Is midodrine contraindicated in aortic stenosis?

Is midodrine contraindicated in aortic stenosis?

Comment by InpharmD Researcher

The evidence is limited to case reports which have documented patients with a history of aortic stenosis receiving midodrine for management of hypotension and heart failure. While the efficacy of treatment varied, there were no notable adverse events reported from midodrine use. The prescribing label’s contraindication includes patients with severe organ heart disease with conditions that might lead to aortic stenosis. However, the label does not explicitly contraindicate aortic stenosis patients or those with aortic valve issues.

Background

In a retrospective study’s introduction section, the authors mentioned that end-stage renal disease (ESRD) dialysis-dependent patients with aortic stenosis who receive midodrine are often referred (supposedly to their institution) for transcatheter aortic valve replacement. The goal of treatment would be to reduce the burden of hypotension during dialysis. The wording implies that patients with aortic stenosis taking midodrine is not unusual. However, there is a lack of follow-up discussion about the topic. [1]

Relevant Prescribing Information

CONTRAINDICATIONS
Midodrine hydrochloride tablets are contraindicated in patients with severe organic heart disease, acute renal disease, urinary retention, pheochromocytoma or thyrotoxicosis. Midodrine should not be used in patients with persistent and excessive supine hypertension. [2]

Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

Is midodrine contraindicated in aortic stenosis?

Please see Tables 1-4 for your response.

Prolonged Supine Hypertension Due to Midodrine Use in an Orthostatic Hypotensive Child
Design	Case report
Case presentation	A 10-year-old boy was admitted due to significant symptomatic orthostatic hypotension. He had slight aortic valve stenosis with an average aortic gradient of 30 mmHg. His treatment regimen included fludrocortisone (0.1 mg daily), midodrine (10 mg daily), and metoprolol (2 mg/kg/day). He experienced nausea, a brief rash, and an itchy scalp following midodrine administration. However, these side effects were not deemed severe enough to necessitate discontinuing the medication. Additionally, he suffered from nighttime headaches. His mother, who is a nurse, observed elevated supine blood pressure (systolic 150–220 mmHg, diastolic 100–130 mmHg) and decided to discontinue midodrine after 12 days. His vanillylmandelic acid levels, biochemical values, and electrocardiogram were within the normal range. Even after discontinuing all medications, his nighttime blood pressure remained elevated. Although he no longer experienced syncope, severe headaches continued to disrupt his sleep. In the supine position, his blood pressure was high (190/110 mmHg), and his heart rate was 54 beats/minute. However, upon standing, his blood pressure returned to normal (110/70 mmHg), and his heart rate increased to 75 beats per minute. Tilting without medication did not induce syncope or any precursor symptoms, but supine hypertension persisted until day 19 after discontinuation. Afterward, supine blood pressure returned to normal, but syncope attacks persisted.
Study Author Conclusions	This case shows that patients receiving midodrine should be observed for supine hypertension for a prolonged period.

References:

Olgar S, Omeroglu RE. Prolonged supine hypertension due to midodrine use in an orthostatic hypotensive child. Pediatr Cardiol. 2007;28(4):309-310. doi:10.1007/s00246-006-0169-y

Use of Midodrine in Heart Failure: Two Case Reports and a Review of the Literature
Design	Case report
Case presentation	An 81-year-old woman with a medical history of arterial stenosis and other heart and kidney conditions was repeatedly hospitalized due to worsening right-sided heart failure and low blood pressure. During her most recent hospitalization, she received intravenous noradrenaline to support her blood pressure and maintain urine output. However, her kidney function worsened, leading to fluid overload and the need for hemofiltration sessions. Despite attempts to reduce noradrenaline support, her blood pressure dropped. After nearly three weeks, the medication midodrine was started in an effort to wean her off intravenous support. The initial dose was 5 mg, taken three times a day. After five days, it was observed that she required higher doses of noradrenaline on dialysis days, so the midodrine dose was increased to 7.5 mg three times a day on those days. On non-dialysis days, the midodrine dose remained at 5 mg three times a day. Eventually, the midodrine dose was increased to 10 mg three times a day on both dialysis and non-dialysis days, and several days after starting midodrine, the noradrenaline was successfully discontinued. Subsequent hemodialysis sessions were conducted without the need for intravenous support, and no major adverse events occurred during the treatment.
Study Author Conclusions	Midodrine is an oral peripheral alpha-1 agonist that may be used off-label to help wean patients with systolic heart failure and low blood pressure off intravenous vasopressors. In addition, because it increases blood pressure, physicians may be able to initiate and up-titrate guideline-directed medical therapy (GDMT).

References:

Hajjiah A, Maadarani O, Bitar Z, et al. Use of Midodrine in Heart Failure: Two Case Reports and a Review of the Literature. Eur J Case Rep Intern Med. 2022;9(3):003246. Published 2022 Mar 18. doi:10.12890/2022_003246

Treatment via oral midodrine in a patient with prolonged hypotension following carotid artery stenting: a case report
Design	Case report
Case presentation	An 82-year-old man with a history of dyslipidemia and smoking experienced temporary vision loss. Tests revealed severe stenosis of the left internal carotid artery. Carotid artery stenting was performed, but the patient developed post-procedure hypotension that didn't respond to fluid therapy. Intravenous dopamine was initiated due to the patient's complaints of dizziness. Despite this treatment, the patient remained hypotensive and symptomatic three days after the procedure. Midodrine was added to his medication regimen at a dose of 15 mg every 6 hours. Within a few hours, his blood pressure increased to 111/78 mmHg, and dopamine was discontinued. The following day, midodrine was stopped, and the patient was discharged without experiencing hypotension or any other symptoms.
Study Author Conclusions	Oral midodrine can be considered in treatment of post-carotid artery stenting hemodynamic complications.

References:

Jenab Y, Hosseini K, Abtahi-Eivary SM. Treatment via oral midodrine in a patient with prolonged hypotension following carotid artery stenting: a case report. J Med Case Rep. 2022;16(1):67. Published 2022 Feb 9. doi:10.1186/s13256-022-03270-5

Ropinirole-Associated Orthostatic Hypotension as Cause of a Prescribing Cascade in an Elderly Man
Design	Case report
Case presentation	A 71-year-old Caucasian male with a medical history including atrial fibrillation, diabetes, hyperlipidemia, hypertension, ischemic heart failure, implantable cardioverter-defibrillator (ICD) placement one year ago, a transient ischemic attack (TIA) six years prior, rheumatoid arthritis, restless leg syndrome (RLS), aortic stenosis with a remote mechanical aortic valve replacement, chronic kidney disease, and a right knee replacement, presented to the emergency department (ED) with generalized weakness. He had difficulty rising from a seated position, which resulted in a fall without head trauma. During the eight months leading up to this hospital presentation, the patients had similar symptoms, which led to four falls, two hospital admissions, and the initiation of new prescriptions for midodrine and compression stockings. Upon admission, the patient's vital signs showed positive orthostatics, with a blood pressure (BP) of 110/74 mmHg and a heart rate (HR) of 86 bpm while in a supine position. When standing, the BP was 87/51 mmHg, and the HR was 70 bpm. Furosemide, carvedilol, and canagliflozin were stopped, and intravenous (IV) fluids were administered. Over the following days, the patient's creatinine levels improved, as did his volume status. However, he remained orthostatic despite using midodrine and stockings. Upon further inquiry, the patient revealed that he had initiated ropinirole at a dose of 0.25 mg three times daily, approximately 10 months before this hospital admission. This was in response to asymptomatic RLS that had been identified in a sleep study. The decision was made to discontinue this medication, which led to a significant improvement in symptoms. Consequently, IV fluids, midodrine, and stockings were discontinued, and carvedilol, furosemide, and canagliflozin were gradually reintroduced. In a follow-up visit one month after his discharge, the patient was completely symptom-free.
Study Author Conclusions	This case illustrates two major points. First, this prescribing cascade potentially induced by ropinirole, as well as the increase in health care costs associated to iatrogenic admissions, is major preventable problem faced mostly by the geriatric population. Second, although OH associated with ropinirole has only been reported in patients treated for Parkinson’s disease, this side effect should be considered when prescribing ropinirole for other indications, with cautious assessment of risks and benefits. Further studies need to be conducted to establish the frequency of OH related to ropinirole.

References:

Becerra AF, Boch M, Al-Mezrakchi YA. Ropinirole-Associated Orthostatic Hypotension as Cause of a Prescribing Cascade in an Elderly Man. Cureus. 2021;13(6):e15506. Published 2021 Jun 7. doi:10.7759/cureus.15506