Use Rexulti with Caution in Post-CABG Patients with Cardiovascular Disease
Rexulti (brexpiprazole) can be used in patients with past CABG surgery, but requires careful cardiovascular monitoring due to the drug's potential to cause orthostatic hypotension and the fact that patients with recent myocardial infarction or unstable cardiovascular disease were excluded from premarketing trials.
Key Safety Considerations from FDA Labeling
The FDA label for Rexulti explicitly states that "REXULTI has not been evaluated in patients with a recent history of myocardial infarction or unstable cardiovascular disease. Such patients were excluded from the premarketing clinical studies" 1. This is the most critical piece of information for your decision-making.
Cardiovascular Monitoring Requirements
Orthostatic vital signs must be monitored in patients with known cardiovascular disease, including those with:
- History of myocardial infarction
- Ischemic heart disease
- Heart failure
- Conduction abnormalities 1
Post-CABG patients clearly fall into this category, as they have established coronary artery disease requiring surgical revascularization.
Clinical Decision Algorithm
Step 1: Assess cardiovascular stability
- If the patient had CABG within the past 3-6 months or has unstable angina, active heart failure, or recent cardiac events → Defer Rexulti until cardiovascular status stabilizes
- If CABG was >6 months ago and patient is on stable cardiac medications → Proceed with caution
Step 2: Baseline cardiovascular assessment
- Obtain baseline orthostatic vital signs (lying, sitting, standing blood pressures)
- Review current cardiac medications, especially antihypertensives
- Assess for dehydration or hypovolemia
Step 3: Initiate at lowest dose with close monitoring
- Start Rexulti at the lowest effective dose
- Monitor orthostatic vital signs at each dose titration
- Watch for dizziness, syncope, or falls (which occurred in 2-3% of patients in trials) 1
Step 4: Coordinate with cardiology
- Ensure patient continues guideline-directed medical therapy post-CABG (aspirin, statins, beta-blockers, ACE inhibitors as indicated) 2
- Monitor for drug interactions, particularly with antihypertensives
Important Caveats
Drug Interactions with Post-CABG Medications
Post-CABG patients are typically on multiple cardiovascular medications. The combination of Rexulti with antihypertensive medications increases the risk of orthostatic hypotension 1. This is particularly relevant since:
- Beta-blockers should be continued indefinitely post-CABG 2
- ACE inhibitors/ARBs are recommended for most post-CABG patients 2, 3
- These medications can potentiate Rexulti's hypotensive effects
Additional Safety Concerns in This Population
- Falls risk: Rexulti causes somnolence, postural hypotension, and motor instability, which may lead to falls 1. Post-CABG patients, especially if elderly, are already at increased fall risk
- Temperature dysregulation: Atypical antipsychotics disrupt core body temperature regulation 1. This matters for post-CABG patients who should maintain cardiac rehabilitation exercise programs
- Seizure risk: While generally low, conditions that lower seizure threshold may be more prevalent in older patients 1
What the Evidence Does NOT Address
The provided guidelines [2-4] focus exclusively on antiplatelet therapy, lipid management, and other cardiac medications post-CABG. There is no specific guidance about antipsychotic use in post-CABG patients. This represents a gap in the literature, requiring clinicians to extrapolate from general cardiovascular safety data.
Bottom Line Recommendation
Yes, you can use Rexulti in patients with past CABG surgery, but:
- Ensure cardiovascular stability (ideally >6 months post-surgery)
- Obtain baseline orthostatic vital signs
- Start at the lowest dose and titrate slowly
- Monitor orthostatic blood pressure at each visit
- Educate patient about fall risk and symptoms of hypotension
- Coordinate care with cardiology to ensure continuation of guideline-directed post-CABG medications 2
- Consider alternative psychiatric medications if the patient has unstable cardiovascular disease or recent cardiac events
The key is recognizing that while not contraindicated, Rexulti requires enhanced cardiovascular monitoring in this population due to the exclusion of such patients from clinical trials and the drug's known cardiovascular effects 1.