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)

CLINICAL TRAILS PERCUTANEOUS CORONARY INTERVENTION VERSUS OPTIMAL MEDICAL THERAPY

Clinical outcomes utilizing Revascularization and aggressive drug

evaluation (COURAGE)No significant difference in outcomes

Bypass Angioplasty Revascularization

Investigation 2 Diabetes (BARI 2D)No significant difference in outcomes

Schömig et al ( 2008)Swiss Interventional Study on Silent

Ischemia Type II (SWISS-II) and

COURAGE trials

Improvement in all-cause mortality in the revascularized group

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).

Characteristics of Included Trials STUDY YEARS OF ENROLMENT, COUNTRY

INCLUSION CRITERIA

Exclusion Criteria

Description of Intervention

Description of Medical Therapy

Primary Outcome

Secondary Outcomes

Follow Up, y

ACME-11987–1990 USA

70%–99% stenosis in proximal two thirds of 1 major coronary artery, stress test with ≥1 mm ST depression in at least 1 lead or filling defect on thallium scan, or MI in past 3 mo

Not reported PTCA 325 mg Aspirin, nitrates, β-blockers, calcium channel blockers

6 mo exercise stress testing: length of time to onset of 1 mm ST depression, maximal ST segment depression, maximal work product

Change in degree of stenosis in index lesion, physical well being questionnaire, employment status

3

ACME-2 1987–1990 USA

History of angina, MI within 3 mo, or ≥3 mm horizontal ST depression on exercise testing; ≥70% stenosis in proximal two thirds of 1 or 2 coronary arteries (data for 1 vessel CAD previously presented as ACME-1)

Unstable angina refractory to medical therapy, prior PCI, primary cardiac diagnosis other than CAD, ≥50% left main stenosis, 3 vessel CAD, LVEF≤30%

PTCA Aspirin plus individualized therapy of Nitrates, β-blockers, and Calcium channel blockers

Primary/secondary outcomes not individually described Angina frequency, 6 mo exercise tolerance testing and angiography:

change in exercise duration, time to onset of angina, maximal rate-pressure product, percent diameter stenosis of index lesions

5

Baseline Characteristics

CLINICAL CHARACTERISTICS OF THE PARTICIPANTS

RESULTS

ALL CAUSE MORTALITYPCI OMT RISK RATIO

All Cause Mortality

• 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.

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

CARDIVASCULAR DEATH

• 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.

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, 0.47–1.06)

RR, 0.70; 95% CI, 0.46–1.08

<5 YEARS RR, 1.53; 95% CI, 0.69–3.38

NONFATAL MIPCI 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 yeartime points

RR 0.99; 95% CI, 0.75–1.30

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

Most updated

analysis to dateNo

significant difference in

outcome

BUT

All-cause mortality

and cardiac death in trial with longer follow up-

PCI

Greater freedom

from angina- PCI

ISCHEMIA-STUDY

• International Study of Comparative Health Effectiveness with Medical and Invasive Approaches