Iloilo Mission Hospital

Internal Medicine Department

CRITICAL APPRAISAL

KARREN MAE T. PLETE

Level I- Medical Resident
 Objective
• To appraise a journal regarding the potential
benefit of dual antiplatelet therapy in patient
with previous myocardial infarction
Clinical Scenario:
M.G Past medical history:
62/F (+)Hypertensive non c
CC:chest pain (-) cardiac problems
(+) MI -2012
HPI:
6 hours prior to consult,patient had chest Personal and social hist
pain after vigorously cleaning the house rated non alcoholic, non sm
as 6/10 hence prompted consult housewife
VS:
BP: 100/60
HR: 87
RR: 25
T:37
 CLINICAL QUESTION
• IS THERE A POTENTIAL BENEFIT OF LONG
TERM DUAL ANTIPLATELET THERAPY FOR
PATIENTS WITH PREVIOUS MYOCARDIAL
INFARCTION?
P Adults (≥18 years of age) with Prior MI
I Dual antiplatelet therapy
C Clopidogrel +ASA vs ASA alone
O Decrease ischemic or cardiovascular
events
 INTRODUCTION
• Patients with myocardial infarction have heightened
platelet activation and aggregation resulting in
atherothrombosis following rupture or fissuring of
an unstable atherosclerotic plaque compared with
patients with stable ischemic heart disease
• A higher predisposition to atherothrombosis may
persist for years following an MI and SIHD patients
are at high risk for major adverse cardiovascular
events.
 DURATION OF DUAL ANTIPLATELET
THERAPY OF PATIENTS WITH
PREVIOUS MYOCARDIAL INFARCTION

 Recent trials have examined the effect of

prolonged dual antiplatelet therapy (DAPT)
in a variety of patient populations
 Heterogeneous results regarding benefit and
safety.
 Methods
 Systematic review and random-effects meta-
analysis of RCTs that compared >1 y of DAPT, with
aspirin alone in patients that presented with, or
had a history of, a prior MI
 Guideline Recommendations
Population ESC Guidelines ACC/AHA/SCAI Guidelines
Acute Coronary Syndrome Maximum of 12 months At least 12 months
(BMS or DES) (Class I-A) (Class I-B)

Longer durations may be Longer durations may be

considered considered in pts w/ DES (Class
(Class IIb-A) IIb-C)
Stable Ischemia and BMS At least 1 month At least 1 month, ideally up to 12
(Class I-A) months
(Class I-B)
Stable Ischemia and DES 6 months At least 12 months
(Class I-B) (Class I-B)
Secondary Prevention Selected patients at high May be considered
ischemic risk (Class IIb-B)
 Objective / Hypothesis
 Need for definitive longer-term data on the CV
benefit and safety of extended DAPT beyond one
year for secondary prevention in patients
following an MI
 APPRAISING DIRECTNESS
• Since data from various randomized controlled
trials showed inconsistent results. This meta
analysis study compares the role of long term
DAPT vs long term ASA alone in prevention of
cardiovascular events in patient with prior MI.
 Eligibility Criteria and Trial selection

Exclusion
• Observational studies
• Trials of DAPT among patients with MI who
were followed no longer than 12 months
• Trials of patients with SIHD alone undergoing
PCI
• Trials of oral anticoagulant therapies
 Search Strategy and Data Extraction
• Search of OVID MEDLine and Cochrane central
register of controlled trial data bases (keywords;
antiplatelet, DAPT, Secondary prevention, MI. death,
mortality, survival
• Supplementary material Online, appendices and
reference lists of eligible papers, cardiovascular
abstracts between 2014 and 2015 and clinical
trials.gov
 Quality Assessment
• Graded based on documentation of trial
conduct criteria such as method of
randomization , allocation concealment,
blinded outcome adjudication, extent of
outcome reporting and ascertainment,
participant attribution and adherence metrics.
 Secondary Endpoints:
Primary Endpoint:
 CV death
 CV death, MI, or  MI
stroke (MACE)  Stroke
 Non-CV death
 All-cause mortality
 Major bleeding
 Stent thrombosis
 APPRAISING VALIDITY
• The criteria of for inclusion of studies used
were appropriate and thorough search of
literature was done both published and
unpublished. The study also include the use of
medical databases, cross references of original
publication
 RESULTS
• Among 1342 records screened, 36 RCTs were
reviewed.
• After exclusion, remaining 6 trials met criteria
for eligibility in the primary meta analysis
Trials Evaluating Prolonged DAPT following MI
Subgroup Duration MACE
Trial /Population N Drug (months) Events Bleeding EP

CHARISMA Stable prior MI 3846 Clopi 28 287 GUSTO

(mean 24 mo.) mod/severe

PRODIGY PCI for ACS 1465 Clopi 6 vs. 24 132 TIMI major

ARCTIC- PCI for ACS Clopi STEEPLE

Interruption (excluded STEMI) 323 or Pras 12 vs. 24 7 major

Clopi GUSTO
DAPT PCI for MI 3576 or Pras 12 vs. 30 167 mod/severe

DES-LATE PCI for ACS 3063 Clopi 12 vs. 24 122 TIMI major
PEGASUS Stable prior MI
21162 Ticag 33 1558 TIMI major
TIMI-54 (median 20 mo.)

Total 33435 30 2273

 Baseline Characteristics
Characteristic Overall (N = 33435)
Age 64 yr
Weight 81 kg
Female 24%
Index MI STEMI 49%
NSTEMI 39%
UA 7%
Time from MI 18 months
Prior PCI 84%
Diabetes 30%
Current Smoker 21%
CKD or eGFR <60 mL/min 19%
Prior Stroke/TIA 3%
Prior CABG 7%
Hx of Additional MI 16%
Primary Endpoint – CV Death, MI, or Stroke
Extended Aspirin Risk Ratio
DAPT Alone (95% CI)
Study Events Total Events Total
CHARISMA 125 1903 162 1943 0.77 (0.61 - 0.98)

PRODIGY 63 732 69 733 0.91 (0.65 - 1.28)

ARCTIC-Int’n 3 156 4 167 0.79 (0.18 - 3.51)

DAPT 59 1805 108 1771 0.52 (0.38 - 0.72)

DES-LATE 56 1512 66 1551 0.85 (0.60 - 1.21)

PEGASUS 980 14095 578 7067 0.84 (0.76 - 0.94)

TOTAL 1286 20203 987 13232 0.78 (0.67 - 0.90)

6.4% 7.5%

P = 0.001 0.2 0.5 1 2

Extended DAPT Better Aspirin Alone Better
 Cardiovascular Death
Extended Aspirin Risk Ratio
DAPT Alone (95% CI)
Study Events Total Events Total
CHARISMA 53 1903 65 1943 0.82 (0.57 - 1.18)

PRODIGY 31 732 31 733 1.00 (0.61 - 1.64)

ARCTIC-Int’n 0 156 1 167 0.36 (0.01 - 8.69)

DAPT 11 1805 16 1771 0.67 (0.31 - 1.44)

DES-LATE 21 1512 21 1551 1.00 (0.55 - 1.83)

PEGASUS 356 14095 210 7067 0.85 (0.71 - 1.00)

TOTAL 472 20203 344 13232 0.85 (0.74 - 0.98)

2.3% 2.6%
0.2 0.5 1 2
P = 0.03 Aspirin Alone Better
Extended DAPT Better

Udell JA, et al. Eur Heart J 2015 at eurheartj.oxfordjournals.org.

Event Rate (%) Individual CV Endpoints

RR 0.78
10 Extended DAPT
9 Aspirin Alone
8 7.5
7 6.4 RR 0.70
6
5 RR 0.85
4.4
RR 0.81
4 3.5 RR 0.50
3 2.3 2.6
2 1.4 1.7 1.4
1 0.6
0
MACE CV Death MI Stroke Stent
Thrombosis
(Def/Prob)
 Major Bleeding
Extended Aspirin Risk Ratio
DAPT Alone (95% CI)
Study Events Total Events Total
CHARISMA 45 1903 39 1943 1.17 (0.76 - 1.79)

PRODIGY 9 732 6 733 1.50 (0.53 - 4.20)

ARCTIC-Int’n 2 156 0 167 5.35 (0.26 - 110.6)

DAPT 34 1805 14 1771 2.38 (1.27 - 4.43)

DES-LATE 39 1512 31 1551 1.27 (0.79 - 2.03)

PEGASUS 242 13946 54 6996 2.50 (1.86 - 3.36)

TOTAL 371 20054 144 13161 1.73 (1.19 - 2.50)

1.9% 1.1%
P = 0.004 0.5 1 2 5
Extended DAPT Better Aspirin Alone Better
Major Bleeding Events and Safety
Event Rate (%)

10 Extended DAPT
9 Aspirin Alone
8
7
6 RR 0.92
5
4.0 4.2
4 RR 1.73
RR 1.03
3
2 1.9 P = NS 1.7 1.6
1.1 P = NS
1 0.4 0.3 0.1 0.2
0
Major ICH Fatal Non-CV All-Cause
Bleeding Bleeding Death Death

Udell JA, et al. Eur Heart J 2015 at eurheartj.oxfordjournals.org.

 Subgroup Analysis: Primary Endpoint
Event Rate (%)
Extended DAPT Aspirin Alone Hazard Ratio
Age < 75 years 5.9 6.8 0.83
≥ 75 years 11.1 12.9 0.88
Sex Male 6.6 7.7 0.84
Female 6.9 7.7 0.84

DAPT Clopidogrel 5.8 6.9 0.82

Regimen Prasugrel NE NE NE
Ticagrelor 7.0 8.2 0.84
Index UA 3.3 4.6 0.68
ACS NSTEMI 7.6 8.2 0.88
STEMI 5.6 7.1 0.73
Time from < 24 months 6.1 7.3 0.76
Index MI ≥ 24 months 6.7 7.4 0.87

History of Yes 5.7 6.7 0.78

PCI No 9.9 11.3 0.83
Overall 6.4 7.5 0.78 (0.67 - 0.90)

0.2 0.5 1 2
All P-interactions >0.05
Abbreviations: NE: no estimate Extended DAPT Better Aspirin Alone Better
 DISCUSSION
• It was found out that overall compared with
aspirin alone than extended DAPT beyond 1
year resulted in a 22% relative and 1.1 %
absolute risk reduction for major adverse
cardiovascular events over a mean 31 months
of follow up.
• The magnitude of this relative risk reduction
was consistent, with no significant
heterogeniety

• The meta analysis showed for the first time

that there is a significant 15%reduction in
cardiovascular deaths in post MI pts rceiveing
extended DAPT.
• There was a 0.8 % absolute increase in the risk
of major bleeding but without significant
excess of ICH or fatal bleeding and no impact
on non cardiovascuar causes of death
 Summary
 Compared with aspirin alone, extended DAPT >1
year among stabilized high-risk patients with
previous MI:
- Decreased the risk of MACE, MI, stroke alone &
CV death alone
- Increased risk of major bleeding, but not fatal
bleeding or ICH
- No excess of non-CV causes of death
 Effect of extended DAPT consistent irrespective of:
- DAPT regimen, time from MI, ST-elevation, or PCI
status
 Who were high-risk pts at low risk of bleeding that
derived benefit from extended DAPT?
- High Risk: ~1-3 years after an MI with additional CV risk
factors
- Low Bleeding Risk: Excluded patients with anticoagulation,
recent bleeding, recent surgery, or any history of ICH
- Caution: Very few patients studied had prior stroke/TIA
 ASSESSING APPLICABILITY
The overall results of the study may be applied
in our hospital setting since most of daily census
in our department include cases of myocardial
infarction. This maybe applied as one of the
secondary prevention of pts with MI.
 Conclusion

These findings indicate that in patients with

prior MI who are at low risk of bleeding,
continuation of dual antiplatelet therapy
beyond a year offers a substantial reduction in
important cardiovascular outcomes, including
cardiovascular death
THANK YOU!