Συντηρητική ή επεµβατική αντιµετώπιση χρόνιας Στεφανιαίας Νόσου

Σεµινάριο Οµάδων Εργασίας της ΕΚΕ Θεσσαλονίκη 2013 Συντηρητική ή επεµβατική αντιµετώπιση χρόνιας Στεφανιαίας Νόσου Μηνύµατα από πρόσφατες κλινικές µελέτες COURAGE, OAT, PARR-2, STICH, ISCHEMIA Απόστολος Χρήστου Καρδιολόγος

δηλωση Δήλωση συµφερόντων;

COURAGE: Background and objective In patients with stable CAD Elective PCI procedures are common in the US (~85% of all PCI) PCI decreases angina frequency but long-term prognostic effects on CV events are not known Antianginal agents also provide symptom relief whereas ACEIs, ASA, β-blockers, and statins have been shown to prevent MI and death COURAGE was designed to evaluate whether PCI plus optimal medical therapy, as initial management strategy, reduces risk of major CV events compared with optimal medical therapy alone in stable CAD patients Boden WE et al. N Engl J Med. 2007;356:1503-16. Boden WE et al. Am Heart J. 2006;151:1173-9.

COURAGE: Study design AHA/ACC Class I/II indications for PCI, suitable coronary artery anatomy + 70% stenosis in 1 proximal epicardial vessel + objective evidence of ischemia (or 80% stenosis + CCS class III angina without provocation testing) Optimal medical therapy* + PCI (n = 1149) Randomized Optimal medical therapy (n = 1138) Primary outcomes: All-cause mortality, nonfatal MI Secondary outcomes: Death, MI, stroke; ACS hospitalization Follow-up: Median 4.6 years *Intensive pharmacologic therapy + lifestyle intervention CCS = Canadian Cardiovascular Society Boden WE et al. Am Heart J. 2006;151:1173-9. Boden WE et al. N Engl J Med. 2007;356:1503-16.

COURAGE: Treatment effect on primary outcome All-cause death, MI (time to first event) 1.0 0.9 Survival free of primary outcome 0.8 0.7 0.6 HR 1.05 (0.87-1.27) P = 0.62* 0.5 0 0 1 2 3 4 5 6 7 Years Medical therapy PCI + medical therapy No. at risk Medical therapy 1138 1017 959 834 638 408 192 30 PCI 1149 1013 952 833 637 417 200 35 *Unadjusted Boden WE et al. N Engl J Med. 2007;356:1503-16.

COURAGE: Treatment effects All-cause death Myocardial infarction 1.0 1.0 Overall survival No. at risk Medical therapy PCI 0.9 0.8 0.7 0 1138 1149 HR 0.87 (0.65-1.16) P = 0.38* 0 1 2 3 4 5 6 7 1073 1094 1029 1051 Years 917 929 717 733 468 488 302 312 38 44 Survival free of MI 0.9 0.8 0.7 0 1138 1149 HR 1.13 (0.89-1.43) P = 0.33* 0 1 2 3 4 5 6 7 1019 1015 962 954 Years 834 833 638 637 409 418 192 200 120 134 Medical therapy PCI + medical therapy *Unadjusted Boden WE et al. N Engl J Med. 2007;356:1503-16.

COURAGE: Treatment effect on hospitalization for ACS 1.0 0.9 Survival free of ACS 0.8 0.7 HR 1.07 (0.84-1.37) P = 0.56* No. at risk Medical therapy PCI 0 0 1 2 3 4 5 6 7 Years 1138 1149 1025 1027 Medical therapy 956 957 833 835 662 667 PCI + medical therapy 418 431 236 246 127 134 *Unadjusted Boden WE et al. N Engl J Med. 2007;356:1503-16.

COURAGE: Treatment effect on angina Angina-free (%) 80 70 60 50 40 30 20 10 0 P = 0.02 NS P < 0.001 NS Baseline 1 year 3 years 5 years PCI + medical therapy Medical therapy Boden WE et al. N Engl J Med. 2007;356:1503-16.

COURAGE: Summary and implications PCI added to optimal medical therapy did not reduce risk of death, MI, or other major CV events compared with optimal medical therapy alone Findings reinforce existing clinical practice guidelines Optimal medical therapy and aggressive management of multiple treatment targets without initial PCI can be implemented safely in the majority of patients with chronic stable angina, even those with objective evidence of ischemia and significant multivessel CAD Boden WE et al. N Engl J Med. 2007;356:1503-16.

www.escardio.org/guidelines

OAT Trial: Study Design 2166 patients with angiography on day 3-28 post-mi with evidence of total occlusion of the infarct-related artery with poor or absent antegrade flow (TIMI flow grade 0 or 1); and met a criterion for increased risk, defined as ejection fraction <50%, proximal occlusion of a major epicardial vessel with a large risk region, or both Exclusions: NYHA class III or IV heart failure, shock, serum creatinine concentration >2.5 mg/dl, angiographically significant left main or three-vessel coronary artery disease, angina at rest, or severe ischemia on stress testing. Randomized. 22% female, mean age 59 years, mean follow-up 3 years, mean EF 48% at baseline Concomitant medications: Aspirin, anticoagulation if indicated, ACE inhibitors, beta-blockers, and lipid-lowering therapy, unless contraindicated PCI with stenting n=1082 Medical Therapy n=1084 Primary Endpoints: Death, MI, or NYHA class IV heart failure

OAT Trial: Primary Endpoint Primary Endpoint of death, reinfarction, NYHA class IV heart failure (% patients) Hazard Ratio 1.16, p=0.20 The primary endpoint of death, reinfarction, or NYHA class IV heart failure occurred in 17.2% of the PCI group and 15.6% of the medical therapy group ([HR] 1.16, p=0.20).

PCI vs Medical Therapy in OAT Trial Total Events Nonfatal Myocardial Infarction (Hochman, NEJM 2006; 355: 2395)

All-Cause Mortality As Randomized HR 0.86 (0.72, 1.04) P = 0.123 0.46 0.41

Cardiovascular Mortality As Randomized HR 0.81 (0.66, 1.00) P = 0.050 Adjusted HR 0.77 (0.62, 0.94) Adjusted P = 0.012 0.39 0.32

Death or Cardiovascular Hospitalization As Randomized 0.68 0.58 HR 0.74 (0.64, 0.85) P < 0.001 Adjusted HR 0.70 (0.61, 0.81) P < 0.001

Time-varying Hazard Ratios As Randomized

In the subset of 601 patients in the trial who had myocardial viability imaging, those with viable myocardium were not less likely to die than those without viable myocardium after adjustment for baseline variables (37% versus 51%,P=0.21)

STICH (Surgical Treatment for IsChemic Heart failure) study Τhe outcomes of patients with ischemic heart disease and a reduced left ventricular ejection fraction are unaffected by whether they show viable myocardium on imaging.

PARR-2 Trial: Results Survival Curves (on the Basis of Time to First Occurring Outcome Out of the Composite Event). The positron emission tomography adherence group versus standard care arm. Adjusted hazard ratio = 0.62, 95% CI 0.42 to 0.93, p = 0.019. Beanlands et al. Journal of the American College of Cardiology Volume 50, Issue 20 2007, 2002 2012

J Am Coll Cardiol. 2012;60(24):2564-2603. doi:10.1016/j.jacc.2012.07.012 Copyright The American College of Cardiology.

Συµπεράσµατα Παρά τη σαφή µείωση της θνητότητας και νοσηρότητας µε την PCI στον τοµέα των οξέων στεφανιαίων συνδρόµων, η φαρµακευτική-συντηρητική αντιµετώπιση αποτελεί ασφαλή εναλλακτική πρακτική όσον αφορά τη χρόνια στεφανιαία νόσο. Εφαρµογή των οδηγιών που προέκυψαν από τις µεγάλες κλινικές δοκιµές σχετικά µε την PCI, στην χρόνια σταθερή στηθάγχη και στη καθυστερηµένη διάνοιξη ολικών αποφράξεων. Εξατοµίκευση της στρατηγικής: Στόχος θα πρέπει να είναι η µείωση ή εξάλειψη της ισχαιµίας ανεξάρτητα του τρόπου που θα επιτευχθεί (συντηρητική ή επεµβατική αντιµετώπιση). Περισσότερη τεκµηρίωση για το ρόλο της ανίχνευσης βιώσιµου µυοκαρδίου για τη λήψη αποφάσεων. Δεδοµένης της τρέχουσας χρηµατοπιστωτικής κρίσης, τώρα είναι πιο σηµαντικό από ποτέ, να αναδείξουµε τη σχέση κόστους-αποτελεσµατικότητας στην κλινική πρακτική µας.