What is the best course of action for a patient with uncontrolled hypertension (blood pressure 140/90), impaired glucose control (A1c 6.5), and impaired renal function (albumin/creatinine ratio 65) currently on Diovan (valsartan) 320mg and Metoprolol Succinate XL (metoprolol succinate) 25mg?

Management of Uncontrolled Hypertension with Albuminuria and Prediabetes

You need to add a third antihypertensive medication immediately—specifically a thiazide-like diuretic (chlorthalidone or indapamide) or a dihydropyridine calcium channel blocker—because your patient has uncontrolled hypertension (140/90 mmHg) with albuminuria (UACR 65 mg/g) despite being on maximum-dose valsartan and a beta-blocker. 1

Immediate Action Steps

1. Optimize Current ARB Therapy

• Your patient is already on valsartan 320 mg daily, which is the maximum approved dose for hypertension 2
• The valsartan should be continued as it provides renoprotection in patients with albuminuria (UACR ≥30 mg/g) 1
• Do not discontinue or reduce the ARB dose unless hyperkalemia or acute kidney injury develops 1

2. Add a Third Antihypertensive Agent

Multiple-drug therapy is required to achieve blood pressure targets in patients with diabetes and albuminuria 1

Preferred third agent options:

• Thiazide-like diuretic (chlorthalidone or indapamide): These long-acting agents are specifically recommended and shown to reduce cardiovascular events 1
• Dihydropyridine calcium channel blocker (amlodipine or nifedipine XL): Equally effective alternative 1

The addition of a diuretic has greater blood pressure-lowering effect than further dose increases of existing medications 1

3. Consider Beta-Blocker Optimization

• Your patient is on metoprolol succinate 25 mg, which is a relatively low dose
• Beta-blockers are NOT indicated as primary blood pressure-lowering agents in the absence of prior MI, active angina, or heart failure with reduced ejection fraction 1
• Consider whether this patient has a compelling indication for beta-blocker therapy; if not, the beta-blocker could be replaced with a more effective agent 1

Blood Pressure Target

Your target blood pressure should be <130/80 mmHg 1

• The 2022-2023 American Diabetes Association guidelines recommend BP <130/80 mmHg for patients with diabetes and albuminuria 1
• This is more aggressive than the older <140/90 mmHg target because your patient has both prediabetes (A1c 6.5%) and albuminuria (UACR 65 mg/g), which confer high cardiovascular risk 1

Addressing the Albuminuria

The UACR of 65 mg/g indicates moderately increased albuminuria (30-299 mg/g range) 1

• ACE inhibitors or ARBs at maximum tolerated doses are first-line therapy for patients with UACR ≥30 mg/g 1
• Your patient is already on maximum-dose valsartan (320 mg), which is appropriate 2, 3
• Better blood pressure control will provide additional renoprotection beyond the ARB effect alone 1, 4
• Empagliflozin or other SGLT2 inhibitors should be strongly considered as they reduce albuminuria progression by 27-39% and provide cardiovascular and renal benefits in patients with diabetes and albuminuria 1

Addressing the Prediabetes (A1c 6.5%)

An A1c of 6.5% meets criteria for diabetes diagnosis, not just prediabetes 1

• SGLT2 inhibitors (empagliflozin, canagliflozin) or GLP-1 receptor agonists (liraglutide, semaglutide) provide both glycemic control and significant renoprotection 1
• These agents reduce progression of albuminuria and cardiovascular events independent of blood pressure effects 1
• Consider initiating one of these agents in addition to optimizing blood pressure control 1

Monitoring Requirements

After adding the third antihypertensive agent, monitor:

• Serum creatinine/eGFR and potassium within 2-4 weeks 1
• Blood pressure should be rechecked within 2-4 weeks to assess response 1
• Continue monitoring potassium and creatinine at least annually once stable 1
• Recheck UACR in 3-6 months to assess response to therapy 1

Common Pitfalls to Avoid

• Do not combine ACE inhibitors with ARBs—this increases risk of hyperkalemia and acute kidney injury without additional cardiovascular benefit 1
• Do not use loop diuretics (furosemide) as first-line therapy—thiazide-like diuretics (chlorthalidone, indapamide) are superior for cardiovascular outcomes 1
• Do not stop the ARB if creatinine increases by <30%—modest increases in creatinine are expected and acceptable with ARB therapy 1, 2
• Do not target blood pressure <120/70 mmHg—excessive lowering may increase cardiovascular risk without additional renal benefit 1, 5

If Blood Pressure Remains Uncontrolled

If blood pressure remains ≥140/90 mmHg on three medications (ARB + beta-blocker + diuretic or CCB), this constitutes resistant hypertension 1

• Add a mineralocorticoid receptor antagonist (spironolactone 12.5-25 mg daily) 1
• Monitor potassium closely (within 1 week, then monthly for 3 months) as hyperkalemia risk increases when combining MRA with ARB 1
• Ensure medication adherence and exclude secondary causes of hypertension before escalating further 1