What medication decreases heart rate without affecting blood pressure?

Ivabradine: The Medication That Decreases Heart Rate Without Affecting Blood Pressure

Ivabradine is the medication that specifically decreases heart rate without affecting blood pressure, making it uniquely valuable when beta-blockers or calcium channel blockers cause problematic hypotension. 1, 2

Mechanism of Action

Ivabradine selectively inhibits the If current in the sinoatrial node, reducing heart rate by slowing diastolic depolarization without any other hemodynamic effects. 1, 2

• The drug has no negative inotropic effects (does not reduce contractility) 2
• It causes no effect on blood pressure—in fact, blood pressure may slightly increase with ivabradine use 1, 3
• There are no effects on ventricular repolarization or myocardial contractility 2
• Ivabradine preserves cardiac output while reducing heart rate by increasing stroke volume proportionally 4

This unique pharmacologic profile distinguishes ivabradine from beta-blockers and calcium channel blockers, which commonly cause hypotension and limit their use in patients with low blood pressure. 1

Clinical Applications and Evidence

Heart Failure with Reduced Ejection Fraction (HFrEF)

Ivabradine is FDA-approved and guideline-recommended (Class IIa) for patients with symptomatic HFrEF (LVEF ≤35%) who are in sinus rhythm with heart rate ≥70 bpm despite maximally tolerated beta-blocker therapy. 1

• The SHIFT trial demonstrated ivabradine reduces heart failure hospitalizations and cardiovascular death in over 6,500 patients 1
• Expected heart rate reduction: approximately 6-10 bpm at therapeutic doses 1, 2
• Particularly beneficial in patients with low blood pressure where beta-blocker optimization is limited by hypotension 1
• A secondary analysis of SHIFT confirmed ivabradine remains effective in improving outcomes even in patients with low systolic blood pressure 1

Inappropriate Sinus Tachycardia (IST)

Ivabradine is the preferred initial pharmacologic therapy for symptomatic IST (Class IIa recommendation) because beta-blockers and calcium channel blockers are often poorly tolerated due to hypotension. 1, 5

• Dosing: Start 2.5-5 mg twice daily with food, titrate to 7.5 mg twice daily based on response 1, 5
• Reduces daytime heart rate by approximately 14-20 bpm 1, 5
• Significantly improves exercise tolerance and symptoms, with some patients achieving complete symptom resolution 1, 5
• Superior efficacy compared to metoprolol in head-to-head comparison 1

Critical caveat: Before initiating ivabradine for IST, you must exclude reversible causes (hyperthyroidism, anemia, dehydration, infection, exogenous substances) and distinguish from focal atrial tachycardia, sinus node reentrant tachycardia, and POTS. 1, 5

Stable Ischemic Heart Disease

The evidence for ivabradine in stable coronary artery disease without heart failure is not supportive—the BEAUTIFUL and SIGNIFY trials showed no mortality benefit in this population. 6, 7

Dosing and Administration

• Standard dosing: 5 mg twice daily initially, may increase to 7.5 mg twice daily 1
• Must be taken with food to optimize absorption 2
• Heart rate reduction is dose-dependent with a plateau effect at doses >20 mg twice daily 2
• Greater heart rate reduction occurs in patients with higher baseline heart rates 2, 3

Safety Profile and Adverse Effects

Ivabradine has an excellent safety profile demonstrated in large randomized trials involving over 17,000 patients. 1, 5, 6

Common Adverse Effects:

• Phosphenes (visual brightness phenomena): Occur in 2.8-3% of patients, usually transient, rarely require discontinuation 1, 5, 2
• Bradycardia: 10% vs 2.2% on placebo—monitor heart rate, especially when combined with other negative chronotropes 2
• Atrial fibrillation: 8.3% vs 6.6% on placebo 2

Absolute Contraindications:

• Atrial fibrillation (drug requires sinus rhythm to work) 5
• Strong CYP3A4 inhibitors (azole antifungals, macrolide antibiotics, HIV protease inhibitors) 2
• Severe hepatic impairment 5
• Pregnancy 2

Clinical Advantages Over Beta-Blockers and Calcium Channel Blockers

The key clinical advantage is that ivabradine reduces heart rate without causing hypotension, making it invaluable when blood pressure is already low or borderline. 1

• In acute heart failure settings, ivabradine can facilitate beta-blocker optimization by allowing heart rate control without additional blood pressure reduction 1
• In patients with advanced heart failure and markedly depressed left ventricular function, ivabradine effectively reduces heart rate while preserving or even increasing cardiac output by augmenting stroke volume 4
• Unlike beta-blockers, ivabradine has no negative effects on myocardial contractility 2, 8

Combination Therapy

Ivabradine can be safely combined with beta-blockers for additive heart rate reduction when monotherapy is insufficient. 1, 5

• In IST, combination therapy with ivabradine plus metoprolol achieved greater heart rate reduction than either agent alone 1, 5
• Monitor closely for excessive bradycardia when combining negative chronotropes 2
• The majority of patients in the SHIFT trial were taking both ivabradine and beta-blockers, demonstrating good tolerability 1

Drug Interactions

Avoid moderate and strong CYP3A4 inhibitors and inducers, as ivabradine is primarily metabolized by CYP3A4. 2

• Contraindicated: Strong CYP3A4 inhibitors (itraconazole, clarithromycin, nelfinavir, nefazodone) 2
• Avoid: Moderate CYP3A4 inhibitors (diltiazem, verapamil, grapefruit juice) 2
• Avoid: CYP3A4 inducers (St. John's wort, rifampicin, barbiturates, phenytoin) 2
• No interaction: Digoxin can be safely coadministered 2