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

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.

Case # 1

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

Revasc Unplanned Angina in FU

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.

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.

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 • Bradycardia

• Heart failure

• Left ventricular dysfunction

• Sick sinus syndrome

• A-V conduction problems

• Sexual dysfunction

• Fatigue

• Depression

• Hypotension

• Syncope

• Headache

• Syncope

• Tolerance

• Hypotension

• Flushing

• Dizziness

• Hypotension

• Edema

• Fatigue

Limitations of Conventional Antianginal Therapies

Findings Combinations Study

No additive benefit of combined therapy

Atenolol

Nifedipine SR

Combination

608 patients

TIBET - Fox KM

Eur Heart J 1996;17:96-103

No additive benefit of combined therapy

Metoprolol

Nifedipine SR

Combination

249 patients

IMAGE - Savonitto S

J Am Coll Cardiol 1996;27:311-316

No additive benefit of combined therapy Amlodipine + Atenolol vs

Diltiazem + Atenolol

CESAR - Knight C and Fox KM

Am J Cardiol 1998;81:133-136

No additive benefit of combined therapy

after 6 hours

-Blocker

Combination

Calcium antagonist Coron Artery Dis 2002; 13:427-436

Meta-analysis (22 studies) Klein W, Jackson G, and Tavazzi L

Combination with beta-blocker or calcium channel blocker vs monotherapy in stable angina:

lack of benefits

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 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

It is known that none of the available long acting nitrates exerts 24-h antianginal and anti-ischemic therapeutic effects

Eur Heart J , August 30, 2013

Eur Heart J , August 30, 2013

Mega J, Circulation 2010

stress rest

stress rest

ranolazine

placebo

Facciamo così?

La gestione della cardiopatia ischemica cronica in Europa ed in Italia

44%

56%

Europa*: la gestione terapeuticadel paziente con CIC

Nuovi Approcci Terapeutici**

Nitrati Long Acting

17%

83%

Italia: la gestione terapeutica del paziente con CIC

Nuovi Approcci Terapeutici**

Nitrati Long Acting

E’ tempo di cambiare paradigma !

Algoritmo per l’ottimale gestione del trattamento sintomatico del paziente con

cardiopatia ischemica cronica stabile

Sintomi non controllati

Ivabradina *

Ranolazina

Associazione con:

Terapia di prima linea:

β –bloccante

Ca – antagonisti Nitrati LA

Trimetazidina

Da valutare:

Ca – antagonisti Nitrati LA

Trimetazidina

Da valutare:

Controindicazioni o intolleranza

Ranolazina

Ivabradina *

* In pz in RS, FC ≥70 bpm, FEVS≤40%

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

Take Home Message

Ranolazina

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