Guideline-Directed Medical Therapy Tolerability in Patients With Heart Failure and Mitral Regurgitation: The COAPT Trial

JACC Heart Fail. 2023 Jul;11(7):791-805. doi: 10.1016/j.jchf.2023.03.009. Epub 2023 Apr 26.

Abstract

Background: In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, a central committee of heart failure (HF) specialists optimized guideline-directed medical therapies (GDMT) and documented medication and goal dose intolerances before patient enrollment.

Objectives: The authors sought to assess the rates, reasons, and predictors of GDMT intolerance in the COAPT trial.

Methods: Baseline use, dose, and intolerances of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), angiotensin receptor neprilysin inhibitors (ARNIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were analyzed in patients with left ventricular ejection fraction (LVEF) ≤40%, in whom maximally tolerated doses of these agents as assessed by an independent HF specialist were required before enrollment.

Results: A total of 464 patients had LVEF ≤40% and complete medication information. At baseline, 38.8%, 39.4%, and 19.8% of patients tolerated 3, 2, and 1 GDMT classes, respectively (any dose); only 1.9% could not tolerate any GDMT. Beta-blockers were the most frequently tolerated GDMT (93.1%), followed by ACEIs/ARBs/ARNIs (68.5%), and then MRAs (55.0%). Intolerances differed by GDMT class, but hypotension and kidney dysfunction were most common. Goal doses were uncommonly achieved for beta-blockers (32.3%) and ACEIs/ARBs/ARNIs (10.2%) due to intolerances limiting titration. Only 2.2% of patients tolerated goal doses of all 3 GDMT classes.

Conclusions: In a contemporary trial population with HF, severe mitral regurgitation, and systematic HF specialist-directed GDMT optimization, most patients had medical intolerances prohibiting 1 or more GDMT classes and achieving goal doses. The specific intolerances noted and methods used for GDMT optimization provide important lessons for the implementation of GDMT optimization in future clinical trials. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079).

Keywords: COAPT trial; guideline-directed medical therapy; heart failure; intolerance; mitral regurgitation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Heart Failure* / complications
  • Heart Failure* / drug therapy
  • Humans
  • Mitral Valve Insufficiency* / complications
  • Mitral Valve Insufficiency* / drug therapy
  • Stroke Volume / physiology
  • Treatment Outcome
  • Ventricular Function, Left

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Adrenergic beta-Antagonists

Associated data

  • ClinicalTrials.gov/NCT01626079