Improvement quality of life with sacubitril/valsartan in heart failure
Health-Related Quality of Life Outcomes in PARADIGM-HF
Background
Health-related quality of life (HRQL) perceptions are predictive of future risk for morbidity and mortality [1,2]. Moreover, for many patients with HF improvement of HRQL is important.
Sacubitril/valsartan combines the neprilysine inhibitor, sacubitril, with the angiotensin receptor blocker (ARB), valsartan, and demonstrated superiority to enalapril on cardiovascular death, heart failure (HF) hospitalization and all-cause death in PARADIGM-HF [3] as well as the clinical progression of HF and risk of sudden cardiac death in patients that survived [4,5].
In this analysis of PARADIGM-HF, a comprehensive analysis of HRQL was performed to determine whether sacubitril/valsartan (LCZ696) was superior to enalapril on HRQL changes at 8 months (primary objective) and beyond 8 months (secondary objective) in HF patients with reduced ejection fraction (HFrEF). In PARADIGM-HF, all patients received enalapril for 2 weeks, followed by 4-6 weeks sacubitril/valsartan during run-in period. HRQL was based on ‘The Kansas City Cardiomyopathy Questionnaire’ (KCCQ) which contains 23 items that were self-administered at the time of randomization, after the run-in phase at 4, 8 and 12 months and annually thereafter. 3460 patients on LCZ696 completed the KCCQ scores at month 8 and 3421 patients on enalapril (together 90% of patients). This was 1087 and 1091 (29% of patients), respectively, at month 36.
Main results
- Patients that did not complete KCCQ were younger, had a lower BMI, less comorbid illness, were more often women or from the Asia Pacific region. Patient characteristics of patients who did complete KCCQ, were similar between treatment groups, although KCCQ clinical summary score (KCCQ-CS) and overall summary score (KCCQ-OS) were significantly higher in the sacubitril/valsartan group.
- At month 8, KCCQ-CS score differences from baseline were +0.64 for sacubitril/valsartan and -0.29 for enalapril (P=0.008), which was +1.13 and -0.14 (P<0.001), respectively, for KCCQ-OS.
- At month 8, improvements with sacubitril/valsartan were noted for all domains of KCCQ, except for symptom stability (-2.9, which was -4.3 with enalapril), and declines with enalapril were noted in most domains. Both scores were consistently higher with sacubitril/valsartan for almost every visit point through month 36.
- Also, the proportion of patients with clinically meaningful improvement in KCCQ-OS scores was significantly greater for sacubitril/valsartan compared to enalapril (35 vs 33%) and the proportion deterioration was less with sacubitril/valsartan (27 vs 31%).
- Higher BMI, NT-proBNP, NYHA functional class III/IV, female sex and history of myocardial infarction (MI), atrial fibrillation (AF) and diabetes mellitus were independently associated with deteriorations in both scores, whereas patients enrolled in Latin America and Asia were associated with improvement in both scores. After correction for these factors, randomization to sacubitril/valsartan remained a significant predictor for score improvement.
- Particularly patients that were hospitalized for HF decreased in scores at month 8. This decline was smaller in the sacubitril/valsartan group (difference 5.66 and 5.14 for OS and CS scores respectively).
Conclusion
In patients with HFrEF, sacubitril/valsartan was superior to enalapril in improving disease-specific HRQL in PARADIGM-HF, despite the relatively higher baseline KCCQ scores that were established after the run-in period that may have mitigated the magnitude of improvement. This difference between treatments was already noted after 4 months and persisted through month 36 and was particularly true for patients hospitalized for HF.
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