Transcript Clopidogrel When For What For How Long

Clopidogrel
When
For What
For How Long
T Benjanuwattra
Chiang Mai Heart Center
Evidence Based Medicine
I don’t want to put you to sleep
But want you to be fully alert
Atherothrombosis: A Generalized
and Progressive Process
Unstable
angina
ACS
MI
Ischemic
stroke/TIA
Critical leg
ischemia
Cardiovascularde
ath
Atherosclerosis
Atherothrombosis
Stable angina
Intermittent claudication
Adapted from Stary HC et al. Circulation. 1995; 92: 1355–74, and Fuster V et al. Vasc Med.
1998; 3: 231–9.
Spectrum of Acute Coronary
Syndromes
Stable
Angina
Unstable
Angina
Non-Q
wave MI
Non ST
Elevation ACS
Q wave
MI
ST Elevation
MI
ECG - ST
ECG - ST
CK-MB
Troponin
ADP, Epinephrine, Collagen, Thrombin
Ticlopidine
Clopidogrel
AA
TxA2
Aspirin
GPIIbIIIa Expression
GPIIbIIIa inhibitors
CAPRIE: Design1





Objective: to compare the efficacy and safety of clopidogrel 75
mg with active control – ASA 325 mg
Double-blind, randomized, prospective trial
Multicenter (384 centers in 16 countries)
Follow-up of 19,185 patients from 1 to 3 years with:
 Ischemic atherothrombotic stroke
 Myocardial infarction (MI)
 Peripheral arterial disease
Combined primary endpoint: cluster of ischemic stroke, MI, and
vascular death
1. CAPRIE Steering Committee. Lancet 1996; 348: 1329–39.
CAPRIE: Long-Term Benefit of
Clopidogrel Compared with ASA1
Cumulative Event Rate
(Myocardial Infarction, Ischemic Stroke or Vascular Death)
ASA
Cumulative event rate (%)
16
8.7%*
Overall
relative
risk
reduction
Clopidogrel
12
8
4
p = 0.043, n = 19,185
0
0
3
6
9
12
15
18
21
24
Months of follow-up
*ITT analysis
1. CAPRIE Steering Committee. Lancet 1996; 348: 1329–39.
27
30
33
36
CAPRIE: Benefit of Clopidogrel over ASA in the Reduction of
Myocardial Infarction1
ASA
19.2%*
Relative
risk
reduction
Clopidogrel
Cumulative event rate (%)
5
ASA 3.6%
4
3
P 0.008
Clopidogrel 2.9%
2
1
p = 0.008, n = 19,185
0
0
3
6
9
12
15
18
21
24
Months of follow-up
*ITT analysis
1. Gent M. Circulation 1997; 96(suppl 8): I-467.
27
30
33
36
Acute Coronary Syndromes
Non ST elevation ACS
(UA/NSTEMI)
ST elevation ACS
(AMI)
Plateletes rich thrombus
Fibrin rich thrombus
• to stabilize plaque
• to prevent further thrombosis
• Revascularization in high risk pt
• Revascularization
Platelets
Fibrin
Thrombin
Subtotal
occlusion
Treatment
Stable plaque
Re-thrombosis
Embolization
Spasm
CURE: Design1
n = 12,562
28 countries
Clopidogrel
Patients with
acute coronary
syndrome
(unstable angina
or non-Q-wave
myocardial
infarction)
ASA 75–325 mg o.d.
R
75mg o.d.
(n = 6,259)
Double-blind treatment up to 12 months
ASA 75–325 mg o.d.
Placebo
1 tab o.d.
(n = 6,303)
R = Randomization
1. The CURE Study Investigators. Eur Heart J 2000; 21: 2033–41.
CURE: Early and Long-Term Benefits
of Clopidogrel1,2
Cumulative Events
(Myocardial Infarction, Stroke, or Cardiovascular Death)
Cummulative hazard rate
0.14
Placebo*
(n = 6,303)
0.12
0.10
Clopidogrel*
(n = 6,259)
0.08
0.06
20% Relative
risk reduction
p = 0.00009
0.04
0.02
0.00
0
3
6
9
Months of follow-up
*On top of standard therapy (including ASA)
1. The CURE Trial Investigators. N Engl J Med 2001; 345: 494–502. 2. Data on file, 2002,
p73 internal CSR-EFC 3307.
12
MI/Stroke/CV Death within 30 Days
Cumulative Hazard Rate
0.06
Placebo
+ ASA*
0.05
0.04
Clopidogrel
+ ASA*
0.03
0.02
21% RRR
P = 0.003
N = 12,562
0.01
0.00
Benefit seen in
0
1st
10
24Hr 34%RRR
20
Days of Follow-Up
* In combination with standard therapy
The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
30
CURE: Consistent Benefit on Top of
Various Standard Therapies1
Concomitant
medication/therapy
Heparin/LMWH
ASA
GPIIb/IIIa Antag
Beta-blocker
ACEI
Lipid-lowering
PTCA/CABG
Events (%)
N
Clopidogrel* Placebo*
No
951
4.9
7.7
Yes
11611
9.7
11.7
< 100 mg
1927
8.5
9.7
100–200 mg 7428
9.2
10.9
> 200 mg
3201
9.9
13.7
No
11739
8.9
10.8
Yes
823
15.7
19.2
No
2032
9.9
12.0
Yes
10530
9.2
11.3
No
4813
6.3
8.1
Yes
7749
11.2
13.5
No
4461
10.9
13.1
Yes
8101
8.4
10.5
No
7977
8.1
10.0
Yes
4585
11.4
13.8
*On top of standard therapy (including ASA)
1. Clopidogrel Prescribing Information, US, February 2002.
Clopidogrel better
0.4
0.6
0.8
1.0
Hazard ratio (95% CI)
Placebo better
1.2
TIMI Risk Score for UA/NSTEMI
7 Independent Predictors







Age 65 years
3 CAD risk factors
( chol, FHx, HTN, DM, smoking)
Prior CAD (cath stenosis >50%)
ASA in last 7 days
2 Anginal events 24 hours
ST deviation
Elevated cardiac markers (CK-MB or troponin)
Antman et al. JAMA. 2000;284:835
RISK OF CARDIAC EVENTS (%)
BY 14 DAYS IN TIMI 11B*
RISK
SCORE
DEATH
OR MI
0/1
3
5
2
3
8
3
5
13
4
7
20
5
12
26
6/7
19
41
DEATH, MI OR
URGENT REVASC
CURE: Effects of Clopidogrel Stratified by TIMI Risk
Score at 12 Months
MI, stroke or vascular death (%)
ARR*
RRR†
1.6
29%
1.6
15%
25
4.8
27%
n = 1,989
20.7
20
15.9
15
11.4
10
p = 0.003
9.8
Clopidogrel
n = 3,276
p = 0.02
5.7
5
Placebo
n = 7,297
4.1
p = 0.03
0
Low risk
Moderate risk
High risk
*Absolute risk reduction
†Relative risk reduction
1. The CURE Trial Investigators. N Engl J Med 2001; 345: 494–502. 2. Budaj AJ et al J Am Coll
Cardiol 2002; 39, (suppl B): 441B.
PCI
Stent
PCI-CURE: 31% Relative Risk Reduction at
Long-Term1
Endpoint: Myocardial Infarction or Vascular Death
Cumulative hazard rate
0.15
Placebo*
(n = 1,345)
Median time
to PCI
0.10
Clopidogrel*
(n = 1,313)
31% Relative
risk reduction
0.05
p < 0.002
0.00
0 10
100
200
Days of follow-up
*On top of standard therapy (including ASA)
1. Mehtra SR et al. Lancet 2001; 358: 527–33.
300
400
CURE: Bleeding Episodes
Event
Major bleeding1
Placebo*
(n = 6,303)
Clopidogrel*
(n = 6,259)
p value
2.7%
3.7%
0.001
•
Life-threatening
1.8%
2.2%
NS
•
Other major bleeding
0.9%
1.5%
0.002
Transfusions of  2 units
of blood1
2.2%
2.8%
0.02
Minor bleeding1
2.4%
5.1%
< 0.001
Major bleeding by
TIMI definition2
1.2%
1.1%
0.70
Major bleeding by
GUSTO definition3
1.1%
1.2%
0.48
*On top of standard therapy (including ASA)
1. The CURE Trial Investigators. N Engl J Med 2001; 345: 494–502. 2. Chesebro JH et al.
Circulation 1987; 76: 142–54. 3. The GUSTO Investigators. N Engl J Med 1993; 329: 673–82.
The CREDO Trial
Clopidogrel for the Reduction of
Events
During Observation
CREDO
Objectives
Objectives
 To evaluate the long term efficacy of prolonged (1
year) therapy with clopidogrel 75mg vs placebo in
patients on top of standard therapy (including
ASA)

To evaluate the effect of pretreatment with a
clopidogrel 300 mg loading dose on the
composite of death (all-cause), MI (Q- or non-Qwave), or UTVR at Day 28, in patients who
underwent PCI

To evaluate the safety of clopidogrel, specifically
the frequency of major bleeding events and early
discontinuation of study drug
UTVR= Urgent Target Vessel Revascularization
Steinhubl S, et al. JAMA, November 20, 2002 – Vol 288, No 19: 2411 – 2420
CREDO
Endpoints
1 Year Endpoint

First occurrence of any component up to 1 year
of the cluster of:
 Death, MI, or stroke
28 Day Endpoint

First occurrence of any component up to 28
days of the cluster of:
 Death, MI, or urgent TVR
Steinhubl S, et al. JAMA, November 20, 2002 – Vol 288, No 19: 2411 – 2420
Overall Study Design
Placebo Arm
Clopidogrel Arm
PCI
28 Days
12 Months
Pretreatment
LD
Clopidogrel#
Clopidogrel#
Clopidogrel*
R
Clopidogrel#
LD Placebo#
LD=loading dose, PT= Pretreatment, R= Randomization
# on top standard therapy including ASA (325 mg)
•on top standard therapy including ASA (81-325 mg)
Steinhubl S, et al. JAMA, November 20, 2002 – Vol 288, No 19: 2411 – 2420
Placebo*
Long-term Benefits of Clopidogrel in PCI
Patients
1 year results
COMBINED ENDPOINT OCCURRENCE (%)
15
(MI, Stroke, or Death)
11.5%
27% RRR
10
p = 0.02
8.5%
5
Placebo*#
Clopidogrel*
0
0
3
6
MONTHS FROM RANDOMIZATION
* On top of standard therapy including ASA
# All patients received clopidogrel post PCI up to day 28
Steinhubl S, et al. JAMA, November 20, 2002 – Vol 288, No 19: 2411 – 2420
9
12
Early Effects of Pretreatment with
Clopidogrel:
Per - Protocol
COMBINED ENDPOINT OCCURRENCE (%)
28 Days results
(Death, MI, UTVR)
8.3%
18.5 % RRR
p = 0.23
6.8%
PT- Clopidogrel*
No-PT Clopidogrel*
0
7
14
21
DAYS FROM RANDOMIZATION
*From PCI to 28 days, on top of standard therapy including ASA (325mg from randomization to Day 28)
PT= Pretreatment
UTVR: Urgent Target Vessel Revascularization
Steinhubl S, et al. JAMA, November 20, 2002 – Vol 288, No 19: 2411 – 2420
28
Timing of Loading Dose - 28
Days
Events (%)
PT-Clopidogrel*
No-PT
Clopidogrel*
PT-Clopidogrel
Better
n
< 6 hrs
7.9
7.0
893
6 to 24 hr
5.8
9.4
851
No-PT Clopidogrel
Better
RRR -13.4
p=NS
RRR 38.6
p=0.05
RRR 18.5
p=0.23
Overall CREDO Results
0.6
0.8
1.0
1.2
Hazard ratio (95% CI)
* On top of standard therapy including ASA, PT= Pretreatment
Steinhubl S, et al. JAMA, November 20, 2002 – Vol 288, No 19: 2411 – 2420
Increased Risk in Other Vascular Beds
After an Atherothrombotic Event1–4
Increased risk of MI
Increased risk of stroke
CHD=coronary heart disease
1.
2.
3.
4.
Adult Treatment Panel II. Circulation 1994; 89: 1333–1435.
Kannel WB. J Cardiovasc Risk 1994; 1: 333–339.
Wilterdink JI et al. Arch Neurol 1992; 49: 857–863.
Criqui MH et al. N Engl J Med 1992; 326: 381–386.
FOR INTERNAL USE ONLY
Clopidogrel in Patients with
ST-Segment Elevation Myocardial
Infarction (STEMI)
N Engl J Med 2005;352:1179
FOR INTERNAL USE ONLY
occlusion
Fibrinolytic, PCI
Lysed clot
Reperfusion
Exposed
clot-bound
thrombin
Activated
platelets
Re-thrombosis
Platelet &
thrombus
emboli
Embolization
TxA2
Spasm
Pathophysiology of STEMI1
Generally caused by a
completely occlusive
thrombus in a coronary artery
Results from stabilization of a
platelet aggregate at site of
plaque rupture by fibrin mesh
Platelet
RBC
Fibrin mesh
GPIIb/IIIa
RBC=red blood cell
1. Adapted from Antman EM. In: Califf RM, ed. Atlas of Heart Diseases, VIII.
Philadelphia, PA: Current Medicine, 1996.
High Risk of Mortality Following Acute MI
NRMI 34
(n=153,486)1
In-hospital mortality
GRACE Registry
(n=5476)2
12.3%
7.8%
 Reperfused
6.6%
–
 Not reperfused
18.7%
–
–
4.8%
6-month* mortality

Despite current therapy, 10% of STEMI patients die
within one month after hospital discharge2

Within 6 years 18% of men and 35% of women
will have another heart attack3
*Post-discharge; GRACE=The Global Registry of Acute Coronary Events; NRMI=National Registry
for Acute Myocardial Infarction
1. NRMI-4.
J Am Coll Cardiol 2003; 41: 365A–366A.
๑๗/๐๗/๕๘
2. Goldberg RJ et al. Am J Cardiol 2004; 93: 288–293.
3. Antman EM, et al. 2004 ACC/AHA STEMI Guidelines.
35
Assessing Reperfusion Options for Patients with
STEMI1

STEP 1: Assess time and risk (time from symptom onset, risk of STEMI, risk of
thrombolysis, time for transport to PCI lab)


STEP 2: Determine whether fibrinolysis or invasive strategy is preferred*
Fibrinolysis preferred if:
Invasive strategy preferred if:
• Early presentation (<3 hours)
• Delay to invasive strategy
• Skilled PCI lab with surgical backup
available
• High risk (i.e. cardiogenic shock)
• Contraindications to fibrinolysis
• Late presentation (>3 hours)
• Diagnosis of STEMI is in doubt
*If presentation is <3 hours from onset and there is no delay to an invasive strategy, there is
no preference for either strategy
1. Antman EM et al. Circulation 2004; 110: 588–636.
FOR INTERNAL USE ONLY
Thrombolysis and ASA in Acute STEMI: ISIS-21
25%*
p <0.00001
23%*
p <0.00001
14
5-week mortality (%)
12
10
42%*
p <0.00001
13.2%
12.0%
11.8%
9.2%
9.4%
8.0%
8
6
4
2
0
Placebo versus
streptokinase
Placebo versus
ASA 162 mg
Neither
versus both
*Odds reduction; ASA=acetylsalic acid
1. ISIS-2 Collaborative Group. Lancet 1988; 2: 349360.
FOR INTERNAL USE ONLY
Study Design1
Double-blind, randomized, placebo-controlled trial in
patients aged 1875 years with STEMI ≤12 hours
Clopidogrel 300 mg loading dose / 75 mg QD†
n=1752
Thrombolysis,
heparin and ASA*
Time-lysis 2.7Hr
R
Study treatment until
angiography (28 days) or
hospital discharge
(maximum 8 days)
Clinical
Follow-up
at 30 days
n=1739
Placebo†
Primary endpoint: occluded artery (TIMI flow grade [TFG] 0/1),
death/MI by time of angiography
*ASA=150–325 mg (if no ASA within prior 24 hours) as loading dose. Patients received heparin if they
received a fibrin specific thrombolytic
†All patients received ASA 75–162 mg/day plus other standard care
1. Sabatine MS et al. New Engl J Med 2005; 352:1179
FOR INTERNAL USE ONLY
Study Endpoints1

•

•
•
•
•
•
•
Primary endpoint:
Composite of occluded infarct related artery (TFG 0/1) on pre-discharge
angiogram, or death or MI before angiography
– Death or MI by hospital discharge (maximum 8 days) if no
angiography performed
Secondary endpoints:
Angiographic (TFG 0/1)
Clinical (death, recurrent MI or recurrent ischemia)
Clinical events* at 30 days
Safety endpoints:
Primary: TIMI major bleeding
Secondary: TIMI minor bleeding, ICH
*CV death, MI, stroke or recurrent ischemia leading to urgent
target vessel revascularization
1. Sabatine MS et al. New Engl J Med 2005
TIMI Flow Grade Definitions1
• TIMI flow grade describes epicardial blood flow:
 Grade 0: complete occlusion
 Grade 1: penetration of obstruction with no distal perfusion
 Grade 2: perfusion of artery with delayed flow
 Grade 3: full perfusion with normal flow
TFG 0
Occlusion
TFG 1
Penetration
1. Gibson CM et al. Circulation 2004: 109: 30963105.
TFG 2
Slow flow
TFG 3
Normal flow
FOR INTERNAL USE ONLY
TIMI Myocardial Perfusion Grade
Definitions1
•
TIMI Myocardial Perfusion Grade (TMPG) or ‘blush score’ describes
blood flow in the microvasculature:
 Grade 0: no dye enters
 Grade 1: dye slowly enters but fails to exit
 Grade 2: delayed entry and exit of dye
 Grade 3: normal entry and exit of dye
TMPG 0
TMPG 1
1. Gibson CM et al. Circulation 2004: 109: 30963105.
TMPG 2
TMPG 3
FOR INTERNAL USE ONLY
Relationship Between Angiographic
Outcomes and Long-term Mortality1
HR: 0.41 (p=0.001)
16
HR: 0.51 (p=0.038)
14.5%
2-year mortality (%)
14
12
9.1%
10
8
6.4%
6
4.8%
4
2
0
TFG 0/1
TFG 2/3
TIMI flow grade
TMPG 0/1
TMPG 2/3
TIMI myocardial
perfusion grade*
*Assessed on 90 minute angiogram in TIMI 10b trial;
HR=hazard ratio
1. Gibson CM et al. Circulation 2002; 105: 19091913.
FOR INTERNAL USE ONLY
Concomitant Medications1
Characteristic
Clopidogrel
(n=1752)
Fibrin-specific thrombolytic (%):
Tenecteplase
47.8
Reteplase
11.9
Alteplase
9.1
Non-fibrin specific thrombolytic (%):
Streptokinase
30.9
No thrombolytic given (%)
0.2
ASA (%)
98.5
Heparin (%):
UFH
46.1
LMWH
30.1
1. Sabatine MS et al. New Engl J Med 2005;
Placebo
(n=1739)
47.3
12.3
8.9
31.2
0.3
98.6
45.5
29.1
Patient Management1
Parameter
Symptom onset to fibrinolytic (hours)
Fibrinolytic to study drug (minutes)
Median doses of study medication
Angiography performed (%)
Time to angiography (hours)
Coronary revascularization (%):
PCI
CABG
1. Sabatine MS et al. New Engl J Med 2005;
Clopidogrel
(n=1752)
Placebo
(n=1739)
2.7
10
4
94
84
63
57
6
2.6
10
4
94
84
63
57
6
Clopidogrel Improved Coronary
Perfusion1
Primary endpoint* (%)
25
36% reduction*
p <0.001
21.7
20
15.0
15
10
5
Clopidogrel
(n=1752)
Placebo
(n=1739)
*Based on odds of an occluded infarct-related artery (TFG 0/1), death or MI by angiography for
clopidogrel versus placebo (OR: 0.64 [0.53 to 0.76]; p <0.001)
1. Sabatine MS et al. New Engl J Med 2005;
FOR INTERNAL USE ONLY
Clopidogrel Reduced Primary Endpoint by 36%1
Clopidogrel Placebo
(n=1752) (n=1739)
Primary composite endpoint (%)
TFG 0/1, MI or death
15.0
21.7
Odds ratio
(95% CI)
p value
0.64 (0.530.76) <0.001
Individual components of primary endpoint (%)
TFG 0/1
11.7
18.4 0.59 (0.480.72) <0.001
Recurrent MI
2.5
3.6 0.70 (0.471.04) 0.08
Death
2.6
2.2 1.17 (0.751.82) 0.49
1. Sabatine MS et al. New Engl J Med 2005;
Consistent Results for Primary Endpoint
Across Subgroups1
Characteristic
Number of
patients
Odds
reduction
3491
36
15.0
21.7
2466
1015
42
22
13.2
19.0
21.0
23.1
2796
685
35
38
14.5
16.9
20.8
24.7
1416
2065
33
38
15.0
15.0
20.7
22.2
2397
1084
31
44
14.7
15.7
20.1
24.9
1429
1431
621
31
42
26
11.4
17.8
17.1
15.7
27.1
21.9
OVERALL
Age
<65 years
65 years
Gender
Male
Female
Infarct location
Anterior
Non-anterior
Fibrinolytic
Fibrin-specific
Non-fibrin specific
Predominant heparin
LMWH
UFH
None
0.4
0.6
0.8 1.0 1.2
Clopidogrel better
1. Sabatine MS et al. New Engl J Med 2005;
1.6
Placebo better
Event rates (%)
Clopidogrel Placebo
Clopidogrel Improved Angiographic Outcomes1
Clopidogrel Placebo
(n=1752) (n=1739)
Angiographic outcomes (%)
TFG 3*
67.8
TMPG 3†
55.8
Thrombus
43.0
*TFG= TIMI Flow Grade
†TPMG= TIMI Myocardial Perfusion Grade
1. Sabatine MS et al. New Engl J Med 2005;
60.8
51.2
50.8
Odds ratio
(95% CI)
p value
1.36 (1.181.57)
1.21 (1.051.40)
0.73 (0.640.84)
<0.001
0.008
<0.001
Clopidogrel Reduced Clinical Events by 20%
at 30 Days1
Incidence of clinical endpoints (%)
15
Placebo
Clopidogrel
20%*
p=0.03
10
5
0
0
5
10
15
20
Time (days)
*Odds Ratio (OR) in CV death, MI or recurrent ischemia leading to
urgent revascularization
1. Sabatine MS et al. New Engl J Med 2005;
25
30
Consistent Benefit Across 30-Day Endpoints1
Odds ratio
(95% CI)
Endpoint
Odds
reduction
Percentage of
patients with event
Clopidogrel Placebo
CV death
3
4.4
4.5
Recurrent MI
31
4.1
5.9
Recurrent ischemia
leading to urgent
revascularization
24
3.5
4.5
Stroke
46
0.9
1.7
CV death or MI
17
8.4
9.9
CV death, MI or stroke
18
9.1
10.9
CV death, MI or recurrent
ischemia leading to urgent
revascularization
20
11.6
14.1
21
12.3
15.0
CV death, MI, stroke or
recurrent ischemia leading
to urgent revascularization
0.4
0.6 0.8 1.0 1.2 1.6
Clopidogrel better Placebo better
1. Sabatine MS et al. New Engl J Med 2005;
Safety1
Clopidogrel Placebo
(n=1733)
(n=1719)
Primary bleeding endpoint (%)
TIMI major
p value
23 (1.3)
19 (1.1)
0.64
Secondary bleeding endpoints (%)
TIMI minor
17 (1.0)
TIMI major or minor
40 (2.3)
Intracranial hemorrhage
8 (0.5)
9 (0.5)
28 (1.6)
12 (0.7)
0.17
0.18
0.38
Bleeding through 30 days (%)
TIMI major
TIMI minor
TIMI major or minor
30 (1.7)
16 (0.9)
46 (2.7)
0.80
0.12
0.24
1. Sabatine MS et al. New Engl J Med 2005;
33 (1.9)
27 (1.6)
59 (3.4)
Summary1
• In patients aged 75 years with STEMI, receiving ASA and standard
fibrinolytic therapy, a loading dose of 300 mg of clopidogrel followed by
75 mg daily resulted in:

A 36% reduction (p <0.001) in the odds of an occluded infarct-related
artery, or death or MI by time of pre-discharge angiography or
hospital discharge (maximum 8 days) ( 41% reduction occluded
infarct-related MI)

Consistent results across all major subgroups

At 30 days, a 20% reduction (p=0.03) in CV death, MI or recurrent
ischemia leading to urgent revascularization ( 31% reduction in
recurrent MI)

No significant excess in TIMI major bleeding or ICH
1. Sabatine MS et al. New Engl J Med 2005;
Slide Source:
Lipids Online
www.lipidsonline.org
Take home message
Previous MI : Aspirin intolerance
Use Clopidogrel
ACS : “Cool down” Tx
Clopidogrel 300 mg
ASA 325 mg/D
75 mg/D
LMWH/Heparin
+/- Statin, +/- Gp IIb /IIIa IV
PCI : Clopidogrel 300 mg 6-24 hr. prior to PCI
Post PCI
Clopidogrel 75 mg/D & low
dose ASA 1 year
Drugs Prescriptions for Mr. Had-enough?
1. Enalapril (20) ½ tab bid pc.
6. Glibencarmide(5) 1½ tab bid ac
2. Bisoprolol (5) 1 tab OD.
7. Metformin (500) 1 tab tid pc
POLYPHARMACY
3. Spironolactone (25) 1 tab OD.
4. Digoxin (0.25) ½ tab E.O.D.
8. Aspirin (300) 1 tab OD.
5. Furosemide (40) 1 tab prn for dyspnea ,edema or weight
gain > 1 kg in 2 days
9. ISDN (10) 2 tab tid ac
13. Warfarin (3) ½ tab o OD.
10. Isordil (5) 1 tab SL prn
11. Amlodipine (10) 1 tab OD.
14. Warfarin (5) ½ tab o OD.
12. Atrovastatin (20) 1 tab pc evening
15. Lorazepam 1 tab prn hs.
The Polypill
Prevention of
Cardiovascular
Complications
Empirical Drug For Life
• One
combination
• One dose
• All patient
The Polypill
12.5 mg of hydrochlorthiazide
10mg of atorvastatin& 10mg
Ezetrol
75 mg of aspirin &
75 mg clopidogrel
2.5mg amlodipine
10 mg of lisinopril
50mg atenolol