How to manage uncontrolled hypertension in a patient taking Mymarda (sacubitril/valsartan) with severe osteoporosis, bronchial asthma, and coronary artery disease?

Managing Uncontrolled Hypertension in a Patient on Mymarda (Sacubitril/Valsartan)

Add a long-acting dihydropyridine calcium channel blocker (CCB) such as amlodipine to the existing sacubitril/valsartan regimen, as this combination is specifically recommended for uncontrolled hypertension in patients with coronary artery disease while avoiding beta-blockers due to the patient's bronchial asthma. 1

Stepwise Approach to Blood Pressure Control

First-Line Addition: Dihydropyridine CCB

• Add amlodipine or another long-acting dihydropyridine CCB to the sacubitril/valsartan (which already contains the ARB valsartan), as this combination is recommended when hypertension remains uncontrolled on a RAS blocker alone 1
• Amlodipine is specifically safe in patients with coronary artery disease and has been validated in heart failure trials 1
• Target blood pressure should be 120-129 mmHg systolic if well tolerated, or use the "as low as reasonably achievable" (ALARA) principle if the target cannot be reached 1
• In patients with coronary artery disease, lower blood pressure slowly and avoid diastolic blood pressure below 60 mmHg to prevent myocardial ischemia 1

Second-Line Addition: Thiazide-Like Diuretic

• If blood pressure remains uncontrolled with sacubitril/valsartan plus CCB, add a thiazide-like diuretic (chlorthalidone or indapamide preferred over hydrochlorothiazide) 1
• This creates the recommended three-drug combination: RAS blocker + dihydropyridine CCB + thiazide/thiazide-like diuretic, preferably as a single-pill combination 1
• Thiazide-like diuretics are less effective than loop diuretics for volume management but superior for blood pressure control 1

Third-Line Addition: Mineralocorticoid Receptor Antagonist

• If blood pressure remains uncontrolled on the three-drug regimen, add spironolactone 25-50 mg daily 1
• Spironolactone provides significant additional blood pressure reduction in resistant hypertension 1
• Critical monitoring required: Check serum potassium and creatinine regularly, as sacubitril/valsartan already affects the RAAS and increases hyperkalemia risk 2
• Consider eplerenone as an alternative if spironolactone causes gynecomastia or is not tolerated 1

Medications to Avoid in This Patient

Beta-Blockers: Contraindicated

• Do not use beta-blockers due to bronchial asthma, as they can precipitate bronchospasm 1
• Beta-blockers are only recommended when there are compelling indications (post-MI, heart rate control, or heart failure with reduced ejection fraction), which must be weighed against asthma risk 1

Non-Dihydropyridine CCBs: Avoid

• Do not use diltiazem or verapamil if there is any degree of left ventricular dysfunction, as they can worsen heart failure 1
• These agents also have negative chronotropic effects that overlap with beta-blocker contraindications 1

Alpha-Blockers: Use with Caution

• Alpha-blockers like doxazosin should be avoided or used only as a last resort, as they increased heart failure risk in the ALLHAT trial 1

Special Considerations for Sacubitril/Valsartan

Blood Pressure Lowering Properties

• Sacubitril/valsartan has superior blood pressure lowering compared to ARBs alone, reducing central aortic systolic pressure by an additional 3.7 mmHg and 24-hour ambulatory blood pressure by 4.1 mmHg 3
• The drug is particularly effective for nocturnal hypertension and central (aortic) systolic hypertension, which are common in elderly patients with arterial stiffness 4, 3
• In the PARAMETER study, sacubitril/valsartan required less add-on antihypertensive therapy (32%) compared to olmesartan (47%) at 52 weeks 3

Hypotension Management

• If symptomatic hypotension occurs, first adjust diuretics and address volume depletion before reducing sacubitril/valsartan dose 2
• Sacubitril/valsartan is more likely to cause symptomatic hypotension compared to SGLT2 inhibitors or MRAs 1
• Permanent discontinuation is usually not required; temporary dose reduction or interruption is typically sufficient 2

Monitoring Requirements

• Monitor serum potassium periodically, especially when adding spironolactone or other potassium-sparing agents, as hyperkalemia risk increases through RAAS inhibition 2
• Monitor renal function closely (serum creatinine), particularly in patients with coronary artery disease who may have underlying renal artery stenosis 2
• Down-titrate or interrupt sacubitril/valsartan if clinically significant renal function decline occurs 2

Osteoporosis Considerations

Thiazide Diuretics: Beneficial

• Thiazide and thiazide-like diuretics may provide additional benefit in severe osteoporosis by reducing urinary calcium excretion and potentially improving bone mineral density 1
• This makes them a particularly appropriate choice in this patient population

Avoid High-Dose Loop Diuretics

• Loop diuretics increase urinary calcium excretion and may worsen osteoporosis; use only if volume overload is present 1

Coronary Artery Disease Considerations

Nitrates: No Contraindication

• Long-acting nitrates can be used for angina management without impacting the antihypertensive regimen 1
• There are no special contraindications to antiplatelet drugs, anticoagulants, or lipid-lowering agents in this setting 1

Blood Pressure Targets

• Target systolic blood pressure <130/80 mmHg in patients with coronary artery disease 1
• Lower slowly to avoid diastolic blood pressure <60 mmHg, which can worsen myocardial ischemia 1

Common Pitfalls to Avoid

• Do not combine sacubitril/valsartan with ACE inhibitors or additional ARBs, as dual RAS blockade increases adverse events without improving outcomes 1
• Do not discontinue sacubitril/valsartan to add other agents; it should remain the foundation of therapy given its cardiovascular benefits 1
• Do not use centrally acting agents (like moxonidine) as early add-ons, as they may increase mortality in heart failure patients 1
• Ensure adequate time between medication adjustments (typically 2-4 weeks) to assess full blood pressure response before adding additional agents 1