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Insights from CURE: using clopidogrel on top of standard therapy
1Cardiology Division, Santo André's Hospital, Leiria, Portugal. jaraujomorais@mail.telepac.pt
Insights
Clopidogrel significantly reduces cardiovascular events in unstable angina (UAP) and non-Q-wave myocardial infarction (NQMI) patients. This antiplatelet therapy, combined with aspirin, offers substantial protection against heart attack and stroke.
Area of Science:
- Cardiology
- Pharmacology
- Thrombosis Research
Background:
- Unstable angina pectoris (UAP) and non-Q-wave myocardial infarction (NQMI) are primarily caused by atherothrombosis.
- Standard therapies, including aspirin, offer limited prognosis improvement for these patients.
Purpose of the Study:
- To evaluate the efficacy of clopidogrel plus standard therapy in patients with UAP and NQMI.
- To assess the impact of clopidogrel on reducing ischemic cardiovascular events.
Main Methods:
- The CURE trial randomized over 12,500 patients to clopidogrel or placebo.
- Patients received clopidogrel (300mg loading, 75mg daily) or placebo alongside aspirin (75-325mg daily).
- Treatment and follow-up averaged 9 months in a double-blind, placebo-controlled design.
Main Results:
- Clopidogrel reduced the composite risk of cardiovascular death, stroke, and myocardial infarction by 20% (p < 0.001).
- Benefits were observed rapidly, consistently long-term, and across risk strata.
- An acceptable bleeding risk profile was noted, with no increase in intracranial hemorrhage.
Conclusions:
- Clopidogrel, added to standard aspirin therapy, is a highly effective treatment for UAP and NQMI.
- This combination therapy represents a new standard of care for patients with these acute coronary syndromes.
Abstract:
The principal pathophysiological mechanism in patients with unstable angina pectoris (UAP) and non-Q-wave myocardial infarction (NQMI) is atherothrombosis--the formation of a platelet-rich thrombus at the site of a disrupted or eroded atherosclerotic plaque. Despite standard therapy, which includes intravenous heparin or low-molecular-weight heparin and acetylsalicylic acid (ASA) during the acute phase followed by ASA on a long-term basis, the prognosis for patients remains poor. The efficacy of early and long-term treatment with clopidogrel (clopidogrel bisulphate) on top of standard therapy including ASA has recently been tested in patients with UAP and NQMI. In the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Ischaemic Events) Trial, more than 12,500 patients were randomized, in a double-blind manner, to receive placebo or clopidogrel, given as an initial 300-mg loading dose, followed by a 75-mg daily dose. All patients received a recommended dose of ASA (75-325 mg daily). The mean duration of treatment and follow-up was 9 months (minimum 3 months, maximum 12 months). CURE clearly showed that clopidogrel reduced the risk of a composite of cardiovascular death, stroke and MI, with a relative risk reduction of 20% (95% confidence interval, 72-90%; p < 0.001). The protective effect of clopidogrel was apparent within 2 h of initiation of therapy, and the benefit was consistent at 30 days and after long-term treatment. The benefit of clopidogrel was observed across the spectrum of high- and low-risk patients and was obtained with an acceptable risk of bleeding and no increase in intracranial haemorrhage. Based on data from CURE, the use of clopidogrel on top of standard therapy including ASA can be expected to become the new foundation therapy in patients with UAP and NQMI.