From the Guidelines
ACE inhibitors do not directly affect heart rate and do not typically cause significant negative chronotropy.
Mechanism of Action
ACE inhibitors work primarily by blocking the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and decreasing blood pressure, which can indirectly cause a modest reduction in heart rate in some patients 1.
Clinical Implications
Any heart rate changes observed with ACE inhibitors are usually secondary to their effects on blood pressure and neurohormonal systems rather than direct chronotropic action.
- In heart failure patients, ACE inhibitors may actually help normalize elevated heart rates by improving cardiac function and reducing sympathetic nervous system activation.
- Common ACE inhibitors include lisinopril (10-40 mg daily), enalapril (5-40 mg daily in divided doses), ramipril (2.5-20 mg daily), and captopril (12.5-150 mg daily in divided doses).
Monitoring and Precautions
Patients should be monitored for hypotension, especially after the first dose, as the blood pressure-lowering effect can occasionally cause reflex tachycardia in some individuals, though this is typically transient 1.
Key Considerations
The use of ACE inhibitors is beneficial for patients with prior or current symptoms of chronic heart failure with reduced ejection fraction (HFrEF) to reduce morbidity and mortality, and they should be started at low doses and titrated upward to doses shown to reduce the risk of cardiovascular events in clinical trials 1.
From the FDA Drug Label
Administration of lisinopril to patients with hypertension results in a reduction of both supine and standing blood pressure to about the same extent with no compensatory tachycardia In hemodynamic studies of lisinopril in patients with essential hypertension, blood pressure reduction was accompanied by a reduction in peripheral arterial resistance with little or no change in cardiac output and in heart rate.
ACE inhibitors and negative chronotropy: ACE inhibitors, such as lisinopril, do not typically cause a significant change in heart rate, including no compensatory tachycardia, in patients with hypertension.
- The reduction in blood pressure is accompanied by a reduction in peripheral arterial resistance with little or no change in cardiac output and in heart rate.
- This suggests that ACE inhibitors do not have a significant negative chronotropic effect, which is a decrease in heart rate. 2 2
From the Research
ACE Inhibitors and Negative Chronotropy
- ACE inhibitors have been found to reduce heart rate in hypertensive patients, particularly in those with faster heart rates 3.
- The study published in the Journal of cardiovascular pharmacology in 2002 found that ACE inhibitors significantly reduced clinic and 24-h heart rate in patients with baseline heart rate >75 beats/min, while calcium antagonists did not significantly change heart rate in various subgroups 3.
- Another study published in Postgraduate medicine in 1990 discussed the safety profile and potential uses of ACE inhibitors, but did not specifically address their effect on heart rate 4.
- A review published in the Journal of the American College of Cardiology in 2018 compared outcomes and adverse events between ACE inhibitors and angiotensin receptor blockers (ARBs) in patients with hypertension, but did not focus on the effect of ACE inhibitors on heart rate 5.
- A study published in the American journal of health-system pharmacy in 2000 reviewed the use of ACE inhibitors in various cardiovascular and renal disorders, but did not specifically address their effect on heart rate 6.
- A recent review published in Current hypertension reports in 2023 discussed the discovery and development of ACE inhibitors, their efficacy, tolerability, and safety, but did not provide new insights into their effect on heart rate 7.
Mechanism of Action
- ACE inhibitors work by inhibiting the conversion of angiotensin I to angiotensin II, resulting in arterial and venous vasodilation, natriuresis, and a decrease in sympathetic activity, which can lead to a reduction in heart rate 3, 7.
- The inhibition of ACE also causes accumulation of bradykinin, which can increase the risk of bradykinin-mediated side effects like angioedema and cough 7.