The Impact of Revascularization on Mortality in Patients with Non-Acute Coronary Artery Disease

1. The Impact of Revascularization on Mortality in Patients with Non-Acute Coronary Artery Disease Allen Jeremias MD MSc, Sanjay Kaul MD, Luis Gruberg MD, Todd K. Rosengart MD, David L. Brown MD Divisions of Cardiovascular Medicine and Cardiothoracic Surgery Stony Brook University Medical Center; Cedars Sinai Medical Center, UCLA

2. Background • Coronary artery revascularization has been shown to • significantly reduce the incidence of death and MI in • the setting of acute coronary syndromes • However, most studies evaluating revascularization • therapy in patients with stable CAD found no difference • in mortality or MI when compared with Med Rx alone • None of these studies were adequately powered to detect • mortality differences

3. Objectives • To compare coronary revascularization with Med Rx alone • with respect to mortality and MI in patients with stable CAD • Since surgical and percutaneous revascularization • therapies have repeatedly been found to be equivalent in • preventing death or MI, we conducted a systematic review • and meta-analysis of all randomized clinical trials that • compared the effect of coronary revascularization by either • PCI or CABG to Med Rx alone

4. Methods • Search Strategy • Medline and Cochrane Central Register of Controlled Trials • databases were searched • Studies published between 1977 and May 2007 • Search terms: coronary revascularization, balloon angioplasty, • stent, coronary artery bypass grafting, medical therapy, angina, • stable, coronary artery disease • Study eligibility assessed by 2 authors; disagreements resolved by • consensus with a third author

5. Methods • Inclusion Criteria • Prospective, randomized trials of coronary revascularization vs. Med Rx • alone in patients with stable CAD • Acute coronary syndromes excluded but stable patients following a • completed MI included • Studies included irrespective of presence of ischemia or any functional • assessment of hemodynamic significance of a coronary stenosis • Outcomes of death or nonfatal MI with minimum follow-up of 1 year • Multiple study designs accepted: • 2 arm randomization to PCI/CABG vs medical therapy • Any revascularization strategy vs medical therapy • 3 arm randomization to PCI vs CABG vs medical therapy

6. Methods • Endpoints • Endpoint definitions were those used in individual trials • All-cause mortality was death from any cause (cardiac or • noncardiac) and was preferentially used unless only cardiac • deaths were reported • MI was defined as elevation of serum markers of myocardial • necrosis along with EKG changes • Endpoints were extracted from each trial at the reported • follow-up closest to 5-year mark

7. Methods • Statistical Analysis • Methods based on odds ratios (OR) were used to calculate the OR • for death and nonfatal MI • The Q statistic failed to indicate statistical heterogeneity (P=0.15) • However, given vast differences in trials included, a summary OR • was calculated using a random-effects model and 95% • confidence intervals (CI) for each study endpoint • Cumulative meta-analysis was performed by sequentially adding • studies one at a time according to date of publication (from • earliest to latest)

8. Results • 28 studies published from 1977-2007 met inclusion criteria • Revascularization modality: • PCI vs. Med Rx in 17 studies • CABG vs. Med Rx in 6 studies • PCI or CABG (non-randomized) vs. Med Rx in 3 studies • PCI or CABG (randomized) vs. Med Rx in 2 studies • Total of 13,121 patients enrolled • 6476 revascularization • 6645 medical therapy alone • Follow-up ranged from 1 to 10 years with median of 3 years

9. Results • Quantitative Analysis • 511 deaths among the 6476 patients in the • revascularization group (7.9%) • 649 deaths among the 6645 patients in the medical therapy • group (9.8%) • Number needed to treat to prevent 1 death is 53

10. Lower Limit Upper Limit Study Name OR Odds Ratio and 95% CI Combined Favors Revasc. Favors Med Rx Revascularization vs. Med Rx on Mortality

11. Lower Limit Upper Limit Cumulative Odds Ratio and 95% CI Study Name OR Combined Favors Revasc. Favors Med Rx Cumulative OR for Mortality

12. Lower Limit Upper Limit Study Name OR Odds Ratio and 95% CI Combined Favors Revasc. Favors Med Rx CABG vs. Med Rx on Mortality

13. Lower Limit Upper Limit Study Name OR Odds Ratio and 95% CI Combined Favors Revasc. Favors Med Rx PCI vs. Med Rx on Mortality

14. Results • Myocardial Infarction • Nonfatal MI rate reported in 26 trials that randomized • 11,768 patients • MI rate was 8.4% in the revascularization group • MI rate was 8.9% in the medical therapy group

15. Lower Limit Upper Limit Study Name OR Odds Ratio and 95% CI Combined Favors Revasc. Favors Med Rx Revascularization vs. Med Rx on MI

16. Limitations • No access to individual patient-level data • Data extracted from randomized clinical trials may not be • representative of patients actually seen in clinical practice • Most studies performed during time of rapid improvements in • both medical and revascularization therapies, including use of • internal mammary artery for bypass grafting and coronary • stents

17. Conclusions • Coronary artery revascularization by either CABG or PCI for • stable CAD is associated with a significant reduction in • mortality • Mortality benefit apparent after inclusion of only 3 trials • Revascularization therapy does not reduce the incidence of • non-fatal MI