Study Name Population Intervention Comparison Outcomes Follow-up Results Bottomline
Retrospective 57,039 NSTE-ACS Receiving No morphine Total mortality From Mortality Although
Cohort Study morphine 01/2001 to. multivariate inconclusive
within 24 hours 06/2003 OR. 1.48,95%, conclusion other
of CI1.33-1.64 studies have
presentation. Mortality raised concerns*
(29.8&) propensity about effects of
score adjusted morphine in
OR 1.41, 95%, patients with ACS
CI 1.26-1.57
ISIS-2 (Secondary 17,187 patients Streptokinase Placebo Vascular 5 weeks RRR 20% ASA has
International Study of suspected acute Mortality (very-short ARR 2.4% unquestionable
Infract Survival) MI within 24 ASA 160 mg Placebo term) NNT = 42 benefits in terms
hours of of ACS (short and
symptom onset Non-fatal MI long-term)
and stroke mortality
No increase in
bleeding
CURRENT & OASIS 7 ASA high dose (300-325mg daily) Increased risk of Low dose just as
(PCI-CURE subgroup ASA low dose (75-10mg daily) bleeding with effective as high
analysis did not show high dose ASA dose and safer
significant difference
between the two
doses)
CHARISMA (primary 15,603 patients Clopidogrel (75 Placebo + low dose Primary outcome Median of RR: 0.93,95%, CI For patients at
prevention) with either mg/day) plus ASA – composite MI, 28 months 0.83-1.05 high risk for
clinically CVD or low dose ASA stroke, or death P = 0.22 primary
multiple RF (75-162 from CV causes) prevention the
(more were mg/day) combination is
w/out a prior CV not better than
event) the monotherapy
COMMIT (secondary 45,852 ACS Clopidogrel Matching placebo Death, re- Until RRR 9%
prevention) patients (93% 75m/day (no (n=22,891) infarction, or discharge or P =0.002
Clopidogrel & STEMI) All on ASA 162 loading) stroke up to 4 RRR 7%
mg
Metoprolol in MI trial ½ receiving fibrinolytic (n=22,961) Mortality weeks in P = 0.03
therapy hospital
*Morphine Concerns: interference with antiplatelet effect of P2Y 12 Receptor Blockers; PD/PK studies show that morphine may reduce the effects of
ticagrelor, clopidogrel and prasugrel (no RCT support of this hypothesis); MIAMI Trial (Metoprolol) & ISIS-1 Trial (Atenolol)
, CLARITY-TIMI 28 3491 patients, Clopidogrel Matching placebo Occluded infarct- 30 days RRR 36% (from
18-75 years of (300mg loading related artery on 21.7% to 15.0%)
age, presented dose, followed angiography or P < 0.001
within 12h after by 75mg once death or rMI
the onset of daily)
STEMI.
All on fibrinolytic agent,
with ASA, and when
appropriate, heparin
(dispensed according to
body weight)
CURE 12,562 NSTEMI Clopidogrel Placebo Composite death 3-12 months 20% RRR (from Combination of
ACS patients (300mg from CV causes, 11.4% to 9.3%) clopidogrel + ASA
within 24h after immediately non-fatal MI, or ARR: 2.1 is more beneficial
the onset of followed by stroke NNT ~48 than ASA alone in
symptoms 75mg once P <0.001 NSTEMI patients.
All patients were on ASA daily) Must give loading
75-325mg daily dose of 300mg
Major bleeding clopidogrel to see
(3.7% vs 2.7%, benefits.
P=0.001,
NNH=100)
Life threatening There is
bleeding (2.2% vs increased
1.8%, P=0.002, bleeding risk b/c
NNH=167) of the
Minor bleeding combination
(5.1% vs. 2.4%, therapy however
P<0.001, NNH=38) benefits > risks
significantly
PCI CURE PCI patients – Clopidogrel + Placebo Combination therapy
Prospectively designed after PCI, stented conservative is very effective in
study of patients patients who are
patients received approach to
undergoing PCI who planning PCI within
an open label ACS treatment the NSTEMI
were in the CURE trial
thienopyridine + (pretreated with population.
ASA for 2-4 weeks ASA + study drug Clopidogrel showed
then back to for a median of 6 significantly less risk
randomly days before PCI) of outcomes vs
placebo
assigned stud
med
*Morphine Concerns: interference with antiplatelet effect of P2Y 12 Receptor Blockers; PD/PK studies show that morphine may reduce the effects of
ticagrelor, clopidogrel and prasugrel (no RCT support of this hypothesis); MIAMI Trial (Metoprolol) & ISIS-1 Trial (Atenolol)
Retrospective 57,039 NSTE-ACS Receiving No morphine Total mortality From Mortality Although
Cohort Study morphine 01/2001 to. multivariate inconclusive
within 24 hours 06/2003 OR. 1.48,95%, conclusion other
of CI1.33-1.64 studies have
presentation. Mortality raised concerns*
(29.8&) propensity about effects of
score adjusted morphine in
OR 1.41, 95%, patients with ACS
CI 1.26-1.57
ISIS-2 (Secondary 17,187 patients Streptokinase Placebo Vascular 5 weeks RRR 20% ASA has
International Study of suspected acute Mortality (very-short ARR 2.4% unquestionable
Infract Survival) MI within 24 ASA 160 mg Placebo term) NNT = 42 benefits in terms
hours of of ACS (short and
symptom onset Non-fatal MI long-term)
and stroke mortality
No increase in
bleeding
CURRENT & OASIS 7 ASA high dose (300-325mg daily) Increased risk of Low dose just as
(PCI-CURE subgroup ASA low dose (75-10mg daily) bleeding with effective as high
analysis did not show high dose ASA dose and safer
significant difference
between the two
doses)
CHARISMA (primary 15,603 patients Clopidogrel (75 Placebo + low dose Primary outcome Median of RR: 0.93,95%, CI For patients at
prevention) with either mg/day) plus ASA – composite MI, 28 months 0.83-1.05 high risk for
clinically CVD or low dose ASA stroke, or death P = 0.22 primary
multiple RF (75-162 from CV causes) prevention the
(more were mg/day) combination is
w/out a prior CV not better than
event) the monotherapy
COMMIT (secondary 45,852 ACS Clopidogrel Matching placebo Death, re- Until RRR 9%
prevention) patients (93% 75m/day (no (n=22,891) infarction, or discharge or P =0.002
Clopidogrel & STEMI) All on ASA 162 loading) stroke up to 4 RRR 7%
mg
Metoprolol in MI trial ½ receiving fibrinolytic (n=22,961) Mortality weeks in P = 0.03
therapy hospital
*Morphine Concerns: interference with antiplatelet effect of P2Y 12 Receptor Blockers; PD/PK studies show that morphine may reduce the effects of
ticagrelor, clopidogrel and prasugrel (no RCT support of this hypothesis); MIAMI Trial (Metoprolol) & ISIS-1 Trial (Atenolol)
, CLARITY-TIMI 28 3491 patients, Clopidogrel Matching placebo Occluded infarct- 30 days RRR 36% (from
18-75 years of (300mg loading related artery on 21.7% to 15.0%)
age, presented dose, followed angiography or P < 0.001
within 12h after by 75mg once death or rMI
the onset of daily)
STEMI.
All on fibrinolytic agent,
with ASA, and when
appropriate, heparin
(dispensed according to
body weight)
CURE 12,562 NSTEMI Clopidogrel Placebo Composite death 3-12 months 20% RRR (from Combination of
ACS patients (300mg from CV causes, 11.4% to 9.3%) clopidogrel + ASA
within 24h after immediately non-fatal MI, or ARR: 2.1 is more beneficial
the onset of followed by stroke NNT ~48 than ASA alone in
symptoms 75mg once P <0.001 NSTEMI patients.
All patients were on ASA daily) Must give loading
75-325mg daily dose of 300mg
Major bleeding clopidogrel to see
(3.7% vs 2.7%, benefits.
P=0.001,
NNH=100)
Life threatening There is
bleeding (2.2% vs increased
1.8%, P=0.002, bleeding risk b/c
NNH=167) of the
Minor bleeding combination
(5.1% vs. 2.4%, therapy however
P<0.001, NNH=38) benefits > risks
significantly
PCI CURE PCI patients – Clopidogrel + Placebo Combination therapy
Prospectively designed after PCI, stented conservative is very effective in
study of patients patients who are
patients received approach to
undergoing PCI who planning PCI within
an open label ACS treatment the NSTEMI
were in the CURE trial
thienopyridine + (pretreated with population.
ASA for 2-4 weeks ASA + study drug Clopidogrel showed
then back to for a median of 6 significantly less risk
randomly days before PCI) of outcomes vs
placebo
assigned stud
med
*Morphine Concerns: interference with antiplatelet effect of P2Y 12 Receptor Blockers; PD/PK studies show that morphine may reduce the effects of
ticagrelor, clopidogrel and prasugrel (no RCT support of this hypothesis); MIAMI Trial (Metoprolol) & ISIS-1 Trial (Atenolol)
