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The Third DANish Study of Optimal Acute Treatment of Patients
with ST-segment Elevation Myocardial Infarction
PRImary PCI in MULTIvessel Disease - DANAMI3-PRIMULTI
Thomas Engstrøm, MD, DMSci, PhD
Rigshospitalet, University of Copenhagen, Denmark
Participating sites and investigators
Rigshospitalet University Hospital
Henning Kelbæk
Steffen Helqvist
Lars Køber
Dan Eik Høfsten
Lene Kløvgaard
Lene Holmvang
Erik Jørgensen
Kari Saunamäki
Frants Pedersen
Peter Clemmensen
Thomas Engstrøm
Aalborg University Hospital
Hans-Henrik Tilsted Hansen
Jan Ravkilde
Svend Eggert Jensen
Anton Boel Villadsen
Jens Aarøe
Bent Raungaard
Clinical Event Comité (CEC)
Kristian Thygesen
Anders Galløe
Jørgen Jeppesen
Data Safety and Monitoring Board (DSMB)
Gorm Bøje Jensen
Gunnar Gislasson
David Erlinge
ClinicalTrials.gov number NCT01960933
DANAMI3-PRIMULTI
Disclosures
No disclosures with regard to the present trial
DANAMI3-PRIMULTI
Background
IRA
30-50% of STEMI patients have additional
stenoses other than the infarct related artery1,2
Current guidelines support culprit vessel PCI only
Contemporary studies have, however, suggested
preventive revascularisation3,4
Non culprit
1 Jong
JA al. Coronary Artery disease 2006
DW et al. Am Heart J 1991
3 Wald et al. NEJM 2013
4 Gershlick et al. ESC 2014
2 Muller
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European guidelines (ESC)
Windecker S et al. Eur Heart J 2014
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American guidelines (ACC/AHA)
I IIa IIb III
PCI of a non-infarct artery at the time of primary PCI in patients
without hemodynamic compromise is not indicated
I IIa IIb III
PCI is indicated in a non-infarct artery at a time separate from primary
PCI in patients who have spontaneous symptoms of myocardial
ischemia.
I IIa IIb III
PCI is reasonable in a non-infarct artery at a time separate from primary
PCI in patients with intermediate- or high-risk findings on noninvasive
testing
O´Gara PT S et al. JACC 2013
DANAMI3-PRIMULTI
PRAMI – cardiac death, non fatal MI, refractory angina
HR 0.35, p<0.001
(95% CI 0.21-0.58)
65% risk reduction
N=234
53
N=231
Wald et al. NEJM 2013
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Cvlprit – total mortality, recurrent MI, heart failure, revascularisation
Gershlick et al. ESC 2014
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Power calculation
One year repeat revascularisation of non-culprit lesions occured in 5-6%1
One year all-cause mortality or nonfatal MI occurred in 12-13%2
Estimated rate of primary endpoint in IRA arm: 18%
A relative reduction in the primary endpoint of 30% can be detected
with a two-sided alpha level of 0∙05 and a power of 80% by enrolling 618
patients.
1Glaser
et al. Circulation 2005
2Lønborg et
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al. EUR H J 2014
DANAMI3-TRIAL PROGRAM
2239 STEMI < 12 hours
Randomise conventional PPCI, iPOST, defer stenting
2212 Successful infarct related artery PCI
627 Multivessel disease
(>50% stenosis in non IRA > 2 mm suitable for PCI)
Randomise
313 IRA PCI only
314 FFR guided complete revascularisation
DANAMI3-PRIMULTI
DANAMI3-TRIAL PROGRAM
627 Multivessel disease
(>50% stenosis in non IRA > 2 mm suitable for PCI)
313 IRA PCI only
313 Received allocated intervention
0 Did not receive allocated intervention
314 FFR guided complete revascularisation
294 Received allocated intervention
15 PCI failed or not feasible
1 Died before PCI
2 Refused subsequently
2 Other reasons
313 Analysed on intention to treat basis
314 Analysed on intention to treat basis
0 Lost to follow up
1 Lost to follow up (emigration)
DANAMI3-PRIMULTI
DANAMI3-TRIAL PROGRAM
627 Multivessel disease
(>50% stenosis in non IRA > 2 mm suitable for PCI)
313 IRA PCI only
313 Received allocated intervention
0 Did not receive allocated intervention
314 FFR guided complete revascularisation
294 Received allocated intervention
15 PCI failed or not feasible
1 Ded before PCI
2 Refused subsequently
2 Oher reasons
313 Analysed on intention to treat basis
314 Analysed on intention to treat basis
0 Lost to follow up
1 Lost to follow up (emigration)
DANAMI3-PRIMULTI
Primary endpoint
Composite
All-cause mortality
Nonfatal myocardial infarction
Ischemia driven revascularisation of non IRA lesions
Assessed when the last included patient had
been followed for 1 year
DANAMI3-PRIMULTI
Baseline characteristics
IRA only
Complete revascularisation
(n = 313)
(n = 314)
64 (range 34 – 92)
64 (range 37 – 94)
255 (82%)
251 (80%)
Diabetes
42 (13%)
29 (9%)
Hypertension
146 (47%)
130 (41%)
Current smoking
151 (48%)
160 (51%)
27 (9%)
17 (5%)
Anterior
112 (36%)
105 (33%)
Inferior
179 (57%)
195 (62%)
20 (6%)
10 (3%)
Three vessel disease
100 (32%)
97 (31%)
Stenosis on proximal portion of LAD
86 (28%)
80 (26%)
Age (years)
Male
Medical history
Previous MI
Infarct location
Posterior
DANAMI3-PRIMULTI
Procedural data
Procedure duration (min)
Contrast volume (ml)
Fluoroscopy dose (Gycm2)
Number of arteries treated per patient
Number of implanted stents
Stent diameter (mm)
Total stent length (mm)
IRA only
Complete revascularisation
(n = 313)
(n = 314)
42 (31 – 59)
76 (56 – 100)
<0·0001
170 (125 – 220)
280 (215 – 365)
<0·0001
49 (33 – 74)
1 (1–2)
77 (52 – 115)
2 (1–3)
<0·0001
1 (1–1)
2 (1–3)
<0·0001
3·5 (2·75–3·5)
3·0 (2·75–3·5)
0·005
18 (15–28)
33 (18–51)
<0·0001
Stent type
P
<0·0001
0·5
No stenting
18 (6%)
12 (4%)
Bare-metal
5 (2%)
3 (1%)
Drug-eluting
290 (93%)
298 (96%)
Use of Glycoprotein IIb/IIIa inhibitor
72 (23%)
64 (20%)
0·4
Use of Bivalirudin
234 (75%)
237 (76%)
0·8
DANAMI3-PRIMULTI
Clinical characteristics
IRA only
(n = 313)
Complete
revascularisation
(n = 314)
P
50 (40–55)
50 (40–55)
0·5
Killip Class II - IV at any time during hospitalization
20 (6%)
22 (7%)
0·8
Length of stay
5 (4-5)
5 (4-5)
0·4
N/A
2 (2-4)
N/A
Left ventricular ejection fraction
Time to staged PCI
DANAMI3-PRIMULTI
Medical theraphy at discharge
IRA only
Complete revascularisation
(n = 313)
(n = 314)
Aspirin
308 (98%)
303 (97%)
0·1
Clopidogrel
38 (12%)
43 (14%)
0·6
Prasugrel
204 (65%)
194 (62%)
0.4
Ticagrelor
67 (21%)
73 (23%)
0.6
Statin
308 (98%)
310 (99%)
0·5
Betablocker
285 (91%)
290 (92%)
0·6
ACE inhibitor or angiotensin-II-receptor blocker
139 (44%)
142 (45%)
0·8
Calcium channel blocker
36 (12%)
29 (9%)
0·4
P
Antiplatelet therapy
DANAMI3-PRIMULTI
Complications
IRA only
(n = 313)
Complete
revascularisation
(n = 314)
P
0
2 (0·6)
0·2
Bleeding requiring transfusion or surgery
4 (1·3)
1 (0·3)
0·2
CIN (>50% rise in p-creatinine)
7 (2·2)
6 (1·9)
0·8
Stroke
1 (0·3)
4 (1·3)
0·2
Periprocedural myocardial infarction
DANAMI3-PRIMULTI
Primary endpoint
DANAMI3-PRIMULTI
Individual components of primary endpoint
Composite
Non fatal MI
Revascularisation
All cause death
DANAMI3-PRIMULTI
DANAMI3-PRIMULTI
IRA only
(n = 313)
Complete
revascularisation
(n = 314)
HR [95% CI]
p
68 (22%)
11 (4%)
16 (5%)
40 (13%)
15 (5%)
15 (5%)
0·56 [0·38 – 0·83]
1·4 [0·63 – 3·0]
0·94 [0·47 – 1·9]
0·004
0·43
0·87
52 (17%)
17 (5%)
0·31 [0·18 – 0·53]
<0·001
9 (3%)
5 (2%)
0·56 [0·19 – 1·7]
0·29
Cardiac death or nonfatal MI
25 (8%)
20 (6%)
0·80 [0·45 – 1·45]
0·47
Urgent PCI
18 (6%)
7 (2%)
0·38 [0·16 – 0·92]
0·03
Non-urgent PCI
27 (9%)
8 (3%)
0·29 [0·13 – 0·63]
0·002
Primary endpoint
All-cause death
Nonfatal MI
Ischemia-driven revascularisation*
Secondary endpoints
Cardiac death
* PCI or CABG
DANAMI3-PRIMULTI
Endpoints
Event rate (%)
p=0.004
68
p<0.001
52
p=0.002
p=0.47
40
p=0.43
11
15
p=0.87
16 15
p=0.29
p=0.03
25
20
17
9 5
27
18
7
8
DANAMI3-PRIMULTI
Subgroup analysis
Number of patients
627
506
121
Events
108
88
20
Hazard Ratio (95% CI)
0.56 (0.34–0.83)
0.53 (0.34 – 0.82)
0.75 (0.31 – 1.8)
Pinteraction
339
288
55
53
0.33 (0.18 – 0.60)
0.89 (0.52 – 1.5)
0.02
556
71
94
14
0.56 (0.37 – 0.85)
0.55 (0.17 – 1.7)
1.0
410
217
72
36
0.67 (0.42 – 1.1)
0.38 (0.18 – 0.79)
0.2
583
44
102
6
0.60 (0.40 - 0.89)
-
-
0.5
* there were no events in patients with prior myocardial infarction randomized
to complete revascularization
DANAMI3-PRIMULTI
Contemporary randomised trials
PRAMI
(n=465)
CvLPRIT
(n=296)
PRIMULTI
(n=627)
No of including centers
5
?
2
No patients pr. center pr. year
19
?
105
> 50% DS
> 70% DS or > 50% DS in 2 views
> 50% DS and FFR <0.80 or > 90%
DS
Strategy for non-IRA lesions
Immediate
Immediate or staged within index
admission
Staged within index admission
Randomisation
After PPCI
“During” PPCI
After PPCI
62 years
65 years
64 years
79%
83%
97%
Lesion criteria
Age
Bivalirudin or GPIIB/IIIA
DANAMI3-PRIMULTI
Contemporary randomised trials
PRAMI
(n=465)
CvLPRIT
(n=296)
PRIMULTI
(n=627)
D/MI/refractory ischaemia
D/MI/HF/isch D R
D/MI/isch D R
Power (80%)
20% reduced to 14%
(30% Rx effect)
37% PEP reduced to 22%
(40% Rx effect)
18% PEP reduced to 13%
(30% Rx effect)
Result
23% reduced to 9%
(65% Rx effect)
21% reduced to 10%
(55% Rx effect)
22% reduced to 13%
(44% Rx effect)
Early Benefit
Yes
Yes
Safe to postpone
Effect on hard endpoints
Yes
No
No
Primary endpoint
DANAMI3-PRIMULTI
Conclusions
Complete FFR guided revascularisation of multivessel disease in STEMI patients,
staged within the index admission, reduced the primary endpoint of all cause death,
reinfarction and repeat revascularisation
40% of repeat revascularisations were urgent
However, the reduction in the primary endpoint was driven by repeat revascularisations
and not by hard endpoints
Therefore, although complete revascularisation should be recommended, any condition
that makes complex PCI unattractive may support a more conservative strategi of IRA
PCI only
DANAMI3-PRIMULTI