Elsevier

JACC: Heart Failure

Volume 11, Issue 7, July 2023, Pages 791-805
JACC: Heart Failure

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

https://doi.org/10.1016/j.jchf.2023.03.009Get rights and content

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)

Section snippets

Data availability statement

The data that support the findings of this study may be made available to qualified researchers upon reasonable request to the COAPT Publications Office ([email protected]).

Study design

The COAPT trial design and results have been previously published.9,10 In brief, the COAPT trial was a multicenter, randomized, controlled, open-label trial of transcatheter edge-to-edge mitral valve repair (TEER) with the MitraClip device (Abbott Laboratories) in patients with HF and symptomatic moderate-to-severe or severe

Study population

Between December 2012 and June 2017, 1,576 subjects were screened at 78 centers in the United States and Canada; 911 (57.8%) of were ineligible. Among the 614 randomized patients, 472 (76.9%) had LVEFs ≤40% at enrollment. Individual GDMT medication class information was available in all 472. Of these, 464 (98.3%) had complete screening GDMT regimen data. Baseline characteristics are presented in Table 1, according to the number of GDMT medication classes used after HF specialist-guided GDMT

Discussion

To our knowledge, COAPT is the first HF trial to require HF medication optimization systematically by a multidisciplinary team of HF experts, providing the first understanding into intolerances limiting GDMT optimization in a HF trial. The major findings are as follows: 1) only 39% of patients with HFrEF tolerated any dose of all 3 required class I GDMT classes simultaneously, whereas 22% only tolerated only 1 or no GDMT class, and only 2.2% of patients with HFrEF tolerated target doses of all

Conclusions

In the COAPT trial, most enrolled patients with HFrEF had medical intolerances prohibiting use of at least 1 of the 3 core GDMT classes and of reaching target goal doses, despite systematic HF specialist-directed GDMT optimization. These findings emphasize that GDMT intolerances frequently underlie low GDMT prescription rates and suboptimal dose prescription in HFrEF and mitral regurgitation, likely contributing to poor prognoses in these high-risk patients. Whether improved hemodynamics and

Funding Support and Author Disclosures

Abbott Laboratories has provided funding for this paper. Dr Cox has received grants from AstraZeneca, and Cumberland Pharmaceuticals; and consulting fees from Roche. Dr Udelson has served on steering committees for Abiomed; and has received consulting fees from Imbria Pharmaceuticals. Dr Lim has received grants from Abbott, Edwards, Medtronic, and Gore; consulting fees from Abbott, Edwards, Keystone Heart, Pipeline, Siemens, Valgen, and Venus; has served on advisory boards for Ancora and Venus;

References (20)

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