The Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction PRImary PCI in MULTIvessel Disease - DANAMI3-PRIMULTI

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The Third DANish Study of Optimal Acute Treatment
of Patients with ST-segment Elevation Myocardial
InfarctionPRImary PCI in MULTIvessel Disease -
DANAMI3-PRIMULTI

• Thomas Engstrøm, MD, DMSci, PhD
• Rigshospitalet, University of Copenhagen, Denmark

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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
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Disclosures
No disclosures with regard to the present trial
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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 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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European guidelines (ESC)
Windecker S et al. Eur Heart J 2014
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American guidelines (ACC/AHA)
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.
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
OGara PT S et al. JACC 2013
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PRAMI cardiac death, non fatal MI, refractory
angina
HR 0.35, plt0.001 (95 CI 0.21-0.58) 65 risk
reduction
53
N234
N231
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 5-61
• One year all-cause mortality or nonfatal MI
  occurred in 12-132
• 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 005 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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DANAMI3-TRIAL PROGRAM
2239 STEMI lt 12 hours
Randomise conventional PPCI, iPOST, defer stenting
2212 Successful infarct related artery PCI
627 Multivessel disease
(gt50 stenosis in non IRA gt 2 mm suitable for PCI)
Randomise
313 IRA PCI only
314 FFR guided complete revascularisation
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DANAMI3-TRIAL PROGRAM
627 Multivessel disease
(gt50 stenosis in non IRA gt 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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DANAMI3-TRIAL PROGRAM
627 Multivessel disease
(gt50 stenosis in non IRA gt 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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DANAMI3-TRIAL PROGRAM
627 Multivessel disease
(gt50 stenosis in non IRA gt 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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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
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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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Procedural data
  IRA only(n 313) Complete revascularisation(n 314) P
Procedure duration (min) 42 (31 59) 76 (56 100) lt00001
Contrast volume (ml) 170 (125 220) 280 (215 365) lt00001
Fluoroscopy dose (Gycm2) 49 (33 74) 77 (52 115) lt00001
Number of arteries treated per patient 1 (12) 2 (13) lt00001
Number of implanted stents 1 (11) 2 (13) lt00001
Stent diameter (mm) 35 (27535) 30 (27535) 0005
Total stent length (mm) 18 (1528) 33 (1851) lt00001
Stent type     05
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) 04
Use of Bivalirudin 234 (75) 237 (76) 08
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Clinical characteristics
  IRA only(n 313) Complete revascularisation(n 314) P
Left ventricular ejection fraction 50 (4055) 50 (4055) 05
Killip Class II - IV at any time during hospitalization 20 (6) 22 (7) 08
Length of stay 5 (4-5) 5 (4-5) 04
Time to staged PCI N/A 2 (2-4) N/A
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Medical theraphy at discharge
  IRA only(n 313) Complete revascularisation(n 314) P
Antiplatelet therapy    
Aspirin 308 (98) 303 (97) 01
Clopidogrel 38 (12) 43 (14) 06
Prasugrel 204 (65) 194 (62) 0.4
Ticagrelor 67 (21) 73 (23) 0.6
Statin 308 (98) 310 (99) 05
Betablocker 285 (91) 290 (92) 06
ACE inhibitor or angiotensin-II-receptor blocker 139 (44) 142 (45) 08
Calcium channel blocker 36 (12) 29 (9) 04
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Complications
  IRA only(n 313) Complete revascularisation(n 314) P
Periprocedural myocardial infarction 0 2 (06) 02
Bleeding requiring transfusion or surgery 4 (13) 1 (03) 02
CIN (gt50 rise in p-creatinine) 7 (22) 6 (19) 08
Stroke 1 (03) 4 (13) 02
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Complications
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Primary endpoint
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Individual components of primary endpoint
Composite
Revascularisation
Non fatal MI
All cause death
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  IRA only(n 313) Complete revascularisation(n 314) HR 95 CI p
Primary endpoint 68 (22) 40 (13) 056 038 083 0004
All-cause death 11 (4) 15 (5) 14 063 30 043
Nonfatal MI 16 (5) 15 (5) 094 047 19 087
Ischemia-driven revascularisation 52 (17) 17 (5) 031 018 053 lt0001
Secondary endpoints        
Cardiac death 9 (3) 5 (2) 056 019 17 029
Cardiac death or nonfatal MI 25 (8) 20 (6) 080 045 145 047
Urgent PCI 18 (6) 7 (2) 038 016 092 003
Non-urgent PCI 27 (9) 8 (3) 029 013 063 0002
PCI or CABG
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Endpoints
p0.004
68
plt0.001
52
Event rate ()
p0.47
p0.002
40
p0.03
27
25
p0.43
p0.87
p0.29
20
18
15
16
17
15
11
8
9
7
5
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Subgroup analysis
Number of patients Events Hazard Ratio (95 CI) Pinteraction
627 108 0.56 (0.340.83)
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 (0.40 - 0.89) -
44 6 -  
there were no events in patients with prior
myocardial infarction randomized to complete
revascularization
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Contemporary randomised trials
PRAMI (n465) CvLPRIT (n296) PRIMULTI (n627)
No of including centers 5 ? 2
No patients pr. center pr. year 19 ? 105
Lesion criteria gt 50 DS gt 70 DS or gt 50 DS in 2 views gt 50 DS and FFR lt0.80 or gt 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
Age 62 years 65 years 64 years
Bivalirudin or GPIIB/IIIA 79 83 97
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Contemporary randomised trials
PRAMI (n465) CvLPRIT (n296) PRIMULTI (n627)
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 (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
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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
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