Ticlopidine: a second look. No further use in routine practice

(1) The clinical file on ticlopidine is based mainly on a placebo-controlled trial involving patients with lower-limb arterial disease, and two large double-blind trials in the post-stroke period, in which the comparator was a placebo in one and aspirin in the other. (2) Ticlopidine proved more effective than the placebo in both indications. In secondary prevention of ischaemic stroke, ticlopidine has a moderate advantage over aspirin in terms of efficacy but carries a risk of serious adverse effects, especially haematological. (3) An indirect comparison suggests that clopidogrel, another antiplatelet drug chemically close to ticlopidine, has comparable efficacy in cardiovascular prevention and no severe adverse effects to date.     

Clopidogrel: new preparation. An alternative to aspirin

(1) Clopidogrel, an antiplatelet drug chemically similar to ticlopidine, is marketed in France for secondary prevention of thrombotic complications in patients with a history of myocardial infarction, ischaemic stroke or peripheral arterial disease. (2) Marketing authorisation was based mainly on the CAPRIE trial, a study that involved 19,815 patients. In this trial of secondary cardiovascular prevention, clopidogrel was slightly more effective than aspirin (325 mg/day) according to a statistical analysis of a combined end point (ischaemic stroke, or myocardial infarction, or death of vascular causes). The difference was more marked in the subgroup of patients with obstructive arterial disease of the lower limbs. (3) Clopidogrel was well tolerated in this trial. The only adverse effects more frequent on clopidogrel than on aspirin were rash and diarrhoea. (4) Clopidogrel showed no haematological toxicity, an adverse effect that restricts the use of ticlopidine. (5) The lack of long-term follow-up in real clinical settings prevents any meaningful estimation of the safety profile or of the risk of drug interactions.     

Clopidogrel and [symbol: see text] ticlopidine--improvements on aspirin?

Clopidogrel (Plavix-Sanofi Winthrop/Bristol-Myers Squibb) and [symbol: see text] ticlopidine (Ticlid-Sanofi Winthrop) are inhibitors of platelet function and are promoted as potential alternatives to aspirin. Clopidogrel is licensed for the secondary prevention of vascular events in patients with established atherosclerotic disease. The manufacturer claims that clopidogrel is "significantly more effective at reducing myocardial infarction, stroke and vascular death" compared to aspirin. Ticlopidine is licensed as an alternative to aspirin for secondary prevention of stroke and coronary complications in patients with intermittent claudication. However, in the UK, ticlopidine is more commonly used with aspirin to prevent complications following insertion of coronary stents during angioplasty. We consider whether the claims for clopidogrel and the current use of ticlopidine are justified.     

Clopidogrel: a review of its use in the prevention of atherothrombosis

Clopidogrel is an ADP receptor antagonist that is indicated for the reduction of atherosclerotic events including myocardial infarction, ischaemic stroke and vascular death in patients with atherosclerosis manifested by recent stroke, myocardial infarction or established peripheral vascular disease. In the 19 185 patients enrolled in the multicentre, randomised double-blind CAPRIE study, the annual risk of the combined end-point of ischaemic stroke, myocardial infarction and death from vascular disease (vascular death) was significantly lower during treatment with clopidogrel 75 mg/day than aspirin 325 mg/day [5.3 vs 5.8%/year, respectively; relative risk reduction (RRR) 8.7%, p = 0.043] after a mean follow-up of 1.9 years. Clopidogrel provided even greater reductions in the risk of recurrent ischaemic events than aspirin in patients with a history of coronary artery bypass surgery, diabetes mellitus and in those receiving concomitant lipid-lowering therapy. Moreover there was a significant reduction in the incidence of hospitalisation in patients treated with clopidogrel. In a patient population (Saskatchewan, Canada) with a greater risk of ischaemic events than the CAPRIE study population, the number of patients needed to be treated with clopidogrel to prevent 1 ischaemic event was estimated to be 70 (vs 200 in the CAPRIE study). In randomised trials and registry surveys, clopidogrel 75 mg/day plus aspirin had similar efficacy (as measured by adverse cardiac outcomes) to ticlopidine 250mg twice daily plus aspirin during the 30 days after placement of intracoronary stents. Tolerability of clopidogrel was significantly better than ticlopidine in the randomised, double-blind CLASSICS study. Among patients treated with clopidogrel or aspirin in the CAPRIE study, the overall gastrointestinal tolerability of clopidogrel was generally better than that of aspirin; the frequency of gastrointestinal haemorrhage was significantly lower among patients treated with clopidogrel than aspirin. Diarrhoea, rash and pruritis were significantly more common with clopidogrel than aspirin. CONCLUSION: Clopidogrel was significantly more effective than aspirin in the prevention of vascular events (ischaemic stroke, myocardial infarction or vascular death) [corrected] in patients with atherothrombotic disease manifested by recent myocardial infarction, recent ischaemic stroke or symptomatic peripheral arterial occlusive disease [corrected] in the CAPRIE study. The overall tolerability profile of the drug was similar to that of aspirin, although gastrointestinal haemorrhage occurred significantly less often in clopidogrel recipients. The drug is widely used in combination with aspirin for the prevention of atherothrombosis after placement of intravascular stents, and available data suggest that this combination is as effective as ticlopidine plus aspirin for this indication.     

Indobufen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in cerebral, peripheral and coronary vascular disease.

Indobufen is an inhibitor of platelet aggregation which acts by reversibly inhibiting the platelet cyclo-oxygenase enzyme. Improvements in walking distances and microcirculatory parameters have been achieved during therapy with indobufen in patients with peripheral vascular disease and intermittent claudication. Indobufen has been shown to be as effective as aspirin plus dipyridamole in preventing the reocclusion of coronary and femoro-popliteal artery bypass grafts and has been shown to significantly reduce platelet deposition on haemodialysis membranes. Initial studies have also indicated that indobufen may have a prophylactic effect on the incidence of secondary thrombotic events following transient ischaemic attack or mild stroke and may be effective in the prophylaxis of migraine. Indobufen is well tolerated following oral administration and has been associated with a low incidence of adverse effects rarely requiring withdrawal of treatment. Thus, available evidence indicates that indobufen may be an effective alternative to aspirin for the treatment of cerebral, peripheral and coronary vascular diseases with the advantage of a lower incidence of gastrointestinal effects compared to high dose aspirin, rendering indobufen more suitable for longer term therapy.     

Ticlopidine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in platelet-dependent disease states

Ticlopidine is an inhibitor of platelet action that has been used in the treatment of a variety of disease states in which platelets play a prominent role. Studies in animals and man have demonstrated that ticlopidine is a potent inhibitor of platelet aggregation induced by adenosine diphosphate (ADP), and variably inhibits aggregation due to collagen, adrenaline (epinephrine), arachidonic acid, thrombin, and platelet activating factor. Inhibition of platelet aggregation is both dose- and time-related, with its onset of activity being 24 to 48 hours, its maximal activity occurring after 3 to 5 days, and its activity still being present 72 hours after a final dose. Ticlopidine also inhibits the release reaction of platelets, prolongs bleeding time, reduces plasma levels of platelet factor 4 and beta-thromboglobulin in patients in whom these proteins are elevated, and may also inhibit platelet adhesion, increase red cell filtrability and decrease whole blood viscosity. In a large number of animal models, ticlopidine markedly inhibits thrombus formation or graft occlusion. Ticlopidine is well absorbed after oral administration. It is extensively metabolised and at least one of its metabolites is pharmacologically active. Therapeutic trials in patients with chronic arterial occlusion due to thrombangitis obliterans or arteriosclerosis obliterans, post-myocardial infarction, cerebrovascular thromboembolic disease, subarachnoid haemorrhage, vascular shunts or fistulas for haemodialysis, and sickle cell disease have shown promise for the use of ticlopidine. However, trials of patients with intermittent claudication, angina pectoris, diabetes mellitus with microvascular disease, aortocoronary bypass grafts, and vascular prostheses have had conflicting results or have shown an unfavourable side effect profile. Further studies are clearly required to establish the role of ticlopidine in many of these areas, some of which are already in progress. Overall, side effects occur in 10 to 15% of patients receiving ticlopidine. The most common side effects are gastrointestinal disturbances and skin rashes. Neither of these necessarily require discontinuation of therapy in most patients. Agranulocytosis, thrombocytopenia, and cholestatic jaundice have also been reported. Bleeding is infrequent except possibly in patients receiving ticlopidine prior to some surgical procedures.     

Secondary stroke prevention: inside the vessels and beyond

Cerebral ischaemic stroke is frequently a relapsing, if not chronic, disease. Its incidence is age-dependent, and with the ageing of society the need for effective therapies increases.This review considers current and alternative hypotheses underlying secondary prevention of stroke. Currently, secondary stroke prevention is widely practiced with aspirin (acetylsalicylic acid), a drug that has been in use for more than 100 years. Newer drugs such as ticlopidine and clopidogrel have subsequently been developed, but their efficacy barely surpasses that of aspirin. Other drugs used in secondary stroke prevention include HMG-CoA reductase inhibitors and antihypertensive agents.The endovascular paradigm has shaped the thinking of secondary stroke prevention, and aspirin, ticlopidine and clopidogrel are known as 'platelet inhibitors'; however, their pharmacological and clinical effects are not fully explained within the platelet paradigm. Moreover, in recent years, reduction of stroke incidence has also been observed with HMG-CoA reductase inhibitors, regardless of their lipid-lowering effects. Hence, current understanding needs to be supplemented by considering mechanisms beyond platelet inhibition. Evidence has shown that aspirin, ticlopidine and clopidogrel share neuroprotective properties not explained by the platelet paradigm and that are reminiscent of a preconditioning effect. This neuroprotective mechanism is also shared with HMG-CoA reductase inhibitors.     

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.     

Ticlopidine: a new antiplatelet agent for cerebrovascular disease

Ticlopidine is a new prototype antiplatelet drug chemically unrelated to currently available agents. It causes an alteration in platelet membrane reactivity to a variety of aggregating stimuli and a marked prolongation of bleeding time, the mechanism of which remains unclear. Two major phase III multicenter trials, the ticlopidine-aspirin stroke study (TASS) and the Canadian-American ticlopidine study (CATS) reported that the agent may reduce the occurrence of stroke, myocardial infarction, or vascular death in patients of both sexes who have had recent cerebral ischemia. Ticlopidine has been well tolerated in preliminary studies, with the most commonly described adverse effects being rash and gastrointestinal complaints. The most important adverse effect is neutropenia, which was reported in both TASS and CATS, approximating a frequency of 0.9% and 0.8%, respectively. Ticlopidine holds considerable promise as adjunctive therapy in selected patients.     

Adverse effects and drug interactions of antithrombotic agents used in prevention of ischaemic stroke

Stroke is the third most common cause of death in the US. Primary prevention of stroke can be achieved by control of risk factors including hypertension, diabetes mellitus, elevated cholesterol levels and smoking. Approximately one-third of all ischaemic strokes occur in patients with a history of stroke or transient ischaemic attack (TIA). The mainstay of secondary prevention of ischaemic stroke is the addition of medical therapy with antithrombotic agents to control the risk factors for stroke. Antithrombotic therapy is associated with significant medical complications, particularly bleeding.Low-dose aspirin (acetylsalicylic acid) has been shown to be as effective as high-dose aspirin in the prevention of stroke, with fewer adverse bleeding events. Aspirin has been shown to be as effective as warfarin in the prevention of noncardioembolic ischaemic stroke, with significantly fewer bleeding complications. Ticlopidine may be more effective in preventing stroke than aspirin, but is associated with unacceptable haematological complications. Clopidogrel may have some benefit over aspirin in preventing myocardial infarction, but has not been shown to be superior to aspirin in the prevention of stroke. The combination of clopidogrel and aspirin may be more effective than aspirin alone in acute coronary syndromes, but the incidence of adverse bleeding is significantly higher. Furthermore, the combination of aspirin with clopidogrel has not been shown to be more effective for prevention of recurrent stroke than clopidogrel alone, while the rate of bleeding complications was significantly higher with combination therapy. The combination of aspirin and extended-release dipyridamole has been demonstrated to be more effective than aspirin alone, with the same rate of adverse bleeding complications as low-dose aspirin. When selecting the appropriate antithrombotic agent for secondary prevention of stroke, the adverse event profile of the drug must be taken into account when assessing the overall efficacy of the treatment plan.     

Ticlopidine-Induced Elevated Liver Enzymes

Ticlopidine is a reasonable alternative to prevent stroke and myocardial infarction when aspirin is intolerable or ineffective. It can be limited, however, by its severe adverse effect profile. The most worrisome of these is neutropenia, although clinicians must be mindful of other adverse events that may be caused by this drug. A patient experienced elevated liver function tests probably due to ticlopidine.     

Prevention of ischaemic stroke--antiplatelets

Aspirin is the treatment of first choice for long-term secondary prevention of vascular events in patients with confirmed non-cardioembolic ischaemic stroke or TIA. However, there is no good evidence that it is of benefit in primary stroke prevention. If aspirin is contra-indicated, dipyridamole monotherapy is a relatively cheap, but slightly less effective, alternative. Aspirin and dipyridamole have an additive effect in secondary stroke prevention, but there is a high incidence of side effects and subsequent discontinuation of treatment with combination therapy. It is reasonable to consider clopidogrel for secondary prevention of vascular events in patients with ischaemic stroke who are intolerant of aspirin or dipyridamole, or who have a history of ischaemic heart disease. However, its cost is considerable. Over the next decade, oral antiplatelet agents directed against specific platelet receptors, or a combination of antiplatelet drugs inhibiting different aspects of platelet function, may improve secondary prevention of stroke.     

Indobufen: an updated review of its use in the management of atherothrombosis

Indobufen inhibits platelet aggregation by reversibly inhibiting the platelet cyclooxygenase enzyme thereby suppressing thromboxane synthesis. Clinical trials have evaluated the efficacy of oral indobufen in the secondary prevention of thromboembolic complications in patients with or without atrial fibrillation, in the prevention of graft occlusion after coronary artery bypass graft (CABG) surgery and in the treatment of intermittent claudication. In the secondary prevention of thromboembolic events indobufen 200 mg once or twice daily was significantly more effective than no treatment although not as effective as ticlopidine 250 mg once or twice daily, during 1-year nonblind clinical trials. Compared with placebo, indobufen 100 mg twice daily significantly reduced the risk of stroke in a small 28-month trial of patients at increased risk of systemic embolism (50% had atrial fibrillation). Furthermore, in patients with nonrheumatic atrial fibrillation and a recent cerebrovascular event enrolled in the 1-year Studio Italiano Fibrillazione Atriale (SIFA) trial, indobufen 100 or 200 mg twice daily was as effective as warfarin (titrated to produce an international normalised ratio of 2.0 to 3.5) in the secondary prevention of thromboembolic events; the incidences of the composite end-point of major vascular events (10.6 vs 9.0%) and recurrent stroke (5 vs 4%) were similar between treatments. In 2 large 12-month trials, the Studio Indobufene nel Bypass Aortocoronarico (SINBA) and the UK study, indobufen 200 mg twice daily was as effective as aspirin (acetylsalicylic acid) 300 or 325 mg plus dipyridamole 75 mg 3 times daily in the prevention of early and late occlusion of saphenous grafts in patients after CABG surgery. Indobufen 200 mg twice daily for 6 months significantly improved walking capacity compared with placebo, and caused a more pronounced improvement in both pain-free and total walking distance than either pentoxifylline 300 mg or aspirin 500 mg twice daily in separate 6- and 12-month studies of patients with intermittent claudication. Oral indobufen up to 200 mg twice daily was generally well tolerated in >5000 patients with atherosclerotic disease. Adverse events (predominantly gastrointestinal), reported by 3.9% of patients, rarely required withdrawal from treatment. In the SINBA and UK studies, fewer adverse events and less gastrointestinal bleeding were seen with indobufen than with aspirin plus dipyridamole treatment, while in the SIFA trial, noncerebral bleeding events occurred significantly less frequently in indobufen than warfarin recipients (0.6 vs 5.1%) and major bleeding events occurred only in the warfarin group. Conclusion: Indobufen is as effective as warfarin in the prophylaxis of thromboembolic events in at risk patients with nonrheumatic atrial fibrillation, as aspirin plus dipyridamole in the prevention of CABG occlusion and may be more effective than aspirin or pentoxifylline in improving walking capacity in patients with intermittent claudication. The improved tolerability profile of indobufen (favourable gastric tolerance and reduced haemorrhagic complications) compared with aspirin 300 to 325 mg 3 times daily or warfarin, in addition to a similar antiplatelet effect, suggests indobufen can be considered a drug with a definite role in the management of atherothrombotic events. In particular, indobufen may be an effective alternative for at risk patients with nonrheumatic atrial fibrillation in whom anticoagulant therapy is contraindicated or who are at higher risk of bleeding.     

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.     

Cilostazol: a new drug in the treatment intermittent claudication

The most common symptom of lower extremity peripheral arterial disease (PAD) is intermittent claudication. The severity of PAD is closely related with the risk of myocardial infarction, ischaemic stroke, and death from vascular causes. Despite the higher prevalence of PAD, far less importance is given to its diagnosis and management. Patients with peripheral arterial disease should be offered secondary prevention strategies including aggressive risk factor modification and anti-platelet drug therapy. Cilostazol, a reversible, selective inhibitor of PDE III with antiplatelet, antithrombotic and vasodilatory effects, was approved by the FDA in 1999 for the treatment of Intermittent Claudication. It is believed that the collective pharmacology effect of cilostazol actually improves blood flow to the lower extremities. The efficacy of cilistazol has been demonstrated in eight Phase three clinical trials. Cilostazol is the first drug to consistently demonstrate clinical efficacy in many double-blind randomised control trials. It is indicated for the improvement of the maximal and pain-free walking distances in patients with IC, who do not have rest pain and who do not have evidence of peripheral tissue necrosis. In this review we highlight the role of Cilostazol in the management of peripheral arterial disease. The combined effect of aspirin with Cilostazol was recently patented.     

Comparative safety and tolerability of clopidogrel and aspirin: results from CAPRIE. CAPRIE Steering Committee and Investigators. Clopidogrel versus aspirin in patients at risk of ischaemic events.

OBJECTIVE: The objective of this study was to provide a comprehensive comparison of the long term safety and tolerability of clopidogrel, a new adenosine diphosphate (ADP) receptor antagonist that inhibits platelet activation induced by ADP, and aspirin (acetylsalicylic acid). PATIENTS AND METHODS: The study population comprised 19,185 patients with symptomatic atherosclerosis manifested as recent ischaemic stroke, recent myocardial infarction or symptomatic peripheral arterial disease. Patients were randomised to receive clopidogrel 75 mg/day or aspirin 325 mg/day for a minimum of 1 year and a maximum of 3 years. RESULTS: Compared with aspirin, clopidogrel reduced the combined risk of ischaemic stroke, myocardial infarction or vascular death by 8.7% (p = 0.043). The incidence of early permanent discontinuations of the study drug due to adverse events was almost identical in both treatment groups (11.94% for clopidogrel vs 11.92% for aspirin). Reported neutropenia was similar in the clopidogrel and aspirin groups (0.10 vs 0.17%, respectively) with corresponding rates (0.05 vs 0.04%, respectively) for severe neutropenia. Thrombocytopenia was identical in the clopidogrel and aspirin groups (0.26%), with the rates of severe thrombocytopenia being 0.19 vs 0.10%, respectively. None of these observed differences was statistically significant. The overall incidence of haemorrhagic events did not differ statistically significantly between treatment groups (9.27% for clopidogrel vs 9.28% for aspirin; p = 0.98). There was a trend towards a lower incidence of intracranial haemorrhage in the clopidogrel group (0.31%) compared with the aspirin group (0.42%). Any reported gastrointestinal haemorrhage was significantly less frequent with clopidogrel (1.99%) than with aspirin (2.66%) [p < 0.002]. The corresponding data for severe gastrointestinal bleeding were 0.49 vs 0.71%; p < 0.05. Overall, there were significantly fewer gastrointestinal adverse events with clopidogrel than with aspirin (27.1 vs 29.8%; p < 0.001), with less abdominal pain, dyspepsia, constipation, or peptic, gastric, or duodenal ulceration with clopidogrel. Diarrhoea was significantly more common in the clopidogrel group (4.46 vs 3.36%; p < 0.001), although the incidence of severe diarrhoea (0.23 vs 0.11%) was low and was not significantly different between groups. There were significantly more patients with rash in the clopidogrel group (6.0%) compared with the aspirin group (4.6%) [p < 0.001]. However, these events were generally mild and transient in nature. CONCLUSION: Given the favourable benefit/risk ratio, clopidogrel represents a clinically important advance in the treatment of patients with manifest atherosclerotic disease.     

Effects of a new anti-inflammatory imidazole derivative, fenflumizole, on platelet aggregation in the rabbit

The antiplatelet effect of fenflumizole, compared with aspirin or ticlopidine, was examined in in vitro, ex vivo and in vivo situations of the rabbit. Unlike ticlopidine, fenflumizole and aspirin effectively inhibited in vitro the platelet aggregation elicited by arachidonate and collagen. The activity of fenflumizole was 350 times more potent than that of aspirin. Fenflumizole (0.3-3 mg/kg) given p.o. was 4.2 and 8.1 times more potent than aspirin in inhibiting arachidonate- and collagen-induced platelet aggregations, respectively. Ticlopidine (300 mg/kg, p.o.) resulted in only weak effects on the aggregations. Fenflumizole (3 mg/kg) as well as aspirin (10 mg/kg) given p.o., unlike ticlopidine (300 mg/kg), effectively prevented the arachidonate-induced sudden death.     

Antiplatelet therapy in peripheral arterial disease

Antiplatelet therapy significantly reduces the incidence of vascular death, nonfatal myocardial infarction, and nonfatal stroke in patients with peripheral arterial disease (PAD) and intermittent claudication, in patients undergoing peripheral grafting, in patients undergoing peripheral angioplasty, and in patients with carotid disease. Aspirin, aspirin plus dipyridamole, ticlodipine, and clopidogrel have been shown to be efficacious in the treatment of PAD. Data from the Clopidogrel versus Aspirin in Patients at Risk for Ischaemic Events (CAPRIE) trial demonstrated in 11,592 patients with PAD that patients randomized to clopidogrel 75 mg daily had a 24% significant (p=0.0028) reduction in vascular death, nonfatal myocardial infarction, and nonfatal stroke than patients randomized to aspirin 325 mg daily. These data favor the use of clopidogrel in patients with PAD.     

噻氯匹定治疗冠心病不良反应的研究

目的本文观察应用噻氯匹定治疗冠心病中患者的短期不良反应,以了解噻氯匹定的安全性。方法对1995年9月~2005年9月用噻氯匹定治疗的213例冠心病临床资料进行回顾性分析。结果噻氯匹定不良反应总的发生率为46%,其中,腹痛、腹泻最常见,占14%,其次是粒细胞减少(10%)和肝功能异常(7%),噻氯匹定不良反应的发生与性别、年龄无关。结论噻氯匹定是预防和治疗冠心病的有效药物,但要注意用药的安全,预防其不良反应,治疗过程中及时检查血常规和肝功能,并进行定期复查以预防粒细胞减少症,对不良反应及早处理。     

Safety of clopidogrel and aspirin for stroke prevention: implications of the CHARISMA trial.

Antiplatelet therapy is universally recommended for the prevention of recurrent events in patients with noncardioembolic ischaemic stroke or transient ischaemic attack (TIA), acute and chronic coronary artery disease, or peripheral arterial disease. However, choosing which antiplatelet agents to use in these situations remains controversial. The use of aspirin, aspirin plus extended-release dipyridamole, or clopidogrel is recommended as initial therapy in patients with noncardioembolic ischaemic stroke or TIA to reduce the risk of recurrent stroke and other cardiovascular events. Based on the results of the MATCH trial, combination therapy with aspirin plus clopidogrel is not recommended for patients with ischaemic stroke or TIA due to the increased risk of haemorrhage.The results of the CHARISMA trial support this recommendation; despite previous data demonstrating a favourable benefit-risk profile of aspirin plus clopidogrel in patients with acute coronary syndrome, this combination should not be used in patients at high risk for atherothrombosis and those with previous stroke or TIA. In these patients, the CHARISMA trial demonstrated a lack of significant clinical efficacy and an increased risk of bleeding with clopidogrel plus aspirin compared with aspirin alone.Further research is needed to assess the benefit-risk ratio of clopidogrel plus aspirin in specific subpopulations of patients at high risk for atherothrombotic events, and to determine the role of clopidogrel plus aspirin in preventing cardioembolic stroke or early recurrent stroke after symptomatic large-vessel atherostenosis. Recent and ongoing studies are seeking to better define the roles of different antiplatelet regimens in preventing recurrent stroke.