Evenity (Romosozumab) and Cardiac Disease: Understanding the Caution
Evenity (romosozumab) is cautioned in patients with cardiac disease because clinical trials demonstrated an increased risk of cardiovascular events, particularly myocardial infarction and stroke, compared to other osteoporosis treatments. 1
Cardiovascular Risk Evidence
Romosozumab has shown a concerning cardiovascular safety profile in clinical studies:
- The ARCH trial demonstrated a higher risk of cardiovascular events in patients receiving romosozumab compared to alendronate (hazard ratio 1.9, CI 1.1 to 3.1) 1
- This increased risk was primarily driven by myocardial infarction and stroke events 2
- The FDA has issued a black box warning that romosozumab should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year 2, 3
Mechanism of Cardiovascular Risk
The exact mechanism behind romosozumab's cardiovascular effects remains unclear:
- Romosozumab inhibits sclerostin, which is expressed not only in bone but also in aortic vascular smooth muscle 4
- Sclerostin has been proposed to have protective effects against vascular calcification, atheroprogression, and inflammation 4
- By inhibiting sclerostin, romosozumab may potentially interfere with these protective cardiovascular mechanisms
Clinical Recommendations
Based on the available evidence, the following approach is recommended:
Absolute contraindications:
Risk stratification:
- Carefully evaluate cardiovascular risk factors before prescribing
- Consider alternative osteoporosis treatments in patients with:
- Established coronary artery disease
- Multiple cardiovascular risk factors
- History of heart failure 6
Monitoring recommendations:
- For patients who do receive romosozumab despite having cardiac risk factors:
- Consider baseline cardiac evaluation
- Monitor for symptoms of cardiovascular disease during treatment
- Implement appropriate cardiovascular risk reduction strategies
- For patients who do receive romosozumab despite having cardiac risk factors:
Alternative Treatment Options
For patients with cardiac disease who need osteoporosis treatment:
- First-line alternatives: Bisphosphonates (alendronate, risedronate, zoledronate) have established efficacy for reducing vertebral, hip, and non-vertebral fractures 7
- Second-line alternative: Denosumab is recommended as an alternative treatment for patients with contraindications to bisphosphonates 7
- Other options: Teriparatide or abaloparatide may be considered for patients with very high fracture risk 7
Important Considerations
- Romosozumab is limited to 12 monthly doses, after which transition to an antiresorptive agent is recommended 7
- The risk-benefit ratio must be carefully assessed - while romosozumab is highly effective for fracture reduction, cardiovascular safety concerns may outweigh benefits in patients with cardiac disease 2
- Post-marketing surveillance continues to monitor for cardiovascular safety signals with romosozumab use in real-world settings 6
By understanding these cardiovascular risks and implementing appropriate patient selection and monitoring strategies, clinicians can optimize the use of romosozumab while minimizing potential cardiac complications.