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Antiplatelet Therapy for Acute Coronary Syndrome Death is inevitable but premature death is not.

- Sir Richard Doll Hennekens Recent Statin Update7/25/2014 4:33:34 PM2Antiplatelet and anticoagulant drugs are a cornerstone of the medical treatment of acute coronary syndrome (ACS), reducing the rates of both morbidity and death 1-4

A key distinction when treating ACS is whether the electrocardiogram shows ST segment elevation or non ST elevation

In ST-elevation myocardial infarction, another distinction is how perfusion is to be restored, ie, with primary percutaneous coronary intervention or with thrombolysis

In cases of non-ST-elevation ACS (ie, unstable angina or non-Stelevation myocardial infarction), a second key question is whether the initial strategy will be invasive (with angiography performed urgently) or conservative (with angiography performed later).

J Am Coll Cardiol 2011; 57:e215e367 J Am Coll Cardiol 2012; 60:645681Lancet 1996; 348:13291339Circulation 1994; 89:8188

Milestones For Aspirin5th century BCHippocrates1897 ADFelix Hoffman/Friedrich Bayer1900 presentMost widely used drug in the world1971Sir John Vane14Benefits of Aspirin on Risk of StrokeIn 158 trials, there were 3,522 nonfatal and 1,424 fatal strokes after randomization.

Antiplatelet therapy, principally with aspirin, reduced stroke by about 25%, regardless of whether the patient entered the trial with prior MI, stroke, TIA, or other high-risk conditions.

Antiplatelet therapy, principally with aspirin, increases the absolute risk of hemorrhagic stroke by 3 per 10,000 treated patients. The upper bound of the 95% confidence interval is less than 1 per 1000 treated patients.AntiThrombotic Trialists Collaboration. Lancet, 2002

ISIS-2 Collaborative Croup Lancet. 1988 Aug 13;332: 349-60. Second International Study of Infarct Survival16

Duration of Dual Anti-Platelet TherapyEuropean and US Guidelines

PCI-CURECV Death or MI

CHARISMAInstantaneous Hazard for Moderate or Severe Bleeding

CHARISMA Primary End Point

TRILOGY-ACS Primary Efficacy End Point to 30 Months (Age < 75 years)

DAPT TrialTotal Enrollment

DES vs BMS

DAPT Trials Unanswered Questions

OPTIMIZESecond-generation DESEffect of Short- and Long-term DAPT

New Trials With Ticagrelor

PARIS RegistryPatterns of Non-Adherence to Anti-Platelet Regimens In Stented Patients: An Observational Single Arm Study

PARIS Registry84Medication Usage

PARIS Registry3582 (71.1%)2014 (40.0%)991 (19.7%)1894 (37.6%)47 (0.9%)5012 (99.6%)5031 (100%)1177 (23.4%)5012 (99.6%)311 (6.2%)Note: discharge data available for 5031 patients. (1 died in hospital, 1 was not yet discharged at 30 days)85Procedural Information

PARIS RegistryNOTE: there are 5 patients for whom stent type was unknown.86Stents by TypeTotal # of stents used: 8434 (1.68 stents/pt)

PARIS Registry87Thienopyridine at Discharge

PARIS RegistryRates of Non-Adherence (Patient-level)

PARIS Registry

PARIS RegistryAny Non-AdherenceVariable Patients Episodes Any Non-adherence104 (2.1)147Disruption, n (%)72 (69)102 (70)Interruption, n (%)20 (19)27 (18)Discontinuation, n (%)12 (12)18 (12)Incidence of Non-Adherence90Non Adherence to Thienopyridine:Variable Patients Episodes Any Non-adherence, n (%) 66 (1.3)69Disruption, n (%) 43 (65)46 (67)Interruption, n (%) 12 (18)12 (17)Discontinuation, n (%) 11 (17)11 (16)Incidence of Non-Adherence (Cont.)

PARIS RegistryNon Adherence to Aspirin:Variable Patients Episodes Any Non-adherence, n (%) 70 (1.4)78Disruption, n (%) 51 (73)56 (72)Interruption, n (%) 12 (17)15 (19)Discontinuation, n (%) 7 (10)7 (9)Incidence of Non-Adherence(Cont.)

PARIS RegistryBleedingNon-ComplianceOtherASA18344Thienopyridine14302

Reasons for Disruption

PARIS RegistrySurgeryOther Medical Procedure (epidural, catheter removal, GI Scope)GI UpsetAllergyCoumadinASA52332Thienopyridine53040

Reasons for Interruption

PARIS RegistryNon-Adherence guided by healthcare professionals

PARIS RegistryTotal episodes of Recommended DAPT non-adherence: 82 Episode level. Refers to only those episodes of stoppage that were guided by a healthcare professional. Who is driving the decisions regarding stoppage? Non-adherence guided by healthcare provider. 95

PARIS RegistryBaseline CharacteristicsVariableAdherentn=4929Non-adherentn=104p-valueAge, years 63.94 [11.33]64.83 [11.31]0.42Male, n (%)3676 (74.6)74 (71.2)0.43Acute coronary syndrome, n (%)1987 (40.5)60 (58.3)