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EuropeanJofHeartFail-2024-Min-APACTforthefutureImprovingmedicationadherenceinheartfailure.pdf

European Journal of Heart Failure (2024) 26, 661–663 INVITED EDITORIAL doi:10.1002/ejhf.3169

A PACT for the future: Improving medication adherence in heart failure Kyung H. Min1, Stephanie A. Jackson2, and Andrew P. Ambrosy3,4* 1Department of Medicine, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA; 2A.T. Still University – School of Osteopathic Medicine, Meza, AZ, USA; 3Department of Cardiology, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA; and 4Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

This article refers to ‘Effect of a transitional care model following hospitalization for heart failure: 3-year out- comes of the Patient-Centered Care Transitions in Heart Failure (PACT-HF) randomized controlled trial’ by T. Averbuch et al., published in this issue on pages 652–660.

Heart failure (HF) currently affects over 64 million people world- wide, placing a growing burden on health care systems due to the costs of disease management and downstream complications.1,2

Contemporary observational studies have highlighted the ongo- ing underutilization of guideline-directed medical therapy (GDMT) as a driving factor for HF morbidity and mortality, while concur- rently emphasizing gaps in knowledge on reducing readmissions and morbidity via medication adherence optimization. For instance, the CHAMP-HF study identified significant percentages of outpatient HF patients that were not on eligible GDMT classes, and more con- cerningly found minimal improvement in medication initiation and titration during follow-up.3 This pattern persists despite significant evidence from studies such as STRONG-HF, which demonstrated that rapid, high-intensity titration of GDMT with close outpa- tient follow-up after an initial HF exacerbation was associated with reduced mortality and readmission risk.4 Transitional HF care pro- grammes have therefore gained interest as a mechanism to facilitate GDMT titration and ensure appropriate monitoring of patients in the vulnerable post-discharge period. In this issue of the Journal, Averbuch and colleagues revisit the results from the PACT-HF trial 3 years post-implementation, reviewing the long-term impacts of a transitional care model on HF mortality, hospital and emergency department (ED) readmissions, as well as its impact on the uptake and utilization of GDMT.5

The PACT-HF study was a stepped-wedge cluster randomized trial of 2494 patients across 10 hospitals which studied the impact of a patient-centred transitional care model on all-cause deaths, ED visits, and readmissions.6 The authors identified that a significant

The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Heart Failure or of the European Society of Cardiology. doi: 10.1002/ejhf.3134.

*Corresponding author. Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA 94612, USA. Tel: +1 415 271-9703, Email: [email protected]

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. number of early readmissions for HF exacerbation were related to issues of suboptimal care coordination and continuity between the inpatient and outpatient setting, and should be commended for the development of a quality improvement care programme aimed at closing this gap in care.5 Patients admitted for HF exacerbations underwent triage according to their assessed risk and were discharged with services aligned with their perceived risk for subsequent HF exacerbations. The interventions ranged from a standardized, structured discharge summary, nurse-led self-care education, or follow-up with a family physician. Highest risk patients were scheduled for nurse-led home visitations or heart function clinic care appointments. Usual care was defined at the discretion of the treating physician.

Each hospital was randomized to cross over from control to intervention monthly, until all hospital locations had implemented the intervention. In addition to the primary composite outcome of all-cause mortality, ED visits, and readmissions, the authors were able to study the impact of this programme on the uptake of indi- vidual classes of GDMT, including angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor– neprilysin inhibitor (ACEi/ARB/ARNi), beta-blocker, and miner- alocorticoid receptor antagonist (MRA). Notably, the study did not examine sodium–glucose cotransporter 2 (SGLT2) inhibitor uptake, as they were not recommended in clinical practice guide- lines during the trial. This analysis revisits the initial PACT-HF study, explores the long-term legacy effects of its transitional care programme, and once again examines the impact of a structured post-discharge transitional care model on mortality and healthcare utilization. With the benefit of a longer study period, this work evaluates the durability of the effect such a transitional care model can have on the degree of extended uptake of GDMT in this at-risk population.5

As the initial PACT-HF trial reported, patients hospitalized for a HF exacerbation are at substantially increased risk of post-discharge mortality and readmission or ED visitation with

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or without the intervention of a transitional care programme.6

There is compelling evidence that proper GDMT titration to target doses is a crucial component to any plan to reduce the risk of HF-related complications. Considering these factors, even apart from practical considerations such as ease of titration and inpatient monitoring for GDMT-related adverse events, hospitalized patients emerge as the prime population to target for medication titration. Prior studies like IMPACT-HF and OPTIMIZE-HF have provided evidence that inpatient initiation of GDMT is associated with better short-term adherence, long-term persistence, and lower risks of mortality and readmissions.7,8 PACT-HF continues to build on the conclusions from these prior studies and expand our understand- ing of the impact and capability of transitional care programmes to continue optimizing a patient’s medication regimen post-discharge.

The PACT-HF study also highlighted the utility of a stepped- wedge cluster randomized control design for analysing the outcomes of future service delivery interventions, such as HF transitional care programmes. There is a high degree of crossover analysis possible from this design, as by staggering the time of deployment, each subsequent study site can function as a control and experimental population versus itself and other clinical sites. This approach safeguards participant blinding, as they perceive their care to align with the ‘standard of care’ received by other local participants, thereby remaining unaware of the interventions at other sites. Finally, this is a highly pragmatic way in which to study public health interventions at scale, as it often can be deployed as part of quality improvement rather than strictly a research endeavour. While the staggered nature of implementation can lead to confounding from different populations who received the intervention at different times, such issues can be addressed, as the authors did, using propensity score matching.5,9

Remarkably, the PACT-HF trial consistently showed no signifi- cant difference in the risk of the primary outcome or HF-specific readmission across subgroups during the 3-year follow-up period. Just as in the original analysis, event rates continued to be high in this follow-up, demonstrating the high baseline level of risk that HF patients are at for readmission and comorbid complications. Given the lack of treatment benefit observed, this study raises the con- sideration that HF patients are being systematically underestimated in their risk for readmission or morbidity by currently utilized risk-stratification tools and may uniformly benefit from even closer high-intensity follow-up.9,10

Perhaps most significantly, the authors found that this tran- sitional care model did not result in a substantial difference in the proportion of uptake of GDMT medications in the interven- tion group, a concerning finding given our understanding that rapid initiation and protocolized, mandated titration of GDMT can be associated with improved long-term outcomes.4 This also reinforces the conclusions of prior studies on transitional care programmes, which found similar limitations in GDMT adherence improvement (Figure 1). For example, the Get With The Guidelines-HF study demonstrated that personalized and tailored performance feedback and physician education about key HF metrics did not lead to any significant improvement in GDMT adherence.11 While the PROMPT-HF trial suggested that built-in electronic health record (EHR) alerts improved outpatient ..

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PACT-HF

STRONG-HF

PROMPT-HF

PROMPT-AHF

GWTG-HF Cluster Randomized Trial

Figure 1 Randomized clinical trials of care strategies and the impact on guideline-directed medical therapy (GDMT) utilization and clinical outcomes.

prescription of GDMT, the PROMPT-AHF trial showed that a similar inpatient EHR-based alert failed to increase prescrip- tion of GDMT at discharge following hospitalization for a HF exacerbation.12,13 Similarly, PACT-HF underscores the challenges of achieving GDMT initiation to current recommendations, as intervention patients were only slightly more likely to be pre- scribed an ARNi as compared to control patients after 3 years (relative risk 6.2, 95% confidence interval 1.92–20.06). Across the board, at the 3-year mark, rates of GDMT uptake remained low despite intervention (3.3% on ARNi, 31.6% on MRA, 48.3% on ACEi, 22.1% on ARBs, and 81.5% on a beta-blocker).5 The fundamental question therefore becomes, why are transitional care programmes unsuccessful in effectively improving the degree of GDMT utilization, one of the few metrics which has been shown to be associated with improved patient outcomes?

PACT-HF demonstrates how transitional care programmes are limited in addressing HF outcomes if they do not solve the issues of suboptimal medication initiation acutely after a HF exacerbation, and ineffective titration in the months to years after an event. The authors raise awareness of the need to further study if the integration of more explicit medication titration into transitional care models would lead to subsequent reductions in readmissions and mortality. Additionally, the authors demonstrate the need for successful transitional care intervention to have a significant emphasis in impacting a patient’s GDMT regimen and dosing. The STRONG-HF system of protocolized, frequent dose increases may have been successful in improving outcomes because of a mandated emphasis in increasing medication doses. Similarly, PROMPT-HF showed the long-term impact outpatient EHR alerts can have on driving up-titration of GDMT, while showing its lim- itation in changing clinician practices in the abbreviated inpatient period. It can be implied that successful interventions must be at a high enough intensity over a sufficient duration to drive behaviour change of both the physician (i.e. overcome inertia) and patient (i.e. overcome non-compliance) to optimize GDMT. In general, programmes focused on patient education rather than direct medication interventions have historically been unsuccessful in impacting HF outcomes, a conclusion further validated in this

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Invited editorial 663

update of PACT-HF. Future studies to understand barriers to implementation of GDMT both in the inpatient and outpatient set- ting are needed to develop effective transitional care programmes, but PACT-HF represents a key step along this journey and informs the structure, design, and goals of future HF care programmes. Conflict of interest: none declared.

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