Initiation, titration, and discontinuation - utilization of heart failure medicines in England (EVOLUTION HF UK)

Abstract

Abstract Background Guidelines advise early initiation and optimisation of several guideline-recommended pharmacological therapies (GRPTs) for managing heart failure (HF) with reduced ejection fraction. Recent guidelines have expanded this list to include two new classes of agents: sodium-glucose cotransporter 2 (SGLT2) inhibitors and angiotensin receptor neprilysin inhibitor (ARNI). Auditing real-world GRPT use is critical in closing the evidence-practice gap. Purpose To generate insights into utilization patterns of novel and established GRPTs after a recent hospitalization for HF (hHF) in England using administrative healthcare records. Methods New users of GRPTs within 12 months of a hHF discharge were identified using linked national electronic health records (Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics mortality data) between January 2021 — May 2022. Time to initiation of dapagliflozin (the only SGLT2 inhibitor approved for HF in January 2021), sacubitril/valsartan, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were considered separately. Titration and discontinuation of the most frequently used drug for each pharmacological class was identified and analysed as representative of the entire class. Doses and discontinuation were assessed in the 12 months following initiation. If a new package isn't collected after the previous one ends, discontinuation is assumed until a new package is collected. Target dose was defined as ≥100% of the guideline-recommended dose. Results Overall, 16,090 new users of GRPTs were identified. Mean times from hHF to GRPT initiation were longer for novel agents (dapagliflozin or sacubitril/valsartan) than for established agents: 195 and 137 vs 48 to 73 days. Similarly, the cumulative percentage of patients initiating a GRPT within 100 days of hHF discharge were lower for novel agents (Figure 1). In the following 12 months, the average target dose achieved was higher for novel agents: 61.8% (dapagliflozin), 32.4% (sacubitril/valsartan), 8.5% (ACE inhibitor: ramipril), 5.9% (ARB: candesartan), 7.6% (beta-blocker: bisoprolol), and 6.6% (MRA: spironolactone). Corresponding discontinuation rates were 32.0%, 24.3%, 36.3%, 38.2%, 23.4%, and 50.1%, respectively (Figure 1 and 2). Conclusion In the UK, early initiation of novel GRPTs after recent hHF in routine clinical practice remains a challenge. For GRPTs requiring uptitration, few patients received the target dose in the 12 months after initiation, and many discontinued treatments. Conversely, dapagliflozin was associated with relatively higher rates of target dose achievement, perhaps because only a single fixed dose is recommended. Our data highlight the need for increased access to appropriate, timely and sustained HF therapeutic optimization.