Nuove opportunità nel trattamento medico ottimale della coronaropatia stabile

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

2 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

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4 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.

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

9 L insostenibile leggerezza della angioplastica nella cardiopatia ischemica cronica

10 JAMA Intern Med. August 25, 2014

11 Metanalisi effetto PCI in pazienti con CAD stabile e documentazione ischemia Stergiopoulos et al. JAMA Intern Med 2014;174: 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 Revasc Unplanned compared with OMT alone. Angina in FU

12 Il ruolo irrinunciabile della terapia medica ottimale nell angina stabile

13 «Gestione terapeutica della cardiopatia ischemica cronica sintomatica"

14 Gestione terapeutica della cardiopatia ischemica cronica sintomatica"

15 Gestione terapeutica della cardiopatia ischemica cronica sintomatica"

16 undergoing PCI, less than half were receiving OMT.

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

18 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

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

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

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

22 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.

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

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

25 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.

26 Eur Heart J, August 30, 2013

27 L amore per i nitrati ai tempi del colera

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29 Rassaf, Eur Heart J 2013

30 Nitrati «long-acting» e funzione endoteliale

31 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

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33 Eur Heart J, August 30, 2013

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35 Eur Heart J, August 30, 2013

36 Mega J, Circulation 2010

37 placebo rest stress ranolazine rest stress

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41 Facciamo così?

42 La gestione della cardiopatia ischemica cronica in Europa ed in Italia Europa*: la gestione terapeutica del paziente con CIC Italia: la gestione terapeutica del paziente con CIC 17% 44% 56% 83% Nuovi Approcci Terapeutici** Nitrati Long Acting Nuovi Approcci Terapeutici** Nitrati Long Acting

43 E tempo di cambiare paradigma!

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

46 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

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48 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 Fonte dati Medical Audit 2013 Ranolazina