RITA-3 Is this a benign lesion in a benign condition? Who Needs Angioplasty in 2008? Stable Angina Stable Angina Keith A A Fox Professor of Cardiology University & Royal Infirmary Edinburgh

Conflicts of interest slide Advanced angioplasty 2008 Device industry: None Grant Funding: British Heart Foundation, Wellcome Trust, Medical Research Council, ESC, Sanofi-Aventis, BMS, GSK Travel & honoraria: Sanofi-Aventis, BMS, GSK

Event Rates: “Primary Prevention”; Stable Angina ; non-ST Elevation ACS. Death / MI after 12 months Wallentin L et al. Lancet 2000;356:9–16 Juul-Moller S et al. Lancet 1992;340:1421–1425 Shepherd J et al. N Engl J Med 1995;333:1301–1307 Poole-Wilson et al ACTION Lancet 2004;364: Death/ MI (%) Months of follow up Unstable angina/non Q wave MI (FRISC II) Stable angina (SAPAT) Primary Prevention (WOSCOPS) ACTION trial (stable CAD) Approx 1.5% Stable CAD

salvage of ischaemic myocardium Stable anginaNon-ST elevation ACSST Elevation MI Concepts: Extent of salvage (infarction) proportional to clinical benefit: death or MI Extent of reversible ischaemia proportional to benefit on relief of angina

Conservative Intervention Cumulative percentage Follow-up time (years) RITA 3, 5 yr outcome: p = odds ratio: % CI % 12.1% Cardiovascular Deaths: p = odds ratio: % CI 0.49 – 0.95 Lancet 2005: 366; Death or MI: odds ratio 0.78, 95%CI , p= 0.04 All deaths BHF RITA-3

Conservative Follow-up time (years) Cumulative risk of death or MI by risk score and treatment group Intervention Fox KAA Lancet 2005, 366: BHF RITA-3

PCI vs. Conservative Therapy: Stable CAD Meta-analysis (pre-COURAGE)  Primary Endpoint: Death, or nonfatal MI, CABG, and PCI during follow- up (in the target vessel or other vessel/segment). PCIn=1476PCIn=1476 Conservative Therapy n=1474 n=1474 Stable CAD & >1 stenosis: 2950 patients from randomized trials (PCI versus conservative medical therapy) Katritsis DG et al Circulation 2005; 111:

PCI vs. Conservative Therapy: Meta-Analysis No significant difference: death, cardiac death or MI, nonfatal MI, and need for CABGNo significant difference: death, cardiac death or MI, nonfatal MI, and need for CABG # patients Katritsis DG et al Circulation 2005; 111:

Stable CAD: PCI vs Conservative Medical Management Meta-analysis of 11 randomized trials; N = 2,950 Death Cardiac death or MI Nonfatal MI CABG PCI Katritsis DG et al. Circulation. 2005;111: P Risk ratio (95% Cl) Favours PCI Favours Medical Management

The 95% confidence intervals excluded relative risk differences of 28%.The 95% confidence intervals excluded relative risk differences of 28%. PCI vs. Conservative Therapy: Death Katritsis DG et al Circulation 2005; 111:

RITA-2: PTCA vs Medical Therapy in Stable Angina(n=1000) PTCAMedicalORP Death/MI 32 (6.3%) 17 (3.3%) CABG 40 (7.2%) 30 (5.8%) Post-rand PTCA 62 (12.3%) 101 (19.9%) Any PTCA 533 (>100.0%) 101 (19.9%) 5.28<< Total procedures << Lancet 1997

RITA-2: Impact on Grade 2 Angina (Med v PTCA) RITA-2 Lancet 1997

RITA 2: Quality of Life over 3 years of Follow-up Pocock et al. JACC 2000

Compared with conservative therapy, PCI does not decrease mortality or the risk of MI during follow-up in patients with chronic CAD. Compared with conservative therapy, PCI does not decrease mortality or the risk of MI during follow-up in patients with chronic CAD. A trend for increased risk of MI in patients undergoing PCI was observed. A trend for increased risk of MI in patients undergoing PCI was observed. Even when analyses were limited to studies that used stents, the meta-analysis found no evidence of superiority for the PCI strategy. Even when analyses were limited to studies that used stents, the meta-analysis found no evidence of superiority for the PCI strategy. Need for more randomized trials… Need for more randomized trials… Compared with conservative therapy, PCI does not decrease mortality or the risk of MI during follow-up in patients with chronic CAD. Compared with conservative therapy, PCI does not decrease mortality or the risk of MI during follow-up in patients with chronic CAD. A trend for increased risk of MI in patients undergoing PCI was observed. A trend for increased risk of MI in patients undergoing PCI was observed. Even when analyses were limited to studies that used stents, the meta-analysis found no evidence of superiority for the PCI strategy. Even when analyses were limited to studies that used stents, the meta-analysis found no evidence of superiority for the PCI strategy. Need for more randomized trials… Need for more randomized trials… PCI vs. Conservative Therapy: Summary Katritsis DG et al Circulation 2005; 111:

objective evidence of myocardial ischemia objective evidence of myocardial ischemia stenosis > 70% in > one proximal coronary artery stenosis > 70% in > one proximal coronary artery Objective myocardial ischemia: ST-segment depression or T-wave inversion on the resting ECG or inducible ischemia (exercise or vasodilator stress) or at least one coronary stenosis > 80% plus classic angina BMS not DES; all patients suitable for PCI; low event rate 2287 patients “Optimal Medical Therapy“ At 5 yrs: 70% had LDL <2.20 mmol per liter) 65% and 94% had systolic and diastolic BP < 130/85 45% of patients with diabetes had Hb A1c <7% High adherence to diet, exercise, and smoking cessation

COURAGE: Freedom from angina Boden WE et al. N Engl J Med Yr (follow-up) PCI (%) Medical therapy (%) p Baseline1213NS 16658< NS

Boden WE et al. N Engl J Med COURAGE: Cumulative event rates (4.6 yrs) Outcome PCI (%) Medical Rx (%) Hazard ratio 95% CI p Death, MI –

Boden WE et al. N Engl J Med COURAGE: Cumulative event rates (4.6 yrs) Outcome PCI (%) Medical Rx (%) Hazard ratio 95% CI p Death, MI – Death, MI, stroke – Death – Nonfatal MI – Stroke – Hospitalization for ACS – Revascularization (PCI or CABG) –0.71<0.001

Rest Mid Base Apex StressRestStress After optimal anti-ischemic medical therapy Before treatment COURAGE study Patient randomized to medical treatment only Case presented at ACC 2003 by Dr. Robert O´Rourke

PCI in stable angina… Event rates of death & MI approx 1.5% per annum - on optimal medical therapy Scope to improve rate of death or MI is very limited - even in patients with proximal stenosis & inducible ischaemia PCI is superior to medical therapy (at least over 3 yrs) in relief of angina, but not longer term Greater benefit in those with more extensive ischaemia (>5% LV) Role of PCI in those with angina and LV dysfunction is unresolved Conclusions: 2008