'AVC (analyse coût-efficacité).

On the basis of the results of the European stroke Prevention Study (ESPS 2) obtained on 6,602 patients, we used a Markov model to perform a cost-effectiveness analysis of a combination of a low-dose of acetylsalicylic acid (ASA) (25 mg b.i.d.) and sustained-release dipyridamole (DP) (200 mg b.i.d.) versus a low-dose of acetylsalicylic acid alone in the prevention of recurrent stroke in Belgium. The perspective was that of the Social Security. Total costs per patient over 5 years amounted to 1,317,718 FB for placebo, 1,312,015 FB for ASA and 1,326,526 FB for ASA-DP, with respectively 3.16, 3.25 and 3.33 stroke-free life years (SFLY). For 1,000 patients followed over 5 years, the number of SFLYs gained by ASA-DP is 170 when compared to placebo and 100 when compared to ASA. As compared to placebo, ASA is a dominant strategy and the combination AAS-DP has a cost-effectiveness ratio of 50,569 FB per SFLY gained. The cost-effectiveness ratio of ASA-DP vs. ASA was 176,963 FB per SFLY gained and was not substantially modified in sensitivity analyses. The favourable cost-effectiveness ratio for ASA-DP is mainly explained by the reduction of costs associated with the acute treatment of stroke.