TOP Cardiovascular Trials in 2012

Worth to remember….

Leonardo Paskah Suciadi, MD

Cardiology & Vascular MedicineUniversitas Padjadjaran, Bandung-Indonesia

Lots of notably trials in CV through 2012 to be hot-button topics for upcoming years

So, what are the remarkable trials in 2012 in each subjects;Coronary artery diseaseHeart failureAtrial fibrillationHypertensionPreventive CV and LipidCardio-imagingInterventional cardiology

The remarkable studies in Coronary Artery Disease ??

Prasugrel in STEMI or low-moderate risk NSTEMI/UAP in conservative therapy ??

N Engl J Med 2012;367:1297-309.

TRILOGY-ACS TRIAL

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FIRST RANDOMISED TRIAL COMPARING TWO REGIMENS WITH AND WITHOUT ASPIRIN IN PATIENTS ON ORAL ANTICOAGULANT THERAPY UNDERGOING CORONARY

STENTING  

WOEST TRIAL

Dewilde W et al. EurHeartJour2012

The WOEST Trial= What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing 

Pts on oral anticoagulant will undergo PCI, still need to get TRIPLE th (OAC, ASA, CPG) ??

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AIM OF THE STUDY

To test the hypothesis that in patients on OAC undergoing

PCI, clopidogrel alone is superior to the combination aspirin

and clopidogrel with respect to bleeding but is not increasing

thrombotic risk in a multicentre two-country study (The

Netherlands and Belgium)

WOEST

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STUDY DESIGN

1:1 Randomisation:

Double therapy group:

OAC + 75mg Clopidogrel qd

1 month minimum after BMS

1 year after DES

Triple therapy group OAC + 75mg Clopidogrel qd + 80mg Aspirin qd

1 month minimum after BMS

1 year after DES

Follow up: 1 year

Primary Endpoint: The occurence of all bleeding events (TIMI criteria)

Secondary Endpoints: - Combination of stroke, death, myocardial infarction, stent thrombosis and target vessel revascularisation- All individual components of primary and secondary endpoints

WOEST

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Primary Endpoint: Total number of TIMI bleeding events

WOEST- RESULT

Days

Cu

mu

lati

ve in

cide

nce

of

blee

din

g

0 30 60 90 120 180 270 365

0 %

10 %

20 %

30 %

40 %

50 %

284 210 194 186 181 173 159 140n at risk: 279 253 244 241 241 236 226 208

Triple therapy groupDouble therapy group 44.9%

19.5%

p<0.001

HR=0.36 95%CI[0.26-0.50]

Secondary Endpoint (Death, MI,TVR, Stroke, ST)WOEST

Days

Cu

mu

lati

ve i

nci

den

ce

0 30 60 90 120 180 270 365

0 %

5 %

10 %

15 %

20 %

284 272 270 266 261 252 242 223n at risk: 279 276 273 270 266 263 258 234

17.7%

11.3%

p=0.025

HR=0.60 95%CI[0.38-0.94]

Triple therapy groupDouble therapy group

All-Cause Mortality

WOEST

Days

Cu

mu

lati

ve i

nci

den

ce o

f de

ath

0 30 60 90 120 180 270 365

0 %

2.5 %

5 %

7.5 %

284 281 280 280 279 277 270 252n at risk: 279 278 276 276 276 275 274 256

6.4%

2.6%

HR=0.39 95%CI[0.16-0.93]

p=0.027

Triple therapy groupDouble therapy group

WOEST

age75

male

t0acs

oacind3cat

des

Overall

FALSE

TRUE

no

yes

no

yes

AF/AFlut

Mechanical valve

Other

No

DES

200

79

50

234

195

86

162

25

47

90

194

284

194

82

65

214

207

69

164

24

48

94

184

279

0.9157

0.8217

0.721

0.1116

0.7761

0.7894

Factor

age

gender

ACS

indicationOAC

Stenttype

Overall

Group

<75 years

>75 years

female

male

no

yes

AF/AFlut

Mechanicalvalve

Other

BMS

DES

Triple

79

200

50

234

195

86

162

25

47

90

194

284

Double

82

194

65

214

207

69

164

24

48

94

184

279

P-value for interaction

0.9157

0.8217

0.7210

0.1116

0.7761

0.7894

Forest plot of primary endpoint Hazard Ratios

double therapy better <=> triple therapy better

0.1 0.4 1

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CLINICAL IMPLICATIONS

Researchers propose that a strategy of oral

anticoagulants plus clopidogrel, but without

aspirin could be applied in this group of high-risk

patients on OAC when undergoing PCI

WOEST

A RANDOMIZED COMPARISON OF RADIAL VS. FEMORAL ACCESS FOR CORONARY INTERVENTION IN ACS

(RIVAL STUDY)

SS Jolly, S Yusuf, J Cairns, K Niemela, D Xavier, P Widimsky, A Budaj, M Niemela, V Valentin, BS Lewis, A Avezum, PG Steg, SV Rao, P Gao, R Afzal, CD Joyner, S Chrolavicius, SR Mehta on behalf of the RIVAL investigatorsJolly SS et al. Am Heart J. 2011;161:254-60.

NSTE-ACS and STEMI(n=7021)

Radial Access(n=3507)

Femoral Access(n=3514)

Primary Outcome: Death, MI, stroke or non-CABG-related Major Bleeding at 30 days

Randomization

RIVAL STUDY DESIGN

Key Inclusion: •Intact dual circulation of hand required•Interventionalist experienced with both (minimum 50 radial procedures in last year)

Jolly SS et al. Am Heart J. 2011;161:254-60.

Blinded Adjudication of Outcomes

RIVAL study

RIVAL STUDY:CONCLUSION

No significant difference between radial and femoral access in primary outcome of death, MI, stroke or non-CABG major bleeding

Rates of primary outcome appeared to be lower with radial compared to femoral access in high volume radial centres and STEMI

Radial had fewer major vascular complications with similar PCI success

NEED ANTICOAGULANT IN RECENT ACS ??

ATLAS ACS 2-TIMI 51 trial

ATLAS ACS 2-TIMI 51 trial

What next in 2013??

More oral novel anticoagulant trials in ACS setting APPRAISE-2 trial (Apixaban)RE-DEEM trial (Dabigatran)

both are still ongoingASA ‘losses its teeth’ in ACS with some

clinical situations ?

What’s new issue in HEART FAILURE ??

WARCEF CLINICAL TRIALN Engl J Med 2012.

Is Warfarin or ASA indicated in HF pts with sinus rhythm ??

WARCEF trial

Other good news in HF issue:

the approval HeartWare Ventricular Assist System

What’s the hottest story in HYPERTENSION ??

SIMPLICITY-HTN2 TRIALRENAL NERVE DENERVATION

SIMPLICITY-HTN2 trial

What about in ATRIAL FIBRILLATION ??

WHAT’S NEXT IN 2013 FOR ATRIAL FIBRILLATION ??

Of course, there will be more and more trials about novel oral anticoagulants, including dabigatran and rivaroxaban

SAYONARA for aspirin ??

What ‘s the spotlight in Interventional cardiology ??

TRANSCATHETER AORTIC VALVE IMPLANTATION: NEW

DEVELOPMENTS AND UPCOMING CLINICAL TRIALS

AbstractTAVI is a relatively new technique that has been introduced to treat

inoperable and high-risk patients with severe aortic stenosis. From its early stages it became apparent that TAVI has tremendous potentialities and thus a considerable effort was made to design new prostheses and advance TAVI technology that would make easier and feasible its application in complex anatomies and in patients with multiple comorbidities. In addition, evidence from randomised control trials have emerged demonstrating that it improves prognosis in inoperable patients (PARTNER trial cohort B) and that it can be considered as an attractive alternative to surgery in patients with a high operative risk (PARTNER trial cohort A). These encouraging data have motivated the scientific community to organise further trials, which will examine the performance of new devices and explore the feasibility of TAVI in different groups.

Bourantas CV., et al. EuroIntervention. 2012 Sep;8(5):617-27. doi: 10.4244/EIJV8I5A94.

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EuroIntervention 2012;8:617-627 published online ahead of print May 2012

Transcatheter aortic valve implantation: new developments and upcoming clinical trials

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EuroIntervention 2012;8:617-627 published online ahead of print May 2012

Transcatheter aortic valve implantation: new developments and upcoming clinical trials

Don’t forget this; IABP-SHOCK II trial

N Engl J Med 2012. DOI: 10.1056/NEJMoa1208410

And then in Cardio-Imaging ??

HAS the CT-scan era of Triage of ACS in Emergency Room COME ??

ROMICAT II ACRIN-PA

Are there good news also in PREVENTIVE CV and DYSLIPIDEMIA ??

Low HDL is a CV risk factor. But what about strategy to increasing HDL level in high risk patients, is that really beneficial ??

Dal-OUTCOMES trial

That’s if we use DALCETRAPIB (CETP inhibitor). What if we use NIACIN to rise HDL up ??

The AIM-HIGH trial

SO, WHAT’RE WE LOOKING FORWARD TO IN TOPIC OF PREVENTIVE CV AND LIPID FOR THE UPCOMING YEAR??

We’r still looking forward to next ‘shocking’ study results in CV; However…………..