At equivalent β‑blocker doses, how do carvedilol and metoprolol differ in their effects on blood pressure and heart rate?

Comparative Effects of Carvedilol and Metoprolol on Heart Rate and Blood Pressure

At equivalent β-blocker doses, carvedilol produces significantly greater blood pressure reduction than metoprolol while causing less heart rate reduction, due to carvedilol's additional α1-adrenergic blockade that causes peripheral vasodilation. 1, 2

Heart Rate Effects

Metoprolol produces greater heart rate reduction than carvedilol at rest and during exercise. 1, 3

• Metoprolol decreased heart rate during exercise by 21-25% compared to carvedilol's 16-18% reduction 3
• At rest, metoprolol consistently reduced heart rate (to 58-62 bpm), while carvedilol paradoxically increased resting heart rate at higher doses (66-69 bpm at 50-100 mg), with some doses failing to differ significantly from placebo 3
• The acute heart rate reduction at 2 hours post-dose was significantly greater with metoprolol than carvedilol 1
• Carvedilol's weaker effect on resting heart rate likely results from reflex sympathetic activation secondary to peripheral vasodilation from α1-blockade 3

Blood Pressure Effects

Carvedilol produces significantly greater blood pressure reduction than metoprolol, particularly for diastolic pressure. 1, 2, 4

Systolic Blood Pressure

• Both drugs reduced systolic blood pressure throughout treatment 1
• Carvedilol produced significantly greater systolic pressure reduction at 2 hours compared to metoprolol 1
• The superior systolic effect persisted during chronic therapy 2

Diastolic Blood Pressure

• Carvedilol persistently reduced diastolic blood pressure, while metoprolol did not 1
• This difference remained significant during both acute and chronic administration 2

Hemodynamic Mechanisms Explaining the Differences

The divergent effects on blood pressure and heart rate stem from fundamentally different hemodynamic profiles. 1, 2

Metoprolol's Hemodynamic Profile

• Significantly reduced cardiac output (measured as aortic systolic blood flow) at all measurement points 1
• Consistently and significantly increased systemic vascular resistance throughout treatment 1, 2
• Increased femoral artery resistance above pretreatment values 1
• These effects persisted after 4 weeks of chronic therapy without tolerance development 2

Carvedilol's Hemodynamic Profile

• Maintained cardiac output at pretreatment levels throughout the study 1, 2
• Reduced systemic vascular resistance acutely and chronically 1, 2
• Decreased femoral artery resistance 1
• The vasodilatory action showed no tolerance development during chronic therapy 2
• Systemic and femoral vascular resistances were significantly lower than the metoprolol group at all measurement points 1

Clinical Implications

The hemodynamic differences translate to distinct clinical profiles that should guide drug selection. 5, 6

• Carvedilol's vasodilatory properties provide additional myocardial oxygen savings through afterload reduction, particularly beneficial in patients with concomitant ischemic heart disease 2
• The maintained cardiac output with carvedilol may be advantageous in heart failure patients where cardiac performance is already compromised 7
• Carvedilol demonstrated 17% greater mortality reduction compared to metoprolol tartrate in heart failure trials, though this comparison used immediate-release metoprolol tartrate rather than the sustained-release metoprolol succinate formulation proven to reduce mortality 5, 6
• No trials have directly compared carvedilol to sustained-release metoprolol succinate at their respective target doses 5

Important Caveats

• The pharmacodynamic differences described above were demonstrated in hypertensive patients and healthy volunteers 1, 3, 2
• Women may experience greater heart rate and blood pressure reduction with metoprolol due to 50-100% higher drug exposure from slower CYP2D6 metabolism, potentially requiring lower doses 5
• Both carvedilol and metoprolol are metabolized by CYP2D6, which may increase adverse drug reactions in women 5
• Carvedilol produces only modest blood pressure reduction (-4/-3 mmHg) at recommended doses, with no significant additional benefit from higher doses 6