What is the difference between captopril (Angiotensin-Converting Enzyme (ACE) inhibitor) and clonidine for treating hypertension?

Captopril vs Clonidine for Hypertension

Captopril, an angiotensin-converting enzyme (ACE) inhibitor, is generally preferred over clonidine for treating hypertension due to its better side effect profile, proven mortality benefits, and organ protection properties. 1

Mechanism of Action

• Captopril: Inhibits angiotensin-converting enzyme (ACE), preventing conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion 2
• Clonidine: Centrally-acting alpha-2 adrenergic agonist that reduces sympathetic outflow from the central nervous system 1

Efficacy in Blood Pressure Control

• Both medications effectively lower blood pressure, with similar overall antihypertensive efficacy 3
• Captopril has been shown to be as effective as thiazide diuretics and beta-blockers in mild to moderate hypertension 3
• Clonidine is particularly effective for rapid blood pressure reduction but has more rebound hypertension concerns 1

Cardiovascular Outcomes and Mortality Benefits

• Captopril has demonstrated significant mortality benefits in patients with:
  • Type 1 diabetes with nephropathy (50% reduction in composite endpoint of death, dialysis, and transplantation) 1
  • Post-myocardial infarction with left ventricular dysfunction (19% reduction in mortality) 1
  • Heart failure (improved cardiac function and exercise tolerance) 1
• Clonidine lacks similar robust outcome data for cardiovascular mortality reduction 1

Organ Protection Benefits

• Captopril provides superior organ protection:
  • Reduces kidney disease progression in type 1 diabetes (48% reduction in risk of doubling serum creatinine) 1
  • Slows progression of non-diabetic chronic renal insufficiency with proteinuria >1g/day 1
  • Reduces left ventricular hypertrophy 1
• Clonidine does not offer comparable organ protection benefits 1

Side Effect Profiles

• Captopril side effects:
  • Dry cough (most common) 3
  • Rash (0.5-4%) 3
  • Taste disturbances (0.1-3%) 3
  • Proteinuria (0.5%) 3
  • Neutropenia (0.3% during first 3 months) 3
  • First-dose hypotension (0.1-3%) 3
• Clonidine side effects:
  • Dry mouth and sedation (very common) 1
  • Rebound hypertension with abrupt discontinuation (significant risk) 1
  • Bradycardia 1
  • Depression 1

Special Populations

• Captopril is preferred in:

  • Diabetes (particularly with nephropathy) 1
  • Heart failure 1
  • Post-myocardial infarction 1
  • Left ventricular dysfunction 1
  • Proteinuric kidney disease 1

• Clonidine may be considered in:

  • Patients with ACE inhibitor-induced cough 1
  • As add-on therapy in resistant hypertension 1
  • Hypertensive emergencies (IV formulation) 1

Contraindications

• Captopril contraindications:

  • Pregnancy (compelling contraindication) 1
  • Bilateral renal artery stenosis 1
  • History of angioedema with ACE inhibitors 1
  • Hyperkalemia 1

• Clonidine contraindications:

  • Severe bradycardia 1
  • Heart block 1
  • Patients at risk for rebound hypertension with poor medication adherence 1

Clinical Decision Algorithm

1. First-line therapy for uncomplicated hypertension:

   • Consider captopril (or other ACE inhibitor) especially if patient has diabetes, heart failure, or high cardiovascular risk 1
   • Consider a thiazide diuretic, calcium channel blocker, or ACE inhibitor based on patient characteristics 1
   • Clonidine is not recommended as first-line therapy 1

2. For patients with compelling indications:

   • Choose captopril for patients with:
     • Diabetes with nephropathy 1
     • Heart failure 1
     • Post-myocardial infarction 1
     • Left ventricular dysfunction 1

3. For resistant hypertension:

   • Consider adding clonidine as a later-line agent after other options have been tried 1

Dosing Considerations

• Captopril:

  • Starting dose: 12.5-25 mg twice or three times daily 3
  • Maximum dose: 150 mg/day 4
  • Requires dose adjustment in renal impairment 1

• Clonidine:

  • Starting dose: 0.1 mg twice daily 1
  • Gradual dose titration to minimize side effects 1
  • Requires gradual tapering when discontinuing to prevent rebound hypertension 1

Common Pitfalls and Caveats

• For captopril:

  • First-dose hypotension can occur, especially in volume-depleted patients; consider administering first dose at bedtime 1
  • Monitor renal function and potassium levels, especially when initiating therapy 1
  • Acute renal failure can occur in patients with bilateral renal artery stenosis 1

• For clonidine:

  • Never discontinue abruptly due to risk of rebound hypertension 1
  • Sedation may limit daytime use in some patients 1
  • May mask symptoms of hypoglycemia in diabetic patients 1