What ACE (Angiotensin-Converting Enzyme) inhibitor is best for blood pressure and heart rate control?

Best ACE Inhibitor for Blood Pressure and Heart Rate Control

For blood pressure and heart rate control, lisinopril is the best ACE inhibitor due to its once-daily dosing, proven efficacy in reducing systolic blood pressure, and minimal effect on heart rate. 1, 2

First-Line Antihypertensive Therapy Options

• According to the 2017 ACC/AHA Hypertension Guidelines, first-line agents for hypertension include thiazide diuretics, calcium channel blockers (CCBs), and ACE inhibitors or ARBs 1
• When choosing a single antihypertensive medication, primary consideration should be given to comorbid conditions (e.g., heart failure, chronic kidney disease) for which specific classes of BP-lowering medication are indicated 1
• For most patients with stage 2 hypertension (BP >20/10 mm Hg above target), initiation with two first-line agents of different classes is recommended 1

Comparative Efficacy of ACE Inhibitors

• In the largest head-to-head comparison of first-step drug therapy for hypertension (ALLHAT trial), the thiazide-type diuretic chlorthalidone was superior to the ACE inhibitor lisinopril in preventing heart failure 1
• ACE inhibitors were less effective than thiazide diuretics and CCBs in lowering BP and in prevention of stroke in the general population 1
• For Black patients specifically, ACE inhibitors were notably less effective than CCBs in preventing heart failure and stroke 1

Specific ACE Inhibitor Characteristics for BP and HR Control

• Lisinopril produces a smooth, gradual blood pressure reduction without affecting heart rate or cardiovascular reflexes 2
• Lisinopril's antihypertensive effect begins within 2 hours, peaks around 6 hours, and lasts for at least 24 hours, making it suitable for once-daily dosing 2
• Lisinopril reduces systolic BP by 11-15% and diastolic BP by 13-17% when given as monotherapy 2
• Enalapril has similar efficacy to lisinopril but may require twice-daily dosing in some patients for optimal 24-hour coverage 3
• Captopril requires multiple daily doses (typically three times daily) which may reduce adherence compared to once-daily options 1, 4

Hemodynamic Effects of ACE Inhibitors

• ACE inhibitors reduce blood pressure by decreasing peripheral arterial resistance with little or no change in cardiac output and heart rate 1, 2
• This hemodynamic profile makes ACE inhibitors particularly beneficial for patients who need blood pressure control without heart rate reduction 2
• Unlike beta-blockers, which directly reduce heart rate, ACE inhibitors maintain cardiac output while reducing afterload 1, 2

Dosing Considerations

• Initial and maximum daily doses for commonly used ACE inhibitors for hypertension 1:
  • Lisinopril: Initial 2.5-5 mg once daily, maximum 20-40 mg once daily 1, 5
  • Enalapril: Initial 2.5 mg twice daily, maximum 10-20 mg twice daily 1, 3
  • Ramipril: Initial 1.25-2.5 mg once daily, maximum 10 mg once daily 1
  • Trandolapril: Initial 1 mg once daily, maximum 4 mg once daily 1

Special Populations and Considerations

• In patients with heart failure, ACE inhibitors improve cardiac function and exercise tolerance 1, 6
• For patients with diabetes and hypertension, ACE inhibitors offer renoprotective effects 6, 7
• In elderly patients, lisinopril has been shown to be effective at dosages of 2.5 to 40 mg/day, with lower doses needed in patients with significant renal impairment 6
• ARBs may be better tolerated than ACE inhibitors in Black patients, with less cough and angioedema, but offer no proven advantage over ACE inhibitors in preventing stroke or cardiovascular disease 1

Common Pitfalls and Caveats

• First-dose hypotension may occur, especially in volume-depleted patients (e.g., those on diuretics) 3
• Hyperkalemia can develop, particularly when ACE inhibitors are combined with potassium-sparing diuretics or potassium supplements 3
• ACE inhibitor-induced cough occurs in approximately 5-20% of patients and may necessitate switching to an ARB 3
• ACE inhibitors are contraindicated in pregnancy and should be avoided in women planning to become pregnant 3
• Renal function should be monitored, especially in patients with pre-existing renal impairment or bilateral renal artery stenosis 7

Conclusion for Clinical Practice

• For most patients requiring an ACE inhibitor for blood pressure control with minimal heart rate effects, lisinopril is the optimal choice due to its once-daily dosing, proven efficacy, and minimal effect on heart rate 5, 2, 6
• For patients with specific comorbidities like heart failure, consider ACE inhibitors with proven benefits in those conditions (e.g., enalapril, lisinopril, or ramipril) 1
• In patients with adherence concerns, once-daily options like lisinopril are preferred over multiple-daily dosing options like captopril 1, 2