Major Cardiology Drug Classes - Clinical Overview

1. Renin-Angiotensin-Aldosterone System (RAAS) Blockers

ACE Inhibitors (e.g., ramipril, lisinopril, captopril, enalapril)

• Mechanism: Block conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion
• Key indications: HFrEF (all NYHA classes), post-MI LV dysfunction, hypertension, diabetic nephropathy, asymptomatic LV systolic dysfunction
• Evidence: RCTs conclusively show increased survival, reduced hospitalizations, and improved NYHA class in HFrEF. ACE inhibitors also delay progression to symptomatic HF in asymptomatic LV dysfunction.
• Key contraindications/cautions: Bilateral renal artery stenosis, pregnancy, angioedema, severe renal impairment (K+ monitoring required), concurrent NSAID use (worsens renal dysfunction)
• Common SE: Dry cough (bradykinin-mediated), hyperkalemia, hypotension, angioedema (rare but serious)

ARBs (e.g., candesartan, valsartan, losartan)

• Mechanism: Block AT1 angiotensin II receptors directly
• Role: First choice when ACE inhibitor is not tolerated. Candesartan reduces CV death + HF hospitalization. Valsartan is non-inferior to captopril post-MI.
• Advantage: No cough (no bradykinin accumulation)

ARNI - Sacubitril/Valsartan (Entresto)

• Mechanism: Combines neprilysin inhibitor (sacubitril, which raises natriuretic peptides, BNP) + ARB (valsartan)
• Role: Now the preferred RAAS blocker for HFrEF (NYHA II-III), replacing ACE inhibitors/ARBs as first-line. PARADIGM-HF trial showed superior mortality reduction vs. enalapril.
• Caution: Do NOT combine with ACE inhibitor (risk of angioedema). Wash out ACE inhibitor for 36 hours before starting.

Mineralocorticoid Receptor Antagonists / MRAs (e.g., spironolactone, eplerenone)

• Mechanism: Block aldosterone receptors; anti-fibrotic, diuretic
• Role: One of the four foundational HFrEF therapies. Also used in resistant hypertension, primary hyperaldosteronism.
• Key trial: RALES (spironolactone), EMPHASIS-HF (eplerenone)
• SE: Hyperkalemia (monitor K+), gynecomastia (spironolactone - eplerenone is more selective)

2. Beta-Blockers (e.g., carvedilol, metoprolol succinate, bisoprolol)

• Mechanism: Block beta-1 (and beta-2/alpha-1 for carvedilol) adrenergic receptors; reduce HR, BP, myocardial oxygen demand; anti-arrhythmic
• Key indications:
  • HFrEF (all three evidence-based agents: carvedilol, metoprolol succinate, bisoprolol)
  • Post-MI (reduce mortality and re-infarction)
  • Angina (reduce oxygen demand)
  • Hypertension
  • Rate control in AF/flutter
  • Specific arrhythmias (SVT, LVOT obstruction)
• Contraindications: Acute decompensated HF (don't initiate; can continue if already on them), high-degree AV block, severe reactive airway disease, severe bradycardia
• Key principle: In HFrEF, start at low dose, up-titrate slowly. Do not abruptly discontinue (rebound ischemia/arrhythmia).

3. SGLT2 Inhibitors (e.g., dapagliflozin, empagliflozin)

• Mechanism: Block sodium-glucose cotransporter 2 in the proximal tubule - glucosuria, natriuresis, osmotic diuresis, reduced preload/afterload, cardiorenal protection (exact cardioprotective mechanism still under study)
• Key indications: Now part of the four foundational HFrEF therapies alongside ARNI, beta-blocker, and MRA (2022 AHA/ACC/HFSA guidelines). Also indicated for HFpEF (dapagliflozin, empagliflozin). Type 2 diabetes with established CV disease.
• Trials: DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, DELIVER
• SE: Genitourinary fungal infections, DKA (rare, especially in T1DM), Fournier's gangrene (rare), euglycemic DKA
• Note: Benefit is seen regardless of diabetes status

4. Diuretics

Loop Diuretics (e.g., furosemide, torsemide, bumetanide)

• Mechanism: Block Na+/K+/2Cl- cotransporter in the ascending loop of Henle
• Role: Congestion control in HF, pulmonary edema, acute decompensation. No proven mortality benefit but essential for symptom relief - nearly all symptomatic HF patients need them.
• SE: Hypokalemia, hyponatremia, hypomagnesemia, hyperuricemia, ototoxicity (high doses), prerenal azotemia
• Principle: Use minimum dose needed to maintain "dry weight." Dose should be flexible based on symptoms/weight.

Thiazide/Thiazide-like (e.g., hydrochlorothiazide, chlorthalidone, indapamide)

• Role: Hypertension, mild HF with preserved renal function. Chlorthalidone preferred over HCTZ for BP (longer duration, better outcome data)
• SE: Hypokalemia, hyperuricemia, glucose intolerance, dyslipidemia

5. Antiarrhythmic Drugs (Vaughan Williams Classification)

6. Calcium Channel Blockers (CCBs)

Dihydropyridines (DHPs) - e.g., amlodipine, nifedipine, felodipine

• Mechanism: Block L-type Ca2+ channels in vascular smooth muscle (mainly) - arterial vasodilation
• Indications: Hypertension, angina (vasospastic and effort), Raynaud's
• Avoid in HFrEF: Some (e.g., nifedipine) may worsen outcomes; amlodipine and felodipine are considered safer in HF if needed

Non-DHPs - diltiazem, verapamil

• Mechanism: Also slow AV node conduction (negative chronotropy)
• Indications: AF rate control, SVT, angina, hypertension
• Avoid in: HFrEF (negative inotropic effect), in combination with beta-blockers (risk of severe bradycardia/heart block)

7. Nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate, GTN/nitroglycerin)

• Mechanism: Donate NO - venous dilation (preload reduction) and coronary vasodilation at higher doses
• Indications: Angina (prophylaxis and acute relief), acute pulmonary edema, ACS, HFrEF (hydralazine-nitrate combination in Black patients: A-HeFT trial)
• SE: Headache (very common), hypotension, tachycardia (reflex)
• Key note: Nitrate tolerance develops with continuous use - a daily nitrate-free interval (8-10 hours) is needed

8. Statins (e.g., atorvastatin, rosuvastatin, simvastatin)

• Mechanism: HMG-CoA reductase inhibitors - reduce hepatic cholesterol synthesis, upregulate LDL receptors, pleiotropic anti-inflammatory effects
• Indications: All patients with atherosclerotic CV disease (ASCVD) regardless of baseline LDL. High-intensity statin (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) is standard for established ASCVD or age ≤75 with prior CV event.
• SE: Myopathy/rhabdomyolysis (rare; check CK if symptoms), elevated transaminases, new-onset diabetes
• Drug interactions: CYP3A4 inhibitors increase myopathy risk (e.g., simvastatin + amiodarone)

9. Antiplatelet Agents

10. Anticoagulants in Cardiology

11. Vasodilators and Other Agents

HFrEF Guideline-Directed Medical Therapy (GDMT) - 2022 AHA/ACC

1. ARNI (sacubitril/valsartan) - preferred; or ACE inhibitor/ARB if not tolerated
2. Beta-blocker (carvedilol, metoprolol succinate, or bisoprolol)
3. MRA (spironolactone or eplerenone)
4. SGLT2i (dapagliflozin or empagliflozin)