Bunyad Haider, M.D.FACC;FACP Professor and Chairman Dept of Medicine UMDNJ-New Jersey Medical School...
-
Upload
alexander-golden -
Category
Documents
-
view
227 -
download
0
Transcript of Bunyad Haider, M.D.FACC;FACP Professor and Chairman Dept of Medicine UMDNJ-New Jersey Medical School...
Bunyad Haider, M.D.FACC;FACP
Professor and ChairmanDept of Medicine
UMDNJ-New Jersey Medical School
Coronary Artery DiseaseCoronary Artery DiseaseEvolving Management StrategiesEvolving Management StrategiesMedicate, Dilate, or Operate?Medicate, Dilate, or Operate?
CV disease: US prevalenceCV disease: US prevalence
American Heart Association. Heart Disease and Stroke Statistics—2007 Update.
Myocardial ischemia 37 million*
Acute MI 865,000/year
Heart failure
5 million
Peripheral vascular disease
8 million
Stroke5.7 million
Chest Pain
4.2 million emergency visits/year6.4 million outpatient visits/year
*Symptomatic coronary artery disease (CAD) or angina pectoris.
3.1 mm3.1 mm
3.1 mm3.1 mm
Angiography Cannot Detect Coronary RemodelingAngiography Cannot Detect Coronary RemodelingIntravascular Ultrasound (IVUS) Necessary
Coronary Artery Disease is Coronary Artery Disease is Caused by Caused by
AtherothrombosisAtherothrombosis Inflammation Lipid accumulation Cell proliferation Cell death & Thrombosis
The result is obstruction of thecoronary arteries
III.2© 2002 PPS®
C
MMP-9MMP-9
Atherosclerosis: An Inflammatory Atherosclerosis: An Inflammatory Disease with or without infectionDisease with or without infection
Preventing CADPreventing CAD1. 1. Preventing endothelial
dysfunction
Focus on risk factors that activate the endothelium
Environmental FactorsDiet/Exercise/Drugs
Genetics
Aging
Smoking Gender
Hypertension
Thrombosis
Arteriothrombotic Risk Factors are additiveArteriothrombotic Risk Factors are additiveas each activates endothelial cellsas each activates endothelial cells
GoalGoal
Treat risk factors that activate endothelium(most risk factors for CAD)
andTreat dyslipidemia
Is Statin Therapy Alone Is Statin Therapy Alone Optimal?Optimal?
25 studies (19 placebo controlled randomized trials) of 69,511 subjects
Statin therapy reduced all-cause mortality by 16%
Statin therapy reduced CHD mortality by 23%
Wilt et al. Arch Internal Medicine 2003; 164: 1427
Solutions?Solutions?
The LDL-C goal should be even lower We need to treat high triglycerides
and low HDL more aggressively We need to decrease atherogenic
chylomicrons We need to treat non-lipid risk
factors (including CRP) more aggressively
All of the above!
Log-linear relationship between LDL-C levels Log-linear relationship between LDL-C levels and relative risk for CHDand relative risk for CHD
RelativeRisk for
CoronaryHeart
Disease
3.7
2.9
2.2
1.7
1.3
1.0
40 70 100 130 160 190
LDL-Cholesterol (mg/dL)
NCEP Report Circulation; 2004: 110:227-239
Statin Titration Yields MinimalStatin Titration Yields MinimalIncremental LDL-C Reduction Incremental LDL-C Reduction
Starting Dose of Statin
1st
Doubling2nd
Doubling3rd
Doubling
20%-46% 3-7% 3-7% 3-7%
20%-46% 18-21%
Ezetemide
Percent LDL-Cholesterol Reduction
Contraversis Surrounds Heart DrugContraversis Surrounds Heart Drug
ENHANCE Effects of Ezetimibe plus
Simvastatin Versus Simvastatin alone in Atheroscelero Carotid
ArteryJAMA ,2 2008
PCI vs. Medical Therapy PCI vs. Medical Therapy for Coronary Artery for Coronary Artery
DiseaseDiseaseSTEMI: STEMI: Primary PCI vs. Primary PCI vs.
thrombolysisthrombolysis
NTEMI and UAP: NTEMI and UAP: Early invasive Early invasive
approach vs. conservative careapproach vs. conservative care
Stable CAD: Stable CAD: PCI + OMT vs. OMTPCI + OMT vs. OMT
AMI: PathophysiologyAMI: Pathophysiology
Ruptured plaque with Ruptured plaque with occlusive thrombusocclusive thrombus
23 Randomized Trials of PCI vs. Lysis23 Randomized Trials of PCI vs. Lysis23 Randomized Trials of PCI vs. Lysis23 Randomized Trials of PCI vs. Lysis
p=0.0002 p=0.0003
N = 7,739N = 7,739
Keeley, Grines. Keeley, Grines. LancetLancet 2003;361:13-20 2003;361:13-20
23 Randomized Trials of PCI vs. Lysis23 Randomized Trials of PCI vs. Lysis23 Randomized Trials of PCI vs. Lysis23 Randomized Trials of PCI vs. Lysis
P<0.0001P<0.0001
N = 7,739N = 7,739
Keeley, Grines. Keeley, Grines. LancetLancet 2003;361:13-20 2003;361:13-20
P<0.0001P<0.0001
p=0.0002p=0.0002
26%41%
60%57%
0%
20%
40%
60%
80%
100%
STOPAMI-I STOPAMI-2
Myo
card
ial s
alva
ge
(% L
V m
yoca
rdiu
m)
t-PA +- Abcx Stent/Abcx
The STOPAMI TrialsThe STOPAMI Trials
Schomig A et al. Schomig A et al. NEJMNEJM and and LancetLancet
STOPAMI-I:STOPAMI-I: 140 pts with AMI rand. to acc t-PA v. stent/abcx 140 pts with AMI rand. to acc t-PA v. stent/abcx
STOPAMI-II:STOPAMI-II: 162 AMI pts rand. to acc t-PA/abcx v. stent/abcx 162 AMI pts rand. to acc t-PA/abcx v. stent/abcx
P<0.001P<0.001 P=0.001P=0.001
ACS: PathophysiologyACS: Pathophysiology
Ruptured plaque with subocclusive thrombusRuptured plaque with subocclusive thrombus
Proceed to diagnostic angiography
UA/NSTEMI diagnosis is likely or definite: Initiate ASA (I:A) or clopidogrel if ASA intolerant (I:A)
Invasive strategy selectedInitiate anticoagulant Rx (I:A)
Acceptable options: Enoxaparin or UFH (I:A) Bivalirudin or fondaparinux (I:B)
Prior to angiographyInitiate ≥1 (I:A) or both (IIa:B) Clopidogrel*, IV GP IIb/IIIa inhibitor*
ACC/AHA 2007: UA/NSTEMI guidelines: ACC/AHA 2007: UA/NSTEMI guidelines: Initial invasive strategy algorithmInitial invasive strategy algorithm
Anderson JL et al. J Am Coll Cardiol. 2007;50:652-726.
*GP IIb/IIIa inhibitor may not be needed if patient received preloading dose of ≥300 mg clopidogrel ≥6 hr earlier (I:B) plus bivalirudin (IIa:B)
(Class: Level of evidence)
Factors favoring administration of both: Delay to angiography · High-risk features · Early recurrent ischemic discomfort
Initiate clopidogrel (I:A) Consider adding IV eptifibatide or tirofiban (IIb:B)
(Continued)
ACC/AHA 2007: UA/NSTEMI guidelines: ACC/AHA 2007: UA/NSTEMI guidelines: Initial conservative strategy algorithmInitial conservative strategy algorithm
Anderson JL et al. J Am Coll Cardiol. 2007;50:652-726.
Conservative strategy selectedInitiate anticoagulant Rx (I:A)
Acceptable options: Enoxaparin or UFH (I:A) or fondaparinux (I:B), but enoxaparin or fondaparinux are preferable (IIa:B)
UA/NSTEMI diagnosis is likely or definite: Initiate ASA (I:A) or clopidogrel if ASA intolerant (I:A)
UFH = unfractionated heparin
Mehta SR et al. Mehta SR et al. JAMAJAMA 2005;293:2908-2917 2005;293:2908-2917
Composite of Death or Myocardial InfarctionNo./Total (%)
SourceSourceRoutine Routine invasiveinvasive
Selective Selective invasiveinvasive
TIMI IIIBTIMI IIIB 86/740 (11.6)86/740 (11.6) 101/733 101/733 (13.8)(13.8)
VANQWISVANQWISHH
152/462 152/462 (32.9)(32.9)
139/458 139/458 (30.3)(30.3)
MATEMATE 16/111 (14.4)16/111 (14.4) 11/90 (12.2)11/90 (12.2)
FRISC IIFRISC II 127/1222 127/1222 (10.4)(10.4)
174/1235 174/1235 (14.1)(14.1)
TACTICSTACTICS 81/1114 (7.3)81/1114 (7.3) 105/1106 105/1106 (9.5)(9.5)
VINOVINO 4/64 (6.3)4/64 (6.3) 15/67 (22.4)15/67 (22.4)
RITARITA 95/895 (10.6)95/895 (10.6) 118/915 118/915 (12.9)(12.9)
TotalTotal 561/4608 561/4608 (12.2)(12.2)
663/4604 663/4604 (14.4)(14.4)
Odds Ratio (95% Cl)
Favors RoutineInvasive
Favors SelectiveInvasive
OR, 0.82[0.72-0.93]
P<0.001
0.1 1.0 10
Meta-analysis of Conservative vs. Meta-analysis of Conservative vs. Invasive Strategies in ACSInvasive Strategies in ACS
9,212 randomized pts in 7 trials9,212 randomized pts in 7 trialsComposite death or MI from rand to latest FUComposite death or MI from rand to latest FU
18%18%
Stable Coronary Artery Stable Coronary Artery DiseaseDiseaseFibrotic plaqueFibrotic plaque
• ““Prior studies have shown only that PCI Prior studies have shown only that PCI decreases the frequency of angina and decreases the frequency of angina and improves short-term exercise performance”improves short-term exercise performance”
Boden WE et al. Boden WE et al. NEJMNEJM 2007;356:1503-16 2007;356:1503-16
First coronary angioplasty lesion (circles) two First coronary angioplasty lesion (circles) two days before (A),days before (A),
immediately after (B), and one month after (C) immediately after (B), and one month after (C) balloon dilationballoon dilation
The First Coronary AngioplastyThe First Coronary Angioplasty for Stable CAD; for Stable CAD; Sept. 16Sept. 16thth, 1977, 1977
DRUG ELUTING CORONARY DRUG ELUTING CORONARY STENTSSTENTS
Cypher(sirolimus)Taxus(paclitaxel)
Xience( everolimus)Endeaver(zotarolimus)
COURAGE: COURAGE: CClinicallinical OOutcomesutcomes UUtilizingtilizing
RRevascularizationevascularization and and AAggressive ggressive GGuideline-uideline-
DrivenDriven Drug Drug EEvaluationvaluation
Boden W et al. NEJM 2007;356:1503-16.
In pts with stable CAD (symptomatic and In pts with stable CAD (symptomatic and
asymptomatic), PCI + Optimal Medical asymptomatic), PCI + Optimal Medical
Therapy will Therapy will reduce death and nonfatal MI reduce death and nonfatal MI
compared to Optimal Medical Therapy compared to Optimal Medical Therapy
alonealone
HypothesisHypothesis
““Thus, the long-term prognostic effect of PCI on Thus, the long-term prognostic effect of PCI on cardiovascular events in pts with stable coronary cardiovascular events in pts with stable coronary
artery disease remains uncertain” (!)artery disease remains uncertain” (!)
Background: Background: Conventional WisdomConventional Wisdom
Boden WE et al. NEJM 2007;356:1503-16Boden WE et al. NEJM 2007;356:1503-16
COURAGE: Background COURAGE: Background and rationaleand rationale
Elective PCI procedures are common in the US (~ 85% of patients)
PCI decreases angina frequency but long-term prognostic effects on CV events are not known
Antianginal agents also provide symptom relief
ACEIs, ASA, β-blockers, and statins have been shown to prevent MI and death
Boden WE et al. N Engl J Med. 2007;356.Boden WE et al. Am Heart J. 2006;151:1173-9.
COURAGE was designed to evaluate whether PCI plus optimal medical therapy reduces risk of major CV events compared with
optimal medical therapy alone in stable CAD patients
In patients with stable CAD
Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation
COURAGE: Study designCOURAGE: Study design
Boden WE et al. N Engl J Med. 2007;356.
Optimal medical therapy* + PCI (n = 1149)
Optimal medical therapy(n = 1138)
AHA/ACC Class I/II indications for PCI, suitable coronary artery anatomyand
≥70% stenosis in ≥1 proximal epicardial vessel + objective evidence of ischemia or
≥80% stenosis + class III angina without provocation testing
Primary outcome:All-cause mortality, nonfatal MI
Follow-up: Median 4.6 years
Randomized
*Intensive pharmacologic therapy + lifestyle intervention
Key Inclusion and Exclusion Key Inclusion and Exclusion CriteriaCriteria
Inclusion criteriaInclusion criteria
1, 2, or 3 vessel disease (>70% visual stenosis of 1, 2, or 3 vessel disease (>70% visual stenosis of proximal coronary segment) amenable to PCIproximal coronary segment) amenable to PCI
CCS Class I-III angina (or asymptomatic)CCS Class I-III angina (or asymptomatic)
Objective evidence of ischemia Objective evidence of ischemia
ACC/AHA Class I or II indication for PCIACC/AHA Class I or II indication for PCI
ExclusionsExclusions
Uncontrolled unstable angina or complicated post-MIUncontrolled unstable angina or complicated post-MI
Revascularization within 6 monthsRevascularization within 6 months
Ejection fraction <30% or cardiogenic shock/severe HFEjection fraction <30% or cardiogenic shock/severe HF
Boden WE et al. NEJM 2007;356:1503-16Boden WE et al. NEJM 2007;356:1503-16
Number at RiskMedical Therapy 1138 1017 959 834 638 408 192 30PCI 1149 1013 952 833 637 417 200 35
Years0 1 2 3 4 5 6
0.0
0.5
0.6
0.7
0.8
0.9
1.0
PCI + OMT
Optimal Medical Therapy (OMT)
Hazard ratio: 1.05Hazard ratio: 1.0595% CI (0.87-1.27)95% CI (0.87-1.27)
P = 0.62P = 0.62
7
Survival Free from Death and Survival Free from Death and MI MI (mean FU 4.6 (mean FU 4.6
yrs); N=2,287 yrs); N=2,287
Fre
edo
m f
rom
De
ath
or
MI (
%)
Death/MIat 4.6 yrs
19.0%18.5%
Boden WE et al. NEJM 2007;356:1503-16Boden WE et al. NEJM 2007;356:1503-16
COURAGE: Summary and COURAGE: Summary and implicationsimplications
PCI added to optimal medical therapy did not reduce risk of death, MI, or other major CV events compared to optimal medical therapy alone
Findings reinforce existing clinical practice guidelines PCI can be safely deferred if intensive medical therapy
is instituted and maintained
Some patients (~1/3) may require eventual revascularization
Initial management approach for many patients includes lifestyle modification + pharmacologic therapy
Boden WE et al. N Engl J Med. 2007;356.
In patients with stable CAD
Angina/QOL at 1 Year: Med Rx Angina/QOL at 1 Year: Med Rx vs. PCIvs. PCI
TrialTrial QOLQOL AnginaAngina ETTETT
ACMEACME PCI PCI betterbetter
PCI PCI betterbetter
PCI PCI betterbetter
ACME 2ACME 2 MASSMASS PCI PCI
betterbetter
ACIPACIP PCI PCI betterbetter
PCI PCI betterbetter
RITARITA 22 PCI PCI betterbetter
PCI PCI betterbetter
AVERTAVERT PCI PCI betterbetter
PCI PCI betterbetter
PCI PCI betterbetter
MASS IIMASS II PCI PCI betterbetter
PCI PCI betterbetter
TIMETIME PCI PCI betterbetter
PCI PCI betterbetter
PCI PCI betterbetter
8 prior randomized 8 prior randomized trialstrials
Does COURAGE Represent PCI in Does COURAGE Represent PCI in the United States?the United States?
962,732(98.5%)
14,268(1.5%)
Canada US VA US non VA
Boden WE et al. NEJM 2007;356:1503-Boden WE et al. NEJM 2007;356:1503-1616
*US data of file, Boston Scientific*US data of file, Boston Scientific
::COURAGE Projections: COURAGE Projections: 3-year death/MI3-year death/MI
21% (OMT) 21% (OMT) vs. vs. 16.4% (PCI + OMT) 16.4% (PCI + OMT) (22%↓)(22%↓)D
ea
th/M
I (%
) at
4.6
D
ea
th/M
I (%
) at
4.6
y
ears
yea
rs
29%↓29%↓27%↑27%↑
P≈0.02
Boden WE et al. Boden WE et al. NEJMNEJM 2007;356:1503-16 2007;356:1503-16
Co
mp
lete
Co
mp
lete
rev
asc
ula
riza
tio
nre
vas
cu
lari
zati
onP
eri-
PC
IP
eri-
PC
IM
IsM
IsPCI OutcomesPCI Outcomes
1149 patients total1149 patients total
46 (4%) procedure not attempted46 (4%) procedure not attempted27 (2%) no lesions crossed27 (2%) no lesions crossed
1077 patients (94%) had PCI attempted1077 patients (94%) had PCI attempted
1577/1688 lesions had PCI success (93%)1577/1688 lesions had PCI success (93%)
Few PCI pts received GPIIb/IIIa inhibitors Few PCI pts received GPIIb/IIIa inhibitors or adequate clopidogrel pre-loadingor adequate clopidogrel pre-loading
787 patients (69%) had 2 or 3 vessel ds.787 patients (69%) had 2 or 3 vessel ds.590 pts (59%) received 1 stent590 pts (59%) received 1 stent
416 pts (41%) received ≥2 stents416 pts (41%) received ≥2 stentsAt least 371 of 787 pts (47%) with multivessel At least 371 of 787 pts (47%) with multivessel
disease had incomplete revascularization disease had incomplete revascularization
14% PTCA14% PTCAonlyonly
86% stents86% stents97% BMS97% BMS3% DES3% DES
Really Really ~85%~85%
PC
I su
cces
sP
CI s
ucc
ess
COURAGE MethodologyCOURAGE Methodology Patients were randomized in COURAGE Patients were randomized in COURAGE
after diagnostic angiographyafter diagnostic angiography Many patients with severe disease who Many patients with severe disease who
might have benefited were undoubtedly might have benefited were undoubtedly excludedexcluded
and thusand thus
The results of COURAGE The results of COURAGE don’t implydon’t imply that that patients with angina and/or inducible patients with angina and/or inducible ischemia should be managed medically, ischemia should be managed medically, without diagnostic angiography!without diagnostic angiography!
Original Article Long-Term Outcomes with Drug-Eluting Stents
versus Bare-Metal Stents in Sweden
Bo Lagerqvist, M.D., Ph.D., Stefan K. James, M.D., Ph.D., Ulf Stenestrand, M.D., Ph.D., Johan Lindbäck, M.Sc., Tage Nilsson, M.D., Ph.D., Lars Wallentin, M.D., Ph.D.,
for the SCAAR Study Group
N Engl J MedVolume 356(10):1009-1019
March 8, 2007
DES vs BMS: Effect on death or DES vs BMS: Effect on death or MIMI
Lagerqvist B et al. N Engl J Med. 2007;356:1009-19.
Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
Curve is an estimation from Cox regression model at mean level of the propensity score
No. at riskBare-metal stent (BMS)Drug-eluting stent (DES)
70
2963580
55201608
86653216
11,4325158
11,7065307
12,8805770
Adjustedcumulative
risk of death or MI
0.10
0.15
0.05
0.000.0 0.5 1.0 1.5 2.0 2.5 3.0
Years
DESBMS
0.20
Landmark analysis: Effect Landmark analysis: Effect on deathon death
Lagerqvist B et al. N Engl J Med. 2007;356:1009-19.
Propensity score-adjusted cumulative event rates at the mean level of the propensity score
Risk assessed during and after the prespecified 6-month landmark
RR: 1.03 (0.84–1.26)
RR: 1.32 (1.11–1.57)
0.06
0.04
0.02
0.000.0 0.5 1.0 1.5 2.0 2.5 3.0
Years
DES
BMS
0.10
0.08
Adjustedcumulative
risk of death
ConclusionConclusion Drug-eluting stents were associated
with an increased rate of death, as compared with bare-metal stents
This trend appeared after 6 months, when the risk of death was 0.5 percentage point higher and a composite of death or myocardial infarction was 0.5 to 1.0 percentage point higher per year
The long-term safety of drug-eluting stents needs to be ascertained in large, randomized trials
Original Article A Pooled Analysis of Data Comparing Sirolimus-
Eluting Stents with Bare-Metal Stents
Christian Spaulding, M.D., Joost Daemen, M.D., Eric Boersma, Ph.D., Donald E. Cutlip, M.D., and Patrick W. Serruys, M.D., Ph.D.
N Engl J MedVolume 356(10):989-997
March 8, 2007
Study OverviewStudy Overview Patients in four randomized trials
comparing sirolimus-eluting coronary-artery stents and bare-metal stents were included in a pooled analysis
ConclusionConclusion Stent thrombosis after 1 year was
more common with both sirolimus-eluting stents and paclitaxel-eluting stents than with bare-metal stents
Both drug-eluting stents were associated with a marked reduction in target-lesion revascularization
There were no significant differences in the cumulative rates of death or myocardial infarction at 4 years
Original Article Drug-Eluting Stents vs. Coronary-Artery Bypass
Grafting in Multivessel Coronary Disease
Edward L. Hannan, Ph.D., Chuntao Wu, M.D., Ph.D., Gary Walford, M.D., Alfred T. Culliford, M.D., Jeffrey P. Gold, M.D., Craig R. Smith, M.D., Robert S.D. Higgins, M.D.,
Russell E. Carlson, M.D., and Robert H. Jones, M.D.
N Engl J MedVolume 358(4):331-341
January 24, 2008
Study OverviewStudy Overview.In this New York State registry study,
outcomes of patients with multivessel coronary disease treated with drug-eluting coronary stents or coronary-artery bypass grafting (CABG) were compared during 18 months of follow-up
The rates of death, death or myocardial infarction, and repeat revascularization were consistently lower after CABG than after treatment with drug-eluting stents
ConclusionConclusion For patients with multivessel disease,
CABG continues to be associated with lower mortality rates than does treatment with drug-eluting stents and is also associated with lower rates of death or myocardial infarction and repeat revascularization