REVASCULARIZATION Vs MEDICAL THERAPY IN STABLE CAD Dr Binjo J Vazhappilly SR Cardiology MCH,...
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Transcript of REVASCULARIZATION Vs MEDICAL THERAPY IN STABLE CAD Dr Binjo J Vazhappilly SR Cardiology MCH,...
REVASCULARIZATION Vs MEDICAL THERAPY IN STABLE CAD
Dr Binjo J VazhappillySR Cardiology MCH , Calicut
Introduction
• Coronary artery disease remains the leading cause of mortality in industrialized countries.
• Majority of percutaneous coronary interventions are performed in pts with chronic stable coronary artery disease.
• Benefit of revascularization among patients with chronic stable CAD is debatable
Introduction
• There are 30 randomized trials comparing medical treatment with revascularization (PCI or CABG ) in pts with chronic stable CAD.
• CABG was applied as revascularization therapy in 13 trials, of which 6 were performed more than 2 decades ago.
• Balloon angioplasty alone was used in 8 studies
• Subsequent trials used stents , but DES implantation was negligible except for BARI-2D.
COURAGE: Clinical Outcomes Utilizing Revascularization and Aggressive Guideline-Driven Drug Evaluation
Hypothesis : PCI + Optimal Medical Therapy will be Superior to Optimal Medical Therapy Alone .
Study period : 1999 to 2004
Follow-up : 2.5 to 7.0 yrs (median, 4.6).
Primary Outcome : Death or non fatal MI
COURAGEInclusion Criteria :
1, 2 or 3 vessel disease ( >70% visual stenosis of proximal coronary segment) , Anatomy suitable for PCI , CCS Class I-III angina , Objective evidence of ischemia at baseline.
Exclusion criteria : Persistent CCS class IV angina Markedly positive stress test ( Stage 1 Bruce protocol +ve ) LMCA disease > 50% Refractory heart failure or cardiogenic shock EF less than 30% Revascularization within previous 6 months Coronary anatomy not suitable for PCI.
Enrollment
Enrollment and Outcomes
Baseline Clinical & Angiographic CharacteristicsCharacteristic PCI + OMT (N=1149) OMT (N=1138) P Value
CLINICAL
Stress test 0.84
Total patients - % 85 % 86 %
Treadmill test 57 % 57 % 0.84
Pharmacologic stress 43 % 43 %
Nuclear imaging - % 70 % 72 % 0.59
Single reversible defect 22 % 23 % 0.09
Multiple reversible defects
65 % 68 % 0.09
ANGIOGRAPHIC
Vessels with disease – % 0.72
1, 2, 3 31, 39, 30 % 30, 39, 31 %
Disease in graft 62 % 69 % 0.36
Proximal LAD disease 31 % 37 % 0.01
Ejection fraction 60.8 ± 11.2 60.9 ± 10.3 0.86
Baseline Clinical andAngiographic Characteristics
Characteristic PCI + OMT (N=1149)
OMT (N=1138) P Value
CLINICAL
History – %
Diabetes 32 % 35 % 0.12
Hypertension 66 % 67 % 0.53
CHF 5 % 4 % 0.59
Cerebrovascular disease
9 % 9 % 0.83
Myocardial infarction
38 % 39 % 0.80
Previous PCI 15 % 16 % 0.49
CABG 11 % 11 % 0.94
OUTCOMES
Need for Subsequent Revascularization
• At a median 4.6 yr follow-up, 21.1% of the PCI patients required an additional revascularization, compared to 32.6% of OMT group who required a 1st revascularization.
• 77 pts in the PCI group and 81 pts in OMT group required subsequent CABG surgery
• Median time to subsequent revascularization was 10.0 mo in the PCI group and 10.8 mo in the OMT group
Freedom from Angina During Long-Term Follow-up
Characteristic PCI + OMT OMT
CLINICAL
Angina free – no.
Baseline 12% 13%
1 Yr 66% 58%
3 Yr 72% 67%
5 Yr 74% 72%
The comparison between the PCI group and the medical-therapy group was significant at 1 year ( P<0.001) and 3 years (P=0.02) but not at baseline or 5 years.
Conclusions
• As an initial management strategy in pts with stable CAD , PCI did not reduce the risk of death, MI or other major CV events when added to OMT
• PCI resulted in better angina relief during most of the follow-up period, but medical therapy was also remarkably effective, with no difference in angina-free status at 5 yrs.
Limitations of COURAGE trial• Only 6.3 % of screened pts were randomized.
• Among 70% of pts assigned to PCI who had 2-vessel disease, only 36% received > 1 stent.
• Only 2.7% were treated with a DES.
• 32% of OMT patients crossed over to PCI.
• Excluded high risk patients.
• Post angiography selection bias.
Copyleft Clinical Trial Results. You Must Redistribute Slides
PCI Stratum (N= 1605)CABG Stratum (N= 763)
BARI 2D Trial: Study Design
OMT alone (N= 385)
CABG +OMT (N= 378)
2368 pts with mild to moderate CAD and Type 2 diabetes prior to randomization.
Study period : January 2001, to March 2005 Mean follow up : 5.3 yrs Primary Endpoint: Death (from any cause) Secondary Endpoint: Composite of Death, MI, or Stroke
R R
BARI 2D Study Group, NEJM 2009
OMT alone (N= 807)
PCI +OMT (N= 798)
BARI 2D
• Inclusion criteria: Diagnosis of both type 2 diabetes & CAD. CAD diagnosis by documented on angiography ( ≥50%
stenosis of a major epicardial coronary artery associated with a positive stress test or ≥70% stenosis of a major epicardial coronary artery and classic angina).
• Exclusion criteria : Pts requiring immediate revascularization or had left main
coronary disease Creatinine level > 2.0 mg per deciliter Glycated Hb > 13.0% Class III or IV heart failure or hepatic dysfunction Undergone PCI or CABG within the previous 12 months.
13.2% 13.5%
0%
5%
10%
15%
20%
Revasc. OMT
• The 5-year death rate for the group receiving revascularization plus optimal medical therapy was 13.2% vs. 13.5% in the group receiving optimal medical therapy alone.
• The difference between the two treatment groups did not reach statistical significance.
Dea
th (
%)
BARI 2D Trial: Primary Endpoint
n =155 n =161
p = 0.97
BARI 2D Study Group, NEJM 2009Copyleft Clinical Trial Results. You Must Redistribute Slides
Copyleft Clinical Trial Results. You Must Redistribute Slides
BARI 2D Trial: Secondary Endpoint
• The rates of MI, stroke and the combined secondary endpoint of death, MI and stroke were similar in 2 groups.
• The difference between the two treatment groups for the combined secondary endpoint of death, MI and stroke did not reach statistical significance (p=0.70)
10.0%
2.6%
22.6%
11.6%
2.8%
23.7%
0%
5%
10%
15%
20%
25%
MI Stroke Death/MI/StrokeRevasc. OMT
n=118
BARI 2D Study Group, NEJM 2009
Card
iova
scul
ar E
vent
(%)
n=138
n=30 n=33 n=266 n=283
Copyleft Clinical Trial Results. You Must Redistribute Slides
BARI 2D Trial
• Summary : Prompt coronary revascularization in pts who
had been treated with intensive medical therapy for diabetes
and stable ischemic disease did not significantly reduce rate
of death from any cause or major cardiovascular events.
• Limitations
Patients who are at high risk for MI revascularization
were excluded from the trial.
BARI 2D Study Group, NEJM 2009
MASS II Trial• Randomized Controlled Clinical Trial of therapeutic strategies for
multivessel CAD, stable angina and preserved ventricular function.• Study period : May 1995 and May 2000• Inclusion criteria: Pts with angiographically documented proximal
multivessel coronary stenosis of more than 70% by visual assessment and documented ischemia.
• Exclusion criteria: Unstable angina or acute MI , ventricular aneurysm requiring surgical repair, LVEF < 40% , history of PCI or CABG and single-vessel disease.
• Primary end point : cardiac mortality, Q-wave myocardial infarction (MI) or refractory angina requiring revascularization.
MASS 2 TRIAL
Hueb W, et al. J Am Coll CardioI 2004; 43:1743-51
1465 patients non-randomized:
Surgery(n=203)
Medical Treatment(n=203)
Angioplasty (n=205)
excluded 18.692 patients:coronary <70% lesion - 5192single coronary disease - 3531previous CABG/PCI - 2908valvar disease 2701other - 4361
refused to participate in this trial or refused the surgical procedure
Database: 20.769 coronary angiographies
Eligible: 2.076 patients(suitable to PCI-CABG)
MASS II Randomized: 611 patients
Demographic Profile
Male, (%)
Age (years) mean ± SD
Medical History
Previous MI (%)
Smoker (%)
Hypertension (%)
Diabetes mellitus (%)
CCS class 2 or 3 (%)
69
60±9
39
33
55
36
78
MT(n = 203)
72
61±8
41
32
63
29
85
CABG(n = 203)
67
60±4
52
27
60
26
76
PCI(n=205)Characteristic
0.412
0.959
0.024
0.013
0.215
0.062
0.006
P
Baseline Characteristics of MASS II
Overall Mortality-Free Survival
Ten-Year Follow-up Event-free Survival
CONCLUSION
• All three groups had similar rates of overall mortality.
• Compared with CABG, angioplasty was associated with elevated rate of myocardial infarction and need for revascularization.
• Medical therapy showed significant incidence of myocardial infarction and high rate of additional revascularization.
Limitations of MASS-II Trial
• Single center study
• Small number of subjects
• No DES usage
• Post-angiography selection bias
STICH TRIAL• Randomized controlled trial, non-blinded• Study period : July 2002 and May 2007 • A total of 1212 pts were randomly assigned to medical
therapy alone (602 patients) or medical therapy plus CABG (610 pts).
Primary Endpoint All-cause mortality
Major Secondary Endpoints Cardiovascular mortality Death (all-cause) + cardiovascular hospitalization
STICH TRIALInclusion criteria
Pts with coronary artery disease that was amenable to CABG and EF of 35% or less
Medical therapy eligible Absence of left main CAD as defined by an intraluminal stenosis
of ≥ 50% Absence of CCS III angina or greater (angina markedly limiting
ordinary activity)Exclusion criteria
• Recent acute MI (within 30 dys) ,Cardiogenic shock (within 72 hrs of randomization) , Plan for percutaneous intervention , Aortic valve disease requiring repair or replacement , Life expectancy of < 3 yrs .
STICH Revascularization HypothesisTreatment Per Protocol
Per protocol: MED (537) vs. CABG (555)
1212
RandomizedCABG
Randomized MED only
610602
Received MED only
Received CABG
555537 55 65
17% 9%
All-Cause Mortality — As Randomized
HR 0.86 (0.72, 1.04)
P = 0.123
Adjusted HR 0.82 (0.68, 0.99)
Adjusted P = 0.039
0.460.41
HR 0.81 (0.66, 1.00)
P = 0.050
Adjusted HR 0.77 (0.62, 0.94)
Adjusted P = 0.012
Cardiovascular Mortality— As Randomized
0.39
0.32
HR 0.74 (0.64, 0.85)
P < 0.001
Adjusted HR 0.70 (0.61, 0.81)
P < 0.001
Death or Cardiovascular Hospitalization — As Randomized
0.58
0.68
Stich trial : summary
No significant difference between the two study groups with respect to the primary end point of the rate of death from any cause.
The rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiac causes were lower among patients assigned to CABG than among those assigned to medical therapy.
FAME 2
• Trial was terminated early. Primary endpoint (death/ MI/ urgent revascularization) for PCI + OMT vs. OMT: 4.3% vs. 12.7%, HR 0.32, 95% CI 0.19-0.53, p < 0.001
• Mortality: 0.2% vs. 0.7%, p = 0.31; MI: 3.4% vs. 3.2%, p = 0.89; urgent revascularization: 1.6% vs. 11.1%, p < 0.001
• Highest benefit if lesion FFR <0.65
Trial design: Patients with stable angina who were appropriate candidates for PCI and had a fractional flow reserve (FFR) value ≤0.80 were randomized to either PCI + optimal medical therapy (OMT) or OMT alone. Patients were followed for a mean of 7 months.
Results
Conclusions
De Bruyne B, et al. N Engl J Med 2012;367:991-1001
(p < 0.001)
PCI + OMT(n = 447)
Primary endpoint• FFR-guided PCI + OMT was superior to OMT in patients
with stable angina, mainly due to a reduction in need for urgent revascularization
• These results suggest that a positive FFR may be a good method to risk stratify these patients
0
50
100
%
4.312.7
(p < 0.001)
1.611.1
50
Urgent revascularization
OMT(n = 441)
0
100
%
Meta-Analysis of Randomized clinical trials
Risk of all-cause mortality
Circ Cardiovasc Interv. 2012;5:476-490
Risk of cardiac death
Circ Cardiovasc Interv. 2012;5:476-490
Risk of revascularization
Circ Cardiovasc Interv. 2012;5:476-490
Freedom from angina
Circ Cardiovasc Interv. 2012;5:476-490
Conclusions
• Pts with stable CAD there is no definitive evidence of an added benefit of PCI to reduce risk of mortality , cardiac death , nonfatal MI and need for revascularization when compared with medical therapy alone.
• PCI provides a benefit over medical therapy in symptom relief of angina in patients with stable CAD.
Meta-Analyses Assessing Impact of PCI Versus OMT
J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S , V O L . 6 , N O . 1 0 , 2 0 1 3
ISCHEMIA :International Study of Comparative Health Effectiveness with Medical and Invasive Approaches
• Study Group : Stable CAD with atleast moderate ischemia.• Primary Aim: to determine whether an initial PCI or CABG + OMT is
superior to a conservative strategy of OMT alone, with cath reserved for OMT failure
• Primary Endpoint: CV death or MI • Secondary Endpoint: angina-related QOL
• Sample size : 8000• Follow up : Average 4 years.
2013 ESC Guidelines Revascularization of stable CAD pts on OMT
ACCF/AHA/SCAI PCI Guidelines: Revascularization to Improve Survival
Revascularization to Improve Symptoms
THANK YOU