Jared Butler, MD, MPH, MBA; Vivian Fonseca, MD; Lance Sloan, MD; and Michael J. Bloch, MD, discuss how to effectively manage resistant hypertension through a comprehensive approach that includes differentiating true resistance from pseudoresistance; implementing lifestyle modifications and optimal medical therapy with ACE inhibitors/ARBs, calcium channel blockers, and diuretics; and incorporating emerging treatments like endothelin receptor antagonists such as aprocitentan, which demonstrated significant blood pressure reduction in the PRECISION trial across diverse patient populations, including those with chronic kidney disease.
Panelists discuss how resistant hypertension is defined as blood pressure remaining above 130/80 mm Hg despite 3 medications, including a diuretic, affecting 10% to 15% of hypertensive patients, and how to differentiate true resistance from pseudoresistance caused by adherence issues, improper measurement, white coat effect, and interfering medications.
Panelists discuss how patients with resistant hypertension should be referred to specialists after 3 to 6 months of unsuccessful treatment, emphasizing that while primary care providers can manage most hypertension cases, specialists with particular interest and experience are needed for complex cases.
Panelists discuss how lifestyle modifications, particularly sodium restriction and plant-based diets, form the foundation of resistant hypertension management, with innovative approaches like teaching kitchens and food-as-medicine programs being more effective than traditional diet counseling.
Panelists discuss how standard ACE therapy leaves multiple pathways unblocked in resistant hypertension, with spironolactone being the most evidence-based fourth-line therapy despite limitations, while emerging therapies target sympathetic nervous system overactivity, aldosterone excess, and endothelin-mediated vasoconstriction.
Panelists discuss how endothelin receptor antagonism addresses resistant hypertension by blocking one of the most potent vasoconstrictors, reducing smooth muscle hypertrophy and fibrosis, with aprocitentan being the only endothelin receptor antagonist approved for resistant hypertension.
Panelists discuss how the PRECISION trial demonstrated aprocitentan’s efficacy in lowering blood pressure by nearly 15 mm Hg within 4 weeks in resistant hypertension patients, including those with advanced chronic kidney disease, with durable effects and minimal adverse effects except for manageable peripheral edema.
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.
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.
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.
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.
Panelists discuss how shared decision-making requires explaining the rationale for blood pressure control, addressing patient fears about medications, and utilizing newer drug classes like endothelin receptor antagonists that offer a “clean slate” approach for patients who have had negative experiences with traditional therapies.
Panelists discuss how follow-up strategies should include monthly visits initially with more frequent monitoring for high-risk situations, emphasizing home blood pressure monitoring and utilizing team-based care approaches with optimal visit intervals of 4 to 6 weeks to avoid both therapeutic inertia and overadjustment.
Panelists discuss how newer therapies will likely be incorporated into guidelines with improved reimbursement structures over time, similar to the evolution seen with lipid-lowering medications, making advanced treatments more accessible for patients with uncontrolled blood pressure.
Panelists discuss how improving adherence requires both individual strategies like smartphone reminders and smart medication monitoring devices, as well as population-level interventions including reducing sodium content in processed foods and harmonizing hypertension guidelines to address the epidemic of poorly controlled blood pressure.
