RESUMEN
Background: Recent trial data refute concerns about neurocognitive off-target effects of neprilysin inhibition with sacubitril and suggest benefit in patients with heart failure and ejection fraction >40%. We hypothesized that sacubitril/valsartan is associated with improved cognitive outcomes in patients with heart failure and reduced ejection fraction (HFrEF). Objectives: The purpose of this study was to compare 3-year cognitive outcomes in patients with HFrEF who receive sacubitril/valsartan vs angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Methods: Retrospective cohort study of: 1) 11,313 adults with HFrEF (International Classification of Diseases-10th Revision-Clinical Modification [ICD-10-CM] codes: I50.2 or I50.4) started on sacubitril/valsartan between 1/1/2015 and 12/31/2019; and 2) 11,313 propensity matched patients receiving ACEI/ARB during that time. Data were obtained from the TriNetX Research Network, encompassing 41 health care organizations in the United States. Primary endpoint was the composite of cognitive decline (ICD-10-CM: R41.8), dementia (ICD-10-CM: F01-F03), and Alzheimer's disease (ICD-10-CM: G30). Results: At 3 years, 858 patients on sacubitril/valsartan met the primary endpoint vs 1,209 on ACEI/ARB (3-year incidence: 10.7% vs 15.0%; HR: 0.69; 95% CI: 0.63-0.75; P < 0.001), with consistently lower rates of cognitive decline (9.5% vs 13.3%; HR: 0.69; 95% CI: 0.63-0.76; P < 0.001), dementia (3.4% vs 5.0%; HR: 0.65; 95% CI: 0.57-0.77; P < 0.001), and Alzheimer's disease (0.6% vs 1.3%; HR: 0.48; 95% CI: 0.35-0.66; P < 0.001) in the sacubitril/valsartan cohort. Results were consistent in matched sex and race subgroups. Three-year mortality was 22.0% on sacubitril/valsartan vs 24.6% on ACEI/ARB (HR: 0.89; 95% CI: 0.84-0.94; P < 0.001). Conclusions: Sacubitril/valsartan was associated with lower 3-year rates of neurocognitive disorders when compared to ACEI/ARBs in patients with HFrEF.
RESUMEN
Background: Disparities in treatment and outcomes of infective endocarditis (IE) between people who use drugs (PWUD) and non-PWUD have been reported, but long-term data on cardiovascular and cerebrovascular outcomes are limited. We aim to compare 5-year rates of mortality, cardiovascular and cerebrovascular events after IE between PWUD and non-PWUD. Methods: Using data from the TriNetX Research Network, we examined 5-year cumulative incidence of mortality, myocardial infarction, heart failure, atrial fibrillation/flutter, ventricular tachyarrhythmias, ischemic stroke, and intracranial hemorrhage in 7132 PWUD and 7132 propensity score-matched non-PWUD patients after a first episode of IE. We used the Kaplan−Meier estimate for incidence and Cox proportional hazards models to estimate relative risk. Results: Matched PWUD were 41 ± 12 years old; 52.2% men; 70.4% White, 19.8% Black, and 8.0% Hispanic. PWUD had higher mortality vs. non-PWUD after 1 year (1−3 year: 9.2% vs. 7.5%, p = 0.032; and 3−5-year: 7.3% vs. 5.1%, p = 0.020), which was largely driven by higher mortality among female patients. PWUD also had higher rates of myocardial infarction (10.0% vs. 7.0%, p < 0.001), heart failure (19.3% vs. 15.2%, p = 0.002), ischemic stroke (8.3% vs. 6.3%, p = 0.001), and intracranial hemorrhage (4.1% vs. 2.8%, p = 0.009) compared to non-PWUD. Among surgically treated PWUD, interventions on the tricuspid valve were more common; however, rates of all outcomes were comparable to non-PWUD. Conclusions: PWUD had higher 5-year incidence of cardiovascular and cerebrovascular events after IE compared to non-PWUD patients. Prospective investigation into the causes of these disparities and potential harm reduction efforts are needed.