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A Systematic Review and Meta-Analysis of
       Randomized Clinical Trials
                   Seema et al.
     Circulation: cardiovascular intervention

      (Circ Cardiovasc Interv. 2012;5:1-15.)
     © 2012 American Heart Association, Inc.
BACKGROUND
• ROLE OF PERCUTANEOUS CORONARY
  INTERVENTION
  – ST SEGMENT ELEVATION MI
  – UNSTABLE ANGINA
  – NSTEMI
• FOR STABLE CORONARY ARTERY DISEASE
  – OPTIMAL TREATMENT STRATEGY?
    • PCI(PERCUTANEOUS CORONARY INTERVENTION)
    • OMT(OPTIMAL MEDICAL THERAPY)
PERCUTANEOUS CORONARY
 CLINICAL TRAILS                            INTERVENTION VERSUS
                                            OPTIMAL MEDICAL THERAPY
Clinical outcomes utilizing                 No significant difference in outcomes
Revascularization and aggressive drug
evaluation   (COURAGE)
Bypass Angioplasty Revascularization        No significant difference in outcomes
Investigation 2 Diabetes   (BARI 2D)
Schömig et al ( 2008)Swiss Interventional   Improvement in all-cause mortality in the
Study on Silent                             revascularized group
Ischemia Type II   (SWISS-II) and
COURAGE trials
OBJECTIVE

whether revascularization
with PCI reduces
cardiovascular outcomes


      when compared with
      OMT in patients with
      stable CAD.
METHODS
• PUBMED, EMBASE And CENTRAL Searchs

• Using medical subject heading or keywords
  – Diagnosis of stable CAD
  – Intervention of PCI
  – Comparision with medical therapy
Eligible trails
• Cohort enrolled- Stable Coronary Artery
  Disease patients
• Comparision of PCI to optimal medical therapy
• Reporting outcomes
  – All-cause mortality
  – Cardiovascular death
  – Nonfatal MI
  – Revascularization
  – Freedom from angina
Selection and quality assesment
               Compilation of searches

                Duplicates removed
Study screened by title and abstract (by two independent
                        reviewer)

 Qualified study(full text review by(by two independent reviewer)


DATA ABSTRACTION AND ASSESMENT FOR SOURCES OF SYSTEMATIC
                          BIAS
Data extraction
• Two independent reviewer extracted data
• Data abstracted measured
  – study characteristics
  – patient characteristics
  – details regarding the intervention
  – comparison group
  – outcome measures
Statistical Analysis
• RevMan software provided by Cochrane
  Collaboration
Sensitivity Analyses
• POTENTIAL IMPACT OF INDUSTRY FUNDING

• EVOLUTION OF PCI
  – potential differential effect of stenting as opposed
    to balloon angioplasty alone.
RESULTS
STUDY SELECTION
•   12 randomized clinical trials
•   participants enrolled from all over the world
•   7182 patients
•   followed-up - 4.9 years (range 1.5–10.2 years).
STUDY YEARS
              Characteristics of Included Trials                    Descrip                                    Secondary
                                               Exclusion                      Description    Primary                            Follo
OF             INCLUSION                       Criteria
                                                                    tion of
                                                                              of Medical     Outcome
                                                                                                               Outcomes         w Up, y
ENROLMENT,                                                          Interve
COUNTRY        CRITERIA                                             ntion     Therapy


               70%–99% stenosis in                                                           6 mo exercise     Change in
ACME-                                          Not reported         PTCA 325 mg
11987–
               proximal two thirds of 1
               major coronary artery,
                                                                              Aspirin,
                                                                              nitrates, β-
                                                                                             stress testing:
                                                                                             length of time
                                                                                             to onset of 1
                                                                                                               degree of
                                                                                                               stenosis in
                                                                                                               index lesion,
                                                                                                                                3
                                                                                                               physical well
1990           stress test with ≥1 mm ST                                      blockers,      mm ST
                                                                                             depression,       being
               depression in at least 1 lead                                  calcium                          questionnaire,
USA            or filling defect on thallium                                  channel
                                                                                             maximal ST
                                                                                             segment           employment
                                                                                                               status
               scan, or MI in past 3 mo                                       blockers       depression,
                                                                                             maximal work
                                                                                             product




               History of angina, MI           Unstable angina      PTCA Aspirin plus        Primary/seco      change in
ACME-2                                         refractory to                                 ndary             exercise         5
               within 3 mo, or ≥3 mm                                          individualiz
1987–                                          medical therapy,
                                                                              ed therapy     outcomes          duration,
               horizontal ST depression        prior PCI, primary                            not               time to onset
1990           on exercise testing;            cardiac diagnosis              of Nitrates,   individually      of angina,
                                               other than CAD,                β-blockers,    described         maximal
USA            ≥70% stenosis in                ≥50% left main                 and            Angina            rate-pressure
               proximal two thirds of 1        stenosis, 3 vessel             Calcium        frequency, 6      product,
               or 2 coronary arteries          CAD, LVEF≤30%                  channel        mo exercise       percent
                                                                                             tolerance         diameter
               (data for 1 vessel CAD                                         blockers
                                                                                             testing and       stenosis of
               previously presented as                                                       angiography:      index lesions
               ACME-1)
Baseline Characteristics
CLINICAL CHARACTERISTICS OF THE
PARTICIPANTS
RESULTS
ALL CAUSE MORTALITY
 PCI   OMT   RISK RATIO
All Cause Mortality
    PCI VS OMT                        RESULT

    longest follow-up duration        risk ratio [RR], 0.85; 95% CI, 0.71–
                                      1.01

    the ≤1 year                       RR, 1.34; 95% CI, 0.87–2.08

    1 to 5 years                      RR, 0.97; 95% CI, 0.56–1.69


    ≥5 years                          RR, 0.82; 95% CI, 0.65–1.02

• Overall, there was no statistically significant difference in mortality
  between the PCI and OMT groups; the point estimate at the longest
  follow-up duration notably did favor the PCI group SWISS-2 and
  ALKK individually showed the most favorable effects of PCI over
  OMT; of note, these 2 trials included those with prior recent MIs.
CARDIVASCULAR DEATH
   PCI VS OMT                           CARDIVASCULAR DEATH

   longest follow-up duration           RR, 0.71; 95% CI, 0.47–1.06


   PCI group (RR, 0.71; 95% CI, 0.47–   RR, 0.70; 95% CI, 0.46–1.08
   1.06)



   <5 YEARS                             RR, 1.53; 95% CI, 0.69–3.38

• The point estimate in the longest follow-up duration
  analysis favored the PCI group and this difference was
  most apparent in those trials with ≥5 years follow-up
  although these were not statistically significant.
NONFATAL MI
PCI vs OMT              result


overall analysis        (RR, 0.93; 95% CI, 0.70–1.24)


≤1 year                 RR, 0.82; (95% CI, 0.37–1.80)


1 to 5 years            RR 1.11(95% CI, 0.47–2.59),


≥5 year                 RR O.92(95% CI, 0.67–1.27)
Revascularization

PCI VS OMT                 RESULT

overall analysis           (RR, 0.93; 95% CI, 0.76–
                           1.14)


≤1 year                    RR, 1.49; 95% CI

1–5 years                  RR 0.98; 95% CI, 0.74–1.30;

≥5 year                    RR 0.99; 95% CI, 0.75–1.30
time points
Freedom From Angina
PCI VS OMT            RESULT


OVERALL               (RR, 1.20; 95% CI, 1.06–1.37


≤1 year               RR, 1.32; 95% CI, 1.13–1.54


1–5 years             1.57; 95% CI, 1.06–2.32


≥5 year               1.06–2.32; RR, 1.17; 95% CI, 1.00–1.38)
Study limitations
• Analysis of symptoms driven
  revascularization
• Freedom from angina
• Dosage of medication administered
• Evolution of therapy
• Variation in target level
Discussion
                             BUT
  Most
 updated
analysis to        All-cause
   date            mortality
                                    Greater
     No          and cardiac
                                   freedom
 significant    death in trial
                                 from angina-
difference in    with longer
                                      PCI
  outcome         follow up-
                      PCI
ISCHEMIA-STUDY
• International Study of Comparative Health
  Effectiveness with Medical and Invasive
  Approaches

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JOURNAL KLUB....PCI VS OMT

  • 1. A Systematic Review and Meta-Analysis of Randomized Clinical Trials Seema et al. Circulation: cardiovascular intervention (Circ Cardiovasc Interv. 2012;5:1-15.) © 2012 American Heart Association, Inc.
  • 2. BACKGROUND • ROLE OF PERCUTANEOUS CORONARY INTERVENTION – ST SEGMENT ELEVATION MI – UNSTABLE ANGINA – NSTEMI • FOR STABLE CORONARY ARTERY DISEASE – OPTIMAL TREATMENT STRATEGY? • PCI(PERCUTANEOUS CORONARY INTERVENTION) • OMT(OPTIMAL MEDICAL THERAPY)
  • 3. PERCUTANEOUS CORONARY CLINICAL TRAILS INTERVENTION VERSUS OPTIMAL MEDICAL THERAPY Clinical outcomes utilizing No significant difference in outcomes Revascularization and aggressive drug evaluation (COURAGE) Bypass Angioplasty Revascularization No significant difference in outcomes Investigation 2 Diabetes (BARI 2D) Schömig et al ( 2008)Swiss Interventional Improvement in all-cause mortality in the Study on Silent revascularized group Ischemia Type II (SWISS-II) and COURAGE trials
  • 4. OBJECTIVE whether revascularization with PCI reduces cardiovascular outcomes when compared with OMT in patients with stable CAD.
  • 5. METHODS • PUBMED, EMBASE And CENTRAL Searchs • Using medical subject heading or keywords – Diagnosis of stable CAD – Intervention of PCI – Comparision with medical therapy
  • 6. Eligible trails • Cohort enrolled- Stable Coronary Artery Disease patients • Comparision of PCI to optimal medical therapy • Reporting outcomes – All-cause mortality – Cardiovascular death – Nonfatal MI – Revascularization – Freedom from angina
  • 7. Selection and quality assesment Compilation of searches Duplicates removed Study screened by title and abstract (by two independent reviewer) Qualified study(full text review by(by two independent reviewer) DATA ABSTRACTION AND ASSESMENT FOR SOURCES OF SYSTEMATIC BIAS
  • 8. Data extraction • Two independent reviewer extracted data • Data abstracted measured – study characteristics – patient characteristics – details regarding the intervention – comparison group – outcome measures
  • 9. Statistical Analysis • RevMan software provided by Cochrane Collaboration
  • 10. Sensitivity Analyses • POTENTIAL IMPACT OF INDUSTRY FUNDING • EVOLUTION OF PCI – potential differential effect of stenting as opposed to balloon angioplasty alone.
  • 13. 12 randomized clinical trials • participants enrolled from all over the world • 7182 patients • followed-up - 4.9 years (range 1.5–10.2 years).
  • 14. STUDY YEARS Characteristics of Included Trials Descrip Secondary Exclusion Description Primary Follo OF INCLUSION Criteria tion of of Medical Outcome Outcomes w Up, y ENROLMENT, Interve COUNTRY CRITERIA ntion Therapy 70%–99% stenosis in 6 mo exercise Change in ACME- Not reported PTCA 325 mg 11987– proximal two thirds of 1 major coronary artery, Aspirin, nitrates, β- stress testing: length of time to onset of 1 degree of stenosis in index lesion, 3 physical well 1990 stress test with ≥1 mm ST blockers, mm ST depression, being depression in at least 1 lead calcium questionnaire, USA or filling defect on thallium channel maximal ST segment employment status scan, or MI in past 3 mo blockers depression, maximal work product History of angina, MI Unstable angina PTCA Aspirin plus Primary/seco change in ACME-2 refractory to ndary exercise 5 within 3 mo, or ≥3 mm individualiz 1987– medical therapy, ed therapy outcomes duration, horizontal ST depression prior PCI, primary not time to onset 1990 on exercise testing; cardiac diagnosis of Nitrates, individually of angina, other than CAD, β-blockers, described maximal USA ≥70% stenosis in ≥50% left main and Angina rate-pressure proximal two thirds of 1 stenosis, 3 vessel Calcium frequency, 6 product, or 2 coronary arteries CAD, LVEF≤30% channel mo exercise percent tolerance diameter (data for 1 vessel CAD blockers testing and stenosis of previously presented as angiography: index lesions ACME-1)
  • 16.
  • 17.
  • 18.
  • 19.
  • 20.
  • 21. CLINICAL CHARACTERISTICS OF THE PARTICIPANTS
  • 22.
  • 23.
  • 24.
  • 25.
  • 26.
  • 27.
  • 29. ALL CAUSE MORTALITY PCI OMT RISK RATIO
  • 30.
  • 31.
  • 32. All Cause Mortality PCI VS OMT RESULT longest follow-up duration risk ratio [RR], 0.85; 95% CI, 0.71– 1.01 the ≤1 year RR, 1.34; 95% CI, 0.87–2.08 1 to 5 years RR, 0.97; 95% CI, 0.56–1.69 ≥5 years RR, 0.82; 95% CI, 0.65–1.02 • Overall, there was no statistically significant difference in mortality between the PCI and OMT groups; the point estimate at the longest follow-up duration notably did favor the PCI group SWISS-2 and ALKK individually showed the most favorable effects of PCI over OMT; of note, these 2 trials included those with prior recent MIs.
  • 33. CARDIVASCULAR DEATH PCI VS OMT CARDIVASCULAR DEATH longest follow-up duration RR, 0.71; 95% CI, 0.47–1.06 PCI group (RR, 0.71; 95% CI, 0.47– RR, 0.70; 95% CI, 0.46–1.08 1.06) <5 YEARS RR, 1.53; 95% CI, 0.69–3.38 • The point estimate in the longest follow-up duration analysis favored the PCI group and this difference was most apparent in those trials with ≥5 years follow-up although these were not statistically significant.
  • 34. NONFATAL MI PCI vs OMT result overall analysis (RR, 0.93; 95% CI, 0.70–1.24) ≤1 year RR, 0.82; (95% CI, 0.37–1.80) 1 to 5 years RR 1.11(95% CI, 0.47–2.59), ≥5 year RR O.92(95% CI, 0.67–1.27)
  • 35. Revascularization PCI VS OMT RESULT overall analysis (RR, 0.93; 95% CI, 0.76– 1.14) ≤1 year RR, 1.49; 95% CI 1–5 years RR 0.98; 95% CI, 0.74–1.30; ≥5 year RR 0.99; 95% CI, 0.75–1.30 time points
  • 36. Freedom From Angina PCI VS OMT RESULT OVERALL (RR, 1.20; 95% CI, 1.06–1.37 ≤1 year RR, 1.32; 95% CI, 1.13–1.54 1–5 years 1.57; 95% CI, 1.06–2.32 ≥5 year 1.06–2.32; RR, 1.17; 95% CI, 1.00–1.38)
  • 37. Study limitations • Analysis of symptoms driven revascularization • Freedom from angina • Dosage of medication administered • Evolution of therapy • Variation in target level
  • 38. Discussion BUT Most updated analysis to All-cause date mortality Greater No and cardiac freedom significant death in trial from angina- difference in with longer PCI outcome follow up- PCI
  • 39. ISCHEMIA-STUDY • International Study of Comparative Health Effectiveness with Medical and Invasive Approaches