The Late Sodium Current in the cardiac myocite: How viable as a new therapeutic target in angina?

1. The Late Sodium Current in the cardiac myocite: How viable as a new therapeutic target in angina? SPONSORED SATELLITE SESSION Dr Stephen Holmberg Lead Consultant for Cardiac Services Brighton & Sussex University Hospitals

3. Management of Stable Angina • GTN • Aspirin (Clopidogrel) • Statin (Ezetimibe) • ACE Inhibitor • β-Blocker • Second-line drug • Calcium antagonist • Long-acting nitrate • K + agonist • If channel blocker

4. Management of Stable Angina What investigations can guide therapy? Where does revascularisation fit in? What other drugs are available? Are there any other options?

5. Management of Stable Angina • What investigations can guide therapy? • Treadmill – MIBI – Stress Echo – CMR • EBT – CT Angio – Invasive Angio • Where does revascularisation fit in? • What other drugs are available? • Are there any other options?

6. Prognosis in Stable Angina • Generally benign • Very difficult to demonstrate prognostic benefit of anti-anginal medication • Exercise Testing • Short treadmill tolerance (for whatever reason) is poor prognostic feature • Scale of Ischaemia • MIBI scan accepted by DVLA/CAA • Angiographic Findings • Triple vessel disease with LV impairment • Significant Left Main Stem disease • But NOT.... Symptoms • Silent ischaemia has same prognosis as painful angina

7. Management of Stable Angina • What investigations can guide therapy? • Where does revascularisation fit in? • What does COURAGE tell us? • What other drugs are available? • Are there any other options?

8. Courage All patients had angiographic assessment Extremely small percentage of eligible patients randomised High level of cross-over to PCI for symptomatic patients No assessment of ischaemia in main trial

9. Courage – Nuclear Sub-study • 314 Patients • MPS scans: Baseline, 6/12, 18/12 • 2 groups • <10% ischaemia • >10% ishaemia • Endpoint • Reduction in ischaemia • PCI -2.7%. Medical -0.5%. • Risk of death/MI significantly reduced for patients with significant reduction in ischaemia especially in those with high baseline ischaemic burden

11. Management of Stable Angina • What investigations can guide therapy? • Where does revascularisation fit in? • What other drugs are available? • Ranolazine – Perhexiline - Trimetazidine • Are there any other options?

14. Mechanisms of Drug Action • Reduce Heart Rate • β-Blockers, Verapamil/Diltiazem, Ivabradine • Reduce Blood Pressure • β-Blockers, Calcium Antagonists • Reduce Contractility • β-Blockers, Verapamil/Diltiazem • Coronary Vasodilators • Diltiazem, Amlodepine, Nicorandil, Nitrates

15. Mechanism of action does not involve interference with haemodynamic variables Ranolazine

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23. Management of Stable Angina • What investigations can guide therapy? • Where does revascularisation fit in? • What other drugs are available? • Are there any other options? • Exercise training – Spinal cord stimulation

24. Conclusions Follow the ESC Guidelines Assessment of ischaemia is important Revascularisation where feasible/sensible New drug therapies such as Ranolazine offer hope to refractory patients