Stable Angina: Beta-Blockers

• Stable angina is a chronic condition resulting from myocardial ischemia due to narrowed coronary arteries.
• The condition is predictable, typically occurring during exertion or stress, and relieved by rest or glyceryl trinitrate (GTN).
• Stable angina affects 2 million people in the UK, increasing morbidity and healthcare costs.
• Uncontrolled angina can progress to acute coronary syndrome (ACS), requiring hospitalization.
• Treatment focuses on symptom control and cardiovascular event prevention.
• First-line therapy includes beta-blockers or calcium channel blockers (CCBs).
• Second-line options involve combining a beta-blocker and a rate-limiting CCB (e.g., diltiazem, verapamil) if monotherapy fails.
• Adjunct therapies include antiplatelets (aspirin), statins, ACE inhibitors, and nitrates for long-term risk reduction.
• Beta-blockers reduce myocardial oxygen demand by decreasing heart rate, contractility, and blood pressure.

Comparing Beta-Blockers

• Bisoprolol is a Beta-1 selective blocker with once-daily dosing, primarily metabolized in the liver (CYP3A4), and requires caution in liver failure.
• Carvedilol blocks Beta-1, Beta-2, and Alpha-1 receptors, causing vasodilation, requires twice-daily dosing, is metabolized in the liver, and requires caution in liver failure.
• Atenolol is a Beta-1 selective blocker with once-daily dosing, renal metabolism, and requires dose reduction in chronic kidney disease (CKD).

Drug Profiles

• Bisoprolol: Selective beta-1 blocker reducing heart rate and myocardial oxygen demand.
• Bisoprolol Dose: 2.5-10 mg once daily.
• Bisoprolol Benefits: Fewer bronchospasms compared to non-selective beta-blockers.
• Bisoprolol Drawbacks: May cause fatigue, bradycardia.
• The CIBIS-II Trial showed bisoprolol reduced all-cause mortality by 34% in heart failure.
• Carvedilol: Blocks beta-1, beta-2, and alpha-1 receptors, reducing afterload.
• Carvedilol Dose: 6.25-25 mg twice daily.
• Carvedilol Benefits: Improves endothelial function, beneficial for patients with hypertension.
• Carvedilol Drawbacks: Increased risk of hypotension, requires twice-daily dosing.
• The COMET Trial showed carvedilol improved survival vs. metoprolol in heart failure.
• Atenolol: Beta-1 selective blocker with low lipophilicity limiting CNS penetration.
• Atenolol Dose: 25-100 mg once daily.
• Atenolol Benefits: Long-acting, renally excreted, fewer hepatic interactions.
• Atenolol Drawbacks: Less effective in preventing cardiovascular events, higher risk of fatigue.
• The INVEST Trial showed atenolol was less effective than verapamil in preventing CV events.

Clinical Effectiveness Comparison

• The CIBIS-II trial reported that Bisoprolol, in 2,647 patients, resulted in a 42% angina reduction, a 15% heart rate reduction, and a 34% mortality reduction.
• The COMET trial reported that Carvedilol, in 3,029 patients, resulted in a 38% angina reduction, an 18% heart rate reduction, and a 17% mortality reduction.
• The INVEST trial reported that Atenolol, in 22,576 patients, resulted in a 29% angina reduction and a 12% heart rate reduction, with no significant impact on mortality.

Adverse Effects & Safety Considerations

• Bisoprolol is generally well-tolerated with minimal CNS effects but may cause fatigue, hypotension, and bradycardia.
• Carvedilol carries a higher risk of hypotension and requires caution in the elderly.
• Atenolol can cause more fatigue and CNS side effects due to its low lipophilicity.

Cost-Effectiveness

• Bisoprolol annual cost: £19.80 - £79.20.
• Carvedilol annual cost: £42.36 - £169.44.
• Atenolol annual cost: £22.60 - £90.40.

Recommendation

• Bisoprolol as the first-line choice due to the best balance of efficacy, safety, adherence, and cost.
• Bisoprolol offers superior mortality reduction (CIBIS-II trial) and once-daily dosing improves compliance.
• Carvedilol is an alternative for hypertensive patients needing vasodilation.