Nuove opportunità nel trattamento medico ottimale della coronaropatia stabile PL. Temporelli Istituti Clinici Scientifici Maugeri Divisione di Cardiologia Riabilitativa, Veruno

DISCLOSURE INFORMATION Temporelli Pier Luigi negli ultimi due anni ho avuto i seguenti rapporti anche di finanziamento con soggetti portatori di interessi commerciali in campo sanitario: Letture per: Sigma-Tau MSD Menarini

Case # 1 A 62-year-old man has sustained an inferior ST segment-elevation MI. He has undergone successful primary angioplasty with implantation of a drug-eluting stent for acute occlusion of the right coronary artery. There were no other significant coronary lesions, and the left ventricular ejection fraction at hospital discharge was 55%. Smoking was the sole cardiovascular risk factor and was stopped at time of MI. Six months after MI, an exercise test was performed (80% of maximum predicted heart rate; negative). At present, two years post-MI, the patient is asymptomatic and is receiving optimal medical therapy for secondary prevention.

Solo due cose sono infinite: l’universo e la stupidità umana… E non sono sicuro della prima

L’insostenibile leggerezza della angioplastica nella cardiopatia ischemica cronica

JAMA Intern Med. August 25, 2014

Metanalisi effetto PCI in pazienti con CAD stabile e documentazione ischemia Stergiopoulos et al. JAMA Intern Med 2014;174:232-40 Morte IMA non fatale CONCLUSIONS AND RELEVANCE: In patients with stable CAD and objectively documented myocardial ischemia, PCI with OMT was not associated with a reduction in death, nonfatal MI, unplanned revascularization, or angina compared with OMT alone. Revasc Unplanned Angina in FU

Il ruolo irrinunciabile della terapia medica ottimale nell’angina stabile

«Gestione terapeutica della cardiopatia ischemica cronica sintomatica"

Gestione terapeutica della cardiopatia ischemica cronica sintomatica"

Gestione terapeutica della cardiopatia ischemica cronica sintomatica"

…undergoing PCI, less than half were receiving OMT ….

Qual’è la terapia ottimale nell’angina stabile secondo le Linee Guida?

Key points Lifestyle changes are vital in the management of stable angina, including  smoking cessation, healthy diet, weight loss and control of lipid levels Associated conditions, such as hypertension and diabetes, should be treated according to relevant guidance Anti-anginal drugs should be titrated to the optimal licensed dose to control symptoms Revascularisation should be considered in selected patients

Medical management of patients with stable coronary artery disease ESC Guidelines. Eur Heart J 2013; 34: 2949-3003

Medical management of patients with stable coronary artery disease ESC Guidelines. Eur Heart J 2013; 34: 2949-3003

Medical management of patients with stable coronary artery disease ESC Guidelines. Eur Heart J 2013; 34: 2949-3003 ESC Guidelines. Eur Heart J 2013; 34: 2949-3003

In the first-line setting, the major changes in the new guidelines are the upgrading of calcium channel blockers, the distinction between dihydropyridines and non-dihydropyridine calcium channel blockers, and the presence of important statements regarding the combination of calcium channel blockers with beta-blockers.

Limitations of Conventional Antianginal Therapies Adapted from Gibbons RJ, et al. ACC/AHA 2002 Guideline Update for Chronic Stable Angina Limitations Comorbidity Challenges Side Effects Beta Blockers Nitrates Calcium Antagonists COPD Bradycardia A-V conduction problems Peripheral Vascular Disease Sick Sinus Syndrome Left ventricular outflow tract obstruction Heart failure Left ventricular dysfunction Sick sinus syndrome Sexual dysfunction Fatigue Depression Hypotension Syncope Headache Tolerance Flushing Dizziness Edema

CESAR - Knight C and Fox KM Meta-analysis (22 studies) Combination with beta-blocker or calcium channel blocker vs monotherapy in stable angina: lack of benefits Study Combinations Findings Atenolol TIBET - Fox KM Nifedipine SR No additive benefit of combined therapy Combination Eur Heart J 1996;17:96-103 608 patients Metoprolol IMAGE - Savonitto S Nifedipine SR No additive benefit of combined therapy J Am Coll Cardiol 1996;27:311-316 Combination 249 patients CESAR - Knight C and Fox KM Amlodipine + Atenolol vs No additive benefit of combined therapy Am J Cardiol 1998;81:133-136 Diltiazem + Atenolol Meta-analysis (22 studies) Klein W, Jackson G, and Tavazzi L -Blocker No additive benefit of combined therapy after 6 hours Calcium antagonist Coron Artery Dis 2002; 13:427-436 Combination

In the first-line setting, the major changes in the new guidelines are the upgrading of calcium channel blockers, the distinction between dihydropyridines and non-dihydropyridine calcium channel blockers, and the presence of important statements regarding the combination of calcium channel blockers with beta-blockers. In the second-line setting, the 2013 ESC guidelines recommend the addition of long-acting nitrates, ivabradine, nicorandil or ranolazine to first-line agents. Trimetazidine may also be considered. However, no clear distinction is made among different second-line drugs, despite different quality of evidence in favour of these agents.

Eur Heart J , August 30, 2013

L’amore per i nitrati ai tempi del colera

Rassaf, Eur Heart J 2013

Nitrati «long-acting» e funzione endoteliale

Long-acting nitrates induce or worsen oxidative stress by It is known that none of the available long acting nitrates exerts 24-h antianginal and anti-ischemic therapeutic effects Long-acting nitrates induce or worsen oxidative stress by Increasing intracellular superoxide Inactivating nitric oxide and formation of peroxinitrite Inhibiting prostacyclin formation Stimulating endothelin expression Inhibiting the activity of soluble guanylate cyclase Long-acting nitrate drugs increase sympathetic activation and apocrine neurohormonal mechanisms by Increasing production of norepinephrine (also called noradrenalin) Increasing production of angiotensin II

Eur Heart J , August 30, 2013

Eur Heart J , August 30, 2013

Mega J, Circulation 2010

stress rest ranolazine placebo

Facciamo così?

La gestione della cardiopatia ischemica cronica in Europa ed in Italia

E’ tempo di cambiare paradigma !

cardiopatia ischemica cronica stabile Algoritmo per l’ottimale gestione del trattamento sintomatico del paziente con cardiopatia ischemica cronica stabile Sintomi non controllati Ivabradina * Ranolazina Associazione con: Ca – antagonisti Nitrati LA Trimetazidina Da valutare: Terapia di prima linea: β –bloccante Controindicazioni o intolleranza Ranolazina Ivabradina * * In pz in RS, FC ≥70 bpm, FEVS≤40% Ca – antagonisti Nitrati LA Trimetazidina Da valutare:

Take Home Message Alla luce delle evidenze cliniche la terapia medica ottimale dovrebbe essere il fondamento nella gestione del paziente con angina stabile Terapia medica ottimale non vuol dire assenza di rivascolarizzazione a priori, piuttosto la presenza di un intensivo approccio farmacologico e non Nell’ambito di un ottimale approccio farmacologico secondo le recenti Linee Guida internazionali e documenti di consenso nazionali le nuove molecole, in particolare ranolazina, occupano un ruolo di rilievo

La gestione del paziente in rivalutazione Lo specialista (CAR-GER-DIA) in quasi l’80% dei casi ripete la prescrizione di nitrati a lunga durata d’azione La gestione del paziente in rivalutazione Ranolazina Fonte dati Medical Audit 2013