Stroke clopidogrel

PROFESS is an ongoing large randomized trial examining combination ER-DP plus aspirin therapy compared with clopidogrel (each group also with or without telmisartan, an angiotensin receptor antagonist) for the secondary prevention of early and late recurrent stroke, and other vascular events. 

The CAPRIE trial found that compared to aspirin (325 mg daily), clopidogrel (75 mg daily) was associated with RRR of 8.7% p = 0.043) for the composite endpoint of ischemic stroke, Ml, or vascular death among 19,185 subjects with stroke, MI, or peripheral arterial disease, but no significant reduction in the composite endpoint in the subgroup with stroke (RRR 7.3%, p = 0.26). No comparison of clopidogrel with aspirin in the acute stroke period was performed. Furthermore, stroke as an endoint was not significantly reduced in the stroke patients entered in this trial (RRR 8.0%, p = NS). 

Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, Leys D, Matias-Guiu J, Rupprecht HJ MATCH investigators. Aspirin and clopidogrel compared with clopidogrel alone after recent ischemic stroke or transient ischemic attack in high-risk patients (MATCH) randomised, double-blind, placebo-controlled trial. Lancet 2004 364(9431) 331-337. 

Aspirin decreases the risk of death, recurrent infarction, and stroke following myocardial infarction. Aspirin prescription at hospital discharge is a quality care indicator in MI patients.3 All patients should receive aspirin indefinitely those patients with a contraindication to aspirin should receive clopidogrel.2,3... 

For patients with NSTE ACS, clopidogrel decreases the risk of death, MI, or stroke. Most patients with NSTE ACS should receive clopidogrel, in addition to aspirin, for up to 12 months. 

Recent Ml or stroke, or established peripheral arterial d/sease For patients with a history of recent Ml, recent stroke, or established peripheral arterial disease, clopidogrel has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new Ml (fatal or not), and other vascular death. 

Acute coronary syndrome For patients with acute coronary syndrome (unstable angina/non-Q-wave Ml) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent) or coronary artery bypass graft (CABG), clopidogrel has been shown to decrease the rate of a combined endpoint of cardiovascular death. Ml, or stroke, as well as the rate of a combined endpoint of cardiovascular death. Ml, stroke, or refractory ischemia. 

Recent Ml, recent stroke, or established peripheral arterial disease The recommended dose of clopidogrel is 75 mg once daily with or without food. 

Activation of platelets is considered an essential process for arterial thrombosis. Thus, treatment with platelet-inhibiting drugs such as aspirin and ticlopidine or clopidogrel is indicated in patients with transient ischemic attacks and strokes or unstable angina and acute myocardial infarction. In angina and infarction, these drugs are often used in conjunction with -blockers, calcium channel blockers, and fibrinolytic drugs. 

The third trial was a subgroup analysis of the CLARITY (29) trial performed in acute Ml. It was demonstrated that in STEM I patients, treated with fibrinolytic and who underwent PCI during the hospitalization period (n = 1863 patients), the dual antiplatelet treatment was able to reduce major vascular events (death, Ml, and stroke) from 12% to 7.5% (RRR = 0.59 95% Cl 0.43-0.81 P = 0.001). Thus, the treatment with clopidogrel + aspirin of 43 STEMI patients followed by PCI prevents one major vascular event. 

The CHARISMA trial (51) enrolled 15,603 patients with either cardiovascular disease or multiple risk factors followed for a median of 28 months. Overall, the dual antiplatelet regimen (aspirin + clopidogrel) was not significantly more effective than aspirin alone in reducing the rate of death, Ml or stroke from cardiovascular causes. 

The results showed that patients treated with clopidogrel had an annual 5,32% risk of ischemic stroke, Ml, or vascular death compared with 5,83% with aspirin (RRR = 8.7% in favor of clopidogrel, P = 0,045). There were no major differences in terms of safety. 

The benefit of clopidogrel was consistent across the different subgroups but was particularly important in high-risk patients in patients with prior CABG (53), 75 mg of clopidogrel compared to aspirin reduced the risk of vascular events (vascular death, Ml, stroke, rehospitalization) from 22,3% to 15,9%, Similar results were obtained in diabetic patients (54) (reduction from 21.5% to 17.7%) of this endpoint and a reduction from 23.8% to 20.4% in patients with a history of Ml or stroke,... 

The study design included three comparisons ACTIVE W ACTIVE A, and ACTIVE I in 14,000 patients, (Maximum follow-up was for 48 months), The primary endpoint was the time to first vascular event (stroke, Ml, vascular death, systemic emboli). ACTIVE W arm was halted when 6600 patients were enrolled because there a clear benefit from warfarin treatment compared to clopidogrel + aspirin 3.63% of vascular events versus 5,64% (P = 0,0002). Subgroup analysis showed that these disappointing results were observed in patients on warfarin prior to study (HR = 1.5, P = 0.0006), but there was no difference between the two strategies—when the patients were not on warfarin prior to study (HR = 1.32, P = 0,17), Nevertheless, further results are awaited from the ACTIVE-A arm (ASA or ASA + clopidogrel) in patients who cannot or would not take OAC. 

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