Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fixed-dose combination of extended-release dipyridamole/aspirin (Aggrenox/Asasantin Retard) combines 2 antiplatelet agents with different mechanisms of action. The combination reduced thrombus formation in human and animal models. Coadministration of extended-release dipyridamole and aspirin in healthy volunteers had no significant effects on the plasma concentrations of either agent. Twice-daily oral extended-release dipyridamole/aspirin (400/50 mg/day) was twice as effective as either agent alone in the secondary prevention of stroke in a large clinical trial involving patients with prior stroke or transient ischaemic attack. The rate of the combined end-point of stroke and death tended to be lower with the combination than with other treatments. The incidence of death was not significantly reduced by any treatment. Most adverse events with extended-release dipyridamole/aspirin were mild and similar to those with either agent alone. Bleeding was more common with the combination than with extended-release dipyridamole alone, as was headache when compared with aspirin alone. Limited pharmacoeconomic analyses suggest that treatment with extended-release dipyridamole/aspirin was cost saving and was cost effective compared with aspirin monotherapy for the secondary prevention of stroke.
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PMID:Extended-release dipyridamole/aspirin. 1049 74

Aggrenox, launched in Belgium by Boehringer Ingelheim, is a fixed-dose combination of extended-release dipyridamole (200 mg) and aspirin (25 mg), two antiplatelet agents with different and complementary mechanisms of action. It is recommended, twice daily, in the protection against secondary stroke and transient ischaemic attacks. The placebo-controlled European study ESPS 2 (European Stroke Prevention Study 2) demonstrated that the administration of this combination was twice as effective as either agent alone in the secondary prevention of stroke in patients with prior stroke or transient ischaemic attack.
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PMID:[Pharma-clinics. The drug of the month. Dipyridamole-acetylsalicylic acid combination (Aggrenox)]. 1124 7

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.
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PMID:Aggrenox: an aspirin and extended-release dipyridamole combination. 1197 16

Aggrenox is a novel combination of 25 mg of aspirin with 200 mg of sustained release dipyridamole. In a recent large trial (ESPS-2), Aggrenox was twice as effective for secondary stroke prevention as either aspirin or dipyridamole alone, suggesting superior platelet inhibition for combination therapy. We sought to compare the time course of platelet inhibition with Aggrenox compared with escalating doses of non-enteric coated aspirin. Data from 10 healthy volunteers were analyzed. Fasting subjects sequentially ingested aspirin in the following order: 325 mg, 81 mg, 25 mg, and then one pill of Aggrenox after a 3-week interval for aspirin washout. Platelet function was assessed at baseline, 15, 30, 60, and 120 min post-medication with 5 microM epinephrine and 5 microM ADP using conventional aggregometry. Aspirin provided significant (P < 0.01) reduction of platelet aggregation at 15 min post 325 mg, 30 min post 81 mg, and unexpectedly within 60 min after taking 25 mg of aspirin. A single pill of Aggrenox also inhibited platelet aggregation within 1 hr after administration. Aspirin inhibits platelets remarkably fast. Both Aggrenox and a matching dose of aspirin (25 mg) exhibit significant antiplatelet properties within 60 min after ingestion. These findings could be relevant for the optimal balance between the reduction of vascular events via sufficient and rapid platelet inhibition and low risk of bleeding complications associated with the Aggrenox therapy.
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PMID:Rapid platelet inhibition after a single capsule of Aggrenox: challenging a conventional full-dose aspirin antiplatelet advantage? 1266 42

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.
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PMID:Aggrenox((R)) versus other pharmacotherapy in preventing recurrent stroke. 1468 Apr 41

The European Stroke Prevention Study showed greater stroke prevention for Aggrenox than either for aspirin or dipyridamole alone. To test whether Aggrenox has superior antiplatelet properties to aspirin alone we conducted the AGgrenox versus Aspirin Therapy Evaluation (AGATE) trial. Forty patients with prior ischemic stroke not taking aspirin for at least 30 days were randomized to Aggrenox (2 pills/daily) or aspirin (81 mg plus matching placebo/daily) for 30 days. Platelet function was assessed at baseline, 24 h, and days 3, 7, 15, and 30 by aggregometry, flow cytometry and cartridge-based analyzers. Both Aggrenox and aspirin provided fast and sustained platelet inhibition. Aggrenox(R), however, especially after 15 days, showed significant prolongation of the closure time (P=0.04), diminished expression of platelet/endothelial cell adhesion molecule-1 (PECAM-1) (P=0.01), glycoprotein IIb (GPIIb) antigen (P=0.02), and GPIIb/IIIa activity (P=0.01) by PAC-1 C antibody, CD63 (P=0.03), as well as inhibition of Protease Activated Receptors (PAR-1) associated with intact (SPAN12, P=0.01) and cleaved (WEDE15, P=0.01) thrombin receptors as compared with aspirin. Surprisingly, GPIb expression increased, especially after aspirin. In the randomized trial of small sample size, aspirin and Aggrenox produced fast and sustained platelet inhibition. In 25 of 90 direct comparisons, Aggrenox was superior to aspirin, whereas in 4 of 90, aspirin was superior to Aggrenox. In 61 of 90 direct comparisons, aspirin and Aggrenox were equivalent. Aggrenox was associated with a profound reduction of PAR-1 receptors, an observation that may be related to the greater clinical benefit of Aggrenox compared with Aspirin in preventing recurrent stroke.
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PMID:Magnitude and time course of platelet inhibition with Aggrenox and Aspirin in patients after ischemic stroke: the AGgrenox versus Aspirin Therapy Evaluation (AGATE) trial. 1538 Oct 54

Extended release dipyridamole (DIP) is widely used in clinical practice as an Aggrenox formulation, which is proven to improve outcomes for secondary stroke prevention in patients after acute vascular events. However, presently established fluorometry techniques are not suitable for trace amount determinations, because of the variable background fluorescence. The authors sought to determine whether biological fluid pH is important for the serial measures of DIP levels in the animal experiments and in patients treated with Aggrenox after ischemic stroke. Post-stroke patient (n = 34) and mice (n = 25) samples were tested to determine DIP levels by established techniques with FluoroMax 3 spectrofluorometer. Both the absorption and emission spectra of DIP were affected by modifications in pH. Fluorescence of DIP was found to be maximal at a wavelength of 490 nm (excitation 420 nm) and the spectral pattern was independent of pH. The intensity of fluorescence, however, was drastically lower at low pH (at pH 2.6, fluorescence was 4% of intensity at pH 9.8). Background plasma fluorescence, however, was completely unaffected by changes in pH. Using these fluorometric characteristics, a regression model that facilitates the efficient and sensitive determination of DIP concentration in biological fluids was formulated. Exploiting pH-dependent characteristics of DIP versus serum fluorescence patterns permits a convenient mathematical model to determine DIP concentration. This relatively inexpensive and time-efficient procedure can quantify drug levels in human/animal plasma/serum, thereby directly determining the level of patient adherence to the prescribed drug regimen, be it in the context of clinical trials or compliance with the animal protocol.
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PMID:Criticality of pH for accurate fluorometric measurements of dipyridamole levels in biological fluids. 1583 62

Aggrenox (Boehringer Ingelheim, Ingelheim, Germany), a novel combination of low-dose aspirin with dipyridamole, represents a safe and promising combination alternative for mild but sustained platelet inhibition, and reduction of both arterial and venous thrombi occurrences. In a large, well-controlled randomized trial (ESPS-2 ) evaluating antiplatelet agents for stroke prevention, Aggrenox was twice as effective as monotherapy with either aspirin or dipyridamole. There is an increasing body of evidence that a delicate strategy with Aggrenox provides modest inhibition of platelet activity, especially in a chronic, long-term setting. Mild platelet inhibition beyond conventional aggregation may represent a substantial advantage over aggressive antiplatelet regimens for the treatment, and especially for secondary prevention, of cerebrovascular ischemic events. Although there is no doubt that the concept of inhibiting platelets is vital for the treatment of vascular ischemic disease in general and ischemic stroke and transient ischemic attack (TIA) in particular, the optimal degree of such inhibition still remains an unsolved mystery. It seems that the concepts of "the more, the better" and "one size fits all" may no longer be valid for ideal antiplatelet protection in such high-risk populations. Without routine individual laboratory assessment of platelet function, mild regimens have the advantage of being more suitable for the majority of patients and will contribute substantially to the success of dipyridamole. Conversely, if we can determine baseline platelet status and intelligently apply therapy based on platelet activity in each particular patient, clinical outcomes may be better. Avoiding excessive bleeding risks after aggressive strategies in patients with normal or already decreased platelet function, but targeting those who exhibit activated platelets, may improve risk stratification and save lives. Therefore, Aggrenox should be considered a drug of choice to prevent the second stroke. Eliminating, or at least minimizing, the most frequent side effect, namely transitory headaches at the beginning of therapy with Aggrenox, will benefit patients and increase the use of this agent. Should the PRoFESS (Prevention Regimen For Effectively avoiding Second Strokes) trial show an advantage in event reduction with Aggrenox over clopidogrel, the increase will be especially dramatic. In short, based on current evidence most guidelines include Aggrenox as a first-line option for secondary prevention of ischemic stroke or TIA, and some recent versions suggest it may be preferable in other clinical scenarios.
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PMID:The action of dipyridamole to prevent thrombosis: practical implications for the treatment and prevention of stroke. 1663 41

Randomized trials showed greater stroke prevention with extended release dipyridamole in combination with low dose aspirin than with either aspirin or dipyridamole alone. However, most studies with this formulation (Aggrenox) were carried out in Europe and North America. Considering potential inter-racial differences in drug response, we conducted a small randomized study in healthy Japanese volunteers to compare antiplatelet regimens with regard to the changes in the platelet biomarkers. Thirty healthy volunteers (18-40 years old, 15 male and 15 female) of Japanese descent were randomized to Aggrenox (n = 17) or aspirin 81 mg (n = 13 volunteers) for 30 days. Platelet function was assessed at baseline, and on days 15, and 30 by conventional aggregometry, whole blood flow cytometry, and cartridge-based analyzer. Both Aggrenox and aspirin provided sustained platelet inhibition at Day 15 and Day 30. Therapy with Aggrenox, however, was associated with more prominent and significant inhibition of collagen-induced aggregation (p = 0.08, Day 15), as well as prolongation of the closure time (p = 0.001, Day 30); diminished expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) (p = 0.02, Day 30), glycoprotein IIb (GPIIb) antigen (p = 0.001 and 0.024 for Day 15 and Day 30), and GPIIb/IIIa activity by PAC-1 antibody (p = 0.014 and 0.03), CD62 (P-selectin) (p = 0.03 for Day 15 and Day 30), as well as inhibition of protease activated receptors (PAR-1) associated with intact WEDE-15 (p = 0.002 and 0.003) and SPAN-12 (p = 0.002 and 0.04) thrombin receptors when compared with aspirin. The magnitude and durability of platelet response after Aggrenox in healthy Japanese is similar to those effects observed in Caucasians and African-Americans. A larger study to assess drug efficacy and safety in the Japanese post-stroke patients is warranted.
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PMID:Magnitude and time course of platelet inhibition with extended release dipyridamole with or without aspirin in healthy Japanese volunteers. The AGgrenox versus Aspirin Therapy Evaluation (AGATE-Japan). 1821 42

Extended release dipyridamole (ERD) is widely used in patients after ischaemic stroke; however, the ability of this antithrombotic agent to be stored in different blood cells has never been explored in post-stroke patients. We hypothesised that since ERD is known to be highly lipophilic, the drug may be present not only in plasma, but also accumulated in platelets, leukocytes, and erythrocytes. Fifteen patients after documented ischaemic stroke were treated with Aggrenox (ERD and low-dose aspirin combination) BID for 30 days, and 12 of them completed the study. ERD concentrations in blood cells and platelet-poor plasma were measured by spectrofluorimetry at Baseline, Day 14, and Day 30 after the initiation of therapy. The background level of spectrofluorometry readings differs slightly among the blood components (132-211 ng/ml) due to the differences in the preparation of samples and cell isolation techniques. As expected, two weeks of ERD therapy produced steady-state plasma concentration of dipyridamole already at Day 14 (1,680 +/- 542 ng/ ml), followed by a slight not significant decrease at one month (1,619 +/- 408 ng/ml). Two weeks of therapy was sufficient to achieve a consistent dipyridamole accumulation in erythrocytes (361 +/- 43 ng/ml), but not in platelets (244 +/- 78 ng/ml), or leukocytes (275 +/- 49 ng/ml). In fact, white blood cells continued dipyridamole intake beyond 14 days period, and this increase (398 +/- 66 ng/ml) was significant (p = 0.02) at 30 days. Treatment with ERD in post-stroke patients resulted not only in achievement of therapeutic plasma dipyridamole concentrations, but also deposition of the drug in erythrocytes and leukocytes, but not in platelets. If confirmed, these data will affect our better understanding of dipyridamole pleiotropy, and may explain long-term benefit of ERD formulation.
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PMID:Distribution of dipyridamole in blood components among post-stroke patients treated with extended release formulation. 1971 75


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