CARE-HK in HF Registry HQ-NIS-CHF-07.2020
Research type
Research Study
Full title
Cardiovascular and Renal Treatment in Heart Failure Patients with Hyperkalaemia or at High Risk of Hyperkalaemia
IRAS ID
293211
Contact name
Manish Saxena
Contact email
Sponsor organisation
Vifor (International) Inc.
Duration of Study in the UK
4 years, 3 months, 31 days
Research summary
Heart failure patients also suffer from reduced kidney function and raised potassium (hyperkalemia) that makes their management with medication difficult as many beneficial medication increase serum potassium levels. This study aims to capture real world evidence about management of these patients.
The Cardiovascular and renal Treatment Implementation in Heart Failure (HF) Patients with Hyperkalaemia or at Risk of Hyperkalaemia is a phase IV, non-interventional, multinational, multi-centre study of assessment and treatment guideline recommendation in HF patient care with one data collection system. The study aims to understand real world clinical practice in HF patient management and RAASi treatment patterns in HF patients with hyperkalaemia with a 24-month enrolment period followed by a 24-month follow-up period.
Summary of results
This non-interventional cohort study evaluated adherence to treatment guideline recommendations in the care of patients with heart failure (HF) in a real-world setting. It also evaluated the effect of Patiromer treatment on renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation in patients with heart failure (HF).
A total of 2,558 patients were eligible for the study and included in the Full Analysis Set (FAS), with most patients being from Europe (67.5%, n=1,726) compared to North America (32.5%, n=832). Of the 234 patients (9.1%) treated with Patiromer and included in the Patiromer Analysis Set (PAS), most were from Europe (n=212) compared to North America (n=22). Demographic characteristics were similar across subgroups by region and by analysis set, with most patients ≥65 years (76.4%), male (68.5%) and White (93.6%).
Approximately one-third of patients had obesity (35.7%), and most patients reported >3 comorbidities at enrolment (76.8%). The most frequently reported comorbidities were hypertension, chronic kidney disease (CKD), coronary artery disease (CAD), atrial fibrillation, and Type II diabetes.
The median time since heart failure (HF) diagnosis was 40.5 months and was similar across North America and Europe.
The most prescribed renin-angiotensin-aldosterone system inhibitor (RAASi) throughout the study period were mineralocorticoid receptor antagonist (MRA) and angiotensin receptor-neprilysin inhibitor (ARNi). At enrolment, more patients in Europe received mineralocorticoid receptor antagonist (MRA) and angiotensin receptor-neprilysin inhibitor (ARNi) and fewer received angiotensin receptor blocker (ARB) compared to patients in North America. More patients with heart failure with reduced ejection fraction (HFrEF) at enrolment received mineralocorticoid receptor antagonist (MRA) and angiotensin receptor-neprilysin inhibitor (ARNi) compared to patients with heart failure with preserved ejection fraction (HFpEF). The most prescribed renin-angiotensin-aldosterone system inhibitor (RAASi) treatment combination throughout the study period was angiotensin receptor-neprilysin inhibitor (ARNi)+ mineralocorticoid receptor antagonist (MRA), which was received by approximately half of European patients and approximately one-fourth of North American patients at enrolment. Use of sodium-glucose co-transporter 2 inhibitor (SGLT2i) was much more common in Europe compared to North America.
Patients receiving angiotensin-converting enzyme inhibitor (ACEi) and mineralocorticoid receptor antagonist (MRA) achieved the highest mean percentage of target dose (up to 88% and 61%, respectively), although the percentage of target dose received was 50% or lower for patients receiving angiotensin receptor blocker (ARB) and angiotensin receptor-neprilysin inhibitor (ARNi). Most patients best achieved sub-optimal renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation throughout the study period and spent the majority of the study period in the sub-optimal renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation category. In general, renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation was better in Europe compared to North America and for patients with Heart failure with reduced ejection fraction (HFrEF) and Heart failure with mildly reduced ejection fraction (HFmrEF) compared to patients with heart failure with preserved ejection fraction (HFpEF).
Overall, most patients (92.5%) with hyperkalaemia (HK) episodes never had short-term renin-angiotensin-aldosterone system inhibitor (RAASi) modifications (within 3 days of episode start) in response to a hyperkalaemia (HK) episode. Modifications were more often observed among mineralocorticoid receptor antagonist (MRA) users compared to other renin-angiotensin-aldosterone system inhibitor (RAASi) and were more common if serum potassium (sK+) levels associated with the hyperkalaemia (HK) episode were higher. Among the small proportion of patients with down-titration in response to a hyperkalaemia (HK) episode, just one-fourth were up-titrated within 6 months of the hyperkalaemia (HK) episode. Less than 10% of patients received Patiromer during the study, more than half of whom discontinued Patiromer. The median duration of Patiromer treatment was 12.0 months. After initiation of Patiromer, slightly more Patiromer treated patients had optimal renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation compared to untreated patients (based on best optimisation category achieved and optimisation category the majority of the time), but this association was not statistically significant and the absolute differences between groups were small.
During the study period, approximately two-thirds of patients experienced at least one documented hyperkalaemia (HK) episode according to the physician’s definition, with more in Europe (74.0%) compared to North America (53.6%). Over 40% of patients having at least one hyperkalaemia (HK) episode had a recurrent hyperkalaemia (HK) episode. More patients with optimal renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation experienced a first hyperkalaemia (HK) episode or arrhythmia compared to patients with sub-optimal renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation, and fewer patients with optimal renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation died.
The most common reasons for not achieving the target dose of renin-angiotensin-aldosterone system inhibitor (RAASi) according to the physician were still being in up-titration and symptomatic hypotension. hyperkalaemia (HK) or high risk of hyperkalaemia (HK) as a reason for not achieving target dose was reported more often for mineralocorticoid receptor antagonist (MRA) compared to other renin-angiotensin-aldosterone system inhibitor (RAASi). Physicians reported that the most common reasons for treatment contraindication/intolerance were symptomatic hypotension for angiotensin receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNi), and angiotensin-converting enzyme inhibitor (ACEi), and hyperkalaemia (HK) for mineralocorticoid receptor antagonist (MRA). Serum potassium (sK+) decreased after Patiromer initiation from an average of 5.5 mEq/l (Milliequivalents per litre) at initiation to an average of 4.9 mEq/l (Milliequivalents per litre) six months later. The serum potassium (sK+) trend over time also shifted from an increasing to a decreasing trend after Patiromer initiation, particularly for patients with serum potassium (sK+) >5.5 mEq/l (Milliequivalents per litre) at the time of Patiromer initiation.
Overall, the results of this study support the existing consensus that renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation is poor for many patients with heart failure (HF). Renin-angiotensin-aldosterone system inhibitor (RAASi) modifications in response to a hyperkalaemia (HK) episode were less common than previously reported, and physician concern for hyperkalaemia (HK) was not the most common reason for discontinuation of angiotensin receptor blocker (ARB), angiotensin-converting enzyme inhibitor (ACEi), and angiotensin receptor-neprilysin inhibitor (ARNi). Patiromer initiation was associated with decreases in serum potassium (sK+). Patients treated with Patiromer had better renin-angiotensin-aldosterone system inhibitor (RAASi) optimisation compared to patients not treated with potassium binders, but this association did not reach statistical significance.REC name
West Midlands - Solihull Research Ethics Committee
REC reference
21/WM/0099
Date of REC Opinion
9 Jun 2021
REC opinion
Further Information Favourable Opinion