What is a good medication option to give at night for a patient with chronic kidney disease (CKD), peripheral vascular disease (PVD), and heart failure with preserved ejection fraction (HFpEF) who experiences high morning blood pressures?

Optimal Nighttime Medication for High Morning Blood Pressure in CKD, PVD, and HFpEF

For a patient with CKD, PVD, and HFpEF experiencing high morning blood pressures, prescribe an ACE inhibitor (or ARB if ACE inhibitor not tolerated) combined with a diuretic, with the ACE inhibitor/ARB administered at bedtime to specifically target morning blood pressure surges. 1

Medication Selection Algorithm

First-Line: ACE Inhibitor or ARB

• ACE inhibitors are reasonable (Class IIa) for patients with CKD to slow kidney disease progression, particularly with stage 3 or higher CKD or albuminuria ≥300 mg/d 1
• ARBs may be reasonable (Class IIb) if ACE inhibitor is not tolerated 1
• For HFpEF with persistent hypertension after volume management, ACE inhibitors or ARBs should be prescribed and titrated to achieve SBP <130 mm Hg (Class I recommendation) 1
• The target blood pressure for patients with both CKD and HFpEF is <130/80 mm Hg 1

Essential Addition: Diuretics

• Diuretics should be prescribed to all patients with HFpEF who have evidence of or prior history of fluid retention (Class I recommendation) 1
• Diuretics are the only antihypertensive class that adequately controls fluid retention in heart failure and are crucial for success of other medications 1
• Loop diuretics (furosemide 40-240 mg/day, bumetanide 1-5 mg/day, or torasemide 10-20 mg/day) are preferred in HFpEF with volume overload 1
• Thiazide-type diuretics can be added for additional blood pressure control once euvolemia is achieved 1

Timing Strategy for Morning Blood Pressure Control

Bedtime dosing of ACE inhibitor/ARB is superior to morning dosing for controlling morning blood pressure surges:

• Valsartan/amlodipine combination administered at bedtime resulted in 24.7/13.5 mm Hg reduction versus 17.4/13.4 mm Hg with morning dosing, with significantly improved sleep-time blood pressure decline 2
• Bedtime dosing of valsartan/HCTZ combination reduced asleep systolic BP by 20.1 mm Hg versus 16.0 mm Hg with morning dosing (p=0.015), and converted 59% of non-dippers to dippers 3
• The proportion of controlled patients was significantly greater with bedtime versus morning dosing (55% vs 40%, p=0.037) 3

However, recent high-quality evidence challenges universal bedtime dosing:

• A large randomized trial (n=1093) found no benefit of evening versus morning valsartan 320 mg dosing on 24-hour, nighttime, or morning blood pressure (mean 24-hour SBP reduction: -10.6 mm Hg morning vs -9.8 mm Hg evening, not significant) 4
• Current European Society of Cardiology guidelines recommend taking antihypertensive medications at whatever time is most convenient for the patient to establish habitual adherence (Class I, Level B), as consistency is more important than timing 5, 6

Practical Implementation

Recommended Regimen

1. Start ACE inhibitor at bedtime (e.g., lisinopril 10-20 mg) or ARB if ACE inhibitor not tolerated (e.g., valsartan 80-160 mg) 1
2. Add loop diuretic in morning if volume overload present (e.g., furosemide 20-40 mg, bumetanide 0.5-1 mg, or torasemide 5-10 mg) 1
3. Titrate ACE inhibitor/ARB to maximum tolerated dose to achieve BP <130/80 mm Hg 1
4. Consider adding thiazide-type diuretic or calcium channel blocker if blood pressure remains uncontrolled 1

Beta-Blocker Consideration for HFpEF

• Beta-blockers (nebivolol, carvedilol, metoprolol succinate, bisoprolol) should be prescribed for HFpEF with persistent hypertension after volume management (Class I recommendation) 1
• Nebivolol showed 19% reduction in mortality or cardiovascular hospitalization in HFpEF patients 1
• Beta-blockers can be administered at bedtime if additional nighttime blood pressure control is needed 1

Critical Monitoring and Caveats

Monitoring Requirements

• Monitor serum creatinine/eGFR and potassium 7-14 days after initiation or dose changes of ACE inhibitor/ARB, then at least annually 7
• Expect modest creatinine increases (up to 30% from baseline) after starting ACE inhibitor/ARB in CKD patients; this is acceptable and indicates appropriate hemodynamic effect 1
• In heart failure trials, >50% creatinine increases occurred in 3.9% of valsartan-treated patients versus 0.9% of placebo 8

Important Contraindications and Warnings

• Avoid nondihydropyridine calcium channel blockers (verapamil, diltiazem) in HFpEF as they have myocardial depressant activity and worse outcomes 1
• Avoid nitrates in HFpEF as they are associated with signal of harm 1
• Never combine ACE inhibitor with ARB as this increases hyperkalemia, syncope, and acute kidney injury without cardiovascular benefit 6, 7
• Diuretic doses must be carefully adjusted to avoid volume depletion, which can worsen renal function and cause hypotension 1

PVD-Specific Considerations

• ACE inhibitors and ARBs are safe and beneficial in peripheral vascular disease 1
• Beta-blockers are not contraindicated in PVD and should be used for HFpEF benefit 1
• Avoid excessive diuresis that could compromise peripheral perfusion 1

Addressing Morning Blood Pressure Specifically

• While older studies suggested bedtime dosing superiority for morning blood pressure control 2, 3, the most recent large trial found no difference 4
• The European Society of Cardiology now prioritizes consistent timing over specific timing for adherence 5, 6
• If patient already takes medications successfully in the morning with good adherence, switching to bedtime is not necessary 5
• For patients with documented morning blood pressure surges despite treatment, consider bedtime dosing of ACE inhibitor/ARB as a trial, monitoring response with home blood pressure measurements 2, 3