What is the recommended pharmacologic regimen and monitoring plan for a non‑diabetic patient with heart failure with preserved ejection fraction after a recent myocardial infarction?

Pharmacologic Regimen and Monitoring for Non-Diabetic HFpEF Post-MI

Initiate an SGLT2 inhibitor (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) immediately as first-line disease-modifying therapy, add loop diuretics as needed for congestion, optimize blood pressure to <130/80 mmHg with ACE inhibitors or ARBs, and start a beta-blocker for post-MI cardioprotection. 1, 2, 3

Immediate Post-MI Pharmacotherapy

SGLT2 Inhibitor – Cornerstone Therapy

• Start dapagliflozin 10 mg once daily (if eGFR >30 mL/min/1.73 m²) or empagliflozin 10 mg once daily (if eGFR >60 mL/min/1.73 m²) immediately upon HFpEF diagnosis, regardless of diabetes status. 2, 3
• Empagliflozin reduces the composite of cardiovascular death or heart failure hospitalization by 21% (HR 0.79,95% CI 0.69-0.90) in HFpEF patients, with benefits occurring within weeks of initiation. 2, 4
• Dapagliflozin demonstrates a 21% reduction in cardiovascular death or heart failure hospitalization in patients with LVEF 41-49%, making it highly effective in this ejection fraction range. 3
• These agents require no dose titration, have minimal impact on blood pressure or heart rate, and provide cardiovascular benefit independent of glucose-lowering effects. 2, 5

Beta-Blocker for Post-MI Protection

• Initiate a beta-blocker at low dose once hemodynamically stable: carvedilol 3.125 mg twice daily, metoprolol succinate 12.5-25 mg daily, or bisoprolol 1.25 mg daily. 1, 6
• Beta-blockers are Class I indicated for post-MI patients to reduce mortality and sudden cardiac death, with uptitration over 8-12 weeks as tolerated. 1, 6
• In HFpEF with atrial fibrillation (if present), beta-blockers provide dual benefit for rate control, though monitor for chronotropic incompetence during exercise. 2

ACE Inhibitor or ARB for Blood Pressure and Post-MI Remodeling

• Start an ACE inhibitor (or ARB if ACE inhibitor not tolerated) to target blood pressure <130/80 mmHg and prevent adverse left ventricular remodeling post-MI. 1, 2
• ACE inhibitors are Class I recommended for post-MI patients with any degree of left ventricular dysfunction to prevent heart failure progression. 1
• While ACE inhibitors/ARBs do not reduce mortality in HFpEF, they effectively lower blood pressure and modestly reduce heart failure hospitalizations. 2

Loop Diuretics for Congestion Management

• Use loop diuretics (furosemide 20-40 mg daily initially) at the lowest effective dose to relieve orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema. 6, 2
• Loop diuretics are the only antihypertensive agents that reliably address fluid retention in heart failure and are essential for symptom control. 2
• Titrate diuretic dose based on daily weights, symptoms, and volume status; once euvolemic, taper to the lowest maintenance dose. 6, 2

Adjunctive Therapy for Selected Patients

Mineralocorticoid Receptor Antagonist (Class 2b)

• Consider adding spironolactone 12.5-25 mg daily if LVEF is in the lower preserved range (40-50%) and patient remains symptomatic despite initial therapy. 1, 2
• Spironolactone reduces heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99) in HFpEF, though evidence is stronger for patients with LVEF closer to 45%. 2
• Monitor potassium and creatinine closely; hold if potassium >5.5 mEq/L or creatinine rises significantly. 1, 6

Statin Therapy

• Initiate high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) for post-MI secondary prevention. 1
• Aggressive lipid management with statins is Class I recommended for all post-MI patients to reduce recurrent cardiovascular events. 1

Critical Medications to Avoid

Contraindicated Agents in HFpEF

• Never prescribe nondihydropyridine calcium channel blockers (diltiazem, verapamil) as they worsen heart failure outcomes through negative inotropic effects. 1, 2
• Avoid thiazolidinediones (pioglitazone, rosiglitazone) which increase heart failure symptoms and hospitalizations. 1, 2
• Do not use DPP-4 inhibitors saxagliptin or alogliptin as they increase heart failure hospitalization risk. 1, 2
• Avoid nitrates in HFpEF due to signal of harm in this population. 2

Monitoring Protocol

Initial Phase (First Month)

• Check blood pressure, heart rate, and symptoms weekly for the first month. 6
• Measure potassium and creatinine 5-7 days after initiating or changing doses of ACE inhibitor, ARB, or MRA, then weekly during uptitration. 6
• Obtain daily weights and instruct patient to report weight gain >2-3 pounds in 24 hours or >5 pounds in one week. 6, 2

Maintenance Phase (After First Month)

• Monitor blood pressure, heart rate, potassium, and creatinine monthly for 3 months, then every 3-6 months once stable. 6
• Reassess LVEF at 3 months post-MI to determine if ejection fraction has changed and whether ICD or CRT evaluation is needed. 6
• Monitor for signs of volume overload (orthopnea, paroxysmal nocturnal dyspnea, peripheral edema, weight gain) at each visit. 6, 2

Laboratory Thresholds for Medication Adjustment

• Hold ACE inhibitor/ARB if creatinine increases >30% from baseline or potassium >5.5 mEq/L; recheck in 3-5 days. 6
• Hold MRA if potassium >5.5 mEq/L; consider patiromer or sodium zirconium cyclosilicate to enable continuation of RAAS inhibition if hyperkalemia recurs. 1
• Reduce beta-blocker dose if heart rate <50 bpm or systolic blood pressure <90 mmHg with symptoms. 6

Comorbidity Management Priorities

Hypertension Control

• Target systolic blood pressure <130 mmHg and diastolic <80 mmHg using the heart failure medications already prescribed (ACE inhibitor/ARB, beta-blocker). 2
• Hypertension is present in 60-89% of HFpEF patients and represents the most important modifiable risk factor. 2

Dietary Sodium Restriction

• Advise dietary sodium restriction to <2-3 grams per day to reduce congestive symptoms and enhance diuretic effectiveness. 2

Anticoagulation if Atrial Fibrillation Present

• Initiate anticoagulation based on CHA₂DS₂-VASc score if atrial fibrillation is present or develops. 2

Common Pitfalls to Avoid

• Do not delay SGLT2 inhibitor initiation waiting for "optimal" medical therapy—start immediately as it provides early benefit within weeks. 2
• Avoid excessive diuresis which precipitates hypotension and worsening renal function, compromising tolerance of other guideline-directed therapies. 2
• Do not treat HFpEF patients identically to HFrEF patients—many HFrEF therapies (digoxin in sinus rhythm, routine high-dose beta-blockers, ivabradine) lack benefit in HFpEF. 2
• Do not overlook comorbidity management (hypertension, obesity, sleep apnea, coronary disease) as these significantly impact HFpEF outcomes. 2, 3