Does COAPT Change the Need to Try Foundational HF Drugs in Functional MR?

Clinicians agreed on the need for an overhaul of the heart failure guideline-directed medical therapy (GDMT) titration process during a debate on a different question: whether patients with functional mitral regurgitation (MR) should exhaust all options before they try transcatheter repair.

JoAnn Lindenfeld, MD, of Vanderbilt University Medical Center in Nashville, asserted that taking appropriate medicines in heart failure can add 8 years to life, citing published data during a debate at TVT: The Structural Heart Summit, an annual meeting held by the Cardiovascular Research Foundation and hosted in Miami.

She urged timely medical treatment even if the COAPT trial showed transcatheter edge-to-edge repair (TEER) therapy to slash heart failure hospitalizations and deaths in people with moderate-to-severe functional MR who had been on maximally-tolerated GDMT.

"Practically from the day of randomization, we see benefits, so if you delay this, for example, to do a procedure, you delay substantial benefits. TEER is great. But medical therapy is pretty good too even early on," she said. "I think sometimes we underestimate this."

Indeed, few heart failure patients stick with the rigorous titration process in the real world: only 1% of eligible patients in the CHAMP-HF registry were taking target doses of their medications, according to a 2018 analysis.

Moreover, the four main classes of drugs -- angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs); angiotensin receptor-neprilysin inhibitor (ARNI) therapy; beta-blockers; and mineralocorticoid receptor antagonists (MRAs) -- may soon become five with the anticipated addition of SGLT2 inhibitors to the list in the next round of guidelines, Lindenfeld said.

But can some selected individuals with functional MR bypass GDMT and go straight to TEER?

This is a good idea but it is hard in practice, she said. "So the best option, I would conclude, is what was done in COAPT: maximally-tolerated GDMT first."

Lindenfeld's opposing debater at TVT, Milton Packer, MD, of Baylor University Medical Center in Dallas, did not disagree, but pointed out problems in the standard GDMT titration process.

"If you do this in a reasonably compulsive way, it will take us 6 months. And people don't do this. Less than 5% of people are taking foundational drugs. There are major delays in initiation of drug classes," he said. "There are hospitalizations that occur and lives that are lost because of delays in implementation of therapy. So we need a better approach."

Packer proposed a rapid approach that gets patients on all four heart failure drugs in 4 weeks: start them on a beta-blocker and SGLT2 inhibitor, then add ARNI 2 weeks later, then an MRA another 2 weeks later if necessary.

"If each of the foundational drugs acts independently of each other, historical sequencing should not matter. The background therapy does influence, however, the safety of these drugs and proper sequencing should account for this," he said.

"Most importantly, low starting doses of foundational drugs had very meaningful effects. So broad-based coverage should be prioritized before uptitration, and people should be on all four classes of drugs within 4 weeks of initiation of therapy. I agree with Joanne. Time is of the essence," Packer concluded.

Panelist Clyde Yancy, MD, of Northwestern University Feinberg School of Medicine in Chicago, agreed that the current approach to titration is imperfect.

"I think Milton is right, we don't really have any guiding biology to say, should it be combination therapy? Should it be sequential? Should it be all at once? We really could benefit with a little bit more biological inference on what we're doing," he said during the session.

Furthermore, it is a "very draconian approach," he said, to titrate until the patient's mental function and blood pressure changes. There should be a more sophisticated surrogate marker of the adequacy of these therapies, he suggested.

Ultimately, Yancy said he has to be "super diligent" to make sure his heart failure patients are on their target doses of medication. "It takes a lot of time and effort that I'm not sure can be applied outside of a major academic medical center with the care team that's involved."

"You make an incredibly important point; we don't have enough heart failure specialists. The ones that we do have are probably not meeting frequently enough with their patients, patients have a lot of side effects from these drugs, they're not necessarily compliant with these drugs, there's insurance issues, etc., etc.," lamented session moderator Gregg Stone, MD, of Icahn School of Medicine at Mount Sinai in New York City.

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