1. 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

2. 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 NCT
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3. No disclosures with regard to the present trial
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4. Background DANAMI3-PRIMULTI 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
2 Muller DW et al. Am Heart J 1991
3 Wald et al. NEJM 2013
4 Gershlick et al. ESC 2014
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5. European guidelines (ESC)
Windecker S et al. Eur Heart J 2014
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6. American guidelines (ACC/AHA)
IIa
IIb
III
PCI of a non-infarct artery at the time of primary PCI in patients without hemodynamic compromise is not indicated B
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 I
IIa
IIb
III B
O´Gara PT S et al. JACC 2013
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7. PRAMI – cardiac death, non fatal MI, refractory angina
HR 0.35, p<0.001
(95% CI )
65% risk reduction 53
N=234
N=231
Wald et al. NEJM 2013
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8. Cvlprit – total mortality, recurrent MI, heart failure, revascularisation
Gershlick et al. ESC 2014
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9. 1Glaser et al. Circulation 2005
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 al. EUR H J 2014
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10. DANAMI3-TRIAL PROGRAM DANAMI3-PRIMULTI Randomise 313 IRA PCI only
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 10

11. DANAMI3-TRIAL PROGRAM DANAMI3-PRIMULTI 313 IRA PCI only
627 Multivessel disease
(>50% stenosis in non IRA > 2 mm suitable for PCI)
313 IRA PCI only
314 FFR guided complete revascularisation
313 received allocated intervention
0 did not receive allocated intervention
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
0 Lost to follow up
314 Analysed on intention to treat basis
1 lost to follow up (emigration)
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12. DANAMI3-TRIAL PROGRAM DANAMI3-PRIMULTI 313 IRA PCI only
627 Multivessel disease
(>50% stenosis in non IRA > 2 mm suitable for PCI)
313 IRA PCI only
314 FFR guided complete revascularisation
313 Received allocated intervention
0 Did not receive allocated intervention
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
0 Lost to follow up
314 Analysed on intention to treat basis
1 Lost to follow up (emigration)
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13. DANAMI3-TRIAL PROGRAM DANAMI3-PRIMULTI 313 IRA PCI only
627 Multivessel disease
(>50% stenosis in non IRA > 2 mm suitable for PCI)
313 IRA PCI only
314 FFR guided complete revascularisation
313 Received allocated intervention
0 Did not receive allocated intervention
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
0 Lost to follow up
314 Analysed on intention to treat basis
1 Lost to follow up (emigration)
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14. Primary endpoint DANAMI3-PRIMULTI 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
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15. Baseline characteristics
IRA only (n = 313)
Complete revascularisation (n = 314)
Age (years)
64 (range 34 – 92)
64 (range 37 – 94)
Male
255 (82%)
251 (80%)
Medical history
Diabetes
42 (13%)
29 (9%)
Hypertension
146 (47%)
130 (41%)
Current smoking
151 (48%)
160 (51%)
Previous MI
27 (9%)
17 (5%)
Infarct location
Anterior
112 (36%)
105 (33%)
Inferior
179 (57%)
195 (62%)
Posterior
20 (6%)
10 (3%)
Three vessel disease
100 (32%)
97 (31%)
Stenosis on proximal portion of LAD
86 (28%)
80 (26%)
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16. Complete revascularisation (n = 314)
Procedural data
IRA only (n = 313)
Complete revascularisation (n = 314) P
Procedure duration (min)
42 (31 – 59)
76 (56 – 100)
<0·0001
Contrast volume (ml)
170 (125 – 220)
280 (215 – 365)
Fluoroscopy dose (Gycm2)
49 (33 – 74)
77 (52 – 115)
Number of arteries treated per patient
1 (1–2)
2 (1–3)
Number of implanted stents
1 (1–1)
Stent diameter (mm)
3·5 (2·75–3·5)
3·0 (2·75–3·5)
0·005
Total stent length (mm)
18 (15–28)
33 (18–51)
Stent type
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
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17. Clinical characteristics
IRA only (n = 313)
Complete revascularisation (n = 314) P
Left ventricular ejection fraction
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)
0·4
Time to staged PCI
N/A
2 (2-4)
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18. Medical theraphy at discharge
IRA only (n = 313)
Complete revascularisation (n = 314) P
Antiplatelet therapy
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
310 (99%)
0·5
Betablocker
285 (91%)
290 (92%)
ACE inhibitor or angiotensin-II-receptor blocker
139 (44%)
142 (45%)
0·8
Calcium channel blocker
36 (12%)
29 (9%)
0·4
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19. Complete revascularisation (n = 314)
Complications
IRA only (n = 313)
Complete revascularisation (n = 314) P
Periprocedural myocardial infarction
2 (0·6)
0·2
Bleeding requiring transfusion or surgery
4 (1·3)
1 (0·3)
CIN (>50% rise in p-creatinine)
7 (2·2)
6 (1·9)
0·8
Stroke
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20. Complications
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21. Primary endpoint
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22. Individual components of primary endpoint
Composite
Revascularisation
Non fatal MI
All cause death
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23. Complete revascularisation (n = 314)
DANAMI3-PRIMULTI
IRA only (n = 313)
Complete revascularisation (n = 314)
HR [95% CI] p
Primary endpoint
68 (22%)
40 (13%)
0·56 [0·38 – 0·83]
0·004
All-cause death
11 (4%)
15 (5%)
1·4 [0·63 – 3·0]
0·43
Nonfatal MI
16 (5%)
0·94 [0·47 – 1·9]
0·87
Ischemia-driven revascularisation*
52 (17%)
17 (5%)
0·31 [0·18 – 0·53]
<0·001
Secondary endpoints
Cardiac death
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
* PCI or CABG
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24. Endpoints DANAMI3-PRIMULTI Event rate (%) 68 52 40 25 27 20 18 15 1617 11 9 5 7 8
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25. Subgroup analysis DANAMI3-PRIMULTI Number of patients Events
Hazard Ratio (95% CI)
Pinteraction
627
108
0.56 (0.34–0.83)
506 88
0.53 (0.34 – 0.82)
0.5
121 20
0.75 (0.31 – 1.8)
339 55
0.33 (0.18 – 0.60)
0.02
288 53
0.89 (0.52 – 1.5)
556 94
0.56 (0.37 – 0.85)
1.0 71 14
0.55 (0.17 – 1.7)
410 72
0.67 (0.42 – 1.1)
0.2
217 36
0.38 (0.18 – 0.79)
583
102
0.60 ( ) - 44 6
* there were no events in patients with prior myocardial infarction randomized
to complete revascularization
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26. 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
Lesion criteria
> 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
Age
62 years
65 years
64 years
Bivalirudin or GPIIB/IIIA
79%
83%
97%
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27. Contemporary randomised trials
PRAMI
(n=465)
CvLPRIT
(n=296)
PRIMULTI
(n=627)
Primary endpoint
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%
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
Safe to postpone
Effect on hard endpoints No
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28. Conclusions DANAMI3-PRIMULTI
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
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