Cardiovascular Pharmacotherapy & Anticoagulation

Cardiovascular Pharmacotherapy & Anticoagulation

Master cardiovascular pharmacotherapy and anticoagulation with free flashcards and evidence-based clinical strategies. This lesson covers heart failure management, anticoagulation therapy selection, and antiarrhythmic drug optimization—essential concepts for NAPLEX success and clinical practice.

Welcome 🫀

Cardiovascular pharmacotherapy represents one of the most high-yield domains on the NAPLEX and in clinical practice. With heart disease remaining the leading cause of mortality worldwide, your ability to optimize antihypertensives, anticoagulants, antiarrhythmics, and heart failure medications will directly impact patient outcomes. This lesson synthesizes guideline-directed medical therapy (GDMT) with practical clinical pearls to help you confidently answer exam questions and manage real patients.

💡 Why This Matters: Cardiovascular questions consistently comprise 15-20% of NAPLEX content. Beyond the exam, these medications have narrow therapeutic windows, significant drug interactions, and require individualized dosing strategies.

Core Concepts

Heart Failure Pharmacotherapy 🫀

Heart failure with reduced ejection fraction (HFrEF) requires a foundational approach using the "Fantastic Four" medication classes:

🧠 Mnemonic: "BEDS" for HFrEF

• Beta blockers (carvedilol, metoprolol succinate, bisoprolol)
• Enalapril/ACEi or Entresto (ARNi)
• Dapagliflozin/SGLT2i
• Spironolactone/MRA

Key Titration Principles:

• Start low, go slow for beta blockers (may worsen HF initially)
• ACEi/ARB/ARNi: Monitor K⁺ and SCr (expect 30% SCr increase is acceptable)
• ARNi requires 36-hour ACEi washout to prevent angioedema
• SGLT2i: Check for genital mycotic infections, volume depletion

💡 Clinical Pearl: Sacubitril-valsartan (Entresto) is superior to enalapril in reducing cardiovascular death and HF hospitalization (PARADIGM-HF trial). Consider switching stable patients from ACEi to ARNi.

Anticoagulation Therapy Selection 🩸

Choosing the right anticoagulant depends on indication, renal function, drug interactions, and patient factors:

Direct Oral Anticoagulants (DOACs) - The "ABCR" Family:

┌─────────────────────────────────────────────────┐
│         DOAC COMPARISON CHART                   │
├─────────────────────────────────────────────────┤
│                                                 │
│  Factor Xa Inhibitors:                          │
│  ├─ Apixaban (Eliquis) - Twice daily, ↓ GI bleed│
│  ├─ Rivaroxaban (Xarelto) - Once daily, with food│
│  └─ Edoxaban (Savaysa) - Once daily            │
│                                                 │
│  Direct Thrombin Inhibitor:                     │
│  └─ Dabigatran (Pradaxa) - Twice daily, ↑ GI bleed│
│                                                 │
│  All DOACs:                                     │
│  ✓ No routine monitoring                        │
│  ✓ Fewer drug-food interactions                 │
│  ✓ Rapid onset/offset (6-12 hours)             │
│  ✗ More expensive than warfarin                 │
│  ⚠️  Avoid if CrCl <15-30 (drug-dependent)      │
│                                                 │
└─────────────────────────────────────────────────┘

Warfarin Management Essentials:

• Target INR: 2-3 (most indications), 2.5-3.5 (mechanical valves)
• Major interactions: Antibiotics, azoles, amiodarone, NSAIDs
• Reversal: Vitamin K (slow), 4-factor PCC (fast)
• Genetic testing (CYP2C9, VKORC1) may guide initial dosing

🧠 Mnemonic: "REVERT" for DOAC Reversal

• Rixaraban → Andexanet alfa
• Edoxaban → Andexanet alfa
• Vitamin K antagonist (warfarin) → Vitamin K, PCC
• Eliquis (apixaban) → Andexanet alfa
• Re-dose if needed
• Thrombin inhibitor (dabigatran) → Idarucizumab

Antiarrhythmic Drugs ⚡

Vaughan Williams Classification remains the framework for understanding antiarrhythmics:

🧠 Mnemonic: "FAST-PASS" for Antiarrhythmic Classes

• Fast Na⁺ blockers (IA, IB, IC)
• Amiodarone (III)
• Sotalol (II + III)
• Thymol (amiodarone thyroid toxicity)
• Propranolol (II)
• ATP-sensitive (Class I avoid post-MI)
• SVT treated with IV adenosine first
• Structural heart disease → avoid IC drugs

Amiodarone Special Considerations:

• Most effective antiarrhythmic but significant toxicity profile
• Loading: 400-600 mg daily × weeks, maintenance 200 mg daily
• Monitor: TFTs every 6 months, PFTs baseline/annual, LFTs, ophthalmology
• Drug interactions: Warfarin (↓ dose 30-50%), digoxin (↓ dose 50%)
• Contains iodine: Can cause hyper- OR hypothyroidism

💡 Did You Know? Amiodarone has a half-life of 40-60 days due to extensive tissue distribution. This means adverse effects can persist for months after discontinuation!

Antiplatelet Therapy 💊

Dual Antiplatelet Therapy (DAPT) is standard post-ACS and after PCI:

DAPT DECISION TREE

         🚑 ACS or PCI with Stent
                  │
                  ↓
         ┌────────────────────┐
         │ Aspirin 81 mg daily│ (Indefinite)
         │        +           │
         │   P2Y₁₂ inhibitor  │
         └────────┬───────────┘
                  │
      ┌───────────┴───────────┐
      │                       │
   ┌──┴──────┐         ┌──────┴──────┐
   │ Standard│         │   High Risk  │
   │ Risk    │         │   Bleeding   │
   └──┬──────┘         └──────┬──────┘
      │                       │
      ↓                       ↓
  Ticagrelor 90 mg BID    Clopidogrel 75 mg
  or Prasugrel 10 mg      (less potent,
  (more potent)           fewer bleeds)
      │                       │
      └───────────┬───────────┘
                  │
                  ↓
          Duration: 12 months
          (minimum 6 months for BMS,
           12 months for DES/ACS)

P2Y₁₂ Inhibitor Comparison:

⚠️ Critical Point: Ticagrelor is LESS effective when combined with aspirin >100 mg daily. Always use aspirin 81 mg with ticagrelor!

Hypertension Management 🩺

Guideline-directed approach (ACC/AHA 2017):

First-Line Agents:

1. Thiazide diuretics (HCTZ, chlorthalidone)
2. ACE inhibitors (lisinopril, enalapril)
3. ARBs (losartan, valsartan)
4. Calcium channel blockers (amlodipine, diltiazem)

Compelling Indications for Specific Agents:

🧠 Mnemonic: "ABCD" for HTN Drug Classes

• ACE inhibitors / ARBs (–prils, –sartans)
• Beta blockers (–olols)
• Calcium channel blockers (–dipines, diltiazem, verapamil)
• Diuretics (thiazides, loops, K-sparing)

African American Patients: First-line should be CCB or thiazide (ACEi/ARB less effective as monotherapy)

Lipid Management 🧬

Statin Intensity Matters More Than Target LDL:

When to Add Non-Statin Therapy:

• Ezetimibe: Add if LDL still elevated on max-tolerated statin (↓LDL additional 20%)
• PCSK9 inhibitors (alirocumab, evolocumab): Very high-risk patients with LDL ≥70 on statin + ezetimibe
• Bempedoic acid: Alternative if statin-intolerant

💡 Clinical Pearl: Avoid simvastatin 80 mg due to increased myopathy risk. Simvastatin is also limited to 10-20 mg when combined with amiodarone or diltiazem due to CYP3A4 interactions.

Examples

Example 1: HFrEF Optimization

Clinical Scenario: JM is a 62-year-old male with HFrEF (EF 25%), currently on lisinopril 20 mg daily. Labs: K⁺ 4.2, SCr 1.1, BP 128/76, HR 84 bpm. What medication changes should be made?

Solution: This patient needs optimization to quadruple therapy:

Key Monitoring:

• Beta blocker: May worsen symptoms initially (reassure patient this is expected)
• K⁺ with MRA + ACEi: Check in 1 week, then monthly
• SCr: 30% increase acceptable with RAAS inhibitors
• BP: Ensure systolic >90 mmHg before each titration

Example 2: Anticoagulation Selection in AF

Clinical Scenario: RS is a 68-year-old female with newly diagnosed atrial fibrillation. PMH: hypertension, type 2 diabetes. CHA₂DS₂-VASc score = 4. CrCl 55 mL/min. Should she receive anticoagulation? Which agent?

Solution:

Step 1: Calculate CHA₂DS₂-VASc

• Congestive HF: 0
• Hypertension: +1
• Age ≥75: 0 (age 65-74 = +1)
• Diabetes: +1
• Stroke/TIA history: 0
• Vascular disease: 0
• Age 65-74: +1
• Sex category (female): +1
• Total: 4 (High risk, definitely anticoagulate)

Step 2: Choose Agent

DOACs preferred over warfarin. All DOACs acceptable with CrCl >30:

Recommendation: Apixaban 5 mg BID (patient doesn't meet dose reduction criteria). Counsel on adherence importance with BID dosing.

Example 3: Amiodarone Drug Interactions

Clinical Scenario: KT is hospitalized with new-onset rapid AF. Started on amiodarone loading (400 mg BID). Home medications: warfarin 5 mg daily (INR goal 2-3 for prior DVT), digoxin 0.25 mg daily. What adjustments are needed?

Solution:

Amiodarone has critical interactions via CYP3A4 and P-glycoprotein inhibition:

AMIODARONE INTERACTION CASCADE

    Amiodarone Started
           |
           ↓
    ┌──────┴──────┐
    │             │
    ↓             ↓
 Warfarin      Digoxin
 (CYP2C9)      (P-gp)
    │             │
    ↓             ↓
↑ INR         ↑ Levels
 Toxicity      Toxicity
    │             │
    ↓             ↓
 Bleeding      Brady/
               AV block

Required Actions:

1. Warfarin: Reduce dose by 30-50% immediately

   • New dose: 2.5-3.5 mg daily
   • Check INR in 3-5 days (interaction takes several days)
   • Expect INR to rise significantly

2. Digoxin: Reduce dose by 50%

   • New dose: 0.125 mg daily
   • Check digoxin level in 5-7 days
   • Monitor for bradycardia (both drugs slow AV node)

3. Additional Monitoring:

   • Baseline TFTs, LFTs, PFTs (amiodarone toxicity screening)
   • EKG for QTc interval
   • Potassium and magnesium (replete if low to prevent torsades)

⚠️ Critical Point: These interactions persist for WEEKS after stopping amiodarone due to its long half-life!

Example 4: Post-STEMI Medication Reconciliation

Clinical Scenario: BN is a 54-year-old male being discharged after anterior STEMI with drug-eluting stent placement. What medications should be prescribed?

Solution:

Mandatory Post-STEMI Therapy ("ABC-DAPT"):

Additional Considerations:

• Check echocardiogram: If EF <40%, add aldosterone antagonist (eplerenone 25 mg daily)
• Nitroglycerin SL 0.4 mg PRN for chest pain
• Cardiac rehabilitation referral
• Smoking cessation if applicable

🧠 Discharge Mnemonic: "ABCDE" Post-MI

• Aspirin + Antiplatelet (DAPT)
• Beta blocker
• Cholesterol management (high-intensity statin)
• Diet and diabetes management
• Enalapril/ACE inhibitor

Common Mistakes ⚠️

1. Incorrect DOAC Dosing in Renal Impairment

Mistake: Using standard DOAC doses when CrCl is reduced Impact: Accumulation and bleeding risk Solution: Always calculate CrCl and adjust:

• Apixaban: Reduce to 2.5 mg BID if meets 2 of 3 criteria (age ≥80, weight ≤60 kg, SCr ≥1.5)
• Rivaroxaban: 15 mg daily if CrCl 15-50
• Edoxaban: 30 mg daily if CrCl 15-50
• Dabigatran: 75 mg BID if CrCl 15-30

2. Starting Beta Blocker During Acute Decompensated HF

Mistake: Initiating or continuing beta blocker when patient has volume overload Impact: Worsens acute symptoms, hypotension Solution: Stabilize with diuretics FIRST, then restart beta blocker at low dose once euvolemic

3. Combining ACE Inhibitor + ARB

Mistake: Using dual RAAS blockade thinking it's more effective Impact: Hyperkalemia, hypotension, acute kidney injury (ONTARGET trial showed harm) Solution: Use ACEi OR ARB, not both. If inadequate, add different class or switch to ARNi

4. Forgetting Amiodarone-Warfarin Interaction

Mistake: Starting amiodarone without adjusting warfarin Impact: INR rises dangerously, major bleeding risk Solution: Reduce warfarin by 30-50% immediately and monitor INR closely (every 3-5 days initially)

5. Using Aspirin >100 mg with Ticagrelor

Mistake: Prescribing standard aspirin 325 mg with ticagrelor post-ACS Impact: REDUCED efficacy of ticagrelor (PLATO trial) Solution: Always use aspirin 81 mg (maximum 100 mg) when combined with ticagrelor

6. Inappropriate Class IC Antiarrhythmic Use

Mistake: Using flecainide or propafenone in patients with structural heart disease or CAD Impact: Increased mortality (CAST trial) Solution: Screen for structural disease (echo) before Class IC drugs. If present, use amiodarone or dofetilide instead

7. Missing Sacubitril-Valsartan Washout Period

Mistake: Switching directly from ACEi to ARNi Impact: Severe angioedema risk Solution: MANDATORY 36-hour washout between last ACEi dose and first ARNi dose

8. Statin Intolerance Mismanagement

Mistake: Discontinuing all statins after muscle complaints without rechallenge Impact: Loss of cardiovascular benefit Solution: Rule out other causes, try different statin, lower dose, alternate-day dosing, or add ezetimibe/bempedoic acid

Key Takeaways 🎯

✅ HFrEF requires quadruple therapy: Beta blocker + ACEi/ARNi + MRA + SGLT2i (all have mortality benefit)

✅ DOACs preferred over warfarin for AF and VTE (except mechanical valves, which REQUIRE warfarin)

✅ Amiodarone has numerous interactions: Reduce warfarin 30-50%, reduce digoxin 50%, and monitor thyroid/liver/lungs

✅ Post-ACS requires DAPT: Aspirin 81 mg + P2Y₁₂ inhibitor for 12 months minimum

✅ Ticagrelor + aspirin rule: Never exceed aspirin 100 mg daily with ticagrelor (reduced efficacy)

✅ Class IC drugs contraindicated in structural heart disease (flecainide/propafenone increase mortality)

✅ ARNi requires 36-hour ACEi washout to prevent angioedema

✅ High-intensity statins for ASCVD: Atorvastatin 40-80 mg or rosuvastatin 20-40 mg

✅ Calculate CHA₂DS₂-VASc for all AF patients: Score ≥2 (male) or ≥3 (female) = anticoagulate

✅ Beta blockers in HF: "Start low, go slow" - may worsen symptoms initially but provide long-term benefit

📚 Further Study

1. ACC/AHA Heart Failure Guidelines: https://www.acc.org/guidelines/
2. 2023 AF Anticoagulation Update: https://www.ahajournals.org/journal/circ
3. NAPLEX Cardiovascular Review (NABP): https://nabp.pharmacy/programs/naplex/