Cardiac Drug Dosing and Administration Guidelines
ACE Inhibitors
Start ACE inhibitors at low doses and titrate upward every 2 weeks to target doses proven in clinical trials, as higher doses significantly reduce hospitalizations and mortality in heart failure. 1
Specific Dosing Regimens
| ACE Inhibitor | Starting Dose | Target Dose |
|---|---|---|
| Captopril | 6.25 mg three times daily | 50-100 mg three times daily [1] |
| Enalapril | 2.5 mg twice daily | 10-20 mg twice daily [1] |
| Lisinopril | 2.5-5 mg once daily | 30-35 mg once daily [1,2] |
| Ramipril | 2.5 mg once daily | 5 mg twice daily or 10 mg once daily [1] |
| Trandolapril | 1 mg once daily | 4 mg once daily [1] |
Administration Protocol
- Double the dose at minimum 2-week intervals until target dose is reached 1
- Monitor blood pressure, renal function (creatinine, BUN), and potassium 1-2 weeks after each dose increase, at 3 months, then every 6 months 1, 3
- Accept creatinine increases up to 50% above baseline or up to 3 mg/dL (266 μmol/L), whichever is greater 1
- Potassium levels up to 5.5-6.0 mmol/L are acceptable 1
Critical Cautions - Seek Specialist Advice When:
Problem Management
For symptomatic hypotension: Reduce or eliminate nitrates, calcium channel blockers, and other vasodilators first; if no congestion present, reduce diuretic dose before adjusting ACE inhibitor 1
For persistent cough: Only discontinue if severe enough to prevent sleep and proven to recur after rechallenge; consider substituting an ARB, though angioedema can still occur 1
For rising creatinine/potassium: Stop NSAIDs, non-essential vasodilators, and potassium supplements; reduce diuretics if no congestion present 1
Beta-Blockers
Only three beta-blockers have proven mortality reduction in heart failure—bisoprolol, carvedilol, and metoprolol succinate extended-release—and benefits cannot be assumed as a class effect. 1
Evidence-Based Dosing
| Beta-Blocker | Starting Dose | Target Dose | Mean Dose in Trials |
|---|---|---|---|
| Bisoprolol | 1.25 mg once daily | 10 mg once daily | 8.6 mg/day [1] |
| Carvedilol | 3.125 mg twice daily | 25-50 mg twice daily | 37 mg/day [1] |
| Metoprolol succinate ER | 12.5-25 mg once daily | 200 mg once daily | 159 mg/day [1] |
Initiation Requirements
- Patient must be relatively stable without IV inotropes or marked fluid retention 1
- Should already be on ACE inhibitor therapy 1, 3
- Double dose every 1-2 weeks if preceding dose tolerated 1
- Monitor heart rate, blood pressure, clinical status, and body weight 1
Managing Adverse Effects
For worsening congestion (dyspnea, edema, weight gain >1.5-2 kg over 2 days): Double diuretic dose first; only halve beta-blocker dose if diuretic increase ineffective 1
For heart rate <50 bpm with symptoms: Halve beta-blocker dose; review other rate-slowing drugs (digoxin, amiodarone, diltiazem); obtain ECG to exclude heart block 1
For symptomatic hypotension: Reconsider need for nitrates and calcium channel blockers before adjusting beta-blocker 1
Aldosterone Antagonists
Aldosterone antagonists are indicated in NYHA class III-IV heart failure in addition to ACE inhibitors and diuretics to reduce mortality. 1
Dosing Regimens
| Drug | Starting Dose | Target/Maximum Dose | Mean Dose in Trials |
|---|---|---|---|
| Spironolactone | 12.5-25 mg once daily | 25 mg once or twice daily | 26 mg/day [1] |
| Eplerenone | 25 mg once daily | 50 mg once daily | 42.6 mg/day [1] |
Monitoring Protocol
- Check potassium and creatinine after 5-7 days, then recheck every 5-7 days until stable 1
- Avoid initiating with potassium-sparing diuretics (amiloride, triamterene) during ACE inhibitor titration 1, 3
- Use only if hypokalemia persists after ACE inhibitor and diuretic initiation 1
Angiotensin Receptor Blockers (ARBs)
ARBs are recommended as alternatives to ACE inhibitors in patients who are ACE inhibitor intolerant, particularly due to cough, to reduce morbidity and mortality. 1
Dosing for Heart Failure
| ARB | Starting Dose | Target Dose | Mean Dose in Trials |
|---|---|---|---|
| Candesartan | 4-8 mg once daily | 32 mg once daily | 24 mg/day [1] |
| Losartan | 25-50 mg once daily | 50-150 mg once daily | 129 mg/day [1] |
| Valsartan | 20-40 mg twice daily | 160 mg twice daily | 254 mg/day [1] |
Critical Warning
Exercise extreme caution when substituting ARBs in patients with ACE inhibitor-induced angioedema, as angioedema can also occur with ARBs. 1
Diuretics
Loop diuretics or thiazides should always be administered in addition to ACE inhibitors for symptomatic fluid overload. 1, 3
Loop Diuretics
| Drug | Starting Dose | Maximum Daily Dose |
|---|---|---|
| Furosemide | 20-40 mg | 250-500 mg [1] |
| Bumetanide | 0.5-1 mg | 5-10 mg [1] |
| Torasemide | 5-10 mg | 100-200 mg [1] |
Escalation Strategy for Insufficient Response
- Increase dose of current diuretic 1
- Combine loop diuretic with thiazide 1
- Administer loop diuretic twice daily for persistent fluid retention 1
- Add metolazone in severe heart failure with frequent creatinine and electrolyte monitoring 1
Renal Considerations
Do not use thiazides if GFR <30 mL/min, except synergistically with loop diuretics 1
Digoxin
The usual daily dose is 0.25-0.375 mg if creatinine is normal; reduce to 0.125-0.25 mg in elderly patients. 1
- No loading dose needed for chronic conditions; can initiate with 0.25 mg twice daily for 2 days 1
- Indicated for atrial fibrillation with any degree of symptomatic heart failure to slow ventricular rate 1
- In sinus rhythm, improves clinical status in patients with persistent symptoms despite ACE inhibitor and diuretic treatment 1
Absolute Contraindications
Bradycardia, second- or third-degree AV block, sick sinus syndrome, carotid sinus syndrome, hypokalemia, hypercalcemia 1
Post-Myocardial Infarction Dosing
For hemodynamically stable patients within 24 hours of acute MI, initiate lisinopril 5 mg orally, followed by 5 mg at 24 hours, 10 mg at 48 hours, then 10 mg once daily for at least 6 weeks. 2
For low systolic BP (≤120 mmHg and >100 mmHg) during first 3 days: Start with 2.5 mg 2
If systolic BP ≤100 mmHg: Maintain 5 mg daily with temporary reductions to 2.5 mg if needed 2
If prolonged hypotension (systolic BP <90 mmHg for >1 hour): Withdraw lisinopril 2