Is 4-pillar therapy beneficial in ST-Elevation Myocardial Infarction (STEMI) induced heart failure?

From the Guidelines

The 4-pillar therapy approach, including ACE inhibitors or ARBs, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, can be beneficial in managing heart failure following a STEMI, as it reduces morbidity and mortality, and improves quality of life, as supported by the 2017 ESC guidelines 1. The 4-pillar therapy approach typically includes:

• ACE inhibitors or ARBs, such as ramipril 2.5-10mg daily or valsartan 40-160mg daily, which reduce cardiac workload and prevent adverse remodeling
• Beta-blockers, like metoprolol 25-200mg daily or carvedilol 3.125-25mg twice daily, which decrease heart rate and blood pressure, reducing the risk of death and recurrent MI
• Mineralocorticoid receptor antagonists, such as spironolactone 25-50mg daily or eplerenone 25-50mg daily, which reduce fluid retention and improve cardiac function, as shown in the EPHESUS study 1
• SGLT2 inhibitors, such as dapagliflozin 10mg daily or empagliflozin 10mg daily, which improve cardiac function and reduce hospitalization for heart failure Treatment should begin as soon as hemodynamically stable after STEMI, with careful dose titration over weeks to months, and regular monitoring of blood pressure, heart rate, renal function, and electrolytes is essential, as recommended by the 2013 ACCF/AHA guideline 1. This comprehensive approach addresses multiple pathophysiological mechanisms in post-STEMI heart failure, including neurohormonal activation, fluid overload, and maladaptive cardiac remodeling, ultimately improving survival and quality of life for patients, as supported by the 2008 European Heart Journal guideline 1 and the 2004 ACC/AHA guideline 1.

From the FDA Drug Label

In two placebo controlled, 12-week clinical studies compared the addition of lisinopril up to 20 mg daily to digitalis and diuretics alone. The combination of lisinopril, digitalis and diuretics reduced the following signs and symptoms of heart failure: edema, rales, paroxysmal nocturnal dyspnea and jugular venous distention The Gruppo Italiano per lo Studio della Sopravvienza nell’Infarto Miocardico (GISSI-3) study was a multicenter, controlled, randomized, unblinded clinical trial conducted in 19,394 patients with acute myocardial infarction (MI) admitted to a coronary care unit Patients receiving lisinopril (n=9,646), alone or with nitrates, had an 11% lower risk of death (p = 0.04) compared to patients who did not receive lisinopril (n=9,672) (6.4% vs. 7. 2%, respectively) at six weeks

The 4 pillar therapy which typically includes ACE inhibitors (like lisinopril), beta blockers, aldosterone antagonists, and diuretics may be beneficial in STEMI induced heart failure.

• The use of lisinopril in combination with digitalis and diuretics has been shown to reduce signs and symptoms of heart failure.
• The GISSI-3 study demonstrated a lower risk of death in patients receiving lisinopril after an acute myocardial infarction. However, the exact benefit of the full 4 pillar therapy in STEMI induced heart failure cannot be directly concluded from this information alone 2.

From the Research

Benefits of 4 Pillar Therapy in STEMI Induced Heart Failure

• The 4 pillar therapy typically includes angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, and statins, which have been shown to be beneficial in patients with heart failure [ 3 ].
• A study published in 2016 found that ramipril and losartan exert a similar effect upon markers of heart failure and endogenous fibrinolysis in survivors of STEMI [ 3 ].
• Another study published in 2020 compared the effectiveness of sacubitril-valsartan and ACE/ARB therapy in heart failure with reduced ejection fraction, and found that sacubitril-valsartan was associated with lower risks of death and hospitalization [ 4 ].

Comparison of Different Therapies

• A study published in 2019 compared the clinical outcomes between statin with ACEI or ARB therapy in STEMI patients after successful PCI with drug-eluting stents, and found that the combination of statin with ACEI may be the preferred treatment strategy to reduce mortality rates [ 5 ].
• A study published in 2024 found that sacubitril/valsartan did not significantly decrease the risk for cardiovascular death and HF in patients with AMI complicated by left ventricular dysfunction, irrespective of the type of AMI [ 6 ].

STEMI Induced Heart Failure Management

• The management of STEMI induced heart failure typically involves a combination of medications, including ACEIs, ARBs, beta-blockers, and statins, as well as lifestyle modifications and possibly device therapy [ 7 ].
• The choice of therapy should be individualized based on the patient's specific needs and medical history, and should be guided by evidence-based guidelines and clinical trials [ 3, 4,5,6 ].