Which medication, losartan (angiotensin II receptor antagonist) or lisinopril (angiotensin-converting enzyme (ACE) inhibitor), is more effective in reducing heart rate (tachycardia)?

Comparison of Losartan and Lisinopril Effects on Heart Rate

Neither losartan nor lisinopril significantly lowers heart rate as their primary mechanism of action, but lisinopril may have a slightly greater effect on reducing sympathetic activity and heart rate in some patients with heart failure.

Mechanism of Action and Heart Rate Effects

Losartan (ARB)

• Selectively blocks angiotensin II type 1 (AT1) receptors 1
• Does not directly affect heart rate as its primary mechanism 1
• According to the FDA label: "There was essentially no change in average heart rate in losartan-treated patients in controlled trials" 1
• Does not inhibit ACE or affect bradykinin metabolism 1

Lisinopril (ACE Inhibitor)

• Inhibits angiotensin-converting enzyme (ACE) 2
• Prevents conversion of angiotensin I to angiotensin II 2
• Also inhibits bradykinin breakdown (which losartan does not) 2
• May indirectly affect heart rate through reduced sympathetic activity 3

Comparative Effects on Autonomic Function

A direct comparison study showed:

• Both lisinopril and valsartan (another ARB similar to losartan) had comparable effects on cardiac vagal control of heart rate 3
• However, valsartan showed more effective modulation of sympathetic activity measured by plasma norepinephrine levels (27% reduction vs 6% with lisinopril) 3
• This suggests that ARBs might actually have a greater effect on sympathetic modulation than ACE inhibitors, though this doesn't necessarily translate to greater heart rate reduction

Clinical Implications

Heart Failure Patients

• In heart failure patients, a study comparing valsartan and lisinopril found no significant differences between them in their effects on autonomic control of heart rate 3
• The European Society of Cardiology guidelines note that both ACE inhibitors and ARBs provide equivalent efficacy in treating heart failure patients 4

Hypertension Management

• For hypertension management, the primary benefit of both medications comes from blood pressure lowering rather than heart rate effects 4
• The European Society of Hypertension and European Society of Cardiology note that "differences in the incidence of cardiovascular morbidity and mortality between different drug classes are small, thus strengthening the conclusion that their benefit largely depends on blood pressure lowering per se" 4

Practical Considerations

• If heart rate control is the primary goal, neither medication would be the first choice
• Beta-blockers would be more appropriate for heart rate control
• For patients with tachycardia and hypertension requiring an ACE inhibitor or ARB:
  1. Consider lisinopril if there's a slight preference for heart rate reduction
  2. Consider losartan if angioedema is a concern (ARBs have lower risk)
  3. Consider adding a beta-blocker if significant heart rate control is needed

Common Pitfalls and Caveats

• Don't expect significant heart rate reduction with either medication alone
• Individual patient responses may vary considerably
• The correlation between BP response to ACE inhibitors and ARBs is only moderate (r = 0.47/0.59 for systolic/diastolic) 5
• In more than one-third of hypertensive patients, the response to one class fails to predict the response to the other 5
• Dosing matters: higher doses of losartan (150mg) provide greater angiotensin II blockade than standard doses (50mg) 6

In conclusion, while neither medication significantly lowers heart rate as a primary effect, lisinopril may have a slight edge in heart rate reduction in some patients due to its effects on bradykinin metabolism, though this effect is minimal and not clinically significant for most patients.