Medical management after PCI Ma Hong 1 st affiliated hospital of Sun Yat-sen University.
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Transcript of Medical management after PCI Ma Hong 1 st affiliated hospital of Sun Yat-sen University.
Medical management after PCI
Ma Hong1st affiliated hospital
of Sun Yat-sen University
Successful PCI is
just the beginning
of another long
journey
Goals of medical management after PCI
• To prevent acute/sub-acute stent thrombosis
• To prevent other coronary events
(improve survival)
• To improve symptoms
Medical management after PCI
• Antiplatelet therapy
• Beta-blocade
• ACEI / ARB
• Statins
• others
After PCI, aspirin should be continued indefinitely.
Postprocedural Antiplatelet Therapy
I IIa IIb III
2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, JACC 2011:58(24)
After PCI, it is reasonable to use 81 mg per day of aspirin in preference to higher maintenance doses.
I IIa IIb III
Postprocedural Antiplatelet Therapy
The duration of P2Y12 inhibitor therapy after stent implantation should generally be as follows:
a) In patients receiving a stent (BMS or DES) during PCI for ACS, P2Y12 inhibitor therapy should be given for at least 12 months (clopidogrel 75 mg daily); prasugrel 10 mg daily; and ticagrelor 90 mg twice daily.
b) In patients receiving a DES for a non–ACS indication, clopidogrel 75 mg daily should be given for at least 12 months if patients are not at high risk of bleeding.
c) In patients receiving a BMS for a non-ACS indication, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months (unless the patient is at increased risk of bleeding; then it should be given for a minimum of 2 weeks).
I IIa IIb III
2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, JACC 2011:58(24)
Continuation of clopidogrel, prasugrel or ticagrelor beyond 12 months may be considered in patients undergoing DES placement.
Postprocedural Antiplatelet Therapy
I IIa IIb III
If the risk of morbidity from bleeding outweighs the anticipated benefit afforded by a recommended duration of P2Y12 inhibitor therapy after stent implantation, earlier discontinuation (e.g., <12 months) of P2Y12 inhibitor therapy is reasonable.
I IIa IIb III
2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, JACC 2011:58(24)
New P2Y12 inhibitor-- prasugrel, ticagrelor
• Prasugrel– Phase 2 PCI: JUMBO – TIMI 26
– Phase 3 PCI in ACS: TRITON – TIMI 38
– TRIGGER-PCI– ……
• Ticagrelor– PLATO– PLATO-INVASIVE– ……
NNSS
OO
ClCl
OO CHCH33CC
Clopidogrel
Prodrug
Prasugrel
NN
SS
OO
CCOO
FFOO
CHCH33
85% Inactive Metabolites
hCE1hCE1
LiverLiver Hydrolysis(Esterases)
NN
SS
OO
FFOO
hCE2
GutGut
HOOCHOOC* HS* HS
NN
OO
FF
CYPs:CYPs: 3A4/5 3A4/5 2B6 2B6 2C9 2C9 2C19 2C19
GutGut
and
LiverLiver
Oxidation(Cytochrome P450)
Active Metabolite
CYPs: 1A2 2B6 2C19
LiverLiver
HOOCHOOC* HS* HS
NN
OO
ClCl
OCHOCH33
CYPs: 3A4/5 2B6 2C9 2C19
LiverLiver
Clopidogrel Prasugrel
Wiviott SD et al. NEJM 2007; 357: 2001-2015
TRITONEfficacy and Safety in Patients with ACS
≥ 60 kg, < 75 years, no previous stroke/ TIA
0
2
4
6
8
10
12
14
16
0 30 90 180 270 360 450
End
poin
t (%
)
Hazard Ratio, 1.240(95% CI, 0.91 - 1.69)P = 0.17
Hazard Ratio, 0.75(95% CI, 0.66 - 0.84)P < 0.001
Clopidogrel 11.0%
Prasugrel 8.3%
Clopidogrel 1.50%
Prasugrel 2.0%
Days
Cardiovascular Death, MI, StrokeCardiovascular Death, MI, Stroke
Major BleedingMajor Bleeding
ITT= 13,608ITT= 13,608 LTFU = 14 (0.1%)LTFU = 14 (0.1%)
Ticagrelor - An Oral Reversible P2Y12 Antagonist
Ticagrelor is a cyclo-pentyl-triazolo-pyrimidine (CPTP)
OH
OH
O
OH
N
F
S
NH
NN
NN
F
Direct acting Direct acting Not a prodrug; does not require metabolic activationNot a prodrug; does not require metabolic activation Rapid onset of inhibitory effect on the P2YRapid onset of inhibitory effect on the P2Y1212 receptor receptor Greater inhibition of platelet aggregation than clopidogrelGreater inhibition of platelet aggregation than clopidogrel
Reversibly boundReversibly bound Degree of inhibition reflects plasma concentrationDegree of inhibition reflects plasma concentration Faster offset of effect than clopidogrel Faster offset of effect than clopidogrel Functional recovery of all circulating plateletsFunctional recovery of all circulating platelets
PLATO study design
Primary endpoint: CV death + MI + Stroke Primary safety endpint: Total major bleeding
6–12-month exposure
ClopidogrelIf pre-treated, no additional loading dose;if naive, standard 300 mg loading dose,
then 75 mg qd maintenance;(additional 300 mg allowed pre PCI)
Ticagrelor180 mg loading dose, then90 mg bid maintenance;
(additional 90 mg pre-PCI)
NSTE-ACS (moderate-to-high risk) STEMI (if primary PCI)Clopidogrel-treated or -naive;
randomised within 24 hours of index event (N=18,624)
PCI = percutaneous coronary intervention; ASA = acetylsalicylic acid; CV = cardiovascular; TIA = transient ischaemic attack
PLATO – INVASIVE study design
6–12 months treatment
PCI = percutaneous coronary intervention; CV = cardiovascular; PI = principal investigator
NSTEMI ACS (moderate-to-high risk) STEMI (if primary PCI) (N=18,624)Clopidogrel-treated or -naive; randomized <24 hours of index event
At randomization, 13,408 (72%) of patients were specified by the Investigator: intent for invasive strategy
Primary endpoint: CV death + MI + Stroke Primary safety endpoint: Total major bleeding
Clopidogrel (n=6,676)If pre-treated, no additional loading dose;if naive, standard 300 mg loading dose,
then 75 mg qd maintenance;(additional 300 mg allowed pre-PCI)
Ticagrelor (n=6,732)180 mg loading dose, then
90 mg bid maintenance;(additional 90 mg pre-PCI)
Primary endpoint: CV death, MI or stroke
00
5
10
15
60 120 180 240 300 360Days after randomization
K-M
est
imat
ed ra
te (%
per
yea
r)
HR: 0.84 (95% CI = 0.75–0.94), p=0.0025
9.02
10.65Clopidogrel
Ticagrelor
No. at risk
ClopidogrelTicagrelor
6,6766,732
6,1296,236
6,0346,134
5,881 4,8154,889
3,6803,735
2,9653,0485,972
K-M = Kaplan-Meier; HR = hazard ratio; CI = confidence interval
Stent thrombosis
Ticagrelor(n=6,732)
Clopidogrel (n=6,676)
HR for ticagrelor (95% CI)
p value*
Stent thrombosis, %
Definite
Probable or definite
Possible, probable, or definite
1.0
1.7
2.2
1.6
2.3
3.1
0.62 (0.45–0.85)
0.72 (0.56–0.93)
0.72 (0.58–0.90)
0.003
0.01
0.003
¶ Evaluated in patients with any stent during the studyTime-at-risk is calculated from the date of first stent insertion in the study or date of randomization* By univariate Cox model
Primary safety event: Major bleeding*
No. at risk
ClopidogrelTicagrelor
6,5856,651
5,2155,235
4,9844,947
4,786
Days after randomization
3,7533,726
2,7542,741
2,4962,503
0 60 120 180 240 300 360
10
5
0
15
Clopidogrel
Ticagrelor11.611.5
4,755
K-M
est
imat
ed ra
te (%
per
yea
r)
HR 0.99 (95% CI = 0.89–1.10), p=0.88
* PLATO definitions
Before we have the new
P2Y12 Inhibitors, what we can
do for high risk patients ?
Low Dose ASA
(75-100 mg)
Mehta SR et al. Am Heart J 2008
25,000 ACS or STEMI PatientsAngiography with intended PCI <72 hrs
No restriction on use of GP IIb/IIIa inhibitors
DOUBLE DOSEClopidogrel 600mgthen 150 mg OD x 6d then 75 mg OD
STANDARD DOSEClopidogrel 300 mg followed by 75 mg
daily
Randomized
High Dose ASA
(300-325 mg)
High Dose ASA
(300-325 mg)
Low Dose ASA
(75-100 mg)
A Randomized, Double-Blind, 2X2 Factorial Trial of Clopidogrel A Randomized, Double-Blind, 2X2 Factorial Trial of Clopidogrel Double vs. Standard Dose and High versus Low Dose ASA in ACS Double vs. Standard Dose and High versus Low Dose ASA in ACS
or STEMI with an Early Invasive Strategy or STEMI with an Early Invasive Strategy and intent for PCIand intent for PCI
Primary Efficacy Outcome CV Death / MI /stroke at 30 days
Secodary OutcomeARC defined STENT THROMBOSIS
CVD/MI/Stroke + Rec Ischemia
Rational for high dose clopidogrel therapyCURRENT -- OASIS 7
23
Definite Stent Thrombosis in 4 Groups (Angiographically Proven)
Days
Cum
ulat
ive
Haz
ard
0.0
0.00
40.
008
0.01
2
0 3 6 9 12 15 18 21 24 27 30
C Standard, A Low
C Standard, A High
C Double, A Low
C Double, A High
Standard Clop
Double Clop HR P
PIntn
High ASA 1.2 0.6 0.49 0.003
Low ASA 1.2 0.8 0.6 0.058 0.35
24
Days
Cum
ulat
ive
Haz
ard
0.0
0.00
50.
010
0.01
5
0 3 6 9 12 15 18 21 24 27 30
Clopidogrel Standard
Clopidogrel Double
HR 0.5495% CI 0.35-0.84
P=0.006
STEMI-PCI: Definite Stent Thrombosis
46%RRR
Mehta SR. TCT 2009 LBCT
DAPT – the longer the better ?
• Duration of DAPT after DES : at least 12
months, possibly longer
• await for RCT
Others – prevention of GIB
Interaction of PPI and Clopidogrel :
what we have known ?
Scientific Basis
Juhász et al. Digestion 2010 ; Taubert D et al. Clin Pharmacol Ther 2006;80:486–501
Lab. result
Observational Data
Randomized Data
The Cogent Trial
• Randomized to Clopidogrel + Omeprazole (CGT
2168) or Clopidogrel + Placebo
• 3627 patients (above the initial target of 3200)
• 393 sites
• Median follow-up 133 days (maximum 362 days)
• 136 adjudicated cardiovascular events (preliminary)
• 105 adjudicated GI events (preliminary)
CONGENT – Primary Endpoint
Bhatt DL. Presented at: NEJM OCTOBER 2010
Prevention of GIB -- guidelines PPI should be used in patients with history of prior
GIB who require DAPT.
PPI use is reasonable in patients with increased risk of gastrointestinal bleeding (advanced age, concomitant use of warfarin, steroids, nonsteroidal anti-inflammatory drugs, H pylori infection, etc.) who require DAPT.
Routine use of a PPI is not recommended for patients at low risk of gastrointestinal bleeding, who have much less potential to benefit from prophylactic therapy.
I IIa IIb III
I IIa IIb III
I IIa IIb III
2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, JACC 2011:58(24)
Second prevention
2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, JACC 2011:58(24)
THANK YOU
Antiplatelet therapy for polymer-free stent and biodegenerable
stents ?
We are not clear need more trials
38
1. Overall, the primary outcome was neutral between the clopidogrel and aspirin dose groups.1
2. In patients undergoing PCI, the double-dose clopidogrel regimen reduced the primary outcome (CV death, MI or stroke) and stent thrombosis
3. The reduction in stent thrombosis was robust and observed in those receiving DES and BMS and in those presenting with STEMI
4. There was a modest excess in major bleeds, but no difference in ICH, fatal bleeds or CABG-related bleeds with the double-dose regimen. No difference in major bleeds between aspirin dose groups.
5. There was an interaction between clopidogrel and aspirin such that the lowest event rates were observed in those receiving double-dose clopidogrel and high-dose aspirin.
2. Mehta et al. Lancet 2010; Online First Sept 11. CURRENT Investigators. N Engl J Med 2010;363:930-42
Rational for high dose clopidogrel therapyCURRENT -- OASIS 7