Introduction and objectives: The win ratio (WR) approach is used to assess composite endpoints in a hierarchical fashion. This novel method offers an excellent opportunity to assess the robustness of the findings yielded by landmark trials, such as the DapaTAVI trial.
Methods: We applied the WR method to evaluate the treatment effect of dapagliflozin in hierarchically ordered clinical outcomes. Several combinations of outcomes were tested, including time-to-event, binary, and continuous endpoints.
Results: The WR of the original primary endpoint was 1.36 (95%CI, 1.03-1.78; P=.028), comparable to the reciprocal of the original hazard ratio (1/HR, 1.38; 95%CI, 1.06-1.81). The win difference was 4.84% (95%CI, 0.55-9.12), confirming consistent findings in terms of absolute effect. Alternative combinations of the primary outcome with different prioritization of its components yielded similar treatment effects and statistical significance. Ignoring a time-to-event approach and including recurrent events did not substantially affect treatment efficacy and its statistical significance. In contrast, the inclusion of the total length of stay for heart failure hospitalizations in the hierarchy shifted the point estimate toward the null. Including New York Heart Association functional class improved the precision of the estimate (WR=1.31; 95%CI, 1.09-1.56; P=.003). Conversely, including quality of life through Kansas City Cardiomyopathy Questionnaire comparisons shifted the overall estimate toward the null (WR=1.10; 95%CI, 0.94-1.30; P=.236).
Conclusions: The WR approach is a solid method to assess treatment efficacy. We observed consistent findings using this approach in the DapaTAVI trial.
Introduction and objectives: Chronic kidney disease is highly prevalent in patients with heart failure (HF), increases clinical complexity, and worsens prognosis. This study quantitatively assessed the impact of renal dysfunction severity, including dialysis, on clinical outcomes, resource utilization, and costs in patients with HF.
Methods: Retrospective cohort study in adult patients with 1 emergency department visit or hospitalization with an HF diagnosis in a university hospital in 2018. One-year clinical outcomes, resources, and costs were compared with the Clinical Outcomes, HEalthcare REsource utilizatioN, and relaTed costs (COHERENT) model according to estimated glomerular filtration rate (eGFR) ≥ 60, 30 to 59, 15 to 29, and <15 (including patients on dialysis) mL/min/1.73 m2.
Results: Of 3274 patients with HF (median age, 84 years; 56% women), 1453 (44.4%) had eGFR ≥ 60. Lower eGFR levels were associated with higher 1-year mortality (20.4% in eGFR ≥ 60 vs 45.4% in eGFR 15 to 29; P<.001 for trend), rehospitalization, and new emergency department visits. Patients with eGFR <15 had the highest readmission rate (50.8%; P<.001 for trend). Days out of hospital without dialysis decreased from 292 (80.0%) in eGFR ≥ 60 to 184 (50.3%) in eGFR <15. Median cost per patient journey increased from €3960 (Q1-Q3, €1750 to €8410) with eGFR ≥ 60 to €9590 (Q1-Q3, €4140 to €28 520; P<.001) with eGFR <15, driven mainly by hospitalizations (84%-90% of total, except for eGFR <15, 59.0%).
Conclusions: Renal dysfunction severity was associated with progressively worse clinical outcomes, increased health resource utilization, and higher costs in patients with HF. Strategies are needed to improve outcomes and reduce costs in patients with HF and severe chronic kidney disease.
Introduction and objectives: The prognostic role of platelet count dynamics in patients hospitalized with acute coronary syndromes (ACS) remains unclear. This study investigated the implications of platelet counts and their changes in ACS patients, using MATRIX trial data.
Methods: In-hospital relative changes in platelet count were analyzed continuously and were categorized into groups. Associations with 1-year risks of mortality and major or clinically relevant nonmajor bleeding were modelled using Cox regression.
Results: Among 7722 ACS patients, a platelet count drop >10% occurred in 47.5% of the patients and a platelet count increase >10% in 6.4%. Platelet count changes showed a U-shaped association with mortality and an L-shaped association with bleeding. Compared with the reference group (from 10% drop to 10% increase; rates: mortality 2.6%, bleeding 6.2%), platelet count drops were associated with an incremental mortality risk of approximately 30% (30%-50% drop: 9.5%; HR, 2.86; 95%CI, 1.93-4.23]; >50% drop: 21.4% HR, 3.86; 95%CI, 2.21-6.74) and a bleeding risk of approximately 10% (10%-30% drop: 8.2%, HR, 1.34; 95%CI, 1.11-1.61; 30%-50% drop: 13.8%, HR, 2.01; 95%CI, 1.48-2.72; >50% drop: 32.1%; HR, 4.59; 95%CI, 3.01-6.99). Platelet count increases were associated with an incremental mortality risk of approximately 10% (10%-30% increase: 5.8%; HR, 1.87; 95%CI, 1.18-2.98; 30%-50% increase: 8.5%; HR, 2.61; 95%CI, 1.05-6.44; >50% increase: 9.7%; HR, 3.51; 95%CI, 1.10-11.22) but not with bleeding.
Conclusion: In ACS patients, platelet count drops were associated with incremental risks of mortality and bleeding, whereas platelet count increases were associated with an incremental risk of mortality but not bleeding.
Introduction and objectives: Pulmonary embolism (PE) may debut as sudden death (SD) in young and middle-aged adults. This study aims to determine the epidemiological and clinicopathological characteristics involved in SD due to PE in this age group and the underlying risk factors.
Methods: Multicenter retrospective noncontrolled study based on forensic autopsies performed in individuals aged 12 to 49 years at 3 forensic pathology services in Spain (Valencia, Biscay, and Seville) over an 8-year period (2010-2017).
Results: A total of 1344 cardiac SD cases were recorded, of which 128 (9.5%) were due to PE (57% male, median age 42 years). The annual incidence was 0.56/100 000 inhabitants/y. The main risk factor was obesity (62%; 18.5% morbid obesity). The mean body mass index was 34.9±13.1. Psychiatric disorders were highly prevalent (44%). Immobilization (26%) and prior trauma (11%) were other relevant antecedents. Among women, 22% were receiving oral contraceptive therapy. Premortem symptoms were reported in 52% of cases, mainly dyspnea (56%). Although 22 individuals sought medical attention, only one was correctly diagnosed. Toxicological analysis was performed in 67% of cases, with positive results for psychotropic drugs (20%) and substances of abuse/alcohol (9%).
Conclusions: PE is a common cause of SD in individuals younger than 50 years and is frequently clinically underdiagnosed. This study provides evidence supporting a strong association with obesity and psychiatric disorders, which facilitate immobilization, venous stasis, and a prothrombotic state. Forensic studies of sudden death due to PE offer complementary data to clinical research, revealing risk factors that are underrepresented in clinical cohorts. .

