Management of patients with heart failure with reduced ejection fraction consists of a combination of older, tried-and-true medications and recently developed, novel pharmacological therapies. Known as the “four pillars” of heart failure therapy, these medications are beta blockers, angiotensin receptor-neprilysin inhibitors (ARNIs), mineralcorticoid receptor antagonists (MRAs) and sodium-glucose co-transporter 2 Inhibitors (SGLT2i). The latest clinical evidence shows patients with heart failure should be put on these drugs all at once.
Historically, the standard practice for cardiologists treating patients with heart failure was to introduce the drugs one by one, usually starting with a beta blocker. Once the beta blocker was titrated to the maximal dose tolerated, then a second drug would be added, titrated to target dose, and so on. When done in such a deliberate fashion, it might take six months to a year to get a patient on the four foundational pillars of therapy. As a result, patients did not receive the benefits of these drugs, which include reduced hospitalizations and reduced mortality.
“The newest recommendation for patients with heart failure, whether hospitalized or outpatient, is to start patients on all four drug classes at the same time and rapidly and aggressively titrate to maximum tolerated dose,” says Shelley Hall, MD, FACC, FHFSA, FAST, chief of transplant cardiology, mechanical circulatory support and advanced heart failure, Baylor University Medical Center, part of Baylor Scott & White Health.
The first pillar – beta blockers – have been around for 30 years, but there is still only 60 percent penetrance with heart failure when it should be around 90 percent, Dr. Hall says. “Many physicians have misconceptions about using beta blockers, but only about 10 percent of patients have true contraindications to the drugs. However, not all beta blockers are appropriate for heart failure. There are only three that are approved and have demonstrated efficacy with heart failure.”
The second pillar (ARNI) is a combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker (ARB) and is now considered first choice for initiation. If a patient still experiences symptoms while on an ARB or angiotensin-converting enzyme (ACE) inhibitor, then an ARNI should replace the ACE or ARB. The current recommendation is to titrate both the beta blocker and ARNI to maximum tolerated dosage. The one limitation to this recommendation is cost. The ARNI is not generic and is currently the only one of its kind in existence.
The third pillar of heart failure therapy are MRAs. Discovered in the 1990s, these drugs are aldosterone antagonists that reduce excess fluid in the body while preventing the loss of potassium. Yet the primary efficacy is from neurohormonal blockage. The normal dose is usually 25 mg daily and does not need up titration unless excessive potassium losses are benefitted by higher doses.
SGLT2 inhibitors – the fourth pillar – are the newest drug class shown to be effective against heart failure. They are being incorporated into practice faster than the other drug classes were when they were first introduced. These drugs have nearly zero side effects, so they are well tolerated by patients. Like sacubitril/valsartan, SGLT2 inhibitors are not generic and therefore expensive and not always covered by insurance.
“We advocate rapid titration of all four medication classes,” Dr. Hall says. “This can be done weekly or simultaneously. Of course, not every patient will tolerate speed, so physicians have to make the appropriate patient assessment. The goal is to go as fast as possible to mitigate disease progression.”