“adjunctive therapy” non st segment elevation acs
Post on 14-Jan-2016
57 Views
Preview:
DESCRIPTION
TRANSCRIPT
“Adjunctive Therapy”Non ST segment elevation ACS
Dr M R ThomasDr M R Thomas
King’s College Hospital.King’s College Hospital.
Advanced Angioplasty 2002Advanced Angioplasty 2002
Plaque Rupture
Unstable angina
Non ST elevationAMI
ST elevationAMI
“Adjunctive Therapy”Non ST segment elevation ACS
Pre-PCI (assume DGH admission)Pre-PCI (assume DGH admission)
Peri-PCIPeri-PCI
Post PCIPost PCI
UK Perspective!!UK Perspective!!
“Adjunctive Therapy”Non ST segment elevation ACS
Pre PCIObvious medical therapy.Obvious medical therapy.
- aspirin.- aspirin.
- anti-anginals.- anti-anginals.
- lipid lowering.- lipid lowering. MIRACL:MIRACL:
80mg atorvastatin v placebo80mg atorvastatin v placebo
Un angina/non Q MIUn angina/non Q MI
Rx for 16 weeksRx for 16 weeks
Primary endpoint: death, non fatal Primary endpoint: death, non fatal MI,cardiac arrest and emergency MI,cardiac arrest and emergency re-hospitalisationre-hospitalisation
13.5
14
14.5
15
15.5
16
16.5
17
17.5
1ary endpoint
Placebo
Atorvastatin
MIRACL TRIAL
P=0.048
Is there a need for Is there a need for revascularisation?revascularisation?
And therefore generally And therefore generally transfer to a tertiary centre.transfer to a tertiary centre.
Cons v Invasive Strategies 4 randomised clinical trials
TIMI IIIB VANQWISH FRISC-2 TACTICS
Years 1989-92 1993-94 1996-98 1998-2000
Patients 1473 920 2457 2220
UA/NSTEMI 68%/32% 0%/100% 41%/59% 62%/38%
Meds ASA/UFH ASA/UFH ASA/Dalteparin
ASA,UFH,Tirofiban
GP IIb/IIIa 0% 0% 10% 100%
Stents 0% 0% 60% 85%
High surgical mortality.7.7% overall and 12% inthe invasive arm
Median time to angiography 4 daysMedian time to revascularisation 4 (PCI) to 7 (CABG)
Median time to angiography 22 hrsMedian time to revasc 25 (PCI) to 89 (CABG) hrs
“Adjunctive Therapy”Non ST segment elevation ACS
So assuming some or all patients will need revasularisation (PCI) what is the best type
and combination of drugs pre PCI
Heparin, UFH or LMWHHeparin, UFH or LMWH IIb/IIIa receptor inhibitorsIIb/IIIa receptor inhibitorsClopidogrelClopidogrel
Heparin: LMWH or UFH
Essence and TIMI 11BEssence and TIMI 11B
These trials have These trials have demonstrated an advantage demonstrated an advantage of LMWH over UFH in UA of LMWH over UFH in UA and other trials have shown and other trials have shown at least equivalence.at least equivalence.
Also ease of use compared to Also ease of use compared to UFH.UFH.
Worries about combination Worries about combination
with IIb/IIIa now resolved.with IIb/IIIa now resolved.
Incidence of death/MI in patients at 1 year: effects of enoxaparin more marked in PCI
patients, TIMI 11B/ESSENCE meta-analysis
17.7
11.6
16.6
12.5 12.411.5
02468
1012141618
% patients
PCI ontreatment
PCI inhospital
ALLdeath/MI
UFHEnoxaparin
OR (95% CI)0.61 (0.35,1.06)
OR (95% CI)0.72(0.49,1.04)
OR (95% CI)0.92(0.81,1.04)
IIb/IIIa receptor inhibitors““National Institute of Clinical Excellence” National Institute of Clinical Excellence”
Guidance on the use of glycoprotein IIb/IIIa inhibitors Guidance on the use of glycoprotein IIb/IIIa inhibitors in the treatment of acute coronary syndromes. in the treatment of acute coronary syndromes.
September 2000September 2000
(1) For high risk patients with unstable angina or non-Q MI, the (1) For high risk patients with unstable angina or non-Q MI, the intravenous use of GP IIb/IIIa inhibitors in addition to low intravenous use of GP IIb/IIIa inhibitors in addition to low (adjusted) dose UFH is recommended.(adjusted) dose UFH is recommended.
(2) In unstable angina, raised blood levels of troponin should be used (2) In unstable angina, raised blood levels of troponin should be used to identify those at high risk.to identify those at high risk.
NB: Pre GUSTO IV ACS
In the absence of revascularisation In the absence of revascularisation value of IIb/IIIa receptor inhibitors value of IIb/IIIa receptor inhibitors “small” and evidence favours small “small” and evidence favours small
molecules.molecules.
CURECURE (OASIS-4)Clopidogrel in Unstable
Angina to preventRecurrent ischemic
Events
Months of Follow-up
Cu
mu
lative
Ha
za
rd R
ate
s
0.0
0.0
20
.04
0.0
60
.08
0.1
00
.12
0.1
4
0 3 6 9 12
Cumulative Hazard Rates for CV Death/MI/Stroke
P < 0.001
Clopidogrel
Placebo
Cum
ulat
ive
Haz
ard
Rat
es
Months of Follow-up0 3 6 9 12
6303
6259
5780
5866
4664
4779
3600
3644
2388
2418
Plac
Clop
No of Pts
9.3%
11.4%20% RRcp 20% Prism + 6/129.6% Pursuit 30 days
Transfer for revascularisation.
Does everyone need to be Does everyone need to be transferred for angiography and transferred for angiography and
possible revascularisation?possible revascularisation?
Risk stratification
Baseline ST segment change
Recurrent Ischaemia
Value of Baseline CPK-MB in ACS (PURSUIT)
1.92.9
4.55.1
6.2
8
0
12
34
56
78
9
0-1 >2-3
>5-10
30 daymortality(%)
10.99.9
6.98.1
5.5
4
0
2
4
6
8
10
12
0-1 >1-2 >2-3 >3-5 >5-10
>10
8 monthmortality (%)
Prognostic value of Baseline Troponins
Gusto IIA: 30 day mortality (%)
3.9
11.8
0
2
4
6
8
10
12
30 day mortality
Trop T negTrop T pos
P<0.001
TACTICS-TIMI 18: Stratified by Troponin T
3.1 2.9
10.6
5.3
0
2
4
6
8
10
12
Trop T<0.01 Trop T>0.01
ConservativeInvasive
OR=0.95p=NS
OR=0.47p=0.002
Low risk patients
Data supports an ischaemia-guided Data supports an ischaemia-guided approach with treadmill exercise or approach with treadmill exercise or pharmacological stress.pharmacological stress.
Transfer!
So we have transferred the high risk patient:So we have transferred the high risk patient:
- troponin +, recurrent ischaemia, ST depression.- troponin +, recurrent ischaemia, ST depression.
ONON
- aspirin, LMWH, clopidogrel, IIb/IIIa in ideal - aspirin, LMWH, clopidogrel, IIb/IIIa in ideal world!! (24 hrs)world!! (24 hrs)
BUTBUT
in UK aspirin, LMWH and clopidogrel (2 in UK aspirin, LMWH and clopidogrel (2 weeks!)weeks!)
Transfer
Is there a problem with LMWH Is there a problem with LMWH and IIb/IIIa?and IIb/IIIa?
“Acute II”
First randomised trial of IIb/IIIa blockers First randomised trial of IIb/IIIa blockers and LMWH in ACS.and LMWH in ACS.
525 ACS patients on aspirin and Tirofiban 525 ACS patients on aspirin and Tirofiban (Aggrastat).(Aggrastat).
Randomised to LMWH (enoxaparin) or Randomised to LMWH (enoxaparin) or UFH.UFH.
Primary endpoint: SAFETY.Primary endpoint: SAFETY.
Safety endpoints in Acute-2
Endpoint Tirofiban plus LMWH Tirofiban plus UFH
Any Bleed 4.7% 5.2%
Major bleed 0.6% 0.5%
Cutaneous bleed 19.4% 21%
Transfusion 2.2% 2.9%
Thrombocytopenia 0.3% 0.5%
30 day event rates in ACUTE II
Event Tirofiban plusLMWH
Tirofiban plusUFH
P value
Death 2.2% 2.4%
MI 7.0% 7.6%
Stroke 0.3% 1.4%
Re-hosp for UA 2.5% 6.6% 0.026
Revascularisation 12.1% 18.1% 0.058
Paragon-B appears to similar results for Lamifiban
International Task ForceRecommendations (Feb 2001)
(Karl Karsch from UK)
no additionalUFH or LM W H
+/- G P IIb/IIIa
cath w ithin <8h of last SC dose
enoxaparin 0.3 m g/kgiv bolus
UFH 50 U/kgACT 200-250s
+ G P IIb/IIIa
enoxaparin 0.3 m g/kgiv bolus
UFH 60 U/kgACT 250-300s
- GP IIb/IIIa
cath w ithin 8-12 h of last SC dose
UA/NST EM ILM W H initiated
IIb/IIIa receptor inhibitors
Which patients…….all or defined by Which patients…….all or defined by coronary anatomy?coronary anatomy?
Which compound………?any Which compound………?any
Delivered when………?upstream or after Delivered when………?upstream or after diagnostic angiogram.diagnostic angiogram.
“Adjunctive Therapy”Non ST segment elevation ACS
Post Discharge
2ary prevention, lipids etc2ary prevention, lipids etc AspirinAspirin ClopidogrelClopidogrel
PCI-A prospective, randomized, double-A prospective, randomized, double-
blind substudy of patients blind substudy of patients undergoing PCI in the CURE trialundergoing PCI in the CURE trial
0.02
0.04
0.06
0.08
5 10 15 20 25 30
Clopidogrel
Placebo
0.0
RR 0.7095% CI 0.50-0.97P=0.03
Days following PCI
Cu
mu
lati
ve H
aza
rd R
ate
Primary Endpoint: CV Death, MI, Urgent Revascularization
Mehta SR et al. Lancet 2001:358:527-33
0 100 200 300 400
0.0
0.02
0.04
0.06
0.08
0.10
Clopidogrel
Placebo
RR 0.7595% CI 0.56-1.00P=0.047
Days following PCI
Cu
mu
lati
ve H
aza
rd R
ate
CV Death, MI:From PCI to End of Followup
Mehta SR et al. Lancet 2001:358:527-33
CV Death or MI at Various Intervals
12.6
5.14.4
3.93.12.9
3.6
8.8
0
2
4
6
8
10
12
14
Overall BeforePCI
PCI to30 d.
30 d. to1 yr
CV
de
ath
or
MI (
%)
PlaceboClopidogrel
RRR 31% 32% 34% 21%
*
*P=0.002 Mehta SR et al. Lancet 2001:358:527-33
Guidelines
““Guidelines for the management of patients Guidelines for the management of patients with acute coronary syndromes without with acute coronary syndromes without persistent ECG ST elevation”persistent ECG ST elevation”
Heart 2001;85:133-142Heart 2001;85:133-142
We live in the UKQuestions
Where should diagnostic angiography be performed?Where should diagnostic angiography be performed?
Where should interventional cardiology be Where should interventional cardiology be performed?performed?
Who should perform interventional procedures?Who should perform interventional procedures?
How do we increase the availability of both of the How do we increase the availability of both of the above? above?
ALL OF THE ABOVE IS AS/MORE ALL OF THE ABOVE IS AS/MORE IMPORTANT AS THE DATA!IMPORTANT AS THE DATA!
ConclusionsI think we know the data:I think we know the data:aspirin, lipid lowering, clopidogrel, LMWH, risk aspirin, lipid lowering, clopidogrel, LMWH, risk
assessment and IIb/IIIa with early revascularisation assessment and IIb/IIIa with early revascularisation in the high risk group.in the high risk group.
Providing an optimal service in the UK Providing an optimal service in the UK via the NHS…….now that’s a via the NHS…….now that’s a different story!!different story!!
top related