Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure Registry to Predict Mortality and Morbidity in Chronic Heart Failure

Abstract

IMPORTANCEAccurate prediction of risk of death or hospitalizations in patients with heart failure (HF) may allow physicians to explore how more accurate decisions regarding appropriateness and timing of disease-modifying treatments, advanced therapies, or the need for end-of-life care can be made. OBJECTIVE To develop and validate a prognostic model for patients with HF. DESIGN, SETTING, AND PARTICIPANTS Multivariable analyses were performed in a stepwise fashion. Harrell C statistic was used to assess the discriminative ability. The derivation cohort was Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF) participants. The models were validated using the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure Trial (ATMOSPHERE) study and in the Swedish Heart Failure Registry (SwedeHF). A total of 8399 participants enrolled in PARADIGM-HF. Data were analyzed between June 2016 and June 2018.MAIN OUTCOMES AND MEASURES Cardiovascular death, all-cause mortality, and the composite of cardiovascular death or HF hospitalization at both 1 and 2 years. RESULTSComplete baseline clinical data were available for 8011 patients in PARADIGM-HF. The mean (SD) age of participants was 64 (11.4) years, 78.2% were men (n = 6567 of 8399), and 70.6% were New York Heart Association class II (n = 5919 of 8399). During a mean follow-up of 27 months, 1546 patients died, and 2031 had a cardiovascular death or HF hospitalization. The common variables were: male sex, race/ethnicity (black or Asian), region (Central Europe or Latin America), HF duration of more than 5 years, New York Heart Association class III/ IV, left ventricular ejection fraction, diabetes mellitus, β-blocker use at baseline, and allocation to sacubitril/valsartan. Ranked by χ 2 , N-terminal pro brain natriuretic peptide was the single most powerful independent predictor of each outcome. The C statistic at 1 and 2 years was 0.74 (95% CI, 0.71-0.76) and 0.71 (95% CI, 0.70-0.73) for the primary composite end point, 0.73 (95% CI, 0.71-0.75) and 0.71 (95% CI, 0.69-0.73) for cardiovascular death, and 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.67-0.74) for all-cause death, respectively. When validated in ATMOSPHERE, the C statistic at 1 and 2 years was 0.71 (95% CI, 0.69-0.72) and 0.70 (95% CI, 0.68-0.71) for the primary composite end point, 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.69-0.72) for cardiovascular death, and 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.68-0.72) for all-cause death, respectively. An online calculator was created to allow calculation of an individual's risk (http://www.predict-hf.com). CONCLUSIONS AND RELEVANCEPredictive models performed well and were developed and externally validated in large cohorts of geographically representative patients, comprehensively characterized with clinical and laboratory data including natriuretic peptides, who were receiving contemporary evidence-based treatment.

Mortality risk in dilated cardiomyopathy: the accuracy of heart failure prognostic models and dilated cardiomyopathy‐tailored prognostic model

“…[33][34][35] Intriguingly, EF was not found to be a significant independent prognostic factor, which is in line with the BCN Bio-HF study, but not with the latest prognostic analysis in HF, that is, PARADIGM-HF (Simpson et al reported a 7% decrease in mortality rate for every 5% increase of EF). 36 Similarly, BB usage was not a crucial factor (probably due to the high rate of use of this treatment in both survivors and non-survivors). As in the BCN Bio-HF, we did not find other HF therapies in the HF cohort to have any significant impact on outcomes in DCM (via multivariate analysis).…”

Liver function and prognosis, and influence of sacubitril/valsartan in patients with heart failure with reduced ejection fraction

“…9,14 CHARM also showed that total bilirubin, which was the strongest predictor among the liver function tests in the present study, and ALP were associated with an increased risk of the composite endpoint (CV death and HF hospitalization), consistent with our results. Importantly, Simpson et al 18 showed that total bilirubin was included as one of the important predictors in a comprehensive HFrEF prognostic model based on PARADIGM-HF.…”

Advanced heart failure

“…В силу мультиколлинеарности между факторами риска парциальное прогностическое значение каждого из них определить сложно и, следовательно, непросто отличить действительно значимые независимые предикторы от случайно выявляемых и не несущих дополнительной информации. Выходом из проблемной ситуации в клинической практике может быть применение многофакторных моделей прогноза, которые, по понятным причинам, имеют преимущества перед монофакторными [9,54,55].…”