Interventional Cardiology Update Advances in Internal Medicine 2010 John S. MacGregor, M.D., Ph.D. Professor of Medicine University of California San Francisco

Evolution of Percutaneous Coronary Interventions

Outline DES v. BMS: Safety and Efficacy Issues Late stent thrombosis v. Restenosis Duration of dual anti-platelet therapy Consequences of early D/C of plavix Genetic factors/drug interactions with plavix Recent Clinical Trials of Thienopyridines Clopidogrel (OASIS-7) Ticagrelor (PLATO) ` Prasugrel (TIMI 38)

Bare Metal Stents

• PTCA - restenosis, acute and subacute occlusion • Bare Metal Stents • Drug-eluting stents

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Endothelialization of DES and BMS

Guagliumi G, Circ 2003

Joner JACC 2006 (48): 193

Virmani R, Circ 2004

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Kaiser C, Lancet 2005

Pfisterer M, ACC 2006

Kaiser C, Lancet 2005

Pfisterer M, ACC 2006

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Stone G, TCT 2006

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Stone G, TCT 2006

Stone G, TCT 2006

Stone G, TCT 2006

Stone G, TCT 2006

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Stone G, TCT 2006

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Spertus JA et al. Circulation 2006;113:2803-9.

Colombo A, ESC 2006

Cumulative incidence, %

Death or MI for DES and BMS by Plavix Use

Eisenstein JAMA 2007 (297)

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PREMIER Registry: Mortality After MI by Thienopyridine Use

Summary: DES v. BMS • DES reduce the risk of restenosis but, due to incomplete endothelialization, there is a small increased risk of late stent thrombosis. • This can be reduced by prolonged dual anti-platelet therapy.

Spertus Circulation 2006 (113): 2803

Considerations: DES v. BMS • Can and will the patient take dual antiplatelet therapy reliably? • Any known bleeding problems that may affect compliance? • Planned surgery? • Risk of restenosis (DM, Renal Failure, small vessels, long lesions)? • CABG?

Considerations: d/c Plavix • Duration of therapy? • Complexity of anatomy (multiple stents, overlapping, bifurcation, LM/prox LAD)? • Caliber of vessels stented? • Type of stent? • Minimize time off Plavix (5 d), resume as soon as possible with loading dose. • Do not stop ASA if possible.

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Recommendations: ACC/AHA Scientific Statement - 2007 • Optimal duration of dual anti-platelet therapy – At least on year. Defer elective surgery at least one year. • Consider longer duration of therapy in high risk patients (e.g. off-label uses (>60%). • Stent thrombosis in 29% with early d/c. Mortality from ST: 20-45%. MI in up to 70%.

ACC/AHA Recommendations • Consider doing surgery on ASA/Plavix • Continue aspirin, if possible. • Resume D.A.P.T. as soon as possible after surgery (loading dose). • Do surgery in a facility with available cath lab with PCI capability. • Monitor patient Grines,Circ(2007)115:813-818

Grines,Circ(2007)115

Future Possibilities

Pharmacogenomics of clopidogrel Simon, NEJM 2009;360:363-75

• New Thienopyridines (to be discussed) • New Stents

• Pro-Drug •Genetic factors in metabolism •Drug-drug interactions •Irreversible inhibition

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Genetic Effects on PK/PD: Clopidogrel

CYP 2C19 allele frequencies Xie et al. Ann Rev Pharmacol Toxicol 2001;41:815-50

Pharmacokinetics

Percent of population tested

90 80 60 50

Caucasian Asian African Am.

40 30 20

Absolute Difference in ∆ MPA P value

% Difference in AUC 0-t

P value

CYP2C19

-32.4