From the Guidelines
Carvedilol is recommended as a first-line treatment for angina due to its ability to block both beta-1 and beta-2 adrenergic receptors as well as alpha-1 receptors, reducing myocardial oxygen demand and cardiac workload. This combined action reduces the heart's workload in several ways, including decreasing heart rate and contractility, which lowers myocardial oxygen demand, particularly beneficial during physical exertion when angina typically occurs 1. The alpha-blocking properties of carvedilol also cause vasodilation, reducing peripheral vascular resistance and blood pressure, which further decreases cardiac workload.
Key Benefits of Carvedilol
- Reduces myocardial oxygen demand by decreasing heart rate and contractility
- Causes vasodilation, reducing peripheral vascular resistance and blood pressure
- Has a neutral or beneficial effect on lipid profiles and may improve insulin sensitivity
Typical Dosing and Administration
- Typical dosing for angina starts at 6.25 mg twice daily, gradually increasing to 25 mg twice daily as tolerated 1
- Patients should take carvedilol with food to slow absorption and reduce the risk of orthostatic hypotension
- Common side effects include dizziness, fatigue, and hypotension
Important Considerations
- Carvedilol should not be abruptly discontinued as this can worsen angina; dosage should be gradually reduced over 1-2 weeks
- Patients with marked first-degree AV block, any form of second- or third-degree AV block, or a history of asthma should not receive beta blockers on an acute basis 1
- Patients with significant chronic obstructive pulmonary disease should be given beta blockers very cautiously, initially with low doses of a beta-1–selective agent 1
From the FDA Drug Label
The mechanism by which β-blockade produces an antihypertensive effect has not been established β-adrenoreceptor blocking activity has been demonstrated in animal and human studies showing that Carvedilol Tablet (1) reduces cardiac output in normal subjects; (2) reduces exercise- and/or isoproterenol-induced tachycardia; and (3) reduces reflex orthostatic tachycardia.
Patients with coronary artery disease, who are being treated with Carvedilol Tablets, should be advised against abrupt discontinuation of therapy. Severe exacerbation of angina and the occurrence of myocardial infarction and ventricular arrhythmias have been reported in angina patients following the abrupt discontinuation of therapy with β-blockers
Beta Blocker Mechanism: Carvedilol helps with angina by reducing cardiac output, exercise-induced tachycardia, and reflex orthostatic tachycardia through its β-adrenoreceptor blocking activity.
- Reduces cardiac workload and oxygen demand, which can help alleviate angina symptoms.
- Slows heart rate and reduces blood pressure, which can also contribute to the reduction of angina symptoms. The FDA drug label does not provide a direct explanation of how carvedilol helps with angina, but it does mention that β-blockers can cause severe exacerbation of angina if discontinued abruptly 2 2.
From the Research
Mechanism of Action
- Carvedilol is a nonselective beta-receptor antagonist with vasodilating properties primarily due to selective alpha-1 antagonism 3.
- It reduces myocardial oxygen demand, increases myocardial blood supply, and scavenges oxygen free radicals, which are capable of ischemic damage 4.
- Carvedilol competitively blocks beta 1, beta 2, and alpha 1 receptors, and has vasodilating properties that are exerted primarily through alpha 1-blockade 5.
Efficacy in Angina
- Carvedilol is effective and safe in treating patients with chronic stable angina, with a significant reduction in time to angina and time to 1-mm ST-segment depression 3.
- It reduces the ischemic burden in patients with unstable angina pectoris, including a reduction in median heart rate, mean systolic blood pressure, and mean rate-pressure product 6.
- Carvedilol improves exercise tolerance and ischemic symptoms in patients with stable angina pectoris, and reduces the frequency and severity of ischemic events in patients with unstable angina 5.
Comparison with Other Treatments
- Carvedilol seems to be somewhat more effective than nifedipine s.r. for improving exercise tolerance and exercise time to onset of angina and 1 mm ST-segment depression 7.
- It has similar efficacy to other beta-blocking agents, calcium antagonists, ACE inhibitors, and hydrochlorothiazide in reducing blood pressure and improving symptoms in patients with hypertension and angina 5.
Safety and Tolerability
- Carvedilol is well tolerated, with an overall incidence of adverse events being lower than with other antianginal agents 3, 4.
- Adverse events with carvedilol appear to be less frequent than with other beta-blocking agents, are dosage-related, and are usually seen early in therapy 5.
- The most commonly reported adverse events are related to the vasodilating and beta-blocking properties of the drug, such as postural hypotension, dizziness, headaches, dyspnea, bronchospasm, bradycardia, malaise, and asthenia 5.