Can Trelegy (fluticasone furoate, umeclidinium, and vilanterol) cause hypertensive crisis, especially in patients with pre-existing hypertension or cardiovascular disease?

Does Trelegy Lead to Hypertensive Crisis?

Trelegy (fluticasone furoate/umeclidinium/vilanterol) does not cause hypertensive crisis, though it can produce cardiovascular effects including increases in blood pressure that require monitoring in patients with pre-existing hypertension or cardiovascular disease. 1

Cardiovascular Effects of Trelegy

The FDA label explicitly states that Trelegy can produce clinically significant cardiovascular effects in some patients, including:

• Increases in systolic or diastolic blood pressure 1
• Increases in pulse rate 1
• Cardiac arrhythmias (supraventricular tachycardia, extrasystoles) 1
• Electrocardiographic changes (T wave flattening, QTc prolongation, ST segment depression) 1

These effects are attributable to the beta2-agonist component (vilanterol), which acts as a sympathomimetic agent. 1

Evidence from Large-Scale Cardiovascular Safety Studies

The SUMMIT trial provides the highest-quality evidence regarding cardiovascular safety in high-risk patients. This study enrolled 16,590 patients with moderate COPD and heightened cardiovascular risk, treating them for a median of 1.5 years. 2

Key cardiovascular findings from SUMMIT:

• No increase in composite cardiovascular events (myocardial infarction, stroke, unstable angina, transient ischemic attack, or cardiovascular death) with fluticasone furoate/vilanterol compared to placebo (HR 0.93,95% CI 0.75-1.14) 2
• Annualized cardiovascular event rates were similar across all treatment groups (2.4-2.7 per 100 patient-years) 2
• Adverse cardiac events occurred in 17-18% of patients across all groups, with no excess risk in treatment arms 2

The IMPACT trial further confirmed cardiovascular safety in 10,355 symptomatic COPD patients with exacerbation history. 3

Critical findings from IMPACT:

• 68% of patients had ≥1 cardiovascular risk factor; 40% had ≥2 risk factors 3
• 29% reported current/past cardiac disorders; 58% reported vascular disorders 3
• Cardiovascular adverse events of special interest occurred in 10-11% across all treatment groups with no statistical difference between triple therapy and dual therapy 3
• Major adverse cardiac events occurred in only 1-3% of patients across all arms 3
• No statistically significant increased cardiovascular risk with FF/UMEC/VI versus comparators 3

Specific Guidance for Patients with Hypertension

The FDA recommends using Trelegy with caution—not avoiding it—in patients with cardiovascular disorders, including hypertension. 1

When prescribing to hypertensive patients:

• Monitor blood pressure and pulse rate regularly during treatment initiation and dose adjustments 1
• If clinically significant cardiovascular effects occur (substantial BP elevation, tachycardia, arrhythmias), Trelegy may need to be discontinued 1
• Consider the risk-benefit ratio in patients with coronary insufficiency, cardiac arrhythmias, and hypertension 1

Distinction from Hypertensive Crisis

Hypertensive crisis is not listed as a known adverse effect in the FDA label or reported in major clinical trials. 1, 2, 3

The cardiovascular effects observed are:

• Generally modest and manageable 1
• Not associated with hypertensive emergency presentations 2, 3
• Similar in frequency to placebo in controlled trials 2

A separate study specifically examining arterial stiffness (measured by aortic pulse wave velocity) in 430 COPD patients found no adverse vascular effects after 24 weeks of treatment with fluticasone furoate/vilanterol. 4

Clinical Monitoring Recommendations

For patients with pre-existing hypertension or cardiovascular disease:

• Establish baseline blood pressure and heart rate before initiating therapy 1
• Monitor cardiovascular parameters at follow-up visits, particularly during the first few months of treatment 1
• Assess for symptoms of cardiovascular decompensation (chest pain, palpitations, dyspnea, dizziness) 1
• Optimize blood pressure control with antihypertensive medications per current hypertension guidelines 5
• Do not withhold Trelegy solely based on controlled hypertension, as the benefits in COPD management typically outweigh cardiovascular risks 2, 3

Important Caveats

Patients with recent major cardiovascular events require careful consideration. The SUMMIT trial excluded patients with a major cardiovascular event in the previous 6 months, current severe heart failure, or uncontrolled hypertension. 4 This suggests deferring initiation in acutely unstable cardiovascular patients until stabilization occurs.

Large doses (4 times the recommended dose) have been associated with clinically significant QTc prolongation, which could theoretically increase arrhythmia risk, but this is not relevant at therapeutic dosing. 1