Laboratorio Aziendale di Interventistica Cardiovascolare Firenze, 9 novembre 2010 L’APPROCCIO INTERVENTISTICO NELLA MALATTIA CORONARICA STABILE E’ LO STANDARD OF CARE Roberto Becherini Laboratorio Aziendale di Interventistica Cardiovascolare Azienda USL 3 Pistoia

Background A differenza di quanto avviene nelle SCA, non ci sono dimostrazioni generali di superiorità in termini di “hard endpoints” di PCI vs OMT nel paziente con angina cronica stabile (CIC) I grandi studi clinici di confronto prodotti negli ultimi anni sembrano ridimensionare il ruolo dell’interventistica nella CIC vs OMT (Courage 2007) La ricorrenza di “hard endpoint” nella popolazione generale di pazienti affetti da CIC è relativamente bassa anche nel medio termine ma molto eterogenea. Oggi vengono confrontati pazienti che hanno eseguito PCI con concetti e materiali oramai non più in uso (Impatto PCI difficilmente misurabile) MA LA ROUTINE CLINICA ATTUALE COMPRENDE IN MOLTI CASI IL RICORSO AL CATHLAB ANCHE NEL PAZIENTE CON CIC

Trattamento della CIC: obiettivi Ridurre l’ischemia e alleviare i sintomi (++) Migliorare la qualità della vita (++) Prevenire morte e infarto (+/-) Angina treatment: Objectives As outlined in the current guidelines, angina treatment is directed towards preventing MI and death (thereby improving the “quantity” of life) as well as preventing further ischemia and related symptoms (thereby improving quality of life). Gibbons RJ et al. ACC/AHA 2002 guidelines. www.acc.org/clinical/guidelines/stable/stable.pdf

CIC: le sfide terapeutiche Farmaci antianginosi La maggior parte dei pazienti non tollerano i dosaggi efficaci nei trials Modifiche della storia naturale della malattia Gli obiettivi terapeutici di PA, Colesterolo e glicemia vengono rivisti continuamente al ribasso PCI Alcuni pazienti non sono candidati “ideali” Modifiche dello stile di vita Gravati da problemi di compliance nel lungo termine CAD: Treatment challenges Clinicians have a number of effective treatment modalities available for managing patients with CAD. However, each has its limitations and tailoring a regimen to the needs of a specific patient can present difficulties, particularly in the elderly and those with diabetes or heart failure. These patients frequently are not suitable candidates for revascularization, can only tolerate a modest exercise regimen, and have a relative intolerance to full doses of beta-blockers, calcium channel blockers, and nitrates.

CIC: PCI vs terapia medica Meta-analysis of 11 randomized trials; N = 2950 Favors medical management Death Cardiac death or MI Nonfatal MI CABG PCI Favors PCI P 0.68 0.28 0.12 0.82 0.34 Stable CAD: PCI vs conservative medical management Katritsis et al conducted a meta-analysis of 11 randomized trials that compared PCI with conservative medical management in patients with chronic stable CAD. While PCI effectively relieves angina, it does not offer any long-term advantage over medical management in terms of death, MI, or need for additional revascularization. 1 2 Risk ratio (95% Cl) Katritsis DG et al. Circulation. 2005;111:2906-12.

Schomig et al JACC 2008;52:894-904

La “crescita incontrollata” di PCI 5% national sample of Medicare beneficiaries Substantial growth in PCI Limitations of older anginal therapies as well as technical improvements in intervention procedures have led to increasing use of elective percutaneous coronary intervention (PCI) to treat stable coronary artery disease (CAD). *Adjusted for age, gender, race Lucas FL et al. Circulation. 2006;113:374-9.

Linee guida ESC angina cronica stabile

Linee guida ESC angina cronica stabile

The Duke Treadmill Score Exercise time - (5 X ST Deviation) – (4 X Angina Index)= Score 9 Angina index: 0 No angina 1 Typical angina during ex 2 Stop ex for angina 8,3 8 7 6 5 Cardiac Death (%) 4 2,9 3 2 Low risk: 5 or greater Medium Risk: -10 to +4 High risk: -11 or less 0,9 1 Low Medium High Mark DB. Ann Inter Med. 1987: 106; 793. Hachamovich R. Circulation 1996; 93: 905.

Treadmill Score: Prognosis and Prevalence of Disease DTS Risk Category 1-Yr Mortality No Stenosis ≥75% 1 VD ≥75% 2 VD ≥75% 3VD ≥75% or LM ≥75% Men    Low   0.9% 52.6% 22.4% 13.6% 11.4%    Mod   2.9% 17.8% 15.6% 27.9% 38.7%    High 8.3% 1.8% 9.1% 17.5% 71.5% Women 0.5% 80.9% 9.4% 6.2% 3.5% 1.1% 65.1% 14.2% 12.4% 10.8% 18.9% 24.3% 46% 50% maschi low-risk (0.9% mortality/year) Hanno CAD di varia estensione   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

Cardiac Death or Myocardial Infarction Rate/Year Stratified by SPECT Quantitative Ischemia 5 Myocardial Infarction 4,2 * 4 Cardiac Death * 2,9 2,9 ** 3 2,7 Event Rate % 2,3 2 1 0,8 0,5 0,3 Normal Mildly Normal Moderately Abnormal Severely Abnormal N = 2946 884 455 898 * Statistically significant increase as function of scan result ** Increased rate of MI vs cardiac death within scan stratum Hachamovitch, Diamond et al. Circ 1998;97:535

Courage Nuclear Substudy (n=314 / 2,287) Hypothesis: Reduction in ischemia will be greater for patients Randomized to PCI+OMT than for those randomized to OMT Serial rest/stress myocardial perfusion SPECT (MPS) To compare patient management strategy for ischemia reduction Documented Pre-Rx Ischemia PCI + OMT OMT (n=159) (n=155) Repeat MPS* Repeat MPS* at 6-18m at 6-18 m Pre-Rx = off meds Post-Rx = on meds *Timing chosen to occur beyond window of in-stent restenosis and delayed to allow effects of medical Rx to be observed Shaw et al. J Nucl Cardiol 2006;13:685

Primary Endpoint: % with Ischemia Reduction  5% Myocardium (n=314) 50 40 33,3 30 Ischemia Reduction  5% P=0.004 19,8 20 10 PCI + OMT (n=159) OMT (n=155) Shaw et al. J Nucl Cardiol 2006;13:685

Ischemia Normalization* on Follow-Up MPS In PTS with Significant Ischemia Resolution 50 P=0.007 40 31,4 % with Low Risk* MPS 30 17,8 20 10 PCI + OMT (n=53) OMT (n=29) *1% ischemic myocardium Shaw et al. J Nucl Cardiol 2006;13:685

Rates of Death or MI by Residual Ischemia on 6-18m MPS 50 39,3 P=0.023 40 30 P=0.063 Death or MI rate (%) 22,3 20 15,6 10 0,0 0% 1 - 4.9% 5 -9.9% 10%  (n=23) (n=141) (n=88) (n=62) Shaw et al. J Nucl Cardiol 2006;13:685

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

“ Stankovich G, Bras J Cardiol 2010

PCI in angina cronica stabile …per molti ma non per tutti… Ecocardiogramma Alterazioni di cinetica, riduzione di EFVSX ANATOMIC ASSESSMENT Test ergometrico: Duke Treadmill score Test provocativi di II livello (SPECT) Riduzione di EF durante stress, punteggio di ischemia >10%

Impatto dell’anatomia coronarica sulla prognosi CIC ACC/AHA appropriateness for PCI; Circulation 2009

PCI in CIC. Livelli di appropriatezza BASSO RISCHIO RISCHIO INTERMEDIO ACC/AHA appropriateness for PCI; Circulation 2009

PCI in CIC. Livelli di appropriatezza nel paziente ad alto rischio ACC/AHA appropriateness for PCI; Circulation 2009

PCI vs CABG Fear for the knife? Questi livelli di appropriatezza non tengono conto dei risultati degli studi dedicati PCI vs CABG come Syntax ACC/AHA appropriateness for PCI; Circulation 2009

Misurazione invasiva della riserva coronarica (FFR) Non più angiografia e “riflesso oculostenotico” OCT IVUS ELASTOGRAPHY M-OA Misurazione invasiva della riserva coronarica (FFR)

Caratteristiche della FFR FFR non influenzata da modifiche in PA, FC o contrattilità FFR normale è sempre 1 in tutte le coronarie ed i tutti i pazienti FFR tiene conto anche dei circoli collaterali nella distribuzione del flusso Bech et al, Circulation 2001

“Decision making” Con FFR 0.75 FFR < 0.75 ischemia inducibile: rivascolarizzazione è giustificata. FFR > 0.75 ischemia altamente improbabile: ? È giustificato posporre (DEFER) PCI anche se l’apparenza angiografica è severa? DEFER trial 325 pat. all accepted for elective PTCA of a single lesion. Just prior to PTCA FFR was determined Dus bij een FFR minder dan 0.75 is revascularisatie gerechtvaaardigd. Maar geldt het omgekeerde ook. Met andere waarde: is afzien van revascularistatie gerechtvaadigd als de FFR meer dan 0.75 bedraagt. Dit was de vraag in het eerste deel van mijn proefschrift die centraal stond in de DEFER studie. In deze studie bij 325 patienten die geaccepteerd waren voor PTCA werd vooraf de FFR gemeten. Bech et al, Circulation 2001

DEFER 2 yrs follow-up: event-free survival No PTCA Na 2 jaar was de event-free survival in de PTCA groep, deze rode lijn, 83%, maar in de groep die geen PTCA kreeg deze blauwe lijn 89%. We moeten dus concluderen dat het dotteren van een vernauwing met een FFR van meer dan 0.75 niet zinvol is en dat deze patienten het beste medicamenteus behandeld kunnen worden. PTCA Bech et al, Circulation 2001

FAME trial. Study Protocol MV lesions warranting PCI identified FFR-Guided Angio-Guided PCI performed on indicated lesions only if FFR ≤0.80 PCI performed on indicated lesions Randomized Primary Endpoint Composite of death, MI and repeat revasc. (MACE) at 1 year Key Secondary Endpoints Individual rates of death, MI, and repeat revasc., MACE, and functional status at 2 years Tonino PA et al. JACC 2010

1 Year Event-Free Survival Absolute Difference in MACE-Free Survival FFR-guided Angio-guided 30 days 2.9% 90 days 3.8% 180 days 4.9% 360 days 5.1% Tonino PA et al. JACC 2010

1 Year Economic Evaluation Bootstrap Simulation Angio Less Costly Angio Better FFR Better QALY FFR Less Costly USD Tonino PA et al. JACC 2010

2 Year Survival Free of MACE FFR-Guided Angio-Guided 730 days 4.5% Tonino PA et al. JACC 2010

FAME investigators Conclusions These results continue to support the evolving paradigm of: “Functionally Complete Revascularization” i.e. stenting of ischemic lesions and medical treatment of non-ischemic ones Tonino PA et al. JACC 2010

Evidence-Based Medicine PCI for Chronic Angina Interpretation of Courage Trial by Duane S. Pinto, M.D (Harvard med school) “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 risk stress test predictors need not undergo angiography Those with high risk stress predictors should undergo further risk stratification with angiography”

- AFFIDARSI ALLA FISIOPATOLOGIA - Insegnamenti della Evidence based Medicine PCI in angina cronica stabile La PCI non è da considerare un’alternativa alla OMT, ma un’integrazione, tanto più utile quanto maggiore è il livello di rischio clinico del soggetto Trattare pazienti sintomatici nonostante terapia medica massimale o con marker di rischio (ECG, SPECT o EchoST) intermedio-elevato La PCI non sposta la storia naturale della malattia CAD: non trattiamo “tubature”, ma organi vivi con una risposta biologia variabile Non cedere alla tentazione del riflesso oculo-stenotico: abbiamo a disposizione mezzi a sufficienza per offrire al paziente una rivascolarizzazione funzionalmente completa (DEFER, FAME) Non è facile orientarsi nella folla di studi e di trials più o meno rigorosi in un campo così eterogeneo che non può essere scansito completamente in un solo gruppo di confronto. - AFFIDARSI ALLA FISIOPATOLOGIA - PIU’ ESTESO E’ IL TERRITORIO A RISCHIO ISCHEMICO, MAGGIORE SARA’ IL BENEFICIO CHE OFFRO AL PAZIENTE CON PCI, COMPATIBILMENTE CON LE SUE CARATTERISTICHE CLINICHE GENERALI