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Cardiovascular disease Perinatal disease Coronary heart disease Stroke Other disease heart Injuries Cancer COPD HIV Other causes... GISSI CASS procedure Julian Gibbon 1972 NHBPEP

Cardiovascular disease

Perinatal disease

Coronary heart disease Stroke Other disease heart

Injuries Cancer COPD HIV Other causes

GISSI CASS

procedure (Julian)

(Gibbon)

1972 NHBPEP

1979 Coronary angioplasty developed (Grüntzig)

2007 Benefit of cardiac resyn- chronization therapy in heart failure demonstrated

2002 Efficacy of drug-eluting

vs bare- metal stents determined

2002 ALLHAT

1992 SAVE

1993 Superiority of primary PCI vs

fibrinolysis in acute MI noted

1985 TIMI 1

1986

1983

and ISIS-2

1985 NCEP

1980 First implantable cardioverter-defibrillator developed (Mirowski)

1969 First description

of CABG (Favaloro)

1976 First HMG CoA reductase inhibitor described (Endo)

1962

1958 Coronary

arteriography

Developed

(Sones)

1961 Risk factors defined

in early-onset

MI described

2009 Deep gene sequencing for responsiveness

to cardiovascular drugs performed

2009 Left-ventricular assist device as destination therapy

in advanced heart failure shown

to be effective

2009 Genome wide association

Foam

Cells Fatty Streak Intermediate Lesion Atheroma Fibrous Plaque Complicated Lesion/Rupture

Endothelial Dysfunction

Smooth muscle and collagen

From first decade From third decade From fourth decade

Adapted from Stary HC et al Circulation 1995;92:1355-1374

UA/NSTEMI

Acute Coronary Syndromes

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Before Infarct After Infarct

Lost Muscle

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–  –  –  – 

APEX-MI Prim PCI n=2,885

GISSI-1

SK n=5,860

ISIS-2

SK + Aspirin n=4,292

GUSTO-1 tPA n=10,396

HORIZONS -AMI n=3,340

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In-HospitalThrombolysis : Clinical Outcomes

Keeley and Grines Lancet 2003

Non-fatal Myocardial Infarction

Recurrent Ischemia Death,Reinfarction, Non-fatal

orStroke

Long-Term Outcomes Short-Term Outcomes

-

Haemorrhagic Stroke

-

Major Bleed

PTCA Thrombolytic therapy

Death Death,

Excluding SHOCKData

Non-fatal Myocardial Infarction

Recurrent Ischemia Stroke Total Haemorrhagic Stroke Major Bleed Death,Reinfarction, Non-fatal

orStroke

On-Site Thrombolysis vs Transfer for PCI

Myocardial Infarction

Total Stroke Haemorrhagic

Stroke

Death, Non-fatal Reinfarction or Stroke

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Do whatever it takes to reduce time

from symptom onset to ER arrival and

time from ER arrival to PCI!

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1.5 0.5

Bare metal stents 2.9%

2.0%

3.1%

Balloon angioplasty 3.0%

2.2%

5.1%

P Value

0.83 0.61 0.0001

RR [95% CI]

0.97 [0.74, 1.27]

0.92 [0.66, 1.27]

0.60 [0.47, 0.77]

<0.0001

0.98 [0.79, 1.10]

0.94 [0.74, 1.20]

0.62 [0.55, 0.69]

De Luca G et al Int J Cardiol 2007;119:306-9

>2 years 0-1 year 1-2 years

>2 years 0-1 year 1-2 years

>2 years 0-1 year 1-2 years

>2 years

HR (95%CI)*

0.93 (0.70-1.22) 0.58 (0.37-0.93) 0.93 (0.65-1.33) 0.85 (0.63-1.16) 1.34 (0.81-2.23) 2.06 (1.22-3.49) 0.90 (0.66-1.23) 1.38 (0.70-2.71) 2.81 (1.28-6.19) 0.48 (0.41-0.58) 0.66 (0.49-0.87) 0.93 (0.62-1.38)

p-value

0.14 0.23 0.18 0.31 0.25

0.03

0.52 0.35

0.04

<0.001 0.01

0.71

DESERT: Pooled pt-level meta-analysis from 11

N=6,298; mean FU 1201 ± 440 days

Cox models with piecewise time-constant regression coefficients

De Luca G et al. Arch Intern Med. 2012;172:611-21

*HR for DES

Vs BMS

Kolandaivelu K et al. Circulation 2011;123:1400-09

Stent Thrombosis is Affected by Stent

Impact of Xience / Promus polymer coating

In vitro pulsatile Chandler loop model with porcine blood

Sabate M et al Lancet 2012;380:1482–90

Meta-analysis of IV vs IC Bolus Abciximab (+ 12° Infusion) During Primary PCI in STEMI

6 RCTs, 1246 total pts randomized

30-Day Mortality

Study or Subgroup

Intracoronary abciximab Events N

Intravenous abciximab Events N Weight

Favors IC

0.69 (0.22, 2.19) 0.29 (0.01, 7.59) Not estimable Not estimable 0.20 (0.04, 0.92) 0.66 (0.11, 4.05) 0.43 (0.20, 0.94)

Odds Ratio M-H, Fixed 95% CI

Favors IV

0.01 0.1 1 10 100

Test for overall effect: Z=2.11 (P=0.03)

Navarese EP et al Platelets 2011:On-line

F.VandeWerf,ACC2013

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artery

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Reperfusion/

p=0.053

p=0.09 p=0.07

Fibrin Platelets p=0.02

Heparin

Thrombin

Fibrin Thrombus

Platelet aggregation

AT

Clopidogrel Prasugrel Ticagrelor Cangrelor

Eptifibatide Abciximab Tirofiban

Xa

Enoxaparin

Fibrinogen Fibrinolytics

Tissue factor

Plasma clotting cascade

AT

Prothrombin Factor

TRA

Platelet activation

Current Standard of Care in ACS

Ÿ Clopidogrel2 or prasugrel3 or ticagrelor4

Ÿ Fondaparinux6 or enoxaparin7 or UFH8 or bivalirudin9

1.AntithromboticTrialists’Collaboration.BMJ.2002;324:71;2.Yusufetal.N Engl J Med.2001;345:494;

3.Wiviottetal.N Engl J Med 2007;357:2001–2015;4.Wallentinetal.NEnglJMed2009;361:1–13;

5.GiulianoNEnglJMed2009;360:2176–90;6.YusufNEnglJMed2006;354.andJAMA 2006;295:

(doi:10.1001/jama.295.13.joc60038);7/8.Hamm&Bassand.EurHeartJ2011;doi:10.1093/eurheartj/ehr236;

9.StoneNEnglJMed2008;358:2218–30andNEnglJMed2006;355:2203–16

Novel Anticoagulants: Prime Time?

HR (95% CI)

ATLASACS2-TIMI51dataisforrivaroxaban2.5mgBIDinStratum2(backgroundaspirin+thienopyridine);notapprovedforuseintheUS

ARDsareapproximatelyperyear

0.79 (0.69 - 0.91) 0.62 (0.47 - 0.82)

0.84 (0.75 - 0.95) 0.92 (0.75 - 1.12)

0.75 (0.59 - 0.95) 0.63 (0.41 - 0.98)

Non-Surgical Major Bleeds:

PLATOInvestigators.NEJM2009;ATLASACS2-TIMIInvestigators.NEJM2012

Coagulation activation and long-term outcome

in ACS: Risk for developing primary events

ArdissinoDetal.Blood2003;102:2731–2735

Modified from: Ptaszek, et al Lancet

ICM

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Regression

Temporal Patterns of DES Failure and

30.3 17.4

11.9 20.4

63.0 52.6

64.5 78.7

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Reperfusion/

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