Michael J. Bloch, MD

Panelists discuss how medication reduction is occasionally possible in well-controlled patients over time, particularly with diuretics when sodium intake decreases or calcium channel blockers to reduce edema, while being cautious about maintaining adequate blood pressure control and avoiding drugs that worsen kidney function.

Scenarios to Discontinue Antihypertensive Medications

Video content above is prompted by the following: 

While antihypertensive therapy typically involves progressive medication addition, certain clinical scenarios allow for careful medication reduction. Long-term well-controlled blood pressure can lead to vascular remodeling and decreased treatment requirements over time. Successful de-escalation most commonly involves diuretic reduction when patients achieve significant dietary sodium restriction, evidenced by BUN-to-creatinine ratios exceeding 20:1 without edema.

GLP-1 receptor agonists causing substantial weight loss create opportunities for both diabetes and hypertension medication reduction. Clinicians should monitor for symptomatic hypotension as patients lose weight and may need to reduce antihypertensive dosing proactively. This represents a paradigm shift toward addressing root causes of hypertension rather than simply adding medications, particularly relevant given the obesity epidemic’s role in resistant hypertension.

When de-escalation becomes necessary, calcium channel blockers represent the preferred choice for reduction due to fewer pleiotropic benefits compared with ACE inhibitors or ARBs. The renin-angiotensin system provides cardiovascular and renal protection beyond blood pressure lowering, including anti-fibrotic and anti-inflammatory effects. However, dihydropyridine calcium channel blockers should never be used without concurrent ACE inhibitor or ARB therapy due to potential adverse renal effects from increased intraglomerular pressure.

Videos

Panelists discuss how aggressive blood pressure targets below 130 mm Hg (preferably 120 mm Hg) should be pursued in most resistant hypertension patients using combination therapies, while individualizing goals based on patient age, tolerability, and comorbidities.

Adding a Fourth Agent for RH

Current evidence supports intensive blood pressure control below 130 mm Hg, with many experts advocating for targets below 120 mm Hg when tolerated. The SPRINT trial and recent diabetes studies demonstrate improved cardiovascular outcomes with lower blood pressure targets, including potential cognitive benefits. Clinicians should not hesitate to add fifth or sixth antihypertensive agents when patients remain above target despite optimal therapy with 4 medications.

Treatment intensification must balance aggressive targets with individual patient factors, including age, comorbidities, and functional status. Younger patients with end-organ damage warrant more aggressive approaches, while older patients require careful assessment for orthostatic hypotension and fall risk. The key principle involves achieving the lowest tolerable blood pressure while monitoring for symptoms and maintaining quality of life.

Successful resistant hypertension management requires combining multiple therapeutic modalities rather than relying on single interventions. Renal denervation, various medication classes, and lifestyle interventions can be used synergistically. With over 10 million Americans having resistant hypertension, clinicians need diverse treatment options including peripheral alpha blockers, combination pills, and newer agents like endothelin receptor antagonists to achieve optimal outcomes across different patient populations.

Panelists discuss how to sequence fourth-line treatments for resistant hypertension, with spironolactone remaining first choice for most patients with normal renal function, while newer endothelin receptor antagonists offer advantages for patients with chronic kidney disease or those intolerant to aldosterone antagonists.

Sequencing Treatment for Resistant Hypertension

Resistant hypertension affects millions of patients worldwide, requiring systematic approaches to fourth-line therapy selection. Clinical experts recommend spironolactone as the primary add-on medication for most patients with normal renal function, given its proven efficacy in resistant hypertension management. However, newer therapeutic options like endothelin receptor antagonists (aprocitentan) provide valuable alternatives for patients who cannot tolerate traditional treatments or have chronic kidney disease.

When selecting fourth-line antihypertensive agents, clinicians must evaluate individual patient factors including kidney function, electrolyte levels, and medication tolerance. Patients with elevated potassium levels or history of gynecomastia may benefit from endothelin receptor antagonists over mineralocorticoid receptor antagonists. The precision trial data demonstrates significant blood pressure reductions with aprocitentan across diverse patient populations, making it particularly valuable for patients with chronic kidney disease where renal denervation may not be appropriate.

Modern resistant hypertension management has evolved beyond routine aldosterone-to-renin ratio testing for treatment selection. Most resistant hypertension patients exhibit salt-sensitive, aldosterone-excess phenotypes regardless of laboratory values. Clinicians should focus on blood pressure response rather than biochemical markers when evaluating treatment effectiveness. The combination of multiple therapeutic approaches, including lifestyle modifications, optimal dosing of core medications, and strategic addition of fourth-line agents, provides comprehensive management strategies for complex resistant hypertension cases.

Panelists discuss how the PRECISION trial subanalysis showed aprocitentan worked equally well in Black patients as in White patients, which is particularly important given the higher prevalence and complications of resistant hypertension in Black populations, with emphasis on adequate diuretic management to prevent peripheral edema.

Subanalysis in Black Individuals From the PRECISION Trial

The PRECISION trial’s subgroup analysis in Black patients demonstrated equivalent efficacy and safety compared with White patients, addressing critical concerns about racial disparities in hypertension treatment response. This finding is particularly significant given that Black patients experience disproportionately higher rates of resistant hypertension, cardiovascular complications, and chronic kidney disease, making effective treatment options essential for reducing health disparities.

Historical concerns about differential antihypertensive responses between racial groups, particularly the perception that Black patients respond better to diuretics than ACE inhibitors or ARBs, are challenged by the PRECISION results showing universal benefit from endothelin receptor antagonism. While initial blood pressure reduction rates may vary between drug classes and racial groups, long-term cardiovascular and renal protection appears consistent across populations when optimal blood pressure control is achieved.

The equivalent response to aprocitentan in Black patients is especially important given their higher prevalence of salt sensitivity and genetic factors like APOL1 variants that increase cardiovascular and renal risk. Clinical management considerations include ensuring adequate diuretic therapy to prevent fluid retention, monitoring BUN-to-creatinine ratios to optimize fluid balance, and recognizing that genetic predisposition combined with dietary and environmental factors creates particular urgency for effective blood pressure control in this high-risk population.

Michael J. Bloch, MD

Articles