Stable CAD

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    Risk Factors

    • Death rates for CVD:
      • African Americans >> Whites
      • American Indians, Hispanics >> Asian Americans.
    • Any degree of albuminuria is an independent risk factor for cardiovascular events, HF hospitalizations and all-cause mortality.
    • INTERHEART study: (MKSAP source)
      • Risk Factor Odds Ratio Attributable Risk
        Cholesterol (ApoB/ApoA1 ratio) 3.25 49.2
        Current Smoking 2.87 35.7
        Psychosocial Stressors 2.67 32.5
        Diabetes Mellitus 2.37 9.9
        Hypertension 1.91 17.9
        Abdominal Obesity 1.62 20.1
        Moderate Alcohol Intake 0.91 6.7
        Exercise 0.86 12.2
        Vegetables and fruit daily 0.70 13.7
        All risk factors 128.20 90.4
        • Modifiable RF’s: (account for 90% of risk of future MI)
        • Dyslipidemia (incl ApoB/ApoB1 ratio)  (High LDL, low HDL – each independently contribute) 
          • Highest modifiable RF
          • For every 1% reduction in LDL level, 1% reduction of risk over 12y period.
          • For every 1% increase in HDL, 2-4% reduction in CAD risk.
          • (but no meds to show increase in HDL lowers CV events)
        • Smoking (2-3x the CV risk)
          • 3-5y after quitting CV events drop to almost non-smoker level.
          • Second most-modifiable RF as a cause of MI.
          • Diabetes (Attributatble risk: 9.9%)
        • Psychosocial stressors (Attr risk: 32.5%)
          • Often precipitating cause, may not be long-term risk.
          • Depression:
            • PHQ9 often recommended to screen.
            • Target Score <10 (normal ≤4)
          • Anxiety:GAD7 for anxiety
        • Anger
        • HTN (Attr. Risk: 17.9%)
        • Abdominal obesity (Attr Risk: 20.1%)
        • Moderate EtOH (Odds Ratio 0.91)
        • Exercise (0.86)
        • Daily intake of vegetable and fruit. (0.70)
      • Risk factors are combined into the Framingham Risk Score (10y CV events such as MI and coronary death). 
        • Identifies pts at risk from combination of RF’s.
        • Identifies what level we should achieve with these RF’s.
    • Metabolic Syndrome:
      • 34% of patients >20yo meet this criteria. 
      • Doubles risk of CAD.
      • Characterized by:
        • Insulin resistance, elevated insulin levels, Hyperglycemia
        • Dyslipidemia
        • HTN
    • Family History
      • Doubles risk of CV disease if family member
      • Man <45
      • Woman <55

    Types of Stress

    • Exercise
      • If patient can exercise, this is preferred.
      • Aso yields information on exercise tolerance (functional, prognostic, and diagnostic information).
    • Dobutamine
      • Increases heart rate and myocardial contractility
    • Vasodilators
      • Increase in coronary flow of myocardial vessels not supplied by stenotic vessels

     

    Diagnosis

    • If there is chronic angina, classify as:
        • Typical angina:
          1. Substernal chest discomfort
          2. Provoked by exertion or emotional stress
          3. Relieved by rest or nitroglycerin (NTG)
        • Atypical Angina
          • Meets 2 of the characteristics
        • Noncardiac chest pain
          • Meets ≤ 1 of the characteristics 
      •  
      • CCS Classification for Anginal Chest Pain Severity
      • CCS Class Description
        1 Pain with strenuous activity
        2 Pain with ordinary activity (≥ 1 flight of stairs, ≥ 2 blocks)
        3 Pain with less than ordinary activity (<1 flight of stairs, or < 2 blocks)
        4 Pain at rest
    • Exercise testing is recommended as the initial test of choice in patients:
      • Intermediate pretest probability of CAD (based on age, sex, and symptoms)
      • Including patients with right bundle branch block or less than 1-mm ST-segment depression at baseline.
    • Routine use of exercise testing with echocardiography to assess left ventricular regional wall motion or perfusion imaging is not recommended for women or men in the absence of baseline ECG abnormalities.
    • Although echocardiography increases the sensitivity of the ECG results, use of stress echocardiography as the initial test has not been found to reduce cardiovascular events compared with exercise ECG testing alone.

     

    Stable Angina

    Diagnosis

    • Key points:
      • Cardiac stress testing is preferred test for symptomatic patients with intermediate CAD probability.
      • Excercise stress testing is preferred to pharmacologic testing (guaging functional capacity).
      • Pharmacologic stressors indicated if patient unable to achieve work load or risk of false positive study increase (i.e. LBBB).
      • Coronary artery calcium scoring not indicated in asymptomatic pts with very low or very high risk or coronary event.

    ChronicAnginaDiagnosis.png

    PreTestPobability.png

    Source: MKSAP

     

    Management

    • Goal: Reduce severity of angina, improve QOL, reduce subsequent CV events, improve survival.

    Anti-Anginal Therapy

    • 1st Line:
      • ASA (>75mg/d)
      • B-Blocker
      • Long-Acting Nitrate
      • Statin
    • 2nd Line (If continues to have sx)
      • Increase B-Blocker Dose
      • Increase LA Nitrate Dose
      • Add CCB (if not already on)
    • 3rd Line
      • Optimize BB, LA Nitrate, CCB
      • Consider Ranolazine
      • Referral for coronary angiography
    • 4rth Line:
      • If coronary anatomy suitable for revascularization --> CABG or PCI
      • If not suitable:
        • External enhanced counterpulsation
        • Spinal Cord Stimulation

     

    Specific Agents:

    • B-blocker:
      • Dose is adjusted to achieve HR of 55-60bpm and 75% of HR that produces angina with exertion.
      • Decrease myocardial oxygen demand (rate, BP, contractility)
      • S/E: Impaired sexual function, decreased exercise capacity, generalized fatigue.
      • Absolute Contraindications:
        • Severe bradycardia
        • Advanced AV block
        • Decompensated HF
        • Severe reactive airways disease.
    • Calcium Channel Blocker
      • If BB contraindicated or if still has symptoms on optimal doses of BB.
    • Nitrates
    • Ranolazine
      • Consider as 4th line (after BB, CCB, and nitrates)
      • Also has sodium blockade effect (has anti-arrhythmic properties)
      • Contraindicated in:
        • Liver Failure (Hepatic Cytochrome clearance)
        • Long QT
        • Other meds that inhibit CYP-P450 (such as diltiazem and verapamil - both increase ranolazine levels).
    • Coronary Revascularization
      • (Surgical or PCI)
      • Only if still has symptoms on maximal medical therapy.

    Other Agents:

    • Allopurinol (Increases myocyte efficiency, more pumping without increasing O2 consumption)
      • Uric acid is an independent RF for CAD (under investigation), usually don't treat symptomatic hyperurecemia.

     

    Cardioprotective Therapy

    • ASA (plavix if ASA not tolerated)
      • Indicated for all pts with chronic stable angina.
      • ASA + Plavix only if coronary stent or recent MI.
    • ACE inhibitors
      • if known CAD + (DMII or HTN or Reduced LV EF)
      • Consider in all stable angina
      • If cough etc.. use ARB.
    • Statins
      • Dislypidemia is the most important modifiable attributable risk factor for CAD.
      • Often considered most effective at lowering risk of future CV events.
      • Reduces risk of death or MI by 25-30% if reaches target for LDL level.
    • Therapies not effective:
      • Ezetimibe
        • Not shown to reduce risk of athersclerosis or future CV events.
        • Studies in progress to use ezetimibe with statin (ongoing as of 2014)
      • Vitamin C, vitamin E (not shown to be effective)
      • Vitamin D (controversial)

    Coronary Revascularization

    • Benefit from coronary revascularization:
      • Extensive/severe Left main or 3 vessel disease.
      • Symptoms and poor QOL (If refractive symptoms despite optimal medical therapy)
      • Significant CAD and LV systolic dysfunction (study: mortality benefit).
    • What type of revascularization? (PCI vs CABG)
      • Controversial, decisions made with coronary anatomy, comorbid conditions (surgical risk), patient preference.
      • Randomized large studies comparing the two shown equivalence in regards to survival.
        • Except: PCI demonstrated much higher need of future interventions due to in-stent thrombosis and stenosis.
        • Post-Hoc Analysis: Diabetic patients have worse survival in PCI group, better with CABG.

    PCI

    • In chronic stable angina:
      • PCI Reduces the frequency of angina, improves QOL
      • DOES NOT reduce future CV events or improve survival.
    • COURAGE TRIAL
      • Contemporary Randomized Trial:
      • Optimal medical therapy alone or with PCI.
      • PCI was NOT superior to optimal medical therapy in reducing death from MI, but did improve symptoms.
    • BARI-2D Trial
      • Randomized pts with DMII with angina to PCI or CABG vs. medical therapy in intention to treat trial.
        • No difference in all-cause mortality, MI at 5 years.
        • No superiority to revascularization.
        • However, many pts in medical therapy group crossed over to intervention group due to angina symptoms.  ---> Potentially making medical therapy look better than it really was (esp b/c it was intention to treat trial)
    • Guidelines:
      • In Chronic Stable Angina

        • PCI indicated for:
          • Symptoms despite optimal medical therapy
          • Unable to tolerate side-effects of meds
          • Those with high-risk findings on non-invasive imaging
        • CABG indicated for:
          • L-main disease 
          • Multi-vessel disease (2-3 vessels) with involvement of proximal LAD and reduced LV systolic dysfunction.
        • NOTE: Drug-eluting stents now allowed for left-main non-complex disease (L-main ostium, proximal, or mid-vessel).
      • NOTE:
        • Historically left main disease was a strict indication for CABG.
        • However: Improvement in devices used, recent studies demonstrate a very low event rate with PCI to non-complex L-main (low-rate of peri-procedural MI, death, and good long-term outcome).
          • RCT of PCI vs. CABG for L-main disease planned (TBD).
          • Drug-eluting stents now allowed for left-main non-complex disease (identified by disease in the L-main ostium, proximal, or mid-vessel).
        • Reduced LVEF requires a need more hemodynamic support (Intra-aortic balloon pumps and ventricular assist devices) b/c large blood flow distribution to LV
    • Follow-up
      • Not recommended to have regular stress tests or EKGs, follow-up care is symptom based.
      • Restenosis Risk
        • Drug Eluting Stents offer significant benefit to dropping restenosis rates (60% reduction in in-stent thrombosis, and rate now is <10%).
        • Antithrombotic therapy post-stent
        • Post-PCI Antithrombotic Therapy

          • Bare Metal Stents - Dual anti-platelet at least 1 month post- stent. (for stable CAD)
          • Drug Eluting Stents - Dual anti-platelet 1 year post-stent. (Takes longer to endothelialize)

          NOTE: Even if you get bare-metal stent in setting of STEMI/NSTEMI current guidelines indicate 1 year of dual antiplatelet therapy.

          NOTE: After dual-antiplatelet therapy, plavix can be discontinued, ASA continued indefinitely.

     

    • Drug Eluting Stents need 1 year dual-antiplatelet therapy b/c they take longer to endothelialize.
      • Very large RCT of shorter vs. extended clopidogrel therapy. (ongoing as of 2014)
      • Late stent thrombosis rate <0.5%/year, so needs thousands of pts, long follow-up for significant reduction.
    • Some features make require longer dual-antiplatelet (multiple layers of stents, etc...) to avoid late stent thrombosis.
    • IMPORTANT: 
      • In-stent thrombosis is deadly!  Usually occlusion is complete, and leads to a large STEMI involving large territiries.
      • Always ask if patients have any surgeries coming up, in which case may require BMS for shorter antiplatelet therapy.
    • New:
      • ASA+clopidogrel may improve venous bypass graft patency compared to ASA alone.

     

    • Bottom line:
    • Stent Type Mechanism Advantages/Disadvantages
      Bare Metal Stent (BMS)

      - Bare metal mesh, re-endothelializes
        quite quickly.  In-stent thrombosis

        risk is only 1 month, so requires only

        1 month of dual-antiplatelet therapy.

      Advantage:

         - 1 month of dual-antiplatelet 

            unless STEMI/NSTEMI, requires 1 year.

      Disadvantage:

         - Higher rates of re-stenosis.

      Drug Eluting Stent (DES)

      - Contains a chemotherapy drug 

        (i.e. tacro etc..) that elutes and prevents

        proliferation of vessel wall cells and collagen

        deposition that cause late-stenosis of BMS stents.

      - However also inhibits endothelialization, causing

        high in-stent thrombosis rates, requiring

        longer dual-antiplatelet therpay.

      Adavntage:

         - Better long-term outcomes for late-stent

           stenosis.

      Disadvantage:

         - High rates of initial thrombosis, requiring

            longer course of dual antiplatelet therapy

     

    Surgical Revascularization

    • Indications: (See above)
    • Surgical Side-Effects:
      • Excessive pain
      • Prolonged hospital stay
      • ***Postoperative neurologic dysfunction***
    • New: "Off-pump bypass" - avoidance of bypass during CABG.
      • Experienced surgeions can achieve similar graft patence rates (operating on beating heart) 
      • This is IMPORTANT: b/c evidence of reduced cognitive performance of patients post-bypass.
        • But no studies showed better protection of neurologic function with off-pump surgery.
      • However, recent RCT found that off-pump surgery was associated with:
        • Higher rate of adverse cardiovascular events at 1 year
        • Poor graft patency compared with traditional on-pump surgery
      • Other studies showing equivalency...
      • Therefore, should only be completed by highly experienced surgeons (hard to show clear benefit).
    • Off-pump surgery may be combined with a minimally invasive approach that uses stabilizers to allow construction of graft anastomoses through small thoracotomy windows, thus reducing the need for a complete sternotomy.
    • At the present: off-pump surgery and minimally invasive techniques only reserved for high-comorbidity patients to shorten recovery time.

     

    Hybrid Revascularization

    • Combination of PCI and CABG.
    • i.e. LIMA grafted to LAD by minimally-invasive bypass surgery (most of survival benefit from CABG) and non-LAD lesions treated percutaneously.
    • Benefit is unclear long-term.

    Notes

    • Radiation to chest (i.e. Lymphoma) can also cause CAD, but mostly "fibrous changes" not atheromatous plaques.  Typically these lesions are very difficult to stent and require bypass surgery.
    • Cocaine users: often have ST elevations.

     

    References

    • Shaw LJ, Bugiardini R, Merz CN. Women and ischemic heart disease: evolving knowledge. J Am Coll Cardiol. 2009;54(17):1561-1575. PMID: 19833255
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