Presentation on theme: "REVASCULARIZATION Vs MEDICAL THERAPY IN STABLE CAD"— Presentation transcript:
1 REVASCULARIZATION Vs MEDICAL THERAPY IN STABLE CAD Dr Binjo J VazhappillySR CardiologyMCH , Calicut
2 IntroductionCoronary 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
3 IntroductionThere 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 studiesSubsequent trials used stents , but DES implantation was negligible except for BARI-2D.
6 COURAGE: Clinical Outcomes Utilizing Revascularization and Aggressive Guideline-Driven Drug EvaluationHypothesis : 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
7 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.
13 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 surgeryMedian time to subsequent revascularization was 10.0 mo in the PCI group and 10.8 mo in the OMT group
14 Freedom from Angina During Long-Term Follow-up CharacteristicPCI + OMTOMTCLINICALAngina free – no.Baseline12%13%1 Yr66%58%3 Yr72%67%5 Yr74%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.
15 ConclusionsAs 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 OMTPCI 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.
16 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.
17 BARI 2D Trial: Study Design 2368 pts with mild to moderate CAD and Type 2 diabetes prior to randomization.CABG Stratum (N= 763)PCI Stratum (N= 1605)RROMT alone (N= 385)CABG +OMT (N= 378)OMT alone (N= 807)PCI +OMT (N= 798)Study period : January 2001, to March 2005Mean follow up : 5.3 yrsPrimary Endpoint: Death (from any cause)Secondary Endpoint: Composite of Death, MI, or StrokeBARI 2D Study Group, NEJM 20092417
18 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 diseaseCreatinine level > 2.0 mg per deciliterGlycated Hb > 13.0%Class III or IV heart failure or hepatic dysfunctionUndergone PCI or CABG within the previous 12 months.
19 BARI 2D Trial: Primary Endpoint 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.Death (%)n =155n =161Copyleft Clinical Trial Results. You Must Redistribute SlidesBARI 2D Study Group, NEJM 2009
20 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)Cardiovascular Event (%)n=138n=283n=118n=33n=266n=30BARI 2D Study Group, NEJM 2009
21 BARI 2D TrialSummary : 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.LimitationsPatients who are at high risk for MI revascularization were excluded from the trial.BARI 2D Study Group, NEJM 2009
22 MASS II TrialRandomized Controlled Clinical Trial of therapeutic strategies for multivessel CAD, stable angina and preserved ventricular function.Study period : May 1995 and May 2000Inclusion 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.
23 Database: 20.769 coronary angiographies (suitable to PCI-CABG) MASS 2 TRIALDatabase: coronary angiographiescoronary <70% lesionsingle coronary diseaseprevious CABG/PCIvalvar disease 2701otherexcluded patients:Eligible: patients(suitable to PCI-CABG)refused to participate in this trialor refused the surgical procedure1465 patients non-randomized:MASS IIRandomized: 611 patientsAngioplasty(n=205)Surgery(n=203)Medical Treatment(n=203)Hueb W, et al. J Am Coll CardioI 2004; 43:
24 Baseline Characteristics of MASS II MT(n = 203)PCI(n=205)CABG(n = 203)PCharacteristicDemographic ProfileMale, (%)Age (years) mean ± SDMedical HistoryPrevious MI (%)Smoker (%)Hypertension (%)Diabetes mellitus (%)CCS class 2 or 3 (%)6760±452276026767261±841326329850.4120.9590.0240.0130.2150.0620.0066960±93933553678
27 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.
28 Limitations of MASS-II Trial Single center studySmall number of subjectsNo DES usagePost-angiography selection bias
29 STICH TRIAL Randomized controlled trial, non-blinded Study period : July 2002 and May 2007A total of 1212 pts were randomly assigned to medical therapy alone (602 patients) or medical therapy plus CABG (610 pts).Primary EndpointAll-cause mortalityMajor Secondary EndpointsCardiovascular mortalityDeath (all-cause) + cardiovascular hospitalization
30 STICH TRIAL Inclusion criteria Pts with coronary artery disease that was amenable to CABG and EF of 35% or lessMedical therapy eligibleAbsence 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 criteriaRecent 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 .OUR RPIMARY ENDPOINT WASALLL CAUSE MORTALITYIMPORTANT SECONDARY ENDPOINTSINCLUDEDCARDIOVASCULAR MORTALITYANDALL CAUSE DEATH OR CARDIOVASCULAR HOSITALIZATION
31 STICH Revascularization Hypothesis Treatment Per Protocol 1212ReceivedMED onlyCABG555537RandomizedMED only610602RandomizedCABG17%9%5565WE ALSO PERFORMEDA PER PROTOCOL ANALYSISCOMPARING ONLY THE 537 PATIENTS RANDOMIZED TO MEDICAL THERAPYWHO REMAINED ON MEDICAL THERAPYANDTHE555 PATIENTS RANDOMIZED TO CABG WHO RECEIVED CABG BY PROTOCOL ONLYPer protocol: MED (537) vs CABG (555)
32 All-Cause Mortality — As Randomized HR 0.86 (0.72, 1.04)P = 0.123Adjusted HR 0.82 (0.68, 0.99)Adjusted P = 0.0390.460.41AFTER ADJUSTING FOR PRE-SPECIFIED BASELINE VARIABLESTHE HAZARD RATIO FOR CABG WAS 0.82WHICH CORRESPONDED TO AP VALUE OF 0.039Model 3 Covariate adjusted – all variables prospectively specified in STICH protocol or with significant prognostic effect.Stratum, age, gender, race, HF class at baseline, MI history, previous revascularization, best available EF, number of diseased vessels, chronic renal insufficiency, MR, stroke hx, AF hx
33 Cardiovascular Mortality — As Randomized HR 0.81 (0.66, 1.00)P = 0.050Adjusted HR 0.77 (0.62, 0.94)Adjusted P = 0.0120.390.32AMONG THE 602 PATIENTSRANDOMIZED TO MEDICAL THERAPY ALONETHE OVERALL CARDIOVASCULAR MORTALITY RATE WAS 39%AMONG THE 610 PATIENTS RANDOMIZED TO MEDICAL THERAPY WITH CABGTHE OVERALL MORTALITY RATE WAS 32%THIS ABSOLUTE RISK REDUCTION OF 7%CORRESPONDED TO A HAZARD RATIO WITH CABG OF 0.8 1AND A P VALUE OF 0.050
34 Death or Cardiovascular Hospitalization — As Randomized 0.680.58HR 0.74 (0.64, 0.85)P < 0.001Adjusted HR 0.70 (0.61, 0.81) P < 0.001FOR THE ENDPOINT OF ALL CAUSE DEATH OR CARDIOVASCULAR HOSPITALIZATIONTHE OVERALL EVENT RATE WAS68% WITH MEDICAL THERAPY ALONEAND58% WITH CABGTHIS ABSOLUTE EVENT REDUCTION OF 10% IN FAVOR OF CABGWAS STATISTICALLY SIGNIFICANT WITH AND WITHOUT ADJUSTMENT
35 Stich trial : summaryNo 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.
36 Urgent revascularization FAME 2Trial 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(p < 0.001)(p < 0.001)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 , p < 0.001Mortality: 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 < 0.001Highest benefit if lesion FFR <0.65100100%50%5012.711.1Conclusions4.31.6FFR-guided PCI + OMT was superior to OMT in patients with stable angina, mainly due to a reduction in need for urgent revascularizationThese results suggest that a positive FFR may be a good method to risk stratify these patientsPrimary endpointUrgent revascularizationPCI + OMT(n = 447)OMT(n = 441)De Bruyne B, et al. N Engl J Med 2012;367:
38 Risk of all-cause mortality Circ Cardiovasc Interv. 2012;5:
39 Risk of cardiac deathCirc Cardiovasc Interv. 2012;5:
40 Risk of revascularization Circ Cardiovasc Interv. 2012;5:
41 Freedom from anginaCirc Cardiovasc Interv. 2012;5:
42 ConclusionsPts 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.
43 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 ,
44 ISCHEMIA :International Study of Comparative Health Effectiveness with Medical and Invasive ApproachesStudy 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 failurePrimary Endpoint: CV death or MISecondary Endpoint: angina-related QOLSample size : 8000Follow up : Average 4 years.