The PROMPT Trials

Heart failure (HF) is the major cause of healthcare expenditure, morbidity, and mortality in the United States. In the United States, heart failure is the primary diagnosis for approximately 1 million and a secondary diagnosis in another 2 million hospitalizations annually. In fact, inpatient admissions account for more than half of HF healthcare expenditure. However, data from several registries over the last three decades has failed to see use of evidence-based therapies at levels noted in clinical trials, despite aggressive recommendations by leaders in the field.

Although it remains unclear as to why many patients with HF reduced ejection fraction (HFrEF) are not on evidence-based therapies, especially post hospital discharge, it could be hypothesized that this is due to a lack of knowledge or providers making individualized decisions about their patients. A simple way to test these hypotheses is to examine whether electronic health record (EHR) based "best practice advisories" (BPAs) can increase use of evidence based therapies. If found to be effective, these low cost interventions can be rapidly applied across large healthcare systems.

Similar to PROMPT-HF Outpatient, PROMPT-HF Inpatient uses a randomized controlled trial to compare the effectiveness of an EHR BPA system that informs physicians of evidence-based medications to prescribe for eligible patients with HFrEF with a usual care group which receives no alert. Between these groups, the primary outcome observed will be the proportion of patients with HFrEF with an increase in prescribed evidence-based medical therapies (beta-blockers, ACE-I/ARB/ARNI, MRA, SGLT2i). Other outcomes observed will include the proportion of patients prescribed each class of evidence-based medication, the percent of filled prescriptions as assessed by Sure Scripts, medication doses, 30-day hospital admission rates, 30-day all-cause ED visits, one year all-cause mortality, and 6 month total healthcare cost.

This study is sponsored in part by a grant from AstraZeneca

Heart failure (HF) is the major cause of healthcare expenditure, morbidity, and mortality in the United States. Without a doubt, it is a major health problem to the country today. However, clinical data suggest that pharmacological therapies lead to dramatic improvements in survival and hospitalization rates in patients with heart failure with reduced ejection fraction (HFrEF). That being said, data over the last 30 years shows a lack of evidence-based therapies at levels noted in clinical trials, despite aggressive recommendations from leaders in the field. In fact, our pilot data across the Yale New Haven Health System confirms this, showing almost identical use of evidence based heart failure therapies as noted in the most current and comprehensive registry—CHAMP-HF.

This is the problem that PROMPT-HF Outpatient seeks to address. Although it remains unclear as to why many patients with HFrEF are not on evidence-based therapies, it could be due to a lack of knowledge of available therapies by clinicians. A simple way to test these hypotheses is to examine whether electronic health record (EHR) based "best practice advisories" (BPAs) can increase use of evidence-based therapies.

Through a randomized controlled trial across outpatient clinics across the Yale New Haven Health System, the study will compare the effectiveness of an EHR BPA system that informs physicians of evidence-based medications to prescribe for eligible patients with HFrEF with a usual care group which receives no alert. Between these groups, the primary outcome observed will be the proportion of patients with HFrEF with an increase in prescribed evidence-based medical therapies (beta-blockers, ACE-I/ARB/ARNI, MRA, SGLT2i). Other outcomes observed will include the proportion of patients prescribed each class of evidence-based medication, the percent of filled prescriptions as assessed by Sure Scripts, medication doses, 30-day hospital admission rates, 30-day all-cause ED visits, one year all-cause mortality, and 6 month total healthcare cost.

This study is sponsored by a grant from AstraZeneca

In the United States and most developed countries, cardiovascular disease (CVD)—including coronary heart disease, stroke, and peripheral artery disease—is the leading cause of death in men and women. A key risk factor for CVD is dyslipidemia, in particular elevations in low-density lipoprotein cholesterol (LDL-C), whose treatment has been shown to dramatically reduce downstream risks of adverse cardiovascular events. Recent professional society guidelines outline the use of pharmacological therapies for the reduction of LDL-C in very high risk patients. Based on favorable results from several large clinical trials, these guidelines support the use of high intensity statin therapy, and then addition of non-statin therapies if the LDL-C remains elevated.

Despite clear recommendations, there is substantial underuse of evidence based lipid-lowering therapies across healthcare systems. Since the benefit of lipid-lowering treatment can only be fully realized if all patients are treated appropriately, there is a strong need for strategies aimed at improving adoption of the practice guidelines and the recommended therapies therein. This is the problem that PROMPT-Lipid seeks to address. Several studies have found that real-time alerting to important clinical conditions, when fired in an appropriate and timely manner and with actionable interventions, can positively impact patient outcomes through increased physician awareness and adherence to best practices.

PROMPT-Lipid seeks to evaluate whether automated electronic alerts with guideline-based recommendations can improve the management of hyperlipidemia among patients at very high risk. 100 physicians from outpatient internal medicine and cardiology practices associated with four teaching hospitals in the Yale New Haven Health System will undergo cluster randomization into the alert group or a non-alert, control group. The alert group physicians will receive an ACC/AHA guideline-directed actionable item upon opening the order entry screen of a patient with hyperlipidemia, while the control group will go through usual care. The primary outcome will be the proportion of patients who have intensification of their lipid lowering therapy at 90 days. The secondary outcomes will be achieved LDL-C at 6-months and rates of hospitalization for myocardial infarction, stroke, unstable angina, coronary or peripheral artery revascularization.

Despite the robust literature demonstrating improved outcomes with the use of mineralocorticoid antagonists (MRAs) in patients with heart failure with reduced ejection fraction, they continue to be underused in clinical practice. This underuse often stems from the perceived risks of hyperkalemia, including a prior history of hyperkalemia and acute or chronic kidney disease, as well as the cautioned use for those with elevated potassium, as recommended in national societal guidelines. In fact, our pilot data across the Yale New Haven Health System confirms this, showing similar use of evidence-based heart failure therapies as noted in the most current and comprehensive registry—CHAMP-HF.

In addition, new potassium binders have recently been approved by the United States Food and Drug Administration (FDA) to treat hyperkalemia that are more advantageous that other currently available alternatives.

This is the problem that PROMPT-MRA seeks to address. Although it remains unclear as to why many patients with HFrEF are not on a mineralocorticoid antagonist, it could be due to a lack of comfort prescribing these medications in the setting on chronic kidney disease and potential hyperkalemia as well as knowledge of available therapies to treat hyperkalemia. A simple way to test these hypotheses is to examine whether electronic health record (EHR) based "best practice advisories" (BPAs) can increase use of evidence-based therapies.

Through a randomized controlled trial across outpatient clinics across the Yale New Haven Health System, the study will compare the effectiveness of an EHR BPA system that informs physicians of mineralocorticoid antagonists to prescribe for eligible patients with HFrEF with a usual care group which receives no alert. The alerts will also inform physicians about available potassium binders to treatment for hyperkalemia. Between these groups, the primary outcome observed will be the proportion of patients with HFrEF with an increase in prescribed mineralocorticoid antagonists. Other outcomes observed will include the incidence of hyperkalemia, proportion of patients prescribed potassium binders, the percent of filled prescriptions as assessed by Sure Scripts, medication doses, 1-, 3-, 6-, and 12-month hospital heart failure admission rates, all-cause ED visits, and all-cause mortality, and 1-, 3-, 6-, and 12-month total healthcare cost.

This study is sponsored by a grant from Vifor Pharma.