"Chronic Coronary Artery Disease"
Chronic Coronary Artery Disease Update Lecture Series Lisa L. Willett, MD General Internal Medicine September 23, 2008 Complicated case 65 yom with newly diagnosed CAD HTN on HCTZ (130/82) DM2 on metformin (A1C 7.5) Obesity (BMI 32) 2 weeks ago, CP and SOB with walking Positive stress test Fixedperfusion, moderate size anterior wall Reversible defect, moderate size anterolateral wall Clinical decisions, NEJM, Oct 25, 2007 Complicated case Cardiac cath: multi-vessel disease Occlusion of D1 of the LAD Long lesion with 70% mid LAD 80% calcified lesion in prox left cicumflex 50% posterior PDA LV-gram anterior wall hypokinesis, EF 45% Wants to discuss treatment options with you Which of the following do you recommend? Initiate appropriate medical therapy and follow for adherence and efficacy Initiate appropriate medical therapy and refer for PCI Initiate appropriate medical therapy and refer for CABG Results from North America 50 40 30 20 10 0 medical therapy medical therapy + PCI medical therapy + CABG Explanations cited Medical: poorly controlled risk factors COURAGE (no mortality benefit) PCI: needs revascularization, not CABG COURAGE (better QOL) CABG: CAD too severe, DM and ↓EF BARI, MASS-II Definition: Chronic CAD Not acute coronary syndromes Not primary prevention Not secondary prevention – too broad Patients with documented CAD Internists perspective Important concepts Road Map Indications for PCI vs medical therapy COURAGE, QOL Role of cardiac catheterization Appropriateness Criteria for Angiography Medical therapy How long to continue Clopidogrel after PCI Optimal Medical Therapy with or without PCI for Stable Coronary Disease Clinical Outcomes Utilization Revascularization & Aggressive Drug Evaluation (COURAGE) Trial Boden, et al, NEJM April 2007 Background In 2004, over 1 million stents in US PCI reduces death and MI in patients with ACS 85% PCI procedures elective in stable CAD PCI decreases frequency of angina and improves exercise, but what about events? Background: Vulnerability “All plaques are not equal” Flow limiting lesions cause angina and ischemia Vulnerable plaques cause AMI Can medical therapy stabilize these? Boden, Am J Cardiol 2008 Study Objective To determine if PCI plus optimal medical management reduces death and MI in patients with stable CAD vs optimal medical management alone vs http://www.drmcdougall.com/misc/2006nl/sept/stent.jpg Methods Randomized control trial 2,300 patients with stable CAD 35,500 evaluated; 32,500 excluded 50 US and Canadian centers Median time from first angina: 5 months 95% objective evidence of ischemia single (23%) or multiple (67%) defects Median follow up 4.6 years (9% lost) Inclusion Criteria Class 4 angina, medically stabilized and: Stenosis >70% in at least one proximal epicardial artery AND objective evidence of ischemia Resting ECG: ST depression or TWI Positive stress test Stenosis >80% and classic angina without stress testing 4,000 excluded Exclusion Criteria Persistent angina (class 4) (1,000) Markedly positive stress test Refractory heart failure or shock EF < 30% (5,000) Revascularization within past 6 months Coronary anatomy not suitable for PCI (1,000 left main disease; 3,000 contraindication to PCI) Groups PCI + OMT OMT Antiplatelet therapy Antiplatelet therapy ASA 81 – 325 mg and ASA 81 – 325 mg or Clopidogrel 75 mg Clopidogrel 75 mg Beta-blocker, amlodipine, nitrates PCI: target lesion, ACE or ARB <20% post stent, no LDL < 60 – 85 (statin) DES until final 6 mos HDL, TG next Lifestyle modification OMT=Optimal Medical Therapy Results: PCI PCI success: 94% received at least one stent 41% more than one Angiographic success 93% Clinical success 89% (no complications) Results: OMT Medical management success (5 yr): 70% had LDL < 85 mg/dL 65% had SBP < 130 mm Hg 94% had DBP < 85 mm Hg 45% of diabetics had A1C < 7.0% High adherence lifestyle modifications (diet, exercise, tobacco cessation) Mean BMI did not decrease Results: PCI vs OMT Hospitalization for ACS → same 12.4% PCI vs 11.8% OMT CI 0.84 to 1.37, p=0.56 Death → same 7.6% PCI vs 8.3% OMT CI 0.65 to 1.16, p=NS Subgroup analysis: multivessel, previous MI, diabetes → same Results Boden, et al, NEJM 2007;356:1503-1516 Limitations Study population Inclusioncriteria (91.5% excluded from study) White (86%) Male (85%) Bare metal stents (although published data without difference thus far) Important Points Profound impact of intensive medical therapy and lifestyle modification Safe and effective PCI is not the only viable and clinically defendable initial strategy All patients had a cath first – cannot directly translate to those who only had stress testing Bottom Line PCI added to optimal medical management did not reduce major cardiovascular events (death and nonfatal MI) compared with optimal medical management alone Stable vs vulnerable plaques Degree of angina relief was better for both groups, but higher in the PCI group Effect of PCI on Quality of Life in Patients with Stable Coronary Disease Clinical Outcomes Utilization Revascularization & Aggressive Drug Evaluation (COURAGE) Trial Weintraub, et al, NEJM Aug 14, 2008 Background PCI does not prevent major cardiovascular events in patients with chronic CAD PCI is indicated for the relief of angina To assess the effect of therapy (PCI vs OMT) on the relief of angina, QOL Methods: Questionnaires PCI + OMT vs. OMT Seattle Angina Questionnaire, 19 item specific to angina (0-100) Quantifies physical limitations due to angina Severity & frequency of angina Satisfaction with treatment, quality of life RAND-36 (SF-36) General health status Analyses truncated at 36 months, power Angina-free over time by group Quality of Life Results – at 36 months Seattle Angina Questionnaire PCI + OMT OMT p-value Physical limitation 74 74 0.68 Angina stability 72 70 0.39 Angina frequency 89 88 0.37 Treatment 92 92 0.78 satisfaction Quality of life 79 77 0.32 General Health Status RAND-36 Both groups similar at baseline Slight advantage to PCI at 3 months in many domains No advantage at 12 months Bottom line In patients with stable CAD, 5 months after first angina Mild improvement in quality of life, angina, and general health for the first 3-6 months Statistically significant, absolute incremental benefit very small No difference by 12 to 36 months Road Map Indications for PCI vs medical therapy COURAGE, QOL Role of cardiac catheterization Appropriateness Criteria for Angiography Medical therapy How long to continue Clopidogrel after PCI Can we extrapolate COURAGE? Rationale: If PCI is no better than medical management for someone with stable CAD, why bother to cath them? can’t I medically manage just as effectively? Appropriateness Criteria for Coronary Angiography in Angina: Reliability and Validity Hemingway, et al Ann Intern Med 2008;149:221-231 August 2008 Background Cardiac caths are one of most frequent procedures done in US 1.3 million in 2005 Questions about appropriateness Overuse is easy to assess (registries) Underuse is not – can’t measure those Patient specific factors may alter guideline recommendations (gray zone) Background ACC/AHA rigorous guideline development RCT evidence and expert opinion Translating ACC/AHA guideline into practice is difficult Appropriateness criteria includes the myriad of factors that influence clinical decisions Faxon, Annals Aug 2008, p276 Study Objective Determine the reliability and prognostic validity of patient specific appropriateness criteria for coronary angiography among patients with suspected angina Can experts agree which patients are appropriate for cath & would benefit from cath? Does it change prognosis? Methods Two independent panels in 9 UK centers 5 cardiologists, 5 FPs, 1 CV surgeon Developed appropriateness ratings for cath Scored 338 indications on 9-point scale Matched ratings to specific patient cohorts >9,000 patients, type of CP, risk factors, ECG Followed for clinical outcomes Death and ACS events, >99% follow up 3 years Results: Appropriateness Panel A Panel B Inappropriate (%) 82 57 Uncertain (%) 10 29 Appropriate (%) 8 15 Agreement between panels: Κ = 0.58 Highest in men patients (K=0.73) Lowest if no/non-diagnostic stress ECG (K=0.24) Use of angiography, by appropriateness ratings by panel A and panel B. Not performed in half of appropriate patients Hemingway, H. et. al. Ann Intern Med 2008;149:221-231 Cardiac death and ACS among appropriate patients by angiography Hemingway, H. et. al. Ann Intern Med 2008;149:221-231 Bottom Line Not undergoing coronary angiography when indicated was associated with a 2.5- fold worse outcome Cardiac death, MI, ACS Important Insights Moderate agreement between panels Speaks to using their tool for QI purposes Guidelines are difficult to apply clinically Ratings predicted adverse outcomes Many patients who were deemed appropriate for cath did not receive it and had worse outcomes Implications of the 2 studies COURAGE – all had a cath Appropriatenss – those appropriate for cath and didn’t get it did worse What is the benefit of the cath, if no PCI done? Revascularization in those with severe disease (left main, for example) More intensive secondary prevention Rx Can we extrapolate COURAGE? Rationale: If PCI is no better than medical management for someone with stable CAD, why bother to cath them? can’t I medically manage just as effectively? Road Map Indications for PCI vs. medical therapy COURAGE, QOL Role of cardiac catheterization Appropriateness Criteria for Angiography Medical therapy How long to continue Clopidogrel after PCI Historical perspective of stents Revolutionized angioplasty (1994) BMS re-stenosis rate still 25% by 6 months DES release medication to suppress neointimal proliferation Sirolimus (2002) Paclitaxel (2004) Kereiakes, JAMA Jan 2007 http://www.ptca.org/des.html Historical perspective of stents Early clinical trials showed DES decreased re-stenosis by 70 -80% Clinical use exceeded evidence clinical trials couldn’t keep up Now, aggregate of multiple small, short clinical trials show increase in very late stent thrombosis with DES After 9-12 months, extends up to 4 years Kereiakes, JAMA Jan 2007 Physiologic theory: Stents and Clopidogrel Drug (DES) may slow arterial healing and endothelial coverage Leads to polymer hypersensitivity, inflammation, and incomplete vessel remodeling at stent apposition site Antiplatelet therapy helps, but.. Discontinuation within 6 months → stent thrombosis and death Clopidogrel Use and Long- term Clinical Outcomes After Drug-Eluting Stent Implantation Eisenstein, et al JAMA January 2007 Study Aim Assess the association between clopidogrel use and long-term rates of death and MI after PCI with DES or BMS Methods Consecutive patients after initial PCI Either BMS (3,200) or DES (1,500) 6, 12, and 24 months after procedure 2 outcomes: death or MI 2 drugs: aspirin and clopidogrel patient response only Landmark analysis 6, 12 months Results: 24 months BMS with clopidogrel BMS without DES with clopidogrel DES without BMS: no difference in death or MI DES: significantly better if on clopidogrel Death (1.6% vs 5.8%) and MI (0.8% vs 3.3%) DES - clopidogrel BMS + clopidogrel DES - clopidogrel Bottom Line BMS does not need long term clopidogrel DES + clopidogrel had better outcomes than BMS DES off clopidogrel = bad IF patient can’t be on clopidogrel for at least one year, should have a BMS Don’t stop clopidogrel unless you need to Ever?? AHA/ ACC Guidelines for Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2006 Update Smith, et al Circulation 2006;113:2363-72 Interventions Smoking Antiplatelets Physical activity Renin-Angiotensin- Weight Aldosterone system Beta Blockers Blood pressure Influenza vaccine Lipids Diabetes See GIM website slides Road Map Indications for PCI vs. medical therapy COURAGE, QOL Role of cardiac catheterization Appropriateness Criteria for Angiography Medical therapy How long to continue Clopidogrel after PCI Take Home Points: Chronic CAD Patients with angina and concern for CAD need a cath Your clinical suspicion is important Positive stress test, age, women If cath shows chronic stenosis (70-80%), medical management is a valid option Take Home Points Medical management needs to be aggressive Monitor closely for the full benefit PCI has value for patients with symptoms despite maximal medical therapy But after 1-3 years the difference wanes Clopidogrel should be continued indefinitely (at least one year) http://gabrielutasi.com/060207.heart_disease.gif Level of Evidence & Classification Estimate of certainty of treatment effect Level A, B, C Quality of the studies (multiple RCTs vs consensus) Size of treatment effect Class I, IIa, IIb, III Risk vs. benefit Should Reasonable (conflict, but weight of evidence favors) May be considered (conflict, less well established) No way (not useful, maybe harmful) Smoking Ask at every visit, advise to quit… cessation Physical 30 minutes, 7 days per week (5 activity days minimum) Weight BMI 18.5 to 24.9 Waist circumference Influenza For all with coronary disease vaccine I (B): Should be done, B evidence Blood pressure Initial treatment with beta < 140/90 mm/Hg blocker and/or ACE-I, then or thiazide I(A) <130/80 if DM or CKD Lipids LDL should be < 100 I(A), LDL < 100 mg/dL if LDL > 100, treat I(A) If TG > 200, non-HDL LDL < 70 IIa (A), for should be <130 I(C) chronic CAD, especially ACS (not for DM) Diabetes Treat to goal I(B) A1C < 7% Antiplatelets ASA 75 - 162 mg indefinitely I(A) Clopidogrel 75 mg plus ASA for up to 1 year after ACS or PCI with stent I (B) Beta Blockers Start and continue indefinitely for those with MI, ACS, LV dysfunction I(A) Consider chronic therapy for all others with CAD or vascular disease or DM IIa (C) RAAS blockers ACE-I: EF<40%, HTN, DM, CKD I(A); all others I(B) If low risk, well controlled and re- vascularized IIa (B) ARBs: for those ACE intolerant Aldosterone blockade: post-MI without renal/hyperkalemia, already on therapeutic ACE and BB, have LVEF <40% and either have DM or heart failure I(A)