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Foundational Heart Failure Therapies: A Practical Board Review [ Medical Education ](https://mdster.com/blog?category=medical-education) Foundational Heart Failure Therapies: A Practical Board Review ================================================================ How to use ARNI, ACEi, ARB, MRA, and SGLT2 inhibitors safely and intelligently [ MDster Editorial Team ](https://mdster.com/about) · Sep 08, 2026 · 2 min read · 54 [ Reviewed by Dr. Ali Ragab, MBBCH, MSc, MCAI ](https://mdster.com/medical-reviewers/dr-ali-ragab) [Editorial Policy](https://mdster.com/editorial-policy) | [Corrections Policy](https://mdster.com/corrections) [ Internal Medicine Boards ](https://mdster.com/blog?tag=internal-medicine-boards) [ Internal Medicine ](https://mdster.com/blog?tag=internal-medicine) [ Heart Failure ](https://mdster.com/blog?tag=heart-failure) [ Cardiovascular Drugs ](https://mdster.com/blog?tag=cardiovascular-drugs) [ Clinical Pharmacology ](https://mdster.com/blog?tag=clinical-pharmacology) [ Guideline-Directed Therapy ](https://mdster.com/blog?tag=guideline-directed-therapy) ![Foundational Heart Failure Therapies: A Practical Board Review](https://mdster.com/storage/blog/images/foundational-heart-failure-therapies-a-practical-board-review.jpg) Share this article Share this post On this page 1. [ Build the Four-Pillar Mental Model ](#build-the-four-pillar-mental-model) 2. [ ARNI, ACEi, and ARB: Choose One Lane ](#arni-acei-and-arb-choose-one-lane) 3. [ MRA Therapy: Potassium Determines Safety ](#mra-therapy-potassium-determines-safety) 4. [ SGLT2 Inhibitors: Think Heart Failure, Not Glucose ](#sglt2-inhibitors-think-heart-failure-not-glucose) 5. [ A Practical Initiation Sequence ](#a-practical-initiation-sequence) 6. [ Key Takeaways ](#key-takeaways) 7. [ Conclusion ](#conclusion) 8. [ Frequently Asked Questions ](#blog-faqs) 9. [ References ](#references-heading) On this page 1. [ Build the Four-Pillar Mental Model ](#build-the-four-pillar-mental-model) 2. [ ARNI, ACEi, and ARB: Choose One Lane ](#arni-acei-and-arb-choose-one-lane) 3. [ MRA Therapy: Potassium Determines Safety ](#mra-therapy-potassium-determines-safety) 4. [ SGLT2 Inhibitors: Think Heart Failure, Not Glucose ](#sglt2-inhibitors-think-heart-failure-not-glucose) 5. [ A Practical Initiation Sequence ](#a-practical-initiation-sequence) 6. [ Key Takeaways ](#key-takeaways) 7. [ Conclusion ](#conclusion) 8. [ Frequently Asked Questions ](#blog-faqs) 9. [ References ](#references-heading) A patient with newly diagnosed HFrEF leaves the hospital taking a loop diuretic and a low-dose ACE inhibitor. The plan is to “add other drugs later.” That familiar strategy is too slow: congestion treatment improves symptoms, but early disease-modifying therapy changes survival and hospitalization risk. Current through **September 8, 2026**, modern care favors prompt initiation of complementary foundational therapies rather than maximizing one drug before starting another. [\[1\]](#cite-1 "Reference [1]") Build the Four-Pillar Mental Model ---------------------------------- For HFrEF, think in four parallel pathways: - Renin–angiotensin system inhibition with **ARNI, ACEi, or ARB** - An evidence-based beta-blocker - A mineralocorticoid receptor antagonist (MRA) - An SGLT2 inhibitor Start low doses of all eligible classes, then titrate according to blood pressure, volume status, renal function, and potassium. Do not delay an SGLT2 inhibitor or MRA merely because the ARNI has not reached its target dose. [\[1\]](#cite-1 "Reference [1]") Be alert to changing terminology. US board questions commonly retain the 2022 AHA/ACC/HFSA categories, including HFrEF at LVEF ≤40%. The August 2026 ESC guideline defines HFrEF as LVEF <50% and calls the highest-evidence regimen **foundational medical therapy**. [\[2\]](#cite-2 "Reference [2]") ARNI, ACEi, and ARB: Choose One Lane ------------------------------------ These agents are alternatives within the same therapeutic pathway—not additive drugs. For symptomatic HFrEF, sacubitril/valsartan is generally preferred when tolerated. Use an ACE inhibitor when ARNI therapy is not feasible, or an ARB when ACEi intolerance exists and ARNI therapy cannot be used. [\[3\]](#cite-3 "Reference [3]") SituationPreferred frameworkCritical trapEligible symptomatic HFrEFARNIWatch blood pressure, potassium, and renal functionARNI unavailable or unsuitableACEiCough, angioedema, hyperkalemiaACEi intolerance and no ARNIARBDo not combine with another RAAS blocker Always allow a **36-hour washout** when switching between an ACE inhibitor and sacubitril/valsartan. Neprilysin and ACE inhibition together excessively increase bradykinin-mediated angioedema risk. Stop an ARB before starting sacubitril/valsartan, but an ARB does not require the ACEi-specific 36-hour interval. [\[4\]](#cite-4 "Reference [4]") Avoid ARNI therapy in patients with previous ACEi- or ARB-associated angioedema. ARNI, ACEi, and ARB therapy are also contraindicated during pregnancy. > **Clinical Pearl:** When hypotension limits therapy, first reassess congestion, unnecessary vasodilators, and excessive diuretic dosing. Do not reflexively discard every disease-modifying drug. MRA Therapy: Potassium Determines Safety ---------------------------------------- Spironolactone and eplerenone reduce morbidity and mortality in symptomatic HFrEF, but their major bedside hazard is hyperkalemia. For the classic US board framework, initiate a steroidal MRA only when **eGFR is >30 mL/min/1.73 m² and potassium is <5.0 mEq/L**. Discontinue it if potassium cannot be maintained below 5.5 mEq/L. [\[2\]](#cite-2 "Reference [2]") Before prescribing, look for preventable risk amplifiers: - CKD or rising creatinine - Potassium supplements or potassium-containing salt substitutes - Concurrent RAAS inhibition without laboratory surveillance - NSAID exposure - Dehydration or acute illness Check potassium and renal function at baseline, within one week after initiation or titration, and regularly thereafter. Monitor more frequently in CKD or when interacting medications are present. Eplerenone causes fewer antiandrogenic effects and is useful when spironolactone causes gynecomastia. [\[5\]](#cite-5 "Reference [5]") The field has broadened beyond HFrEF. Finerenone received US approval for HF with LVEF ≥40% in July 2025, and the 2026 ESC guideline recommends an MRA for symptomatic HF independent of LVEF. Do not confuse this update with permission to ignore potassium surveillance. [\[6\]](#cite-6 "Reference [6]") SGLT2 Inhibitors: Think Heart Failure, Not Glucose -------------------------------------------------- Dapagliflozin and empagliflozin reduce HF events regardless of whether the patient has diabetes. Their benefit now extends across the LVEF spectrum, making diabetes status the wrong gatekeeper for prescribing. [\[3\]](#cite-3 "Reference [3]") These agents are operationally simple: HF dosing is once daily without titration, and blood-pressure lowering is usually modest. Screen for volume depletion, genital mycotic infection, and ketoacidosis risk. A small early eGFR decline may be hemodynamic and should not automatically trigger discontinuation. Hold empagliflozin or dapagliflozin for at least three days before major surgery or procedures involving prolonged fasting. Suspect **euglycemic ketoacidosis** when nausea, abdominal pain, dyspnea, or metabolic acidosis occurs despite a glucose level that is not markedly elevated. [\[7\]](#cite-7 "Reference [7]") A Practical Initiation Sequence ------------------------------- 1. Confirm HF phenotype, hemodynamic stability, and volume status. 2. Start low doses of eligible foundational classes during hospitalization or early follow-up. 3. Delay beta-blocker initiation or escalation until congestion and hypoperfusion are controlled. 4. Recheck blood pressure, potassium, creatinine, and volume status after relevant changes. 5. Titrate every one to two weeks when clinically feasible rather than waiting months. [\[1\]](#cite-1 "Reference [1]") Key Takeaways ------------- - Treat ARNI, ACEi, and ARB as mutually exclusive options within one pathway. - Enforce the 36-hour ACEi–ARNI washout. - Start steroidal MRA therapy in HFrEF only with potassium <5.0 and eGFR >30. - Monitor potassium within one week of starting or titrating an MRA. - Prescribe SGLT2 inhibitors for HF benefit, not merely for glycemic control. - Favor rapid, monitored deployment of complementary therapies over sequential therapeutic inertia. Conclusion ---------- Foundational HF therapy is an exercise in balancing speed with surveillance. Start the drugs that alter outcomes early, then protect the patient by actively monitoring blood pressure, renal function, potassium, and volume status. Frequently Asked Questions ---------------------------- ### Can sacubitril/valsartan be started immediately after stopping an ACE inhibitor? No. Allow a 36-hour washout between an ACE inhibitor and sacubitril/valsartan to reduce angioedema risk. ### What laboratory values permit starting spironolactone in HFrEF? The classic US guideline threshold is serum potassium below 5.0 mEq/L and eGFR above 30 mL/min/1.73 m². ### Should an SGLT2 inhibitor be prescribed when the HF patient does not have diabetes? Yes. Dapagliflozin and empagliflozin provide HF benefits independent of diabetes status. ### Does an early eGFR decline require stopping an SGLT2 inhibitor? Not automatically. A modest early hemodynamic decline may occur; assess volume status and the overall renal trajectory before discontinuing therapy. ### Is finerenone interchangeable with spironolactone in HFrEF? No. Steroidal MRAs remain foundational for HFrEF. Finerenone is approved in the United States for HF with LVEF ≥40% and has separate dosing and monitoring requirements. References (8) ------------------ 1. 1. [ 2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF ](https://www.acc.org/latest-in-cardiology/ten-points-to-remember/2024/03/06/19/22/2024-acc-expert-consensus-hfref) [↩](#cite-ref-1-1 "Back to text") 2. 2. [ 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure ](https://professional.heart.org/-/media/832EA0F4E73948848612F228F7FA2D35.pdf) [↩](#cite-ref-2-1 "Back to text") 3. 3. [ www.acc.org/Latest-in-Cardiology/ten-points-to-remember/2022/03/29/19/53/2022-AHA-ACC-HFSA-Heart-Failure-Guideline-gl-hf ](https://www.acc.org/Latest-in-Cardiology/ten-points-to-remember/2022/03/29/19/53/2022-AHA-ACC-HFSA-Heart-Failure-Guideline-gl-hf) [↩](#cite-ref-3-1 "Back to text") 4. 4. [ FDA Prescribing Information: Entresto ](https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218591Orig1s000%2C%20207620Orig1s025lbl.pdf) [↩](#cite-ref-4-1 "Back to text") 5. 5. [ FDA Prescribing Information: Aldactone ](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/012151s080lbl.pdf) [↩](#cite-ref-5-1 "Back to text") 6. 6. [ FDA Prescribing Information: Kerendia ](https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215341Orig1s009lbl.pdf) [↩](#cite-ref-6-1 "Back to text") 7. 7. [ FDA Prescribing Information: Jardiance ](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204629s063lbl.pdf) [↩](#cite-ref-7-1 "Back to text") 8. 8. [ 2026 ESC Guidelines for the Management of Heart Failure ](https://www.escardio.org/guidelines/clinical-practice-guidelines/all-esc-practice-guidelines/heart-failure/) Next Turn reading into Internal Medicine performance ------------------------------------------------- - System‑based, exam‑style questions + explanations - Smarter review to reinforce weak topics - Build confidence with measurable progress [ Start practicing ](https://mdster.com/user/dashboard) [ Internal Medicine ](https://mdster.com/speciality/internal-medicine) [ View pricing ](https://mdster.com/pricing) [ Explore features ](https://mdster.com/features) No credit card required. Full access to all features\*. No commitment. Cancel anytime. \*AI SOE Examiner is limited to 10 cases monthly for Advanced & Bundle subscribers. 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