What are the hypertension (HTN) treatment medications that have less impact on orthostasis?

From the Guidelines

For treating hypertension while minimizing orthostatic hypotension, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and calcium channel blockers are generally preferred options. These medications work through mechanisms that typically cause less orthostatic hypotension compared to diuretics, beta-blockers, and alpha-blockers, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. Specific medications include lisinopril (10-40 mg daily), ramipril (2.5-20 mg daily), losartan (25-100 mg daily), valsartan (80-320 mg daily), amlodipine (2.5-10 mg daily), and diltiazem extended-release (120-540 mg daily).

When initiating therapy, it is essential to start with lower doses and titrate gradually while monitoring blood pressure in both sitting and standing positions, as suggested by the guidelines 1. For elderly patients or those with autonomic dysfunction, even these medications should be used cautiously with close monitoring. Combination therapy using lower doses of complementary agents may also help achieve blood pressure targets while minimizing orthostatic effects.

Key considerations in managing hypertension with orthostatic hypotension include:

• Testing for orthostatic hypotension before starting or intensifying BP-lowering medication, by measuring BP 1 and/or 3 min after standing 1
• Pursuing non-pharmacological approaches as the first-line treatment of orthostatic hypotension among persons with supine hypertension, and switching BP-lowering medications that worsen orthostatic hypotension to an alternative BP-lowering therapy 1
• Maintaining BP-lowering drug treatment lifelong, even beyond the age of 85 years, if well tolerated, as recommended by the guidelines 1

From the FDA Drug Label

The adverse events, regardless of drug relationship, reported with an incidence of ≥4% of patients treated with losartan and occurring with ≥2% difference in the losartan group vs placebo on a background of conventional antihypertensive therapy, were asthenia/fatigue, chest pain, hypotension, orthostatic hypotension, diarrhea, anemia, hyperkalemia, hypoglycemia, back pain, muscular weakness, and urinary tract infection. In two placebo controlled, 12-week clinical studies compared the addition of lisinopril up to 20 mg daily to digitalis and diuretics alone. The combination of lisinopril, digitalis and diuretics reduced the following signs and symptoms of heart failure: edema, rales, paroxysmal nocturnal dyspnea and jugular venous distention In one of the studies, the combination of lisinopril, digitalis and diuretics reduced orthopnea, presence of third heart sound and the number of patients classified as NYHA Class III and IV; and improved exercise tolerance.

HTN treatment meds that have less impact on orthostasis are not explicitly identified in the provided drug labels. However, losartan is associated with a lower incidence of orthostatic hypotension compared to other antihypertensive therapies, such as ACE inhibitors like lisinopril 2.

• Losartan may be a suitable option for patients with concerns about orthostatic hypotension.
• Lisinopril may have a greater impact on orthostasis due to its mechanism of action as an ACE inhibitor. It is essential to consider individual patient factors and medical history when selecting an antihypertensive medication 3.

From the Research

HTN Treatment Meds with Less Impact on Orthostasis

• The following medications are suggested to have less impact on orthostasis:
  • Angiotensin receptor blockers 4
  • Calcium channel blockers 4, 5
• These medications are considered preferable for patients with hypertension and orthostatic hypotension, as they may have a lower risk of worsening orthostasis compared to other antihypertensive medications.

Medications to Avoid

• Certain medications can worsen orthostatic hypotension and should be avoided or used with caution, including:
  • Tamsulosin 4
  • Tizanidine 4
  • Sildenafil 4
  • Trazodone 4
  • Carvedilol 4

Alternative Treatment Strategies

• Non-pharmacological interventions, such as abdominal binders and acarbose, may be effective in preventing orthostatic hypotension and postprandial hypotension without increasing baseline blood pressure 4.
• Upright blood pressure can be improved with medications such as atomoxetine and pyridostigmine, which harness residual sympathetic tone and facilitate cholinergic neurotransmission in autonomic ganglia 4.