Real-World Sacubitril/Valsartan Adoption and Post-Initiation Dose Reassessment and Titration in Heart Failure with Reduced Ejection Fraction: An Explanatory Sequential Mixed-Methods Study from Northern Saudi Arabia

Background/Objectives: Sacubitril/valsartan is a foundational therapy for heart failure with reduced ejection fraction (HFrEF), but real-world implementation extends beyond initiation to laboratory monitoring, follow-up, dose reassessment, and documentation of reasons for sub-target therapy. We evaluated this prescribing pathway in a regional Saudi heart-failure service. Methods: This explanatory sequential mixed-methods study included 296 adults with HFrEF (left ventricular ejection fraction ≤40%) treated at a public referral hospital in Al-Qurayyat, Saudi Arabia, during 2020–2025. Quantitative analyses described active prescription, calendar-period variation, selected physiological caution features among non-users, initiation pathways, early monitoring, follow-up, escalation attempts, and dose status. Fifteen clinicians participated in semi-structured interviews analyzed using the Framework Method and the updated Consolidated Framework for Implementation Research; reporting followed COREQ. Results: Sacubitril/valsartan was active in 239/296 patients (80.7%). Among 57 non-users, 41 (71.9%) had at least one selected physiological caution feature. In 221 treated patients with ≥6 months of follow-up, 75.1% completed renal-function/potassium reassessment within 14 days, 67.9% had follow-up within six weeks, and 60.6% had an escalation attempt within 90 days. Current target-dose use was 16.7%, and 21.7% had reached target at any point. Of 116 patients currently receiving 24/26 mg twice daily, 91 had never been documented above the lowest dose, and 25 had previously reached a higher dose. Reasons for current lowest-dose therapy were clinical/physiological in 49, health-system/access-related in 5, patient preference/adherence-related in 4, and undocumented in 58. Qualitative findings emphasized monitoring continuity, explicit role ownership, appointment access, dose availability, and communication. Conclusions: High ARNI uptake did not ensure complete post-initiation dose reassessment and titration. The clearest measurable gap was uncertainty around current lowest-dose therapy when no reason or reassessment plan was documented; this represents a documentation/reassessment gap rather than proof of inappropriate care. Clinical audit should distinguish target-dose attainment, clinically limited sub-target dosing, active titration, return to a lower dose after prior escalation, access-related barriers, patient preference/adherence, and unresolved sub-target therapy.