Ignite Creation Date:
2024-05-05 @ 12:02 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00222573
Status:
COMPLETED
Last Update Posted:
2006-05-05
First Post:
2005-09-13
Brief Title:
Efficacy and Safety of Adding Clopidogrel to Aspirin or Use of Metoprolol in Myocardial Infarction
Sponsor:
University of Oxford
Organization:
University of Oxford
Study Overview
Official Title:
Clopidogrel Or Metoprolol in Myocardial Infarction Trial
Status:
COMPLETED
Status Verified Date:
2005-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
COMMITCCS2 is a large randomised trial of the effects of clopidogrel plus Aspirin versus Aspirin alone in acute heart disease Patients presenting within 24 hours of the onset of suspected acute MI were potentially eligible provided they were thought to have ST elevation or other ischaemic ECG abnormality with no clear indication for or contraindication to trial treatment All patients were to be given 162 mg ASA daily and in addition 75 mg clopidogrel daily or matching placebo for 4 weeks or until prior discharge or death Patients were also randomised separately in a 2 X 2 factorial design between metoprolol versus placebo The two main study endpoints are death and the composite outcome of death non-fatal reinfarction or stroke during the scheduled treatment period in hospital
Detailed Description:
Clopidogrel
Despite considerable improvements in the emergency treatment of acute myocardial infarction MI including the use of aspirin early mortality and morbidity remain high The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute coronary syndromes without ST-segment elevation but its effects on mortality and morbidity in patients with ST-elevation MI were unclear
45852 patients admitted to 1250 hospitals within 24 hours of the onset of suspected acute MI were randomly allocated to receive clopidogrel 75 mg daily or matching placebo both in addition to aspirin 162 mg daily 93 had ST-segment elevation or bundle branch block and 7 had ST-segment depression Treatment was to continue until discharge or up to a maximum of 4 weeks in hospital mean 15 days in survivors and 93 completed it The two pre-specified co-primary outcomes were i the composite of death reinfarction or stroke and ii death from any cause during the scheduled treatment period Comparisons were between all clopidogrel-allocated and all placebo-allocated patients ie intention-to-treat and used the log-rank method
Allocation to clopidogrel produced a highly significant 9 95 CI 3-14 proportional reduction in the primary composite outcome of death reinfarction or stroke 2121 92 clopidogrel vs 2310 101 placebo p0002 corresponding to 9 SE 3 fewer events per 1000 patients treated for about 2 weeks There was also a significant 7 95 CI 1-13 proportional reduction in the co-primary outcome of any death 1726 75 vs 1845 81 p003 These effects on death reinfarction and stroke appeared to be consistent across a wide range of patients and independent of other treatments being used Considering all transfused fatal or cerebral bleeds together no significant excess risk was observed with clopidogrel either overall 134 058 vs 125 055 p059 or among patients aged 70 years or older 50 084 vs 43 072 p048 or among those given fibrinolytic therapy 74 065 vs 72 063 p088
In a wide range of patients with acute MI adding clopidogrel 75 mg daily to aspirin and other standard treatments such as fibrinolytic therapy reduces mortality and major vascular events in hospital without any material increase in major bleeding
Metoprolol
Despite previous randomised trials of early beta-blocker therapy in the emergency treatment of suspected acute myocardial infarction MI substantial uncertainty has persisted about the value of adding it to currently standard interventions eg aspirin and fibrinolytic therapy and the balance of potential benefits and hazards was unclear even in high-risk patients
45852 patients admitted to 1250 hospitals within 24 hours of the onset of suspected acute MI were randomly allocated to receive metoprolol up to 15 mg intravenous followed by 200 mg oral daily or matching placebo 93 had ST-segment elevation or bundle branch block and 7 had ST-segment depression Treatment was to continue until discharge or up to a maximum of 4 weeks in hospital mean 15 days in survivors and 89 completed it The two pre-specified co-primary outcomes were i the composite of death reinfarction or cardiac arrest and ii death from any cause during the scheduled treatment period Comparisons were between all metoprolol-allocated and all placebo-allocated patients ie intention-to-treat and used the log-rank method
Neither of the co-primary outcomes was significantly reduced by allocation to metoprolol For the primary composite outcome of death reinfarction or cardiac arrest 2166 94 patients had at least one such event among the 22 929 allocated metoprolol compared with 2261 99 among the 22 923 allocated matching placebo odds ratio OR 096 95 CI 090-101 p01 For the co-primary outcome of death alone there were 1774 77 in the metoprolol group versus 1797 78 in the placebo group OR 099 092-105 p069 Allocation to metoprolol was associated with 5 fewer people having reinfarction 464 20 metoprolol vs 568 25 placebo OR 082 072-092 p0001 and 5 fewer having ventricular fibrillation 581 25 vs 698 30 OR 083 075-093 p0001 per 1000 treated Overall these reductions were counter-balanced by 11 more per 1000 allocated metoprolol developing cardiogenic shock 1141 50 vs 885 39 OR 130 119-141 p000001 The excess of cardiogenic shock was chiefly during days 0-1 after hospitalisation whereas the reductions in reinfarction and ventricular fibrillation emerged more gradually Consequently the overall effect on death reinfarction arrest or shock was significantly adverse during days 0-1 and significantly beneficial thereafter There was substantial net hazard among haemodynamically unstable patients and moderate net benefit among those who were relatively stable particularly after days 0-1
The use of early beta-blocker therapy in acute MI reduces the risks of reinfarction and ventricular fibrillation but increases the risk of cardiogenic shock especially during the first day or so after hospitalisation Consequently it may generally be prudent to consider starting beta-blocker therapy in hospital only when the haemodynamic condition following MI has stabilized and then based on previous evidence to continue such therapy long-term following discharge
Despite considerable improvements in the emergency treatment of acute myocardial infarction MI including the use of aspirin early mortality and morbidity remain high The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute coronary syndromes without ST-segment elevation but its effects on mortality and morbidity in patients with ST-elevation MI were unclear
45852 patients admitted to 1250 hospitals within 24 hours of the onset of suspected acute MI were randomly allocated to receive clopidogrel 75 mg daily or matching placebo both in addition to aspirin 162 mg daily 93 had ST-segment elevation or bundle branch block and 7 had ST-segment depression Treatment was to continue until discharge or up to a maximum of 4 weeks in hospital mean 15 days in survivors and 93 completed it The two pre-specified co-primary outcomes were i the composite of death reinfarction or stroke and ii death from any cause during the scheduled treatment period Comparisons were between all clopidogrel-allocated and all placebo-allocated patients ie intention-to-treat and used the log-rank method
Allocation to clopidogrel produced a highly significant 9 95 CI 3-14 proportional reduction in the primary composite outcome of death reinfarction or stroke 2121 92 clopidogrel vs 2310 101 placebo p0002 corresponding to 9 SE 3 fewer events per 1000 patients treated for about 2 weeks There was also a significant 7 95 CI 1-13 proportional reduction in the co-primary outcome of any death 1726 75 vs 1845 81 p003 These effects on death reinfarction and stroke appeared to be consistent across a wide range of patients and independent of other treatments being used Considering all transfused fatal or cerebral bleeds together no significant excess risk was observed with clopidogrel either overall 134 058 vs 125 055 p059 or among patients aged 70 years or older 50 084 vs 43 072 p048 or among those given fibrinolytic therapy 74 065 vs 72 063 p088
In a wide range of patients with acute MI adding clopidogrel 75 mg daily to aspirin and other standard treatments such as fibrinolytic therapy reduces mortality and major vascular events in hospital without any material increase in major bleeding
Metoprolol
Despite previous randomised trials of early beta-blocker therapy in the emergency treatment of suspected acute myocardial infarction MI substantial uncertainty has persisted about the value of adding it to currently standard interventions eg aspirin and fibrinolytic therapy and the balance of potential benefits and hazards was unclear even in high-risk patients
45852 patients admitted to 1250 hospitals within 24 hours of the onset of suspected acute MI were randomly allocated to receive metoprolol up to 15 mg intravenous followed by 200 mg oral daily or matching placebo 93 had ST-segment elevation or bundle branch block and 7 had ST-segment depression Treatment was to continue until discharge or up to a maximum of 4 weeks in hospital mean 15 days in survivors and 89 completed it The two pre-specified co-primary outcomes were i the composite of death reinfarction or cardiac arrest and ii death from any cause during the scheduled treatment period Comparisons were between all metoprolol-allocated and all placebo-allocated patients ie intention-to-treat and used the log-rank method
Neither of the co-primary outcomes was significantly reduced by allocation to metoprolol For the primary composite outcome of death reinfarction or cardiac arrest 2166 94 patients had at least one such event among the 22 929 allocated metoprolol compared with 2261 99 among the 22 923 allocated matching placebo odds ratio OR 096 95 CI 090-101 p01 For the co-primary outcome of death alone there were 1774 77 in the metoprolol group versus 1797 78 in the placebo group OR 099 092-105 p069 Allocation to metoprolol was associated with 5 fewer people having reinfarction 464 20 metoprolol vs 568 25 placebo OR 082 072-092 p0001 and 5 fewer having ventricular fibrillation 581 25 vs 698 30 OR 083 075-093 p0001 per 1000 treated Overall these reductions were counter-balanced by 11 more per 1000 allocated metoprolol developing cardiogenic shock 1141 50 vs 885 39 OR 130 119-141 p000001 The excess of cardiogenic shock was chiefly during days 0-1 after hospitalisation whereas the reductions in reinfarction and ventricular fibrillation emerged more gradually Consequently the overall effect on death reinfarction arrest or shock was significantly adverse during days 0-1 and significantly beneficial thereafter There was substantial net hazard among haemodynamically unstable patients and moderate net benefit among those who were relatively stable particularly after days 0-1
The use of early beta-blocker therapy in acute MI reduces the risks of reinfarction and ventricular fibrillation but increases the risk of cardiogenic shock especially during the first day or so after hospitalisation Consequently it may generally be prudent to consider starting beta-blocker therapy in hospital only when the haemodynamic condition following MI has stabilized and then based on previous evidence to continue such therapy long-term following discharge
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| H6RDCN0 | None | None | None |