The Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction

PRImary PCI in MULTIvessel Disease - DANAMI3-PRIMULTI

The Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction

PRImary PCI in MULTIvessel Disease - DANAMI3-PRIMULTIThomas Engstrøm, MD, DMSci, PhD

Rigshospitalet, University of Copenhagen, Denmark

DANAMI3-PRIMULTI

Rigshospitalet University HospitalHenning KelbækSteffen HelqvistLars KøberDan Eik HøfstenLene KløvgaardLene HolmvangErik JørgensenKari SaunamäkiFrants PedersenPeter ClemmensenThomas Engstrøm

Participating sites and investigators

ClinicalTrials.gov number NCT01960933

Aalborg University HospitalHans-Henrik Tilsted HansenJan RavkildeSvend Eggert JensenAnton Boel VilladsenJens AarøeBent Raungaard

Data Safety and Monitoring Board (DSMB)Gorm Bøje JensenGunnar GislassonDavid Erlinge

Clinical Event Comité (CEC)Kristian ThygesenAnders GalløeJørgen Jeppesen

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No disclosures with regard to the present trial

Disclosures

Background

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30-50% of STEMI patients have additionalstenoses other than the infarct related artery1,2

Current guidelines support culprit vessel PCI only

Contemporary studies have, however, suggested preventive revascularisation3,4

IRA

Non culprit

1 Jong JA al. Coronary Artery disease 20062 Muller DW et al. Am Heart J 19913 Wald et al. NEJM 20134 Gershlick et al. ESC 2014

Windecker S et al. Eur Heart J 2014

European guidelines (ESC)

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O´Gara PT S et al. JACC 2013

American guidelines (ACC/AHA)

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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

I IIa IIb III

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

HR 0.35, p<0.001(95% CI 0.21-0.58)

65% risk reduction

PRAMI – cardiac death, non fatal MI, refractory angina

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N=234 N=231Wald et al. NEJM 2013

53

Cvlprit – total mortality, recurrent MI, heart failure, revascularisation

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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 al. EUR H J 2014

Randomise conventional PPCI, iPOST, defer stenting

627 Multivessel disease

313 IRA PCI only 314 FFR guided complete revascularisation

2239 STEMI < 12 hours

Randomise

(>50% stenosis in non IRA > 2 mm suitable for PCI)

2212 Successful infarct related artery PCI

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627 Multivessel disease

313 IRA PCI only 314 FFR guided complete revascularisation

(>50% stenosis in non IRA > 2 mm suitable for PCI)

DANAMI3-TRIAL PROGRAM

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313 Received allocated intervention 0 Did not receive allocated intervention

294 Received allocated intervention 15 PCI failed or not feasible1 Died before PCI2 Refused subsequently 2 Other reasons

313 Analysed on intention to treat basis0 Lost to follow up

314 Analysed on intention to treat basis1 Lost to follow up (emigration)

627 Multivessel disease

313 IRA PCI only 314 FFR guided complete revascularisation

(>50% stenosis in non IRA > 2 mm suitable for PCI)

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313 Received allocated intervention 0 Did not receive allocated intervention

294 Received allocated intervention 15 PCI failed or not feasible1 Ded before PCI2 Refused subsequently 2 Oher reasons

313 Analysed on intention to treat basis0 Lost to follow up

314 Analysed on intention to treat basis1 Lost to follow up (emigration)

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Primary endpoint

CompositeAll-cause mortalityNonfatal myocardial infarctionIschemia driven revascularisation of non IRA lesions

Assessed when the last included patient hadbeen followed for 1 year

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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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) <0·0001

Fluoroscopy dose (Gycm2) 49 (33 – 74) 77 (52 – 115) <0·0001Number of arteries treated per patient 1 (1–2) 2 (1–3) <0·0001Number of implanted stents 1 (1–1) 2 (1–3) <0·0001Stent diameter (mm) 3·5 (2·75–3·5) 3·0 (2·75–3·5) 0·005Total stent length (mm) 18 (15–28) 33 (18–51) <0·0001Stent 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%) 0·4Use of Bivalirudin 234 (75%) 237 (76%) 0·8

Procedural data

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IRA only(n = 313)

Complete revascularisation

(n = 314)P

Left ventricular ejection fraction 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

Time to staged PCI N/A 2 (2-4) N/A

Clinical characteristics

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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 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

Medical theraphy at discharge

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IRA only(n = 313)

Complete revascularisation

(n = 314)P

Periprocedural myocardial infarction 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

Complications

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Primary endpoint

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Individual components of primary endpoint

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Composite

Non fatal MI All cause death

Revascularisation

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%) 15 (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

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* PCI or CABG

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EndpointsEv

ent r

ate

(%) 68

40

27

11 15 1516

52

817

9 5

2520

7

18

p=0.004

p=0.43 p=0.87

p<0.001

p=0.29

p=0.47

p=0.03

p=0.002

Subgroup analysis

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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) 0.5121 20 0.75 (0.31 – 1.8)

339 55 0.33 (0.18 – 0.60) 0.02288 53 0.89 (0.52 – 1.5)

556 94 0.56 (0.37 – 0.85) 1.071 14 0.55 (0.17 – 1.7)

410 72 0.67 (0.42 – 1.1) 0.2217 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

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 After PPCI

Age 62 years 65 years 64 years

Bivalirudin or GPIIB/IIIA 79% 83% 97%

Contemporary randomised trials

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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%(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

Contemporary randomised trials

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Conclusions

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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 revascularisationsand not by hard endpoints

Therefore, although complete revascularisation should be recommended, any conditionthat makes complex PCI unattractive may support a more conservative strategi of IRAPCI only