HFrEF: Guideline-Directed Medical Therapy (GDMT)
| Drug Class | Examples | Mortality Benefit | Key Points |
|---|
| ACE-I or ARB or ARNi | Lisinopril, valsartan; sacubitril/valsartan (Entresto β preferred) | Yes β ARNi superior to ACE-I (PARADIGM-HF: 20% RR reduction in CV death/HHF) | Start low, titrate up. Entresto: do not use with ACE-I; wait 36 hrs if switching from ACE-I. Monitor K+, creatinine, BP |
| Beta-blockers | Carvedilol, metoprolol succinate (Toprol-XL), bisoprolol β ONLY these 3 proven in HF | Yes β 34% reduction in mortality (MERIT-HF, COPERNICUS, CIBIS-II) | Initiate when euvolemic (NOT during acute decompensation); start low, titrate over weeks. Do NOT stop abruptly. Hold if HR <60 or systolic BP <90 |
| MRA (Mineralocorticoid Receptor Antagonist) | Spironolactone (Aldactone), eplerenone (Inspra) | Yes β RALES (spironolactone): 30% mortality reduction; EPHESUS (eplerenone post-MI) | Indicated when EF β€35% + symptomatic. Monitor K+ (hyperkalemia risk), renal function; avoid if K+ >5.0, Cr >2.5 (women) or >2.0 (men) |
| SGLT-2 inhibitors | Dapagliflozin (Farxiga), empagliflozin (Jardiance) | Yes β DAPA-HF/EMPEROR-Reduced: reduce HHF and CV death regardless of diabetes status | New 4th pillar of GDMT; also benefit HFpEF (EMPEROR-Preserved, DELIVER trials). Start at eGFR β₯20 |
| Diuretics (loop) | Furosemide, torsemide, bumetanide | No mortality benefit β symptom management | Essential for symptom relief (dyspnea, edema). Torsemide has better oral bioavailability than furosemide. Titrate to euvolemia; target weight loss 0.5β1 kg/day |
| Hydralazine + nitrate | Hydralazine + isosorbide dinitrate (BiDil) | Yes β in self-identified Black patients (A-HeFT trial) | Alternative vasodilator when ACE-I/ARB/ARNi not tolerated; improves outcomes in Black patients specifically; 3Γ daily dosing is challenging |
| Ivabradine (Corlanor) | Ivabradine | Yes β reduce HHF (SHIFT trial) | If (funny current) inhibitor β reduces HR without affecting contractility; indicated if: HR β₯70 bpm on max beta-blocker, SR, EF β€35%, symptomatic HF |
| Digoxin | Digoxin (Lanoxin) | No mortality benefit; reduces HHF | Na-K-ATPase inhibitor β βintracellular Ca2+ β βcontractility; also AV node slowing (AF rate control). Narrow therapeutic index (0.5β0.9 ng/mL target in HF). Toxicity: N/V, yellow-green halos (xanthopsia), arrhythmias. Worsened by hypokalemia. Digoxin toxicity antidote: digoxin-specific Fab antibody fragments (Digibind) |
Beta-Blockers β Clinical Comparison
| Drug | Selectivity | Additional Properties | Key Use |
|---|
| Metoprolol succinate/tartrate | Ξ²1-selective (cardioselective) | Succinate = long-acting (once daily); tartrate = short-acting (BID-TID) | HTN, HFrEF (succinate only), rate control, post-MI |
| Carvedilol (Coreg) | Non-selective Ξ² + Ξ±1 blocking | Vasodilation from Ξ±1 blockade; no ISA | HFrEF (proven benefit), HTN; more hypotension than selective agents |
| Atenolol | Ξ²1-selective | Renally eliminated β reduce dose in CKD | HTN, angina; NOT proven in HF |
| Propranolol | Non-selective Ξ²1/Ξ²2 | Crosses BBB β anxiety, essential tremor, migraine prophylaxis | HTN, portal HTN (varices), thyroid storm, performance anxiety, migraine, essential tremor; AVOID in asthma (Ξ²2 blockade β bronchospasm) |
| Labetalol | Non-selective Ξ² + Ξ±1 | IV form available; preferred in hypertensive urgency in pregnancy (safe) | Hypertensive urgency/emergency, pregnancy-induced HTN |
π― Boards PearlBeta-blockers contraindicated in: decompensated HF (wet, edematous β wait until euvolemic), cardiogenic shock, 2nd/3rd degree heart block (without pacemaker), active bronchospasm/severe asthma. Beta-blocker withdrawal syndrome: abrupt cessation β rebound tachycardia, hypertension, angina, MI β ALWAYS taper over 1β2 weeks when discontinuing.
Statins (HMG-CoA Reductase Inhibitors)
| Intensity | Drugs | LDL Reduction | Indication |
|---|
| High-intensity | Atorvastatin 40β80mg, rosuvastatin 20β40mg | >50% | ASCVD, post-ACS, LDL >190, T2DM age 40β75 with risk factors, 10-yr ASCVD risk β₯20% |
| Moderate-intensity | Atorvastatin 10β20mg, rosuvastatin 5β10mg, simvastatin 20β40mg, pravastatin 40β80mg | 30β50% | Primary prevention with moderate risk, T2DM age 40β75 |
| Low-intensity | Simvastatin 10mg, pravastatin 10β20mg, lovastatin 20mg | <30% | Not recommended for primary prevention in most guidelines; use only if higher intensity not tolerated |
π₯ Statin Side EffectsMyopathy/myalgia (1β5%): mild CK elevation; discontinue if CK >10Γ ULN or symptomatic. Rhabdomyolysis (rare). Risk increased with: high dose, drug interactions (fibrates, niacin, azithromycin, amiodarone, CYP3A4 inhibitors with simvastatin/lovastatin). Hepatotoxicity: rare; do NOT routinely monitor LFTs unless symptomatic. Statin-associated new-onset DM: slight increased risk (~9%); risk:benefit strongly favors statin use. Teratogenic (Category X): discontinue in pregnancy. Add ezetimibe or PCSK9 inhibitor (alirocumab, evolocumab) if LDL goal not achieved on maximally-tolerated statin.
Antiarrhythmics (Vaughan Williams Classification)
| Class | Mechanism | Drugs | Key Uses & Toxicities |
|---|
| Ia | Na+ channel blocker (moderate block); also blocks K+ β βQT | Quinidine, procainamide, disopyramide | AF, VT; quinidine β cinchonism (tinnitus, diarrhea, thrombocytopenia); procainamide β drug-induced lupus (anti-histone Ab); disopyramide β anticholinergic |
| Ib | Na+ channel blocker (weak block); shorten AP duration | Lidocaine, mexiletine, phenytoin | Lidocaine: acute VT (IV only β first-line for ventricular arrhythmia in cardiac arrest); local anesthetic. Mexiletine: oral for VT. Phenytoin: digoxin-induced arrhythmias |
| Ic | Na+ channel blocker (strong block); markedly slow conduction | Flecainide, propafenone | AF/flutter in structurally normal hearts; CONTRAINDICATED post-MI or structural heart disease (CAST trial β increased mortality); propafenone has mild beta-blocking effect |
| II | Beta-blockers β reduce sympathetic activity β slow SA/AV node | Metoprolol, propranolol, esmolol, atenolol | AF rate control, SVT, VT storm; esmolol IV: very short-acting (9 min), ideal for acute settings |
| III | K+ channel blocker β prolong repolarization β βQT interval | Amiodarone, sotalol, dofetilide, ibutilide | Amiodarone: most effective antiarrhythmic; used for AF, VT, VF. Multiple toxicities: pulmonary fibrosis, thyroid (hypo/hyper), hepatotoxicity, corneal microdeposits, photosensitivity, peripheral neuropathy, blue-gray skin discoloration. Very long half-life (40β55 days). Monitor TFTs, LFTs, PFTs, ophthalmology. Sotalol: AF maintenance; avoid if QTc >500ms; renal dosing. Dofetilide: hospital initiation (QT monitoring Γ 3 days) |
| IV | Ca2+ channel blockers (non-DHP): slow SA/AV node | Verapamil, diltiazem | AF/flutter rate control, SVT, hypertension, angina; AVOID in HFrEF (negative inotropy β worsens HF); AVOID with beta-blockers IV (severe bradycardia/heart block) |
| Other | Various | Adenosine, digoxin, atropine, magnesium | Adenosine: first-line for SVT (AVNRT/AVRT); 6mg IV push β 12mg if needed; very short-acting (6β10 sec); side effects: flushing, chest tightness, bronchospasm (avoid in asthma/COPD). Atropine: symptomatic bradycardia. Magnesium: torsades de pointes (K+ channel block from hypomagnesemia), digoxin toxicity arrhythmias |
Anticoagulants
| Drug | Mechanism | Reversal Agent | Key Indications & Notes |
|---|
| Warfarin (Coumadin) | Vitamin K antagonist β inhibits factors II, VII, IX, X and proteins C and S; monitor INR (therapeutic 2β3; mechanical valves 2.5β3.5) | Vitamin K (delayed); FFP or 4-factor PCC (rapid reversal); Kcentra (4-factor PCC) for life-threatening bleed | AF, DVT/PE treatment, mechanical heart valves, hypercoagulable states. Many drug/food interactions (CYP2C9). Teratogenic (avoid in pregnancy β use heparin). Initial procoagulant effect (proteins C & S depleted first β bridge with heparin for β₯5 days) |
| Heparin (UFH) | Activates antithrombin III β inhibits thrombin (IIa) and Xa; IV/SQ; monitor aPTT (1.5β2.5Γ control) | Protamine sulfate (reverses ~60β70% of LMWH effect; full reversal of UFH) | ACS, PE, DVT (therapeutic), VTE prophylaxis (SQ low-dose), bridging therapy. HIT (heparin-induced thrombocytopenia): drop in platelets by >50% β must stop heparin β use direct thrombin inhibitor (argatroban, bivalirudin). Check PF4 antibody |
| LMWH (Enoxaparin) | Anti-Xa (primarily); more predictable pharmacokinetics than UFH | Protamine (partial, ~60%) | VTE prophylaxis and treatment; preferred in pregnancy; ACS (enoxaparin); dose reduction required in CrCl <30; monitor anti-Xa levels in renal failure, extremes of weight, pregnancy |
| Rivaroxaban (Xarelto) | Direct oral anticoagulant (DOAC); direct Factor Xa inhibitor | Andexanet alfa (Andexxa) | AF (non-valvular), DVT/PE treatment and prevention, ACS; once-daily dosing with evening meal for AF; twice daily for acute DVT/PE (21 days); CrCl <15: avoid |
| Apixaban (Eliquis) | Direct Factor Xa inhibitor | Andexanet alfa (Andexxa) | AF (preferred β lowest bleeding risk per ARISTOTLE), DVT/PE; twice daily; fewer drug interactions; CrCl <15: avoid for AF; can use for VTE down to CrCl 25 |
| Dabigatran (Pradaxa) | Direct thrombin inhibitor (DTI); oral Factor IIa inhibitor | Idarucizumab (Praxbind) | AF, DVT/PE; twice daily; prodrug requiring acidic gastric pH (take with food; avoid PPIs); renally cleared β avoid if CrCl <15 for AF |
π§ Mnemonic β DOAC Reversal AgentsFactor Xa inhibitors (rivaroxaban, apixaban, edoxaban) β Andexanet alfa (Andexxa). Direct thrombin inhibitor (dabigatran) β Idarucizumab (Praxbind). UFH β Protamine sulfate. Warfarin β Vitamin K + PCC/FFP.
Antiplatelets
| Drug | Mechanism | Use | Notes |
|---|
| Aspirin (ASA) | Irreversible COX-1/2 inhibitor β βthromboxane A2 β βplatelet aggregation for life of platelet (7β10 days) | ACS/post-MI (DAPT Γ 12 months), ischemic stroke/TIA, stable CAD; primary prevention: only if high CVD risk + low bleed risk per 2022 USPSTF | GI bleeding risk; minimize with lowest effective dose (81mg). 2022 USPSTF: do NOT initiate aspirin for primary prevention in adults β₯60 (harm outweighs benefit) |
| Clopidogrel (Plavix) | Irreversible P2Y12 ADP receptor antagonist β βplatelet aggregation | DAPT post-ACS (with aspirin Γ 12 months), post-PCI (stent), ischemic stroke/TIA if not aspirin-tolerant | Prodrug β requires CYP2C19 activation; reduced efficacy in poor metabolizers; check genotype if concern. AVOID omeprazole (CYP2C19 inhibitor β reduces activation) |
| Ticagrelor (Brilinta) | Reversible P2Y12 antagonist; more potent than clopidogrel; NO hepatic activation needed | DAPT post-ACS (preferred over clopidogrel per PLATO trial) | BID dosing; dyspnea (10β15% β bradykinin-mediated, usually resolves); do NOT give aspirin >100mg/day (reduces efficacy); avoid in hemorrhagic stroke history, severe hepatic impairment |
| Prasugrel (Effient) | Irreversible P2Y12 antagonist; most potent antiplatelet | DAPT post-ACS (especially PCI β TRITON-TIMI 38) | More effective but higher bleeding risk; CONTRAINDICATED in prior stroke/TIA, age >75, weight <60kg (relative); avoid if planned CABG within 7 days; prodrug β faster activation than clopidogrel |
ACS Acute Pharmacotherapy
π₯ STEMI/NSTEMI Acute Drug Protocol: MONA + DAPT + Heparin + High-Intensity StatinMorphine (severe pain; may worsen NSTEMI outcomes β use selectively) Β· Oxygen (if SaO2 <90%) Β· Nitroglycerin (SL/IV β angina relief, preload reduction; avoid if hypotension, inferior MI with RV involvement, recent PDE5 inhibitor use within 24β48h) Β· Aspirin 325mg (loading dose immediately) Β· THEN: P2Y12 inhibitor (ticagrelor 180mg or prasugrel 60mg loading dose for STEMI/PCI; clopidogrel 300β600mg if others contraindicated) Β· Anticoagulant (UFH IV bolus 60 units/kg for STEMI/PCI, or enoxaparin for NSTEMI) Β· High-intensity statin (atorvastatin 80mg or rosuvastatin 40mg) Β· Beta-blocker (within 24h if no contraindications) Β· ACE-I (within 24h for anterior MI, EF <40%, HF, or diabetes)