Angioplasty: A Reality Check! What Does Evidence Based Medicine Tell Us?

1. Angioplasty: A Reality Check!What Does Evidence Based Medicine Tell Us? Duane S. Pinto, M.D. Director Peripheral Angiographic Core Laboratory, TIMI Data Coordinating Center Director, Cardiology Fellowship Training Program Interventional Cardiologist, Beth Israel Deaconess Medical Center Assistant Professor of Medicine, Harvard Medical School

2. Conventional Wisdom • Treatment Assumptions in CAD Management: • Patients with symptomatic CAD and chronic angina who have significant coronary stenoses “need” revascularization • Revascularization is required to improve prognosis • PCI is less invasive than CABG surgery (i.e., is safer) and, therefore, should be selected

3. Real Patient! To: Pinto,Duane (Cardiology) <dpinto@bidmc.harvard.edu>Sent: Tue Jun 27 15:41:21 2006Subject: are you back?I have a patient who had a positive stress today - I think he needs a cath (though, in retrospect, perhaps I should have sent him straight for cath - but he's hard to convince)

4. Straight to Cath? Costs of care are increased with greater pretest risk, but are elevated by 30% to 40% for patients undergoing direct catheterization Direct Cath NIVT + Selective Cath 4.8 4.2 2.9 2.8 Dollars (Thousands) Dollars (Thousands) 2.4 2.0 N=813 N=1682 N=816 N=1631 N=2928 N=3379 Economics of Noninvasive Diagnosis Multicenter Study Group. J Am Coll Cardiol. 1999; 33: 661

5. Stress Test Results Exercised for 5 Minutes on the Bruce Protocol. Stopped for fatigue. Achieved RPP 20,000 (85% Maximum predicted HR). 0.5 mm horizontal ST depressions.

6. Pop Quiz #1! • Based on this result, this patient’s annual risk of MI is estimated to be: • 0.5% • 2.9% • 7.4% • 9.3% • 12.7%

7. Our Patient: 5 - 2.5 - 0= 2.5 The Duke Treadmill Score Exercise time - (5 X ST Deviation) – (4 X Angina Index)= Score Angina index: • 0 No angina • 1 Typical angina during exercise • 2 Stop exercise for angina • Low risk: 5 or greater • Medium Risk: -10 to +4 • High risk: -11 or less Cardiac Death (%) Mark DB. Ann Inter Med. 1987: 106; 793. Hachamovich R. Circulation 1996; 93: 905.

8. ½ of men at low clinical risk (0.9% mortality/year) will have CAD Treadmill Score: Prognosis and Prevalence of Disease VD = Vessel Disease;  LM = Left Main Alexander KP, et al. J Am Coll Cardiol 1998; 32:1657-64 Mark DB, et al. Ann Int Med 1987; 106:793-800. Mark DB, et al. N Engl J Med 1991; 325:849-53

9. Stress Test Results Exercised for 5 Minutes on the Bruce Protocol. Stopped for fatigue. Achieved RPP 20,000 (85% Maximum predicted HR). 0.5 mm horizontal ST depressions.

10. Perfusion Imaging Adds to Prognosis Event Rate (%/yr) Hachamovitch R. Circulation. 1998; 97: 535.

11. History

12. Everybody’s Happy! • Patient’s Happy-”My blockage is now fixed!” • Referring MD Happy -”Whew! Heart attack averted!” • Interventional Cardiologist Happy-”Another successful (billable?) procedure!” • Hospital’s Happy-”I like that DRG!” What were the goals of care? Did we practice evidence based medicine?

13. The Truth • There is no evidence that the stent placed in this patient altered his long-term rate of death or MI • I am happy/lucky he did not have a periprocedural MI • Certainly, his risk of stent thrombosis (10% in hospital mortality) is increased compared with medical therapy now that he has a stent! • If dyspnea was an anginal equivalent (ischemic MR), then that may get better • It did at 3 month follow-up • Procedures don’t always go well • The risk for providing this symptom control was periprocedural MI, stroke, emergency CABG, bleeding, vascular injury & need for long-term anti-platelet therapy

14. 1 .30 to 2 .97 (57) 1 .10 to < 1 .30 (47) 0 .90 to < 1 .10 (83) 0 .75 to < 0 .90 (51) 0 .35 to < 0 .75 (68) Not Populated Ratio of Rates of Percutaneous Coronary Intervention to the U.S. Average (1996)

15. PCI Facts • Rates of cardiac catheterization and coronary revascularization among Medicare acute myocardial infarction patients increased by 45% and 70% between 1987 and 1992 • There are 1,000,000 PCI procedures in the US per year and 2,000,000 worldwide

16. Assessing Quality in Medical Care • Current paradigm of quality improvement generally focuses on identifying of specific processes of care (e.g., guidelines) and assessing how frequently they are achieved in an “ideal patient population” • JCAHO, HEDIS measures, etc. • Much less attention has traditionally been paid to the frequency of overuse of treatments in patients for whom there is little or no evidence of benefit • As compliance with standard performance measures increases, however, much of the real opportunity to improve quality of care may lie in identifying inappropriate care/overuse

17. PCI Appropriateness by Hospital • NY State 1990 • Random sample of 1306 pts undergoing PCI • Appropriateness based on modified Delphi Method • Independent angiographic readings suggests another 10% may also be inappropriate as well Hilborne LH et al. JAMA 1993;269:761-5

18. Evidence-Based Medicine Potential Impact of Inappropriate PCI • Low-volume hospital • 900,000 PCI/yr in US • 15% of PCI at low-volume hospital (LVH) • 1.3 x mortality risk at LVH vs. HVH • 0.5% in-hospital mortality for elective PCI • Inappropriate/Uncertain PCI • 900,000 PCI/yr in US • 6% inappropriate and 38% uncertain • 0-25% of uncertain PCI are actually inappropriate • 0.5% in-hospital mortality for elective PCI 270 - 698 deaths avoidable by eliminating inappropriate PCI 214 avoidable deaths (by switching all LVH to HVH)

19. Appropriateness of PCI: Weighing the Evidence • Although more than 27 million pts have undergone PCI since 1977, only ~6,500 have been enrolled in RCTs of PCI vs. medical therapy (0.02%) • RCTs of PCI vs. both medical therapy and bypass surgery are limited by outdated technology and highly restricted patient populations • <4% of current PCI population • ACC/AHA guidelines leave much of current PCI practice in the “gray-zone”

20. Lies, Damned Lies, and…. 6 Common Misconceptions about PCI

21. Evidence-Based Medicine PCI Misconception #1 Misconception “Doc said I had a 90% blockage. Thank goodness he fixed it in time and saved my life” • Facts • There is no such thing as a 90% stenosis • Even if there were, in most cases PCI is not a life-saving intervention

22. Evidence-Based Medicine PCI Misconception #2 Misconception “Mr. Jones had severe 2-vessel disease but really didn’t want a bypass operation, so I stented both vessels” • Facts • PCI is often the first step on the road to CABG • If a patient really wants to avoid CABG at all costs, medical therapy is the way to go

23. Pop Quiz #2 • How many patients with 3 Vessel Coronary Disease need to be sent to CABG vs. Medical Therapy to save a life at 10 years? A. 1 (CABG is better than medical therapy) B. 10 C. 15 D. 25

24. Pop Quiz #2 • How many patients with 3 Vessel Coronary Disease need to be sent to CABG vs. Medical Therapy to save a life at 10 years? A. 1 (CABG is better than medical therapy) B. 10 C. 15 D. 25 (10 yr Mortality CABG 26.4% vs. 30.5% Medical Therapy; p=0.03)

25. Evidence-Based Medicine PCI Misconception #3 Misconception “For most patients with multivessel disease, PCI can provide comparable long-term survival benefits and quality of life as bypass surgery” • Facts • The randomized trials of PCI vs. CABG have included only highly selected patients • Observational data still suggest improved survival with CABG in severe multivessel dz

26. Evidence-Based Medicine PCI Misconception #4 Misconception “Everyone should get primary PCI for ST-Elevation MI” • Facts • The randomized trials of PCI vs. fibrinolyis have included only highly selected patients with rapid treatment times • Observational data still suggest that treatment times are very prolonged in the US, particularly for transfer patients

27. Times in Randomized Trials vs. the “Real World” Median Door to Balloon Time: 180 min Median Door to Door (Transfer) Time: 120 Min Median PCI Hospital DB time: 53 Min <5% of patients had Total DB time <90 Min if a transfer was involved Compare this to the randomized studies with: Total DB times of 90 min, Transport times of 30 min, and PCI hospital DB times of 25 min BK Nallamothu, ER Bates, HM Krumholz, et al. Circulation 2005; 761

28. Evidence-Based Medicine PCI Misconception #5 Misconception An asymptomatic patient with an abnormal ETT is at high risk for short term complications “Thankfully, doc ordered that screening stress test when I turned 50 and that other nice doctor did an angioplasty the next day. I could have had a heart attack!” • Facts • The benefit of revascularization in asymptomatic patients (even our high-risk diabetic patients) is likely restricted to those with high risk stress test findings. • Risk of periprocedural MI approximates annual risk insome cases Sorraja P. Circulation. 2005; 112: I311

29. Evidence-Based Medicine PCI Misconception #6 Misconception Stable Angina means the patient needs revascularization to prevent a heart attack “Thankfully, doc sent me to the hospital for those chest pains and that other nice doctor did an angioplasty the next day. I could have had a heart attack!” • Facts • PCI reduces symptoms in chronic angina and may increase the risk of MI, or needing a CABG Sorraja P. Circulation. 2005; 112: I311

30. Evidence-Based Medicine PCI in Chronic Angina • 6 randomized trials (n=1904) • Symptomatic relief favored PCI (risk ratio=0.70) • All other outcomes (death, MI, CABG) tended to favor medical rx, but only CABG statistically significant • Unknown whether recent advances (stents, Gp2b/3a) have abolished excess ischemic complications PCI  Reduced Angina PCI  More Complications ? Bucher H et al. BMJ 2000;321:73-7

31. Stable CAD: PCI vs ConservativeMedical Management Meta-analysis of 11 randomized trials; N = 2,950 Favors PCI Favors Medical Management 0 1 2 Risk ratio (95% Cl) Katritsis DG et al. Circulation. 2005;111:2906-12.

32. Evidence-Based Medicine PCI for Chronic Angina • PCI compared with medical therapy is associated with better control of angina and improved functional status but increases the chances of subsequent CABG • Data analyzed are prior to widespread use of DES • It is appropriate to treat patients without high risk noninvasive testing with anti-anginal therapy and then refer those who fail medical therapy • Assess the amount of myocardium at risk • Those with low or intermediate risk stress test predictors need not undergo angiography • Those with high risk stress predictors should undergo further risk stratification with angiography

33. FFR FFR  0.75 FFR < 0.75 Randomize PCI Med Rx PCI P=NS 11% 17% 22% 2-year death/MI/repeat revasc. Evidence-Based Medicine PCI in Possible Angina without Ischemia PCI ????? • 57% of patients scheduled for PCI had normal FFR (i.e, no ischemia) • No difference in f/u anginal class • Costs ~$2500/pt higher with PCI strategy (no change in DES era) Pt scheduled for PCI but without documented ischemia (n=327) DEFERTrial Bech GW et al. Circulation 2001;103:2928-34

34. Evidence-Based Medicine What is “appropriate” PCI? • What are the proven benefits of PCI? • Key barriers to controlling overuse • Suggestions for improving appropriateness • Who should not receive PCI in 2007?

35. Evidence-Based Medicine PCI for STEMI:Short Term Clinical Outcomes PCI Fibrinolysis P < 0.0001 Frequency (%) P < 0.0001 P=0.0002 P=0.032 P=0.0003 P < 0.0001 P=0.0004 P < 0.0001 Hem.Stroke Death Death, no SHOCKdata ReMI Rec.Ischemia Total Stroke Major Bleed DeathMICVA N = 7739 Keeley E. et al., Lancet 2003; 361:13-20.

36. Conservative Invasive Risk Stratification ECG and Outcome in TACTICS/TIMI 18 Death / MI / Rehospitalization at 6 Months ST-segment s ( n = 852 ) No ST-segment s ( n = 1368 ) Cannon et al. N Engl J Med 2001; 344: 1879-87

37. Risk Stratification Troponin and Outcome in TACTICS/TIMI 18 30 Days 6 Months <0.001 <0.001 Tn T > 0.01 ng/ml Tn T > 0.01 ng/ml 0.082 0.002 Death/MI/hosp Death/MI Death/MI/hosp Death/MI Conservative 0.46 Tn T < 0.01 ng/ml Tn T < 0.01 ng/ml Invasive 0.80 0.58 0.90 Death/MI/hosp Death/MI Death/MI/hosp Death/MI Cannon et al. N Engl J Med 2001; 344: 1879-87

38. Evidence-Based Medicine Revascularization in Asymptomatic Diabetics • The benefit in this study was confined to those with high-risk perfusion abnormalities PCI  Improved survival Sorraja P. Circulation. 2005; 112: I311

39. Challenges to Controlling Overuse of PCI • Increasing safety of PCI • Perceived to be a “minor procedure” with virtually no downside • Drug-eluting stents • Remove fear of restenosis as a restraint • Self-referral bias and profound incentives to “overtreat” • Supply drives demand • Difficult to truly assess appropriateness without full clinical data and review of the angiogram

40. Potential Approaches to Overuse • Better education (of patients and physicians) • Eliminate self-referral • Mandatory second opinion? • But… would eliminate one of the key advantages of PCI • Reduce economic incentives • Pay as much for not doing angioplasty as for doing it (!) • Develop enforceable, evidence-based guidelines • Require demonstrable myocardial ischemia or evidence of myonecrosis for reimbursement

41. Summary: Who Needs a Cath After a Diagnosis of CAD in 2007 • Certain high risk stress test situations suggesting LMCA or 3VD as preparation for CABG • Purpose of cath is diagnostic rather than therapeutic • High Risk ACS (troponin positive, ST Segment Changes and/or high risk clinical features like CHF) • Patients with STEMI (as long as can be done rapidly and with trained personnel) • Failed medical therapy with demonstrable ischemia • Consider asymptomatic diabetic patients with high risk stress tests

42. Who should not receive PCI in 2007? • No angina • Except for patients with acute STEMI or NSTEMI, PCI remains a procedure whose primary benefit is symptomatic relief • No ischemia • PCI in absence of ischemia only increases complications and costs • No stenosis • “Vulnerable plaque” remains a sexy but unproven concept • No hope Four “No’s”

43. The Future: Is Today!