Should a patient with tachycardia at a low dose of Zepbound stop the medication?

Heart Rate Increase with Zepbound (Tirzepatide): Management Recommendations

A 10 bpm heart rate increase at a low dose of Zepbound does not require medication discontinuation in most patients, as this magnitude of increase is expected and documented in clinical trials, though close monitoring is warranted. 1

Understanding the Heart Rate Effect

Tirzepatide causes a predictable increase in heart rate of 2-4 beats per minute on average compared to placebo. 1 This is a known class effect of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists like tirzepatide. 2

Clinical Trial Data on Heart Rate Changes

• In placebo-controlled trials, episodes of sinus tachycardia with a concomitant increase from baseline of ≥15 bpm were reported in 4.3% of placebo patients versus 4.6%, 5.9%, and 10% of patients on Zepbound 5 mg, 10 mg, and 15 mg respectively. 1
• Notably, Japanese patients showed higher rates: 7% (placebo) versus 7.1%, 9.3%, and 23% across the three Zepbound doses. 1
• The FDA label explicitly states "the clinical relevance of heart rate increases is uncertain." 1

When to Continue vs. Discontinue

Continue Medication If:

• The patient has no underlying cardiac conduction disease (no second or third-degree AV block, no sick sinus syndrome without pacemaker). 3
• The patient is hemodynamically stable with no symptoms of decompensated heart failure, hypotension, or cardiogenic shock. 3
• The heart rate increase is isolated without accompanying symptoms such as chest pain, palpitations, dizziness, or syncope. 1
• The patient is not on multiple medications that affect SA/AV nodal conduction (beta-blockers, calcium channel blockers, digoxin, amiodarone). 3

Consider Discontinuation or Dose Reduction If:

• The patient develops symptomatic tachycardia with palpitations, chest discomfort, or hemodynamic compromise. 1
• Pre-existing cardiac conduction abnormalities are present (PR interval >0.24 seconds, second/third-degree AV block without pacemaker). 3
• The patient has decompensated heart failure or severe left ventricular dysfunction. 3
• Concurrent use of multiple rate-controlling medications creates risk for unpredictable heart rate effects. 3

Monitoring Strategy

Implement weekly heart rate monitoring during the first month of therapy and with each dose escalation. 1 This can be accomplished through:

• Patient self-monitoring of pulse rate at rest and with activity
• Office-based vital sign checks
• Consider 24-hour Holter monitoring if symptomatic or if baseline cardiac disease exists 2

Specific Monitoring Parameters:

• Resting heart rate should be checked at consistent times of day 2
• Assess for symptoms including palpitations, chest pain, dyspnea, dizziness, or syncope 1
• Monitor for gastrointestinal adverse effects (nausea, vomiting, diarrhea) which occur in 12-18% of patients and may contribute to dehydration-related tachycardia 1
• Evaluate volume status as dehydration from GI side effects can exacerbate heart rate increases 1

Clinical Context from Recent Outcomes Data

The SUMMIT trial demonstrated cardiovascular benefit with tirzepatide in patients with heart failure with preserved ejection fraction and obesity, showing a 38% reduction in cardiovascular death or worsening heart failure events (HR 0.62,95% CI 0.41-0.95, P=0.026). 4 This suggests that in appropriately selected patients, the cardiovascular benefits may outweigh concerns about modest heart rate increases.

Common Pitfalls to Avoid

• Do not reflexively discontinue for asymptomatic heart rate increases <15 bpm from baseline, as this is within the expected range and may deprive patients of significant metabolic and cardiovascular benefits. 1, 4
• Do not ignore concurrent medications that affect heart rate—review the entire medication list for beta-blockers, calcium channel blockers, digoxin, or antiarrhythmic agents. 3
• Do not attribute all tachycardia to the medication—evaluate for dehydration from GI side effects, hypoglycemia (if on insulin or sulfonylureas), or other medical causes. 1
• Do not fail to assess baseline cardiac status—patients with pre-existing conduction disease require more cautious monitoring. 3

Practical Management Algorithm

1. Verify the heart rate increase with repeat measurements at rest
2. Assess for symptoms (palpitations, chest pain, dyspnea, dizziness)
3. Review baseline cardiac history and current ECG if available
4. Check for dehydration from GI side effects and ensure adequate hydration 1
5. Review concomitant medications for drug interactions affecting heart rate 3
6. If asymptomatic with HR increase <15 bpm: Continue medication with weekly monitoring 1
7. If symptomatic or HR increase ≥15 bpm: Consider holding next dose, obtain ECG, and reassess in 3-5 days
8. If persistent symptomatic tachycardia: Discontinue and consider alternative weight management therapy 1