Evenity (Romosozumab) in Patients with Cardiovascular History
Evenity should NOT be initiated in patients who have had a myocardial infarction or stroke within the preceding year, and should be discontinued immediately if these events occur during treatment. 1
Absolute Contraindications
- Recent cardiovascular events: Do not start romosozumab in patients with MI or stroke within the past 12 months 1
- Active cardiovascular event: Discontinue immediately if MI or stroke occurs during therapy 1
Cardiovascular Risk Assessment Required
The FDA black box warning exists because romosozumab may increase the risk of myocardial infarction, stroke, and cardiovascular death 1. This warning stems from:
- ARCH trial findings: Higher rate of major adverse cardiac events (MACE) in romosozumab-treated patients compared to alendronate 1
- FDA Adverse Event Reporting System: Suggested higher risk for major adverse cardiovascular events 2
Before prescribing, you must explicitly weigh whether fracture prevention benefits outweigh cardiovascular risks in patients with ANY cardiovascular risk factors 1. This includes:
- Age ≥65 years 2
- Current or previous long-term smoking 2
- History of cardiovascular disease (heart attack, stroke, coronary artery disease) 2
- Hypertension 3
- Diabetes mellitus 3
- Hyperlipidemia 3
Guideline Recommendations on Use
The American College of Rheumatology conditionally recommends AGAINST using romosozumab due to cardiovascular risks (myocardial infarction, stroke, or death), reserving it only for highest-risk fracture patients unable to tolerate other agents 2, 4.
The American College of Physicians limits romosozumab to postmenopausal women with osteoporosis at very high fracture risk (mean age >74 years in trials) and only after careful consideration of cardiovascular contraindications 2, 4.
When Romosozumab May Be Considered Despite CV Risk
Romosozumab is appropriate for patients with:
- Very high fracture risk: History of recent major osteoporotic fracture (within 2 years), multiple fractures, or failure/intolerance to other osteoporosis therapies 2, 4, 5
- Low cardiovascular risk profile: No recent MI/stroke, minimal traditional CV risk factors 6, 3
- Imminent fracture risk: Where the dramatic fracture reduction benefit (superior to bisphosphonates) outweighs potential CV concerns 7, 6
Critical Treatment Parameters
Treatment duration is strictly limited to 12 monthly doses maximum because the anabolic effect wanes after 12 months 2, 4, 1. Sequential anti-resorptive therapy (bisphosphonate or denosumab) is mandatory after completion to maintain bone mineral density gains 4, 7.
Monitoring Requirements
- Monitor for cardiovascular symptoms: Instruct patients to seek immediate medical attention for chest pain, shortness of breath, neurological symptoms 1
- Correct hypocalcemia before starting: Romosozumab is contraindicated in hypocalcemia 1, 5
- Ensure adequate calcium and vitamin D supplementation throughout treatment 1
Clinical Context
The cardiovascular signal remains controversial—the FRAME trial (romosozumab vs placebo) showed no increased CV risk, while ARCH trial (romosozumab vs alendronate) demonstrated higher MACE rates 6, 3. This discrepancy suggests the CV risk may be related to the comparator or patient population rather than romosozumab itself, but regulatory agencies have taken a conservative stance 3.
Bottom line: Romosozumab is reserved for severe osteoporosis patients at imminent fracture risk with low cardiovascular risk profiles, never in those with recent MI/stroke, and requires explicit benefit-risk discussion for any patient with cardiovascular risk factors 2, 1, 3.