Treating Lows: Management of Orthostatic Hypotension

Abstract

Orthostatic hypotension is a prevalent clinical condition, caused by heterogenous etiologies and associated with significant morbidity and mortality. Management is particularly challenging in patients with uncontrolled hypertension. A thorough assessment is needed to draw an appropriate management plan. The treatment aims to improve postural symptoms while minimizing side effects and reducing iatrogenic exacerbation of supine hypertension. A personalized management plan including rationalizing medications, patient education, identification, and avoidance of triggers, as well as nonpharmacological therapies such as compression devices, dietary modifications, and postural aids, make the first steps. Among pharmacological therapies, midodrine and fludrocortisone are the most prescribed and best studied; pyridostigmine, atomoxetine, and droxidopa are considered next. Yohimbine remains an investigational agent. A multidisciplinary team may be required in some patients with multiple comorbidities and polypharmacy. However, there is a lack of robust efficacy and safety evidence for all therapies. Building robust real-world and stratified clinical trials based on underlying pathophysiology may pave the way for further drug development and better clinical strategies and in this challenging unmet medical need.

FIGURE 1.

Physiological compensatory mechanisms that maintain blood pressure and heart rate on standing. ADH, antidiuretic hormone; BP, blood pressure.

FIGURE 2.

Conditions associated with orthostatic hypotension. At the centre of the Venn diagram is the patient presenting with acute illness (e.g., sepsis) in an elderly patient with multiple co-morbidities in the background such as benign prostatic hyperplasia, hypertension, diabetes mellitus, and/or neurodegenerative disorders on at-risk-polypharmacy such as α-blockers, diuretics, and levodopa.

FIGURE 3.

Clinical presentation and evaluation of patients with suspected OH. BP, blood pressure; ECG, electrocardiogram; FBC, full blood count; TSH, thyroid-stimulating hormone.

FIGURE 4.

Proposed management algorithm including a summary of nonpharmacological and pharmacological therapies. TDS, three times daily.

FIGURE 5.

Site of action of pharmacotherapies used in orthostatic hypotension. 1. Fludrocortisone, 2. Midodrine, 3. Droxidopa, 4. Atomoxetine, 5. Pyridostigmine, 6. Yohimbine (Adapted from Palma et al).