Εξελίξειρ ζηην Ανηιαππςθμική Φαπμακεςηική Αγωγή

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1 Εξελίξειρ ζηην Ανηιαππςθμική Φαπμακεςηική Αγωγή Κων/νορ Π. Πολςμεπόποςλορ, FESC, FACC Δπ Ιαηπικήρ ΑΠΘ Επιμεληηήρ Α`, Καπδιολογική Κλινική Γ.Ν.Θ. «Γ. Παπανικολάος»

2 Δεν σπάρτει ζύγκροσζη ζσμθερόνηων με τορηγούς εηαιρείες ηοσ Σσνεδρίοσ

3 Ειζαγωγή Eςπεία σπήζη αλλά πεπιοπιζμένη αποηελεζμαηικόηηηα ΑΑ Πποαππςθμική δπάζη και εξωκαπδιακέρ ανεπιθύμηηερ ενέπγειερ RFA για AF και VT? ανάγκη ανάπηςξηρ και σπήζηρ νέων ΑΑ Πεπιοπιζμοί εξαιηίαρ ελειμμαηικήρ καηανόηζηρ κςηηαπικών διαύλων

5 Dronedarone

Dronedarone??? Financial associations: 4 of the 12 members (33%) of the AHA panel; 19 of the 34 members (56%) of the CCS panel; and 10 of the 25 members (40%) of the ESC panel.

10 Dronedarone??? Financial associations: 4 of the 12 members (33%) of the AHA panel; 19 of the 34 members (56%) of the CCS panel; and 10 of the 25 members (40%) of the ESC panel. For the 2012 update of the ESC guideline, 6 of the 8 panel members (75%) had financial associations with the manufacturer; for the 2012 Canadian update, 8 of the 21 panel members (38%) had financial associations with the manufacturer

11 Budiodarone Hydrophilic with a short plasma half-life (7 hours) Cleared in 48 hours due to rapid metabolism by plasma and tissue esterases instead of the CYP450 Rapid onset of action and steady state within 2 to 3 days

13 Εpisode frequency Εpisode duration

14 Celivarone

16 Celivarone tends to reduce VT/VF triggered ICD therapies, but this effect was not statistically significant

18 Novel Agents Targeting ionic currents found predominantly in atrial tissue, such as IKur, the ultra-rapid delayed-rectifier potassium current, to minimize ventricular effects and thus proarrhythmia. In atrial tissue IKur inhibition prolongs repolarization IKAch, the acetylcholine-activated inward rectifier potassium current, is another atrial predominant ion current. Activation of this current shortens atrial APD, ERP, and stabilizes the resting membrane potential

19 Vernakalant

28 Median time to the first recurrence of symptomatic sustained AF was 29 days in the placebo group and 90 days in the vernakalant 500 mg group (hazard ratio, 0.735; P 0.028) 49 % (vernakalant) versus 36 % (placebo) remaining in SR at the end of the 90 day study period (P 0.074)

30 Vernakalant????

31 Ranolazine Piperazine derivative with a chemical structure similar to that of lidocaine It is currently approved in the US for adjunctive treatment of chronic stable angina

32 1. Incidence of non-sustained VT (<30 seconds) was significantly reduced by ranolazine compared to placebo 2. Incidence of new-onset AF, a pre-specified outcome, was also lower in the active drug group (1.7 %) compared to placebo (2.4 %), but this finding did not reach statistical significance (p=0.08) 3. No indication of proarrhythmia with ranolazine despite modest QT prolongation

35 Am J Cardiol 2011;108: AF occurred in 26.5% of the amiodarone-treated patients and 17.5% of the ranolazine-treated patients (p 0.035) PACE 2012; 35:

36 Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion (RAFFAELLO) This study is ongoing, but not recruiting participants Dose-effect relationship of 3 doses of Ranolazine, given for a maximum of 16 weeks, in terms of maintenance of SR after successful DCC in patients with nonpermanent AFib versus placebo Assessment of efficacy (time to AFib recurrence) by Ranolazine versus placebo

37 Anti-arrhythmic Effects Mechanism Prolongs APD by inhibiting the slow sodium current (INa) and the slow component of the delayed rectifying potassium current (IKr) Late INa current in the ventricles leads to cellular Na overload which in turn can lead to intracellular Ca overload (as in ischemia) by way of the NCX, Na Ca exchanger. By inhibiting late INa, this sodium mediated calcium overload can be ameliorated restoration of normal calcium handling in the myocyte Blocks peak INa in the atria prolongation of the ERP Song Y. J Cardiovasc Pharmacol. 2004;44:192-9 Burashnikov A. Circulation 2007; 116:

38 Azimilide Investigated for suppression of VA Not only inhibits IKr, but also IKs, the slow delayed-rectifier potassium current

39 RRR 57%, p RRR 47%, p Risk of TdP ranged from %

41 p=0.02 p=0.02

43 p=0.087

44 Ivabradine Selectively inhibit the SA node by targeting the If current HR in sinus rhythm is reduced with minimal effects on atrial and ventricular EP properties, despite mild inhibition of IKur, IKr, and ICa,L It has a plateau dose and rate-dependent relationship making it more effective at higher heart rates

46 Reduced admissions for fatal and nonfatal infarction and revascularization in patients with ischemic cardiomyopathy, CHF and resting HR > 70 bpm

50 Conversion within 24 hours (primary end point) was achieved in 22 patients (88%) in group A+R versus 17 patients (65%) in group A (p 0.056). Time to conversion was shorter in group A+ R than in group A (9.8±4.1 vs 14.6±5.3 hours, p 0.002)

51 Σςμπεπάζμαηα Ανηιαπςθμικά απαπαίηηηα, παπά αποηελεζμαηικόηηηα και ανεπιθύμηηερ ενέπγειερ Ανάλογα αμιωδαπόνηρ? πηωσή αποηελεζμαηικόηηηα Το Μέλλον: Ανηιαπςθμικά «εκλεκηικά» ηος κολπικού μςοκαπδίος

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