Safety of Romosozumab (Evenity) for Patients with History of Ischemic Stroke >2 Years Ago
Romosozumab should not be used in patients with a history of ischemic stroke, even if it occurred more than 2 years ago, due to potential increased cardiovascular risk. 1
Cardiovascular Risk of Romosozumab
Romosozumab (Evenity) carries a black box warning regarding cardiovascular safety. The FDA label explicitly states that Evenity may increase the risk of myocardial infarction, stroke, and cardiovascular death 1. The warning specifically indicates:
- Evenity should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year
- Clinicians should consider whether benefits outweigh risks in patients with other cardiovascular risk factors
- If a patient experiences a myocardial infarction or stroke during therapy, Evenity should be discontinued
While the FDA label specifically mentions contraindication within one year of stroke, the presence of a history of ischemic stroke is considered a very high-risk condition for cardiovascular events according to the 2021 AHA/ASA guidelines 2. These guidelines identify a history of ischemic stroke as a major risk factor for atherosclerotic cardiovascular disease.
Evidence on Cardiovascular Safety
The cardiovascular safety concerns with romosozumab emerged from clinical trials:
- The ARCH trial showed a higher risk of cardiovascular events in patients receiving romosozumab compared to alendronate 3
- A meta-analysis found that romosozumab therapy might increase the risk of 4-point major adverse cardiovascular events (4P MACE) among elderly patients with osteoporosis 4
Although some nonclinical studies did not identify evidence linking sclerostin inhibition with adverse cardiovascular function 5, the clinical evidence suggests caution is warranted, particularly in patients with established cardiovascular risk factors like prior stroke.
Risk Stratification for Patients with Prior Stroke
The 2021 AHA/ASA guidelines for prevention of stroke in patients with stroke and TIA classify patients with a history of ischemic stroke as having established atherosclerotic cardiovascular disease 2. This classification places them in a very high-risk category for future cardiovascular events.
For patients with osteoporosis who have a history of stroke:
- Alternative osteoporosis treatments should be considered
- Other agents like bisphosphonates, denosumab, or selective estrogen receptor modulators may provide fracture reduction benefits without the cardiovascular concerns associated with romosozumab
Conclusion
Given the black box warning, the evidence of increased cardiovascular risk in clinical trials, and the high-risk status conferred by a history of ischemic stroke, romosozumab should be avoided in patients with prior ischemic stroke, regardless of the time since the event. The potential benefits for osteoporosis treatment do not outweigh the cardiovascular risks in this population.