Chronic Stable Angina

CHRONIC STABLE ANGINA : symptoms controlled or not - if not controlled, short term risk of death or MI not consistent with Intermediate to High Risk for UA (see below) - Antianginal Medications (PCI does not improve survival) - Cardioprotective Medications - Tobacco use and other lifestyle counseling

Diagnosis:
Treat the patient even when diagnosis is Suspected, and Firm Diagnosis has not been established. 
Evaluation:
  • First Step in Evaluation: Assess the likelihood of Clinically Significant CAD (?? is Clinically Significant)
    • What is Clinically Significant CAD? : Severe Angina, Advanced Age, Female Sex, Smoking Co-existing illness, abnormal EKG if present correlate to the presence of clinically significant CAD. Note: This may overestimate the prevalence of the disease
    • CTA may overestimate the extent of the disease. 
  • Second Step: Assess the prognosis
    • the duration of exercise, presence of ST-segment changes, and occurrence of angina confer prognostic information 
    • The exercise ejection fraction is one of the most important prognostic variables in patients with coronary artery disease. 


Treatment:
  • Cardioprotective Interventions
    • ASA (18 % decrease in MACE due to 23 % decrease in MI) (Metaanalysis of primary prevention trials)
    • HTN: 25 % decrease in MACE when SBP is aimed at 120 or less (SPRINT Trial NEJM 2015) 
    • Statin: 
      • Lower rate of ischemic CV events in patient taking Statin than those who underwent PCI
      • Also, decrease Anginal symptoms, and exercise tolerance

  • Anti-anginal Interventions
    • Should be initiated as soon as diagnosis is suspected
    • Medication adjusted in 2 weeks 
    • Note: Statins can improve anginal symptoms, and exercise tolerance.





Identification of severe coronary artery disease using simple clinical parameters. Annals 1992
2013 ESC guidelines on the management of stable coronary artery disease
Stable Ischemic Heart Disease In the Clinic Annals 2014 
Current Concepts: Percutaneous Coronary Interventions without On-Site Cardiac Surgical Backup NEJM 2012
Myocardial Infarction Due to Percutaneous Coronary Intervention NEJM 2011



Additional References on Management of Chronic Stable Angina:




Antithrombotic Drugs

ASA
  • Full effect at > 75 mg 
  • No difference between coated vs non-coated 
ADP P2Y12 Receptor Inhibitor
  • Clopidrogrel
    • Extensive hepatic metabolism
    • Converted to active drugs
      • CURE trial
      • CREDO trial 
    • Clopidrogel Resistence
      • TRITON Trial
        • No way to modify drug resistance 
        • No role of routine testing for resistance testing 
    •  interaction with omeprazole
      • COGENT Trial 
      • No difference in the ischemic event 
    • CHARISMA Trial: 2006
      • Patients with vascular disease has benefit of long term therapy
        • Now supported by PEGASUS trial
          • Further supported by DAPT Trial 
  • Prasugrel
    • Better metabolism than Clopidrogel
    • 60 % reduction in platelet activity 
      • Prasugrel vs Clopidrogrel
        • TRITION -38
  • Ticagrelor
    • PLATO Trial
      • Vs Clopidrogel
    • Is reversible 
    • Use with low dose ASA (high dose ASA had worse outcome; mechanism is not clear)
    • PEGASUS Trial
      • Longterm use of TIcagrelor in a patients with prior MI 
        • NEJM 2015
        • Increased risk of bleeding
        • Lower dose has less side effects
  • Cangrelor
    • New, approved Mid 2015
    • CHAMPION Trial 
    • Parenteral
    • Ticagrelor given IV (to understand)
Trombin Receptor Antagonist
  • Vorapaxar
    • TRACER: Stopped due to excess risk of bleeding (NEJM 2012)
    • TRA-2P: (NEJM 2012)
      • ICH was a major issue 
      • No prior hx of stroke, then risk is less
GP IIb/IIIa

  • ISAR - REACT
    • NO advantage when added to clopidrogel
  • EARLY-ACS Trial
    • Eptifibatide
  • Less preferred in the NSTEMI / UA due to increased risk of bleeding 
  • STEMI
    • FABOLUS PRO
      • Benefit seen 
Review the summary slide  is good
Heparin did as good or better than Bivalirudin
Earlier improved outcome of Bivalirudin was when compared to heparin +IIb /IIIa
  • MATRIX Trial
    • Bivalirudin vs UFH in ACS (7213 patients)
  • So, increased risk of bleeding, concern for instant thrombosis leads to its controversy 
  • Even after  3 missed dose of Ticagrelor, the benefit is similar or still better than clopidrogel
    • 30 % platelet function inhibiotion vs 60 % platelet function inhibition
  • Definition (different definition used by the trials):
    • CASS
    • COURAGE

    • BARI 2D 
      • elective PCI in next 4 weeks
  • Mortality:
    • 5 yr mortality is 5 % in all above studies 
    • MI and Death is 15  % in all these studies
    • COURAGE Trial (Medication vs PCI) NEJM 2007
      • No difference in death and MI.
      • No difference from MI
      • No difference from hospitalization
    • BARI-2D (PCI vs CABG in a DM 2 patient vs optimal medical therapy) NEJM 2009
      • No mortality benefit of either approach with optimal medical therapy 
      • intent to treat trial (treatment can change based on patient outcome) 

  • Does revasculization Prevent MI?
    • It does, but of note MI happen in arteries < 50 % stenosis as well. 
    • AMRBOSE 1988
    • FAME 2 Trial 
CABG vs PCI
  • SYNTAX Trial
    • LM disease: PCI is Syntax score < 22(<33 per guideline, and esp if high risk surgery) 
    • Triple vessel disease or LM with two vessel disease: CABG
    • 4 th generation stent (TAXUS) vs CABG 
      • No difference in all cause mortality in 5 yr
      • SYNTAX Score
        • An anatomical score
        • 0-22 
      • SYNTAX 2 Score
  • BARI-2D 
    • RCT, 2 arms
      • Physician decided PCI vs CABG
        • RCT:
          • PCI vs Med
            • No diff in two group 
          • CABG vs Med
            • Benefit of surgery to decrease MI 
  • FREEDOM Trial
    • Diabetic patient with multi vessel disease 
    • Except for Stroke Risk that is high in CABG, all other cardiovascular event (death, MI) were better with CABG
      • Likely due to lower rate of MI with CABG 
  • Reference
CAD and DM
  • SYNTAX-DM
    • Syntax > 22 has meaning
    • Syntax > 33 has significant advantage of CABG
  • FREEDOM
    • Largest dedicated trial for DM revascularization
    • 1900 patients
    • Had to be eligible for CABG or PCI (3rd generation DES)
      • Death, MI, Stroke were primary outcome
      • Except for Stroke, all less with CABG
  • Metanalysis by Verma S Lancer Diabetes Endocrinoloy 2013
    • Increased risk of stroke with CABG
    • Increased revascularization with PCI
    • CABG had 1/3 reduction of all cause mortality
  • CABG indication in DM 
    • 3VD
    • 2VD with proximal LAD
    • LIMA-lAD
    • Good surgical candidate  
FFR and CFR 
  • Identify microvascular disease vs epicardial disease 
  • During this maximum vasodilatation using Adenosis (given intracoronary) is important. 
  • FAME Trial (NEJM 2009) 
    • Intermediate lesoin: better with deferred PCI
  • FAME - 2 
    • Critical lesion needs angioplasty
    • This degree of information was not given by the COURAGE Trial  


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