Clopidogrel and CYP2C19 in Acute Coronary Syndrome Should Pharmacogenetic Testing be Standard of Care?
September 22, 2017
Kelsey Melloy, PharmD PGY1 Pharmacy Resident Seton Healthcare Family
9/14/2017
1
ASCENSION TEXAS
Kelsey Melloy, PharmD
PGY1 Pharmacy Resident
Seton Healthcare Family
September 22, 2017
Clopidogrel and CYP2C19 in Acute
Coronary Syndrome Should pharmacogenetic testing be standard of
care?
• The author of this presentation has no conflicts of interest
to disclose
2
Conflict of Interest
• Review oral antiplatelet agents
• Explain the FDA black box warning for clopidogrel
pharmacogenetics
• Analyze the clinical impact of CYP2C19 polymorphisms
on clopidogrel efficacy
• Evaluate the evidence for genotype-guided antiplatelet
therapy
3
Objectives
• A 75 year old Chinese female weighing 55 kg presents
with an NSTEMI and is scheduled to undergo PCI
• Of note, the patient is taking St. John’s Wort
• Which antiplatelet option would you recommend?
• A. Clopidogrel
• B. Ticagrelor
• C. Prasugrel
• D. Order CYP2C19 genetic test
4
Meet the patient…
• Life-threatening situation from destabilization of
atherosclerotic plaque
- Includes STEMI, NSTEMI, and UA
• ACS occurs every 25 seconds in the United States
• 1.4 million patients hospitalized for ACS each year in the
United States
- 810,000 for MI
5
Acute Coronary Syndrome (ACS)
Meier P, et al. Heart. 2013;99:1488-1493.
Wachira JK, et al. S D Med. 2013;66:366-369.
Kumar A, et al. Mayo Clin Proc. 2009;84:917-938.
• 2013 ACCF/AHA STEMI Guidelines
- P2Y12 inhibitor load for PCI with stenting, then continued for at
least 12 months
• Clopidogrel, prasugrel, or ticagrelor (LOE B)
• 2014 AHA/ACC NSTEMI Guidelines
- P2Y12 inhibitor for at least 12 months for PCI with stenting
• Clopidogrel, prasugrel, or ticagrelor (class I, LOE B)
- Ticagrelor over clopidogrel in for early invasive or ischemia-guided
strategy (class IIa, LOE B)
6
Antiplatelet Therapy in ACS
Glenn NL, et al. JACC. 2011;58(24).
O’Gara PT, et al. Circulation. 2013;127(4).
Amsterdam EA, et al. Circulation. 2014;136(7).
9/14/2017
2
Clopidogrel
(Plavix)
Prasugrel
(Effient)
Ticagrelor
(Brilinta)
Dose LD: 300 or 600 mg
MD: 75 mg/d
LD: 60 mg
MD: 10 mg/d
(5 mg in < 60 kg)
LD: 180 mg
MD: 90 mg bid
Cost $ $$$ $$$
Metabolism Prodrug;
CYP2C19 (major),
CYP3A4 (minor)
Prodrug;
CYP2B6 (major),
CYP3A4 (minor)
CYP3A4 (major)
Contraindications Active bleeding Active bleeding,
prior stroke or
TIA
Active bleeding,
prior intracranial
hemorrhage
7
Comparison of Oral Antiplatelet Agents
Plavix (clopidogrel) [prescribing information]. Bridgewater, NJ: Bristol-Myers Squibb; July 2017.
Effient (prasugrel) [prescribing information]. Indianapolis, IN: Eli Lilly and Company; July 2016.
Brilinta (ticagrelor) [prescribing information]. Wilmington, DE: AztraZeneca; April 2017.
Appendix B
8
Clopidogrel FDA Warning
Plavix (clopidogrel) [prescribing information]. Bridgewater, NJ: Bristol-Myers Squibb; July 2017.
Appendix C
9
Clopidogrel Metabolism and Mechanism of Action
Clopidogrel • CYP1A2,
CYP2B6, CYP2C19
2-oxo-clopidogrel
• CYP2C9, CYP2B6, CYP3A4, CYP3A5, CYP2C19, PON1
Active metabolite
• Inhibits P2RY12 on platelet
Sangkuhl Katrin, Klein Teri E, Altman Russ B . Pharmacogenetics and genomics (2010).
Appendix D 10
CYP2C19 Variant Alleles and Frequencies
Scott SA, et al. Clinical Pharmacology & Therapeutics. 2013; 94(3): 317-323.
Functional Status Activity Level Alleles
Functional (wild-type) Normal *1
Loss-of-function (LOF) Little to none *2, *3, *4, *5, *6, *7, *8
Increased function Increased *17
Allele Caucasians Africans Asians
*2 15% 15% 29-35%
*3 <1% <1% 2-9%
Appendix E
Phenotype Genotype Clopidogrel
Implication
Frequency
Ultrarapid
metabolizer
(UM)
Homozygous or heterozygous
increased function (not loss of
function carrier)
Increased active
metabolite
5-30%
Extensive
metabolizer
(EM)
Homozygous normal function Normal active
metabolite
35-50%
Intermediate
metabolizer
(IM)
Heterozygous loss of function +
normal or increased function
Reduced active
metabolite
18-45%
Poor
metabolizer
(PM)
Homozygous loss of function Significantly
reduced active
metabolite
2-15%
11
CYP2C19 Polymorphisms and Clopidogrel
Scott SA, et al. Clinical Pharmacology & Therapeutics. 2013; 94(3): 317-323.
Appendix F 12
Pharmacokinetic Response to Clopidogrel Based on
CYP2C19 Phenotype
Mega JL, et al. N Engl J Med. 2009;360:354-362.
Clopidogrel active metabolite formation
Appendix G
9/14/2017
3
13
Pharmacodynamic Response to Clopidogrel Based on
CYP2C19 Phenotype
Mega JL, et al. N Engl J Med. 2009;360:354-362.
Reduction in platelet aggregation 24 hours after clopidogrel
Appendix H 14
CYP2C19 Genotype and Outcomes
Mega JL, et al. N Engl J Med. 2009;360:354-362.
Composite:
death from
cardiovascular
causes, MI, or
stroke
LOF Carriers (IMs + PMs)
Noncarriers
12.1%
8.0%
HR 1.53 (p = 0.01)
Appendix I
15
CYP2C19 Genotype and Stent Thrombosis
Mega JL, et al. N Engl J Med. 2009;360:354-362.
Noncarriers
2.6%
0.8%
HR 3.09 (p = 0.02)
LOF Carriers (IMs + PMs)
Appendix J
How does clopidogrel compare to other
antiplatelet agents?
16
17
Clopidogrel vs. Prasugrel – TRITON-TIMI 38
Safety: non-CABG related major hemorrhage
2.4% 1.8% HR 1.32 (p = 0.03)
Primary: composite death from CV causes, MI, or stroke
9.9% 12.1% HR 0.81 (p < 0.001)
13,608 patients with moderate-to-high-risk ACS with scheduled PCI
Prasugrel 60 mg load then 10 mg/day Clopidogrel 300 mg load then 75mg/day
Wiviott SD, et al. N Engl J Med. 2007; 357: 2001-2015.
Outcome Prasugrel Clopidogrel HR (95% CI)
Cardiovascular death, MI, and stroke
Noncarrier 9.6% 9.8% 0.98 (0.80-1.20)
LOF carrier 8.5% 15.0% 0.57 (0.39-0.83)
Major or minor bleeding
Noncarrier 4.7% 3.4% 1.38 (1.00-1.93)
LOF carrier 5.5% 3.5% 1.60 (0.80-3.10)
18
TRITON-TIMI 38 Genetic Substudy
Sorich MJ, et al. J Thromb Haemost. 2010;8:1678-1684.
*Estimates of outcome risks over 15 months for patients with UA or NSTEMI scheduled for PCI
(excluded STEMI patients)
Conclusion
CYP2C19 genotype can distinguish which patients will receive extensive benefit
from prasugrel over clopidogrel
9/14/2017
4
19
Clopidogrel vs. Ticagrelor - PLATO
Safety: non-CABG related major bleeding
4.5% 3.8% HR 1.18 (p = 0.03)
Primary: composite death from CV causes, MI, or stroke
9.8% 11.7% HR 0.84 (p < 0.001)
18,624 patients admitted with ACS, with or without ST-segment elevation
Ticagrelor 180 mg load then 90 mg bid Clopidogrel 300-600 mg load then
75mg/day
Wallentin L, et al. N Engl J Med. 2009;361:1045-1057.
Outcome Ticagrelor Clopidogrel HR
Cardiovascular death, MI, and stroke
Noncarrier 8.3% 9.4% 0.86 (p = 0.0608)
LOF carrier 8.3% 10.7% 0.77 (p = 0.0380)
Non-CABG major bleeding
Noncarrier 3.4% 3.1% 1.08 (p = 0.5500)
LOF carrier 4.1% 3.0% 1.39 (p = 0.1100)
20
PLATO Genetic Substudy
Wallentin L, et al. Lancet. 2010;376(9749):1320-8.
Conclusion
Ticagrelor more efficacious regardless of CYP2C19 polymorphism and
eliminates the need for genetic testing before dual antiplatelet treatment
• 2011 ACCF/AHA/SCAI PCI Guidelines - Testing might be considered to identify patients at high risk for poor
clinical outcomes
- If PM status identified, consider alternate P2Y12 therapy
- Routine genetic testing not recommended
• 2013 ACCF/AHA STEMI Guidelines - Acknowledges possibility of relationship between CYP2C19
polymorphisms and clopidogrel
- No mention of pharmacogenetic testing
• 2014 AHA/ACC NSTEMI Guidelines - Routine genetic testing not recommended
21
What do guidelines say about testing?
Glenn NL, et al. JACC. 2011;58(24).
O’Gara PT, et al. Circulation. 2013;127(4).
Amsterdam EA, et al. Circulation. 2014;136(7).
• CYP2C19 intermediate and poor metabolizer status
associated worse outcomes with clopidogrel
- Black box warning/ FDA safety alert
• Prasugrel and ticagrelor are much more expensive and
cannot be used in certain patients
• Guidelines still do not recommend testing
22
What We Know
23
Does pharmacogenetic testing improve
outcomes?
24
RAPID Gene Study
• Single-center, prospective, randomized, blinded, N=200
• Rapid genotyping vs. standard treatment
Study Design
• Inclusion: age 18-75 undergoing PCI for NSTEMI or stable ACS
• Exclusion: warfarin or dabigatran use, history of stroke or TIA, weight < 60 kg, platelets < 100,000, known bleeding diathesis, Hct < 30%, severe liver dysfunction, or CrCl < 30 ml/min
Patient Population
• Proportion of CYP2C19*2 carriers with high on-treatment platelet reactivity (P2Y12 reactivity units (PRU) > 234) after 1 week of dual antiplatelet therapy
Primary Outcome
Roberts JD, et al. Lancet 2012;379:1705-11.
9/14/2017
5
N=200
Rapid genotyping
(n=102)
CYP2C19*2 carriers (n=23)
Prasugrel 10 mg daily
CYP2C19*2 noncarriers
(n=74)
Clopidogrel 75 mg daily
Standard treatment
(n=98)
Clopidogrel 75 mg daily
CYP2C19*2 23 carriers
73 noncarriers
25
RAPID Gene Study
Roberts JD, et al. Lancet 2012;379:1705-11.
Rapid Genotyping
(n=91)
Standard Treatment
(n=96)
P-value
Primary Outcome
Patients with PRU
> 234 at day 7
9 (10%) 16 (17%) 0.0672
Secondary Outcomes
Patients with PRU
> 208 at day 7
14 (15%) 30 (31%) 0.0008
26
RAPID Gene Study
Roberts JD, et al. Lancet 2012;379:1705-11.
PRU: P2Y12 reactivity units
CYP2C19*2
Subgroup
Rapid Genotyping
(n=23)
Standard Treatment
(n=23)
P-value
Patients with PRU
> 234 at day 7
0 (0%) 7 (30%) 0.0092
Authors’ Conclusions
• Point-of-care genetic testing after PCI can be done
effectively at the bedside
• Treatment of CYP2C19*2 carriers with prasugrel can
reduce high on-treatment platelet reactivity
27
RAPID Gene Study
Roberts JD, et al. Lancet 2012;379:1705-11.
RAPID Gene Study
Strengths
• Prospective
• Genotype-guided vs.
traditional selection
• Compared LOF carriers to
LOF carriers
Weaknesses
• Universal clopidogrel load
• Only tested for CYP2C19*2
• Surrogate endpoint
• Primary outcome timing
• 95% of study population of
western European ancestry
28
29
Genotyping-Approach vs. Conventional Approach in
Chinese Patients
• Single-center, prospective, randomized, open-label, N=132
• CYP2C19 genotype-guided P2Y12 antiplatelet therapy in ACS
Study Design
• Inclusion: ACS (STEMI, UA/NSTEMI) +/- PCI, Chinese
• Exclusion: P2Y12 blocker w/in 6 months, chronic renal failure on HD or plan for HD, serious hepatic disease, CI to clopidogrel or ticagrelor, pregnant
Patient Population
• Platelet reactivity at 24 hours and 1 month after first loading dose of clopidogrel
Primary Outcome
Tam CC, et al. Journal of International Medical Research. 2017;45:134-146.
30
Genotyping-Approach vs. Conventional Approach in
Chinese Patients
Clopidogrel loading dose
Genotype-guided
CYP2C19*2/3 Carrier
Ticagrelor 180 mg load
Ticagrelor 90 mg bid
Noncarrier
Clopidogrel 75 mg/day
Traditional
Clopidogrel 75 mg/day
Tam CC, et al. Journal of International Medical Research. 2017;45:134-146.
9/14/2017
6
On-treatment
platelet reactivity
Genotype-guided Standard P value
HTPR at 24 hours 6/65 (9.2%) 27/67 (40.3%) <0.001
HTPR at 1 month 4/62 (6.5%) 20/62 (32.3%) <0.001
31
Genotyping-Approach vs. Conventional Approach in
Chinese Patients
Intermediate metabolizers
HTPR at 24 hours 0/33 (0.0%) 12/27 (44.4%) NR
HTPR at 1 month 0/31 (0.0%) 10/27 (37.0%) NR
Poor metabolizers
HTPR at 24 hours 0/7 (0.0%) 5/8 (62.5%) NR
HTPR at 1 month 0/6 (0.0%) 5/7 (71.4%) NR
HTPR: high on-treatment platelet reactivity = P2Y12 reaction units > 208
NR: not reported
Tam CC, et al. Journal of International Medical Research. 2017;45:134-146.
Authors’ conclusions
• Rapid genotyping-guided approach for selecting P2Y12
blockers is feasible
• Genotype-guided approach reduces the incidence of high
on-treatment platelet reactivity
32
Genotyping-Approach vs. Conventional Approach in
Chinese Patients
Tam CC, et al. Journal of International Medical Research. 2017;45:134-146.
Genotyping-Approach vs. Conventional Approach in
Chinese Patients
Strengths
• Prospective
• Use of genotype-guidance
randomized
• High risk patient population
Weaknesses
• Surrogate endpoint
• PRU cutoff > 208
• Small sample size
• Patient population not
generalizable
• LOF patients loaded with
clopidogrel and ticagrelor
33 34
Prospective Clinical Implementation of CYP2C19
Genotype Guided Antiplatelet Therapy After PCI
• Prospective, multicenter
• CYP2C19 genotype-guided antiplatelet therapy post-PCI
Study Design
• Average patient: early 60s, male, white, unstable ACS w/PCI
• 54 PMs + 518 IMs 572 (31.5%) actionable genotypes
Patient Population
• Major adverse cardiac events (MACE): death, MI, or stroke within 12 months following index PCI
Primary Outcome
Cavallari LH, IGNITE Investigators. AHA’s Scientific Sessions. 2016.
35
Prospective Clinical Implementation of CYP2C19
Genotype Guided Antiplatelet Therapy After PCI
*p<0.0001 for alternative therapy between LOF and NON-LOF groups
ƚPrasugrel >60% of alternative therapy
LOF = loss of function carrier
Cavallari LH, IGNITE Investigators. AHA’s Scientific Sessions. 2016.
36
Prospective Clinical Implementation of CYP2C19
Genotype Guided Antiplatelet Therapy After PCI
Cavallari LH, IGNITE Investigators. AHA’s Scientific Sessions. 2016.
LOF = loss of function carrier
CLOP = clopidogrel
ALT = alternative
8.0%
4.6%
Appendix K
9/14/2017
7
37
Prospective Clinical Implementation of CYP2C19
Genotype Guided Antiplatelet Therapy After PCI
Cavallari LH, IGNITE Investigators. AHA’s Scientific Sessions. 2016.
Authors’ conclusions
• Genotype-guided approach feasible
• Higher risk for MACE in CYP2C19 LOF treated with
clopidogrel vs. alternative
• Genotyping can improve clinical outcomes after PCI
Prospective Clinical Implementation of CYP2C19
Genotype Guided Antiplatelet Therapy After PCI
Strengths
• Genotype-guided antiplatelet
selection
• Prospective
• Real world setting
• Antiplatelet selection up to
physician
Limitations
• Use of genotype-guidance
not randomized
• High dose clopidogrel
• Outcomes based on carrier
status
• Limited study information
available
38
39
Summary of Evidence
Trial Overall Conclusion
Roberts, et al Genotyping reduces high on-treatment platelet
reactivity at day 7 in CYP2C19*2 carriers
Tam, et al Genotyping reduces high on-treatment platelet
reactivity at 24 hours and 1 month
Cavallari, et al Genotyping reduces risk for MACE outcomes
Roberts JD, et al. Lancet 2012;379:1705-11.
Tam CC, et al. Journal of International Medical Research. 2017;45:134-146.
Cavallari LH, IGNITE Investigators. AHA’s Scientific Sessions. 2016.
40
Ongoing Trial
2700 STEMI patients
undergoing PCI
CYP2C19 genotyping
2C19 LOF prasugrel or
ticagrelor
Wild-type clopidogrel
Routine ticagrelor or prasugrel
41
POPular Genetics Study
Bergmeijer TO, et al. Am Heart J. 2014;168(1)16-22.e1
• Clinical benefit
- Death, recurrent MI, definite stent thrombosis, stroke, platelet
inhibition and patient outcomes
• Safety
- Clinical benefit and major or minor bleeding
• Cost-effectiveness
• Quality of life
42
POPular Genetics Study Endpoints
Bergmeijer TO, et al. Am Heart J. 2014;168(1)16-22.e1
9/14/2017
8
• A 75 year old Chinese female weighing 55 kg presents
with an NSTEMI and is scheduled to undergo PCI
• Of note, the patient is taking St. John’s Wort
• Which antiplatelet option would you recommend?
• A. Clopidogrel
• B. Ticagrelor
• C. Prasugrel
• D. Order CYP2C19 genetic test
43
Back to the patient…
• Data not strong enough to support testing everyone
• Use genetic information when available
• Consider testing higher risk ethnicities
44
Recommendation
• Antiplatelet agents are not one size fits all
• Clopidogrel response variation can be partly explained by CYP2C19 polymorphisms
• CYP2C19 LOF carriers at higher risk for poor outcomes
• Evidence to support genotyping all patients is still limited - Surrogate endpoints, small sample size, focused on feasibility
• Watch for results of the POPular Genetics Study
45
Conclusion
Evan J. Peterson, PharmD, BCPS
Clinical Pharmacy Specialist – Cardiology
Seton Medical Center Austin
Tamara B. Knight, PharmD, BCPS
Clinical Pharmacy Specialist – Internal Medicine
Seton Northwest Hospital
46
Acknowledgements
ASCENSION TEXAS
Kelsey Melloy, PharmD
PGY1 Pharmacy Resident
Seton Healthcare Family
September 22, 2017
Clopidogrel and CYP2C19 in Acute
Coronary Syndrome Should pharmacogenetic testing be standard of
care?
9
Appendix A: Abbreviations Appendix B: Comparison of Oral Antiplatelet Agents Appendix C: Clopidogrel FDA Warning Appendix D: Clopidogrel Metabolism and Mechanism of Action Appendix E: CYP2C19 Variant Alleles and Frequencies Appendix F: CYP2C19 Polymorphisms and Clopidogrel Appendix G: Pharmacokinetic Response to Clopidogrel Based on CYP2C19 Phenotype Appendix H: Pharmacodynamic Response to Clopidogrel Based on CYP2C19 Phenotype Appendix I: CYP2C19 Genotype and Outcomes Appendix J: CYP2C19 Genotype and Stent Thrombosis Appendix K: Cumulative MACE Rate Based on CYP2C19 Phenotype
10
Appendix A: Abbreviations
ACCF: American College of Cardiology Foundation
ACS: acute coronary syndrome
AHA: American Heart Association
ALT: alternative
CABG: coronary artery bypass grafting
CLOP: clopidogrel
CV: cardiovascular
CYP: cytochrome P450
EM: extensive metabolizer (normal metabolizer)
FDA: Federal Drug Administration
HD: hemodialysis
HR: hazard ratio
HTPR: high on-treatment platelet reactivity
IM: intermediate metabolizer
LD: loading dose
LOE: level of evidence
LOF: loss of function
MACE: major adverse cardiac events
MD: maintenance dose
MI: myocardial infarction
MPA: maximal platelet aggregation
NR: not reported
NSTEMI non-ST elevated myocardial infarction
PCI: percutaneous coronary intervention
PM: poor metabolizer
PRU: P2Y12 reactivity units
STEMI: ST elevated myocardial infarction
TIA: transient ischemic attack
UA: unstable angina
UM: ultra-rapid metabolizer
Clopidogrel
(Plavix)
Prasugrel
(Effient)
Ticagrelor
(Brilinta)
Dose LD: 300 or 600 mg
MD: 75 mg/d
LD: 60 mg
MD: 10 mg/d
(5 mg in < 60 kg)
LD: 180 mg
MD: 90 mg bid
Cost $ $$$ $$$
Metabolism Prodrug;
CYP2C19 (major),
CYP3A4 (minor)
Prodrug;
CYP2B6 (major),
CYP3A4 (minor)
CYP3A4 (major)
Contraindications Active bleeding Active bleeding,
prior stroke or
TIA
Active bleeding,
prior intracranial
hemorrhage
11
Appendix B: Comparison of Oral Antiplatelet Agents
Plavix (clopidogrel) [prescribing information]. Bridgewater, NJ: Bristol-Myers Squibb; July 2017.
Effient (prasugrel) [prescribing information]. Indianapolis, IN: Eli Lilly and Company; July 2016.
Brilinta (ticagrelor) [prescribing information]. Wilmington, DE: AztraZeneca; April 2017.
12
Appendix C: Clopidogrel FDA Warning
Plavix (clopidogrel) [prescribing information]. Bridgewater, NJ: Bristol-Myers Squibb; July 2017.
13
Appendix D: Clopidogrel Metabolism and Mechanism of
Action
Clopidogrel • CYP1A2,
CYP2B6, CYP2C19
2-oxo-clopidogrel
• CYP2C9, CYP2B6, CYP3A4, CYP3A5, CYP2C19, PON1
Active metabolite
• Inhibits P2RY12 on platelet
Sangkuhl Katrin, Klein Teri E, Altman Russ B . Pharmacogenetics and genomics (2010).
14
Appendix E: CYP2C19 Variant Alleles and Frequencies
Scott SA, et al. Clinical Pharmacology & Therapeutics. 2013; 94(3): 317-323.
Functional Status Activity Level Alleles
Functional (wild-type) Normal *1
Loss-of-function (LOF) Little to none *2, *3, *4, *5, *6, *7, *8
Increased function Increased *17
Allele Caucasians Africans Asians
*2 15% 15% 29-35%
*3 <1% <1% 2-9%
Phenotype Genotype Clopidogrel
Implication
Frequency
Ultrarapid
metabolizer
(UM)
Homozygous or heterozygous
increased function (not loss of
function carrier)
Increased active
metabolite
5-30%
Extensive
metabolizer
(EM)
Homozygous normal function Normal active
metabolite
35-50%
Intermediate
metabolizer
(IM)
Heterozygous loss of function +
normal or increased function
Reduced active
metabolite
18-45%
Poor
metabolizer
(PM)
Homozygous loss of function Significantly
reduced active
metabolite
2-15%
15
Appendix F: CYP2C19 Polymorphisms and Clopidogrel
Scott SA, et al. Clinical Pharmacology & Therapeutics. 2013; 94(3): 317-323.
16
Appendix G: Pharmacokinetic Response to Clopidogrel
Based on CYP2C19 Phenotype
Mega JL, et al. N Engl J Med. 2009;360:354-362.
Clopidogrel active metabolite formation
17
Appendix H: Pharmacodynamic Response to Clopidogrel
Based on CYP2C19 Phenotype
Mega JL, et al. N Engl J Med. 2009;360:354-362.
Reduction in platelet aggregation 24 hours after clopidogrel
18
Appendix I: CYP2C19 Genotype and Outcomes
Mega JL, et al. N Engl J Med. 2009;360:354-362.
Composite:
death from
cardiovascular
causes, MI, or
stroke
LOF Carriers (IMs + PMs)
Noncarriers
12.1%
8.0%
HR 1.53 (p = 0.01)
19
Appendix J: CYP2C19 Genotype and Stent Thrombosis
Mega JL, et al. N Engl J Med. 2009;360:354-362.
Noncarriers
2.6%
0.8%
HR 3.09 (p = 0.02)
LOF Carriers (IMs + PMs)
20
Appendix K: Prospective Clinical Implementation of
CYP2C19 Genotype Guided Antiplatelet Therapy After PCI
Cavallari LH, IGNITE Investigators. AHA’s Scientific Sessions. 2016.
LOF = loss of function carrier
CLOP = clopidogrel
ALT = alternative
8.0%
4.6%
Top Related