ACS (Post)


    **NOTE: This page is on secondary prevention of coronary events**




    • SecondaryPreventionAlgorithm.png


    • Source: CJC 2016 "Secondary Prevention Beyond Hospital Discharge for ACS: Evidence-Based Recommendations"
    • Post-ACS Period (6-12mo) is a high risk of death and CV events
      • SYNERGY Trial - studied pts with NSTE-ACS
        • 8% died in the first year (half of deaths in first 60 days)
        • 18% death or recurrent MI (75% of these events were in first 30 days)
        • Diabetes = TWICE mortality
      • GRACE (Global Registry of Acute Coronary Events) - 5 year follow-up of pts with ACS from UK and Belgium
        • 19.8% died
        • 9.3% recurrent MI
        • 7.7% stroke
        • 31% readmitted to hospital
        • 1/5 of deaths occured during initial hospitalization
        • CV Mortality for STEMI = NSTEMI
      • Overall: 18.3% risk of Non-fatal MI, non-fatal stroke, or CV death in first year.
      • PROSPECT Study 
        • 20% had recurrent MI
        • Recurrent MI = from RE-OCCLUSION of same site or NEW atherosclerotic site (50:50)
    • Risk can be reduced with the measures discussed in this section.
      • Hospitals adhering to Class I AHA recommendations had lower in-hospital mortality (CRUSADE Registry)
      • Uptitration of therapy has been a key performance measure
      • Most common non-adherence reasons: "not high-enough risk" and "no evidence/guidelines to support use".
    • 3 pillars of secondary prevention:

                  1.  Vascular Protection  (reduce risk of recurrent events and cardiac mortality)

                  2.  Cardiac Protection (in patients with systolic LV dysfunction to prevent adverse remodeling)

                  3.  Risk Factor Control


    3 Pillars of Secondary Prevention

    1. Vascular protection to reduce risk of recurrent ACS/mortality
    2. Cardiac protection for systolic LV dysfunction
    3. Risk factor control


    A. Vascular Protection

    Antiplatelet Therapy

    • Clopidogrel
      • Combination of ASA with clopidogrel (P2Y12 inhibitor) reduced recurrent MI by 20% in 1yr post-MI
        • CURE Trial - studied NSTE-ACS patients
          • Largely reduced recurrent MI (no effect on CV death and stroke)
          • Benefit in PCI and medically treated patients
        • COMMIT Trial - studied STEMI patients
          • Short-term mortality benefit post-STEMI
      • Drawbacks:
        • Slow onset of action
        • Variable effect (must be converted by 2 steps to active metabolite, also many drug interactions)
        • Weak anti-platelet effect (50-60% inhibition)
        • Irreversible inhibition (delays surgery by 5-7 days)
    • Prasugrel
      • Much faster acting than clopidogrel
      • Also binds P2Y12, also irreversible
      • BENEFIT: only requires 1 step to convert to active metabolite
      • TRITON-TIMI 38 Study
        • Prasugrel vs. Clopidogrel after PCI in ACS pts (all candidates for PCI)
        • Prasugrel reduced CV death/MI/stroke by 19% vs. clopidogrel
        • Major bleeding increased by 32% (esp if <60kg and >75yo)
        • No benefit over clopidogrel in medically managed ACS patients
      • Bottom line:
        • Only indicated for patients undergoing PCI
        • More effective than placebo
        • More major bleeding (avoid in pts <60kg and >75yo)
          • Contraindicated in prev stroke or TIA
    • Ticagrelor
      • Faster acting, does not require activation step. 
      • PLATO
        • Investigated ticagrelor 180mg vs. clopidogrel 300mg in ACS patients 
        • Enrolled early --> so have data for PCI, medical management, and CABG
        • Reduced CV death, MI, and stroke by 16%
        • No increase in major bleeding (non-CABG bleeding increased by 19-25%)
          • Fatal ICH more common in ticagrelor, while fatal non-ICH bleeding for clopidogrel. 
          • Fatal bleeding was similar
      • Benefits:
        • Can use for CABG, PCI, and medical management. 
        • A wide range of patients benefit (diabetes, elderly, previous TIA/stroke, etc..)
        • Lower mortality in NSTE-ACS
      • Drawbacks:
        • Transient dyspnea (13.8% vs. 7.8%), at rest (through adenosine-like mechanism)
          • Dyspnea was minimal  (drugs were not discontinued), recommend continuation.
    • How long to treat?
      • Studies tried treating with different agents:
      • Clopidogrel
        • DAPT Trial
          • Examined clopidogrel or prasugrel after 1 year in pts with drug-eluting stents. 
          • Continuation of DAPT
            • = lower thrombosis (1.4% --> 0.4%)
            • = lower ischemic events (5.9% --> 4.3%)  [MI 4.1 --> 2.1%]
            • BUT
            • = higher major bleeding (1.6% --> 2.5%)
            • = MORTALITY = higher for continuation of DAPT (2.0% vs. 1.5%)
          • Less coronary events if continuing DAPT >1yr, but more bleeding and higher mortality. 
          • New generation stents have even less thrombosis (so may not need >1yr tx)
          • Decreased CV mortality is NOT offset by increased non-CV mortality
            • Per 1000 DAPT-treated pts per year = 8 fewer MIs, and 6 more major bleeds than shorter DAPT treatment. 
        • CURE and TRITON-TIMI 38 trials show benefit is front-loaded to first 3mo
          • All other trials including PLATO show benefits of P2Y12 inhibition continued for 1yr.
        • Longer studies (>2yrs) CHARISMA and SWEDEHEART registry
          • No benefit in primary composite endpoint (but 17% reduction of MI over 28mo of tx)
      • Ticagrelor
        • PEGASUS-TIMI 54 trial
          • Prolonged tx with ticagrelor of 60 or 90mg bid vs. placebo for 33mo
          • Composite CV death/MI/stroke by 15%
          • 60 and 90mg had same effect
          • For every 1000pts who receive ticagrelor 60mg bid x3y = 42 CV events prevented at expense of 31 major bleeds. 
          • All cause mortality was better with 60mg ticagrelor
          • Subgroup analysis: benefit was for continuation or brief interruption of ticagrelor (vs stopping for 1-2 years and continuing). 
      • Bottom Line:
        • Definitely continue DAPT for 12-months
        • Safe to stop second antiplatelet at 12mo (keep ASA indefinitely)
        • Can continue in selected patients who have high vascular risk (i.e. DMII, recent MI) and low bleeding risk. 



    • Warfarin combined with ASA has been shown to decrease recurrent MI.
      • WARIS-II trial
        • ASA + warfarin reduce CVdeath/MI/stroke by 29% vs. ASA alone
        • Major bleeding was 4x higher in warfarin+ASA group. 
    • However: combining warfarin with DAPT = very high bleeding risk!
      • Reduce by:
        • 1.  Avoid DAPT if possible
        • 2.  Shorten DAPT to 1mo for BMS and 3mo for DES
        • 3.  Use PPI for higher risk patients
    • ASA+clopidogrel+rivaroxaban = lower CV events, but very high bleeding risk
      • ATLAS ACS-TIMI 51 trial
        • ASA+clopidogrel+rivaroxaban (low dose 2.5-5mg bid)
        • 16% lower CV event rate (8.9 vs 10.7%)
        • Major bleeding incr. 3.5 fold
        • Unacceptably high bleeding risk (proposed using ASA+prasugrel or ASA+ticagrelor without anticoagulant)
    • In pts treated with ASA+warfarin, bleeding risk of ASA exceeds any benefits
      • CORONOR registry
        • Bleeding risk from ASA (in ASA+warfarin combo) exceeds any benefits from ASA in CV events. 
    • Conclusions:
      • Evidence Based:

        • All post-ACS patients need DAPT x12mo
          • Includes low-dose ASA (81mg od) and ticagrelor (90bid) x12mo
        • If received a stent --> Ticagrelor 90mg bid OR prasugrel 10mg OR clopidogrel 75mg od x12mo.
        • At 1 year:
          • Consider continuing second antiplatelet (ticagrelor 60mg bid or clopidogrel 75mg bid) in patients with HIGH risk of CV events and LOW risk of bleeding
        • ASA 81mg indefinitely

        Consensus Based

        • Triple Therapy: Patients who need anticoagulation (i.e. AFib) should receive clopidogrel (instead of prasugrel or ticagrelor)
        • VERY high bleeding risk patients requiring triple-therapy: consider omitting ASA
        • Consider gastric protection with PPI for pts with high bleeding risk
        • DAPT preferred over warfarin if no anticoagulation indication exists. 




    Lipid-Lowering Therapy

    • Statin is the mainstay of risk reduction
    • Reducing LDL by 1 mmol/L reduces risk of major CV events by 20% (independent of baseline LDL level)
    • Statins decrease death+MI by 23%
      • CARE Trial (Pravastatin initiated within 1yr of MI => reduced composite death+MI by 23%)
    • High-dose statin is better than lower dose post-MI
      • PROVE IT - TIMI 22 - randomized to pravastatin 40mg or atorvastatin 80mg a median of 7d after acute MI
        • Aggressive reduction with atorvastatin = better (additional 0.6 mmol/L LDL reduction, and 16% RRR of death/CVE at 30mo follow-up
      • 2000 - TNT Study
        • Lipitor 10mg vs. Lipitor 80mg
        • On 10mg lipitor (got to 2.5 LDL)
        • On 80mg lipitor (got to 2.0 LDL)
        • Therefore: everyone must be on high-dose statin
    • Better to start a statin early post-MI (24-96hrs)  (and decreases stroke too!)
      • MIRACL Trial: randomized pts with ACS within 24-96hrs of admission to atorvastatin 80mg or placebo
        • Atorvastatin 80mg group = 17.4% RRR vs. 14.8% placebo (composite mortality, MI, arrest, revasc)
        • NNT=38 (driven mostly by reduction in rehosp. for ACS)
        • Also found decreased stroke substantially
    • Poor prescribing rates post-MI (27%), and compliance drops to 40% at 2 years (Rosenston JACC 2015)
    • Ezetimibe in combination with mod-intensity statin decreases LDL-C 
      • IMPROVE-IT Trial - 18144pts within 10d of ACS rand: simvastatin 40 vs simvastatin 40 + ezetimibe 10md od
        • LDL-C 1.81 in simvastatin group vs 1.38 in simva+ezetimibe
        • 7 year followup: 6.4% RRR of CV death/MI/UA/revasc/stroke, and 2% ARR (NNT=50)
        • NO reduction in all-cause-mortality (but mostly reduced MI and stroke)
        • Criticism: mod-intensity statin used (currently recommended high-intensity)
    • Cholestyramine (bile acid sequestrant) reduces CV events as monotherapy, may be option if statins not tolerated
      • NO TRIALS tested combination with statins.
      • New agent: colesevelam (lowers LDL-C by 15-20%)
    • PCSK9 inhibitors combined with statins lower LDL by additional 50-60%
      • CETP = cholesterol ester transfer protein  (inhibitors failed in trials)
      • PCSK9 = protein promotes degradation of LDL-C receptor.
      • Anti-PCSK9 + statin reduces LDL by additional 50-60% over statin therapy
      • evolocumab 140mg q2w or alirocumab 75-150mg q2w
        • PCSK9 inhibitors
        • If cannot reach LDL target --> randomized to placebo or PCSK-9
        • 62% reduction in LDL cholesterol  (reduced to 1.2)
    • Other Agents:
      • Fenofibrates are not effective compared to statin
        • ACCORD Study
          • simvastatin vs. simvastatin + fenofibrate
          • No Benefit of fenofibrate
      • Niacin is contraindicated
        • HPS-2-TRHIVE Study
          • Niacin+laropirant+ statin vs. statin alone. (laropirant = decreases flushing in niacin)
          • No Benefit of Niacin
          • RISK OF HARM!!!! (3.7% Absolute risk of glycemic disturbance in DMII, 1.3% newly diagnosed DMII, 1% more serious GI s/e, and infection 1.4%)
          • Therefore: Niacin is contraindicated!!!
    • Evidence-based:

      1.  All patients with recent MI or ACS should receive atorvastatin 80mg daily

      2.  Consider adding ezetimibe if pts do not achieve LDL-C < 2.0 mmol/L or 50% reduction




      1. High-risk pts who fail to achieve targets despite maximally tolerated statin dose 

          (or statin intolerance) and ezetimibe, consider PCSK9 inhibitors or bile acid sequesterant


          PCSK-9 inhibitors: alirocumab 150mg or evolocumab 140mg q2w

          bile acid sequestrant: colesevelam 3.75 g/d



    • ACEi beneficial in pts with proven atherosclerotic vascular disease or at high risk of CAD (even if no impaired LV function or HF)
      • HOPE trial (ramipril)
        • Enrolled pts with MI within past 4w
        • Over 5 years reduced composite CVdeath/MI/stroke by 22% (all components reduced significantly)
      • EUROPA (perindopril)
        • Reduced CVdeath/MI/arrest by 20% among pts with CAD
    • ARBs also have the benefit, but may not be as much as ACEi (do not combine both)
      • ONTARGET Trial (Telmisartan)
        • Telmisartan non-inferior to ramipril (same study population as HOPE, but >20,000 pts)
        • Combination of telmisartan + ramipril = increased harm and no benefit
        • Telmisartan vs. placebo in ACEi intolerant pts failed to show improved CVD outcomes with telmisartan.
    • Conclusion
      • 1.  Pts with LVEF > 40% and no HF should be considered for ACEi (ramipril 10mg or perindopril 8mg) for secondary prevention.

        2.  Pts intolerant of ACEi can receive an ARB (telmisartan 80mg daily studied)

    B. Cardiac Protection


    • AHA/ACC and ESC Guidelines: Use beta-blocker in patients recovering from STEMI and NSTE ACS.
    • Evidence:
      • The initial trial that showed the benefit of Beta blockers post-ACS was:
        • BHAT Trial  (done 35y ago)
          • 30,000 pts post-MI randomized to propranolol vs. placebo
          • Done in different time: NO Thrombolytics, NO PCI, NO Statin, NO ACE inhibitors
          • Hence "POOR evidence", in patients post-MI with normal EF (there is great evidence if EF is low)
      • Meta-Analysis Freemantle et al BMJ 1999
        • 2-year period of treatment reduced mortality by 23%.  NNT = 42 (to save life)
        • Greatest benefit was in patients with LV dysfunction & heart failure
      • CAPRICORN Study
        • Examined carvedilol post-MI with decreased EF (most were on ACEi and 46% revascularized)
        • Decrease in mortality by 23%
        • Atrial/ventricular arrhythmias suppressed (afib reduced by 69%)
      • Bangalore et al (2014)
        • B-Blockers reduce mortality in pre-reperfusion era, but not in reperfusion era
        • In reperfusion era: Reduction of recurrent MI (NNT=209), BUT increased risk of heart failure and cardiogenic shock
      • Long-term use unclear (all trials 1day-6weeks) and 2 placebo controlled trials 
      • In the reperfusion era: No evidence to support B-blocker treatment for more than 6mo, except in pts with heart failure or severely reduced LV function
        • If preserved LV function + revascularized: 2a recommendation (weak) to use B-blockers


    • Evidence Based: 

      1.  Initiate B-blockers in pts with acute MI who have sustained more than minor damage

          (defined by LV WMA or LV EF < 50%)

          - Start treatment in the first 24hrs of admission when hemodynamically stable


      2.  Use trial doses (metoprolol 50mg BID, atenolol 50mg od, bisoprolol 10mg od, carvedilol 25mg bid)


      3.  Severely impaired LV function (i.e. LVEF < 40%), continue B-blocker indefinitely



      1.  In pts with MI and single-vessel CAD who undergone successful revascularization and have normal

           EF, benefits of B-blocker are less certain.  If initiated, 6mo treatment is reasonable.


      2.  For pts with mild-to-mod reduction of LV function with successful reperfusion, can consider d/c treatment

           after 6 months.



    C. Risk Factor Modification


    Smoking Cessation

    • Smoking:
      • Accelerates Atherosclerosis
      • Destabilizes coronary plaques (promotes MI)
    • Wilson et al (2000) Meta-Analysis
      • Persistent smokers = 20% mortality over 4.8yrs
      • Smoking cessation = 46% reduction in mortality (13pts stop smoking, 1 life saved over 4 yrs)
    • Intense counseling during or shortly after hospitalization is the best time to discuss. 
    • Refer to smoking cessation clinic
    • Cessation Aid Dosing Notes
      Nicotine Transdermal

      if >10 cigs/day (half-pack): 21mg/day q24h

      x6w, then 14mg/d x2w, then 7mg/d x2w

      (If <10 cigs/day or <45kg start with 14mg/d)

      - Vivid dreams reported

      (can take off at night, same efficacy)


      varenicline 0.5 mg od x3d

      then 0.5 mg BID x4d

      then 1 mg BID for remainder of a

          12-week course.


      (Titrate up to reduce nausea)

      Stop cigarettes 1w after starting varenicline

      - Most effective 

      - Not studied with recent MI

      - 3 reviews published 2011-2013 all show mild rise in CV rates.  

      Only one of them (Singh et al) showed a statistically

      significant increase in CV events. 

      Cohrane Review 2013 - 0.6% CVE rate vs. 0.5% placebo

      - Take with food and full glass of water (nausea rates)

      Bupropion   Not studied in recent MI
    • Treat depression if occurs (causes relapse in smoking)




    • Hyperglycemia early in ACS = poor outcomes (correlates to mean 24-hr glucose)
    • DIGAMI Trial
      • Acute MI + Hyperglycemia  --> early glucose control with IV insulin, then multidose insulin x3mo
      • = better outcomes compared to poor glucose control (28% lower mortality at 1yr)
    • Glycemic control post-MI:
      • HbA1c target < 7.0% in most pts. 
      • HbA1c target 7.1-8.5% if high risk of hypoglycemia and lower targets difficult to achieve.
    • Treatment:
      • Metformin is usually first line (UKPDS 34 Trial)
      • If A1c > 9% --> usually use insulin or 2 oral hypoglycemic agents. 
      • Preference to drugs with proven CV outcomes: DPP-4 inhibitors
      • Avoid using drugs with CV harm: certain sulfonylureas and rosiglitazone
    • Notable Trials:
      • Alogliptin (DPP-4) vs standard care (EXAMINE Study) -> outcomes not worse with recent MI
      • Lixisenatide (GLP-1 agonist) (ELIXA Study) --> safe with recent MI
      • Empagliflozin (EMPA-REG OUTCOME Study 2015) -->
        • Included pts with TIIDM, age ≥ 18, BMI ≤45, GFR > 30 MDRD, known CVD (MI >2mo ago, multivessel CAD, single-vessel CAD + positive stress test or UA hosp in last year, UA >2mo ago and evidence of CAD, stroke >2mo ago, occlusive PAD)
        • Excluded uncontrolled hypoglycemia (FBG >13.3), liver disease (liver enzymes >3xULN), planned CV sx or angioplasty in 3mo, GFR < 30, steroids, EtOH abuse.
        • Empagliflozin 10 or 25mg vs. placebo
        • @3.1y -->
          • Reduction in all-cause mortality (5.7 vs. 8.3% NNT=38)
          • Reduction in CV mortality (3.7 vs. 5.9%, NNT=45)
          • Reduction non-fatal MI/Stroke (10.5% vs. 12.1% NNT=62)
          • Reduction in weight, sBP
          • F/U study: lower rates of renal dysfunction (12.7 vs. 18.8%)
          • Only 0.5% HbA1c reduction (ACCORD, ADVANCE, VADT did not demonstrate CV event reduction with HbA1c reduction)... unclear mechanism.
        • Two doses of empagliflozin similar outcomes, similar s/e. If can tolerate, go to 25mg.
      • CDA Guidelines March 2016

        • Patients with clinical CVD in whom glycemic targets are not met, an SGLT2 inhibitor (empagliflozin) should be added to reduce CV risk and all-cause mortality.


    BP control

    • CHEP Target: < 140/90  (< 130/80 for diabetes)
    • CHEP recommends dBP > 60 if has flow-limiting CAD
    • Use ACEi/ARB, B-blocker (benefit beyond BP control), and if not controlled can add CCB or thiazide.
    • SPRINT Trial
      • Intensive BP control (<120mm) or standard care (sBP < 140)
      • Included pts with high CVD risk, or established/subclinical CVD (incl. if >3mo post-mi)
      • Excluded diabetics
      • Stopped early at 3.26y:
        • Primary outcome: ACS/stroke/HF/CVmort reduced 2.19% --> 1.65%
        • Outcome driven by CV mortality and acute HF decompensations. (ACS/stroke were not reduced)
        • AKI, syncope, electrolyte disturbances higher in intervention roup. 
      • Intensive BP control (sBP < 120mm) should be attemped post-MI. 



    • Benefits:
      • Prescribes exercise program
      • Risk factor modification
      • Education/counselling
    • Reduces re-infarction by 47%, cardiac mortality by 26%, rehospitalization, exercise performance.
    • If complete exercise program: 40% lower mortality (compared to those that don't attend)



    Consensus-Based Recommendations:

    • Smoking cessation and referral is recommended in all smokers.
    • BP control is recommended as per CHEP algorithm (updated with SPRINT findings)
    • Glycemic control according to CDA (updated with EMPA-REG Outcome findings)
    • Rehab referral for all patients
    • Depression counselling if appropriate. 



    • Depression common post-MI (60-70%!!), SADHART --> starting sertraline was safe in recent ACS. (no effect on CVD events)

    Heart Failure

    • The mainstay of therapy is: ACEi (ARB if ACEi not tolerated), aldosterone inhibitors, B-blockers. 
    • PARADIGM-HF --> neprilysin inhibitor + ARB superior to ACEi
    • B-Blockers
      • CCS Guidelines: All patients with LVEF < 40% should be clinically proven B-Blocker
        • Metoprolol succinate - MERIT-HF Trial (mortality benefit)
          • Note: long-acting metoprolol succinate was used not canadian short-acting tartrate. 
        • Carvedilol - COPERNICUS Trial
          • Better than metoprolol tartrate in mortality reduction.
        • Bisoprolol - CIBIS-II Trial
          • Survival better with bisoprolol
    • B-Blocker Starting Dose Target Dose Notes
      Metoprolol Succinate     Not Available In Canada
      Metoprolol Tartrate     No proven benefit (all trials used succinate)
      Bisoprolol 1.25mg od 10mg od CIBIS-II Trial
      Carvedilol 3.125mg bid 25mg bid COPERNICUS Trial
    • Aldosterone Inhibitors
      • Spironolactone
        • RALES Study (1999)
          • Benefit of spironolactone in pts with HF LVEF<35%
          • Inclusion Criteria:
            • NYHA Class IV (within 6mo pre-enrollment)
            • NYHA Class III or IV at time of enrollment
            • On ACEi, furosemide
            • LVEF < 35% 6mo pre-enrollment (No CV events in interim)
            • (Excluded: Creat > 221 & K+>5.0 at enrollment)
          • (stable patients)
          • Less mortality in spiro group (46% vs. 35%) at 2y
          • Rehospitalization rates improved 0.54 vs. 0.77
          • Improved symptoms (NYHA)
          • 10% gynecomastia rate in men.   (serious hyperkalemia was rare)
      • Eplerenone
        • EPHESUS (2003)   [Note: EMPHASIS-HF was 2011]
          • Aldosterone Antagonist eplerenone 25-50mg given to 3-14d post-MI pts who:
            • LVEF < 40% + Clinical HF
            • LVEF < 40% + Diabetes
            • (Excluded if Cr > 221 and K+ > 5)
          • Reduced mortality by 15% in addition to standard therapy (started with ACEi/ARB)
          • Drawback: Hyperkalemia risk was higher in eplerenone group (3.4% vs. 2.0%)
          • Done in era of widespread BB use (unlike RALES, which had 10% use)
        • EMPHASIS-HF (2011)
          • 2737pts NYHA II EF < 35% randomized to eplerenone up to 50mg od vs. placebo
            (in addition to standard therapy)
          • 21mo F/U: Composite death from CV / Hosp for HF ARR imrpoved (18.3% vs. 25.9%)
            • Mortality benefit: 10.8% vs.13.5% [ARR~3%]
          • Hyperkalemia (>5.5) risk higher (11.8% vs. 7.2%)
        • Drug Starting Dose Target Dose Notes
          Spironolactone 12.5-25mg od 25mg od Available and cheap.  RALES study
          Eplerenone 25mg x4w 50mg od Dose held for hyperkalemia >5.5
      • Angiotensin-Neprilysin Inhibitors
        • PARADIGM-HF
          • Entresto 200mg BID [combo: sacubitril 200+valsartan 160mg) vs. enalapril 10mg bid
          • Included:
            • NYHA 2-4 (despite optimal mgmt with full med therapy)
          • Composite CV mortality/hosp for HF by 20%
            • Death from any cause down by 16%
          • NOTE: Did not recruit pts until 3mo post-ACS
            (initially should get ACE/ARB, transition to Entresto 3mo later if needed)
      • Ivabardine (Sinus node modulator)
        • SHIFT Study
          • 6559pts with :
            • HF symptoms
            • LVEF < 35%
            • Sinus rhythm, HR > 70bpm
            • Hosp for HF in last 1 yr + standard med mgmt. 
          • 2yr F/U: HospHF/CVdeath down by 18%
            • HF Hosp reduced by 26% (HF mortality lower, but not CV mortality)
          • As of 2016 - not approved by Health Canada
      • ICD
        • SCD-HeFT Trial
          • 1486pts with IHD remote MI (>40d ago), LVEF < 35%
            • Baseline mortality in  HF mosty due to ventricular arrhythmias
          • with an ICD had 21% reduction in mortality (43% vs. 36%)
        • MADIT II
          • Previous MI, LVEF < 30%
          • ICD group had 31% reduced mortality (19.8 vs. 14.2)
        • DINAMIT Trial
          • Patients randomized to ICD in 6-40d post-MI had no benefit in mortality
      • CRT
        • Symptoms despite optimal medical therapy + QRS > 130ms, LVEF < 35%
      • Calcium Channel Blockers (not used in HF)
        • Thought to improve coronary perfusion through vasodilation
        • Cardiac specific ones (non-dihydropuridine class: Diltiazem or Verpamil)
          • Significant negative inotropic effect
          • Shown beneficial in pts with ACS (reducing recurrent angina if EF is normal)
        • Non-cardiac specific (dihydropuridine class: Amlodipine, Felodipine)
          • Little effect on the heart (mostly peripheral vasodilation)
    • Evidence-Based:

      1.  All pts with LVEF < 40% should receive ACEi at dose used in clinical trials (ramipril 5mg bid, trandolapril 2mg od)

           - If intolerant to ACEi, use ARB (valsartan 240mg)


      2.  All pts with LVEF < 40% should receive a B-blocker

           - (target doses bisoprolol 10mg od or carvedilol 25mg bid)


      3.  IF HF-REF and sx persist despite optimal med therapy (OMT): 
                     Replace ACE/ARB with valsartan/sacubitril 200mg bid

      4.  Combination of spironolactone 25-50mg daily or eplerenone 25-50mg daily recommended for HF and low EF


      5.  For pts with LVEF < 35% post-MI, should be considered for ICD


      6.  Pts with HF symptoms despite OMT, LVEF < 35%, QRS > 140ms, should be considered for CRT


      7.  CCB contraindicated in LV dysfunction or AV block after ACS. 

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