From the Guidelines
A reasonable indication for concurrent use of Ramipril and Midodrine is the management of symptomatic orthostatic hypotension in a patient with vasovagal syncope (VVS) who also has hypertension, heart failure, or diabetic nephropathy, as long as the patient is closely monitored for potential adverse effects.
Key Considerations
- Ramipril, an ACE inhibitor, would be used to treat the underlying condition such as hypertension or to provide cardio-renal protection, as supported by the 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease 1.
- Midodrine, an alpha-1 adrenergic agonist, would help manage the orthostatic hypotension symptoms like dizziness upon standing, as recommended in the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope for patients with recurrent VVS and no history of hypertension, heart failure, or urinary retention 1.
Monitoring and Dosage
- This combination requires careful monitoring as the medications have opposing effects on blood pressure.
- Typically, ramipril would be dosed once daily (2.5-10mg) and taken in the evening, while midodrine would be taken during daytime hours (2.5-10mg, 2-3 times daily, with the last dose at least 4 hours before bedtime) to avoid supine hypertension at night.
- Blood pressure should be monitored in both supine and standing positions to ensure the ramipril is controlling baseline hypertension while midodrine is preventing symptomatic drops in blood pressure upon standing.
Rationale
- This combination therapy addresses the paradoxical situation where a patient needs both blood pressure support when upright and blood pressure reduction for their baseline condition.
- The use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers can be effective to reduce the risk of cardiovascular ischemic events in patients with peripheral artery disease, as shown in the HOPE trial and the ONTARGET study 1.
From the Research
Indications for Concurrent Use
The concurrent use of Ramipril (Angiotensin-Converting Enzyme Inhibitor) and Midodrine (Alpha-Adrenergic Agonist) may be reasonable in certain cases, including:
- Patients with heart failure with reduced ejection fraction (HFrEF) and symptomatic hypotension, where midodrine can be used off-label to allow optimization of medical therapy, including the use of ramipril 2, 3.
- Patients with refractory hypotension, where midodrine can serve as bridge therapy for the initiation or continuation of Guideline-Directed Medical Therapy (GDMT), including the use of ramipril 3.
Rationale
The use of midodrine in patients with HFrEF and hypotension can help to increase standing blood pressure and improve symptoms of orthostatism, allowing for the optimization of medical therapy, including the use of ramipril 2, 4. Ramipril, on the other hand, has been shown to be effective in reducing the risk of all-cause mortality in patients with clinical evidence of heart failure after acute myocardial infarction, and can be used in combination with other medications, including midodrine, to achieve optimal therapy 5.
Key Considerations
When considering the concurrent use of ramipril and midodrine, it is essential to carefully evaluate the patient's individual needs and medical history, including the presence of any underlying conditions that may affect the use of these medications 6. Additionally, the potential for adverse effects, such as piloerection and urinary hesitancy, should be carefully monitored and managed 4.