Clinical trial NCT04505007: Guideline-Directed Medical Therapy in Patients After Implantation of Implantable Cardioverter Defibrillators to Improve Long-Term Outcomes
Official title: Guideline-Directed Medical Therapy in Patients After Implantation of Implantable Cardioverter Defibrillators to Improve Long-Term Outcomes
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Heart Failure
ICD
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
Collaborators: name: Nova Scotia Health Authority
First posted: 2020-08-07
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized 1:1 to either arm
Primary purpose: SUPPORTIVE_CARE

Brief summary: Guideline-directed medical therapy (GDMT) and the mortality benefit it provides in the heart failure with reduced ejection fraction (HFrEF) population are well-established by multiple professional society guidelines. GDMT refers to initial medical therapy with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB), beta-blockers (BB), and mineralocorticoid receptor antagonists (MRA) titrating to maximally tolerated doses for patients with HFrEF. Cardiac implantable electronic devices (CIEDs) such as the implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) have also become a mainstay in the management of HFrEF after implementation of GDMT. ICD therapy is an effective and established treatment for HFrEF patients for both primary and secondary prevention of SCD.

Regarding the use, adherence and results of GDMT after ICD/CRT implantation, there is very limited data available in the literature. There are a few retrospective trials that show this, however very limited randomized controlled data.

This proposed study would randomize patients with primary prevention ICDs and CRT into a specialized clinic with a heart failure nurse practitioner vs usual clinical care, with the goal of determining outcomes such as change in LVEFs, heart failure hospitalizations, and visits to the ER for heart failure. Consequently, this would determine whether targeted clinics are needed for ICD/CRT patients with HFrEF to optimize GDMT, improve patient outcomes and thus implement new guidelines/recommendations for this specific patient population.

Detailed description: Guideline-directed medical therapy (GDMT) and the mortality benefit it provides in the heart failure with reduced ejection fraction (HFrEF) population are well-established by multiple professional society guidelines. GDMT refers to initial medical therapy with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB), beta-blockers (BB), and mineralocorticoid receptor antagonists (MRA) titrating to maximally tolerated doses for patients with HFrEF. Cardiac implantable electronic devices (CIEDs) such as the implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) have also become a mainstay in the management of HFrEF after implementation of GDMT. ICD therapy is an effective and established treatment for HFrEF patients for both primary and secondary prevention of SCD. Canadian guidelines recommend ICD implantation for patients with ischemic or non-ischemic cardiomyopathy (NICM) and persistent ejection fraction ≤ 30%, when persistent refers to at least 3 months of optimal medical therapy (OMT) in all patients and, in patients with ischemic heart disease, at least 3 months after revascularization and at least 40 days after a myocardial infarction (MI). These guidelines also suggest that ICDs be considered for the same population with a left ventricular ejection fraction (LVEF) of 31-35% as well. CRT device therapy is indicated for use in patients in sinus rhythm with New York Heart Association (NYHA) class II-III, or ambulatory NYHA class IV heart failure symptoms, a LVEF ≤ 35%, and QRS duration \> 130 ms because of left bundle branch block (LBBB).

The use and adherence to GDMT before and after ICD implantation is of critical importance. Adherence to GDMT before implantation has the potential to improve survival and may even improve left ventricular ejection fraction (LVEF) enough so that an ICD may no longer be indicated. However, adherence to GDMT is notoriously difficult to assess in conventional clinical practice due a multitude of factors. These include information about outpatient prescription use, prescription filling pattern/barriers, reported patient adherence to GDMT, and various electronic health records/documentation linked to pharmacies to name a few. In one retrospective study, it was demonstrated that just over half (61.1%) of patients filled any GDMT prescription before ICD implantation. Futhermore, patients receiving GDMT versus those who did not receive GMT had a lower 1 year mortality rate after ICD implantation (11.1% vs 16.2%) after adjustments for comorbidities, LVEF, and NYHA class heart failure. In a similar study assessing prescriptions claim data to assess beta-blocker use prior to ICD implantation, the median number of days covered by a beta-blocker in the 90 days prior to ICD implantation was 46 days. From the results of these studies, it is clear that there is room for improvement for implementation of GDMT prior to ICD implantation.

Regarding the use, adherence and results of GDMT after ICD/CRT implantation, there is very limited data available in the literature. One of the first studies to exhibit the effect of medical therapy in HFrEF patients after ICD/CRT implantation was a retrospective cohort study that stratified ICD/CRT patients according to combination treatment with HFrEF medical therapy; patients on none or one HFrEF medications were in group 0/1, patients on two HFrEF medications (ex: ACEi + BB) were in group 2, and patients on all three HFrEF medications (ACEi/ARB + BB + MRA) were in group 3. Results showed a higher hospitalization rate per patient/year in the undertreated population (group 0 and 1) (28% vs 12%, p = 0.001). Also, in multivariate analysis, patients treated with better medical therapy (groups 2 and 3) had less hospitalizations for heart failure and better survival (p \< 0.001). In addition to benefits with hospitalizations and better survival, adjunctive optimization of GDMT can result in quantitative benefits as well. One study compared usual post-implant care was compared to protocol-driven clinical care with a dedicated nurse and cardiologist. Protocol-driven care was associated with significant improvements in LVEF, LV internal diastolic diameter, and improvements in maximum exercise capacity. Interestingly, these improvements appeared to be driven not only by device-related management, but also by concomitant optimization of GDMT and heart failure education. As evidenced by these promising results, it is of utmost importance to assess and optimize the use of GDMT in patients with CIEDs and HFrEF, as there can be potential improvements in LVEF, exercise capacity and survival.

This proposed study would randomize patients with primary prevention ICDs and CRT into a specialized clinic with a heart failure nurse practitioner vs usual clinical care, with the goal of determining outcomes such as change in LVEFs, heart failure hospitalizations, and visits to the ER for heart failure. Consequently, this would determine whether targeted clinics are needed for ICD/CRT patients with HFrEF to optimize GDMT, improve patient outcomes and thus implement new guidelines/recommendations for this specific patient population.

Eligibility criteria: Inclusion Criteria:

- patients who underwent ICD or CRT (pacemaker or defibrillator) implantation therapy at the QEII Health Sciences Centre between 2002 and 2019 and had a left ventricular ejection fraction ≤ 35% at the time of the initial implantation.

Exclusion Criteria:

* unable to provide informed consent, has a life expectancy of less than one year, dementia, cirrhosis, or metastatic malignancy.
* Patients who underwent primary prevention ICD implantation for arrhythmogenic right ventricular cardiomyopathy (ARVC), ion channelopathies, hypertrophic cardiomyopathy, or infiltrative cardiomyopathy will be excluded from this analysis.

Primary outcomes:
measure: Change in Left Ventricular Ejection Fraction (LVEF)
timeFrame: 1 year
Secondary outcomes:
measure: Mortality rate
timeFrame: 1 year
measure: Heart failure hospitalization frequency
timeFrame: 1 year
measure: Rate of adherence to guideline directed medical therapy
timeFrame: 1 year
Other outcomes:
Locations:
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
Study officials:
affiliation: NSHA
name: Ratika Parkash, MD
role: PRINCIPAL_INVESTIGATOR
References:
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