Use of Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, and Risk of Dementia in Heart Failure

Chitnis, A.S.; Aparasu, Rajender R.; Chen, Hua; Kunik, Mark E.; Schulz, Paul E.; Johnson, Michael L.

doi:10.1177/1533317515618799

Cited by 8 publications

(11 citation statements)

References 45 publications

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“…Statin use in a month was defined as use when the days' supply for statins covered 15 or more days in that month. No statin use in a month was defined as no prescription for statin or days' supply covered less than 15 days in that month or any preceding months . Thus statin users could become nonusers of statin during follow‐up.…”

Section: Methodsmentioning

confidence: 99%

“…Two different approaches were used to examine the treatment effect of statin on mortality outcomes of HF. First, a time‐dependent Cox model was developed, and second, a marginal structural Cox model using inverse probability weights was constructed . Missing data for variables were handled by multiple imputation approach based on the pattern for all available observations.…”

Section: Methodsmentioning

confidence: 99%

“…To estimate the causal effect of statin versus no statin use on mortality outcomes in the presence of time‐varying confounding factors, marginal structural Cox model using inverse‐probability‐treatment‐weighting (IPTW) was employed. The IPTW approach creates a pseudopopulation of original subjects who account for themselves and for subjects with similar characteristics who received the alternate exposure . With time‐independent exposure, IPTW creates a pseudopopulation in which all subjects are considered conditionally exchangeable by achieving a balance between the treated and nontreated groups on the baseline covariates at the start of the study .…”

Section: Methodsmentioning

confidence: 99%

“…The IPTW approach creates a pseudopopulation of original subjects who account for themselves and for subjects with similar characteristics who received the alternate exposure . With time‐independent exposure, IPTW creates a pseudopopulation in which all subjects are considered conditionally exchangeable by achieving a balance between the treated and nontreated groups on the baseline covariates at the start of the study . Unlike time‐independent exposures, longitudinal studies with time‐varying treatment employ marginal structural models (MSMs) using the IPTW, which is updated at various time points to achieve balance between the groups not only at baseline but also at different time points.…”

Section: Methodsmentioning

confidence: 99%

“…Second, the censoring history weight to adjust for censoring by loss to follow‐up or end of study was calculated by an approach similar to the estimation of treatment history weights. The 2 calculated weights (treatment and censoring) were multiplied to create stabilized weights for each subject in each period . Finally, to estimate the treatment effect of statin on observed mortality outcomes, we constructed a weighted Cox regression model with robust standard errors estimation, treating each person‐period as an observation.…”

Section: Methodsmentioning

confidence: 99%

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Statin Treatment and Clinical Outcomes of Heart Failure Among Africans: An Inverse Probability Treatment Weighted Analysis

Bonsu

Owusu

Buabeng

et al. 2017

JAHA

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BackgroundRandomized control trials of statins have not demonstrated significant benefits in outcomes of heart failure (HF). However, randomized control trials may not always be generalizable. The aim was to determine whether statin and statin type–lipophilic or –hydrophilic improve long‐term outcomes in Africans with HF.Methods and ResultsThis was a retrospective longitudinal study of HF patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for HF (index admission) and followed up to time of all‐cause, cardiovascular, and HF mortality or end of study. Multivariable time‐dependent Cox model and inverse‐probability‐of‐treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person‐years of observation. Using the time‐dependent Cox model, the 5‐year adjusted hazard ratios with 95% CI for statin treatment on all‐cause, cardiovascular, and HF mortality were 0.68 (0.55–0.83), 0.67 (0.54–0.82), and 0.63 (0.51–0.79), respectively. Use of inverse‐probability‐of‐treatment weighting resulted in estimates of 0.79 (0.65–0.96), 0.77 (0.63–0.96), and 0.77 (0.61–0.95) for statin treatment on all‐cause, cardiovascular, and HF mortality, respectively, compared with no statin use.ConclusionsAmong Africans with HF, statin treatment was associated with significant reduction in mortality.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Statin Treatment and Clinical Outcomes of Heart Failure Among Africans: An Inverse Probability Treatment Weighted Analysis

Bonsu

Owusu

Buabeng

et al. 2017

JAHA

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Dementia‐related adverse events in PARADIGM‐HF and other trials in heart failure with reduced ejection fraction

Cannon

Shen

Jhund

et al. 2016

European J of Heart Fail

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AimsInhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM‐HF which compared the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid‐β peptides from the brain, there is a theoretical concern about the long‐term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia‐related adverse effects (AEs) in PARADIGM‐HF and placed these findings in the context of other recently conducted HFrEF trials.Methods and resultsIn PARADIGM‐HF, patients with symptomatic HFrEF were randomized to sacubitril/valsartan 97/103 mg b.i.d. or enalapril 10 mg b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the Medical Dictionary for Regulatory Activities (MedDRA), using Standardized MedDRA Queries (SMQs) with ‘broad’ and ‘narrow’ preferred terms related to dementia. In PARADIGM‐HF, 8399 patients aged 18–96 years were randomized and followed for a median of 2.25 years (up to 4.3 years). The narrow SMQ search identified 27 dementia‐related AEs: 15 (0.36%) on enalapril and 12 (0.29%) on sacubitril/valsartan [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.33–1.59]. The broad search identified 97 (2.30%) and 104 (2.48%) AEs (HR 1.01, 95% CI 0.75–1.37), respectively. The rates of dementia‐related AEs in both treatment groups in PARADIGM‐HF were similar to those in three other recent trials in HFrEF.ConclusionWe found no evidence that sacubitril/valsartan, compared with enalapril, increased dementia‐related AEs, although longer follow‐up may be necessary to detect such a signal and more sensitive tools are needed to detect lesser degrees of cognitive impairment. Further studies to address this question are warranted.

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Cognitive Dysfunction in Heart Failure: Pathophysiology and Implications for Patient Management

Huynh

Potter

2022

Curr Heart Fail Rep

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Use of Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, and Risk of Dementia in Heart Failure

Abstract: This study found no difference in risk of dementia among the current and former users of ACEI/ARB as compared with the nonusers in an already at-risk HF population.

Cited by 8 publications

References 45 publications

Statin Treatment and Clinical Outcomes of Heart Failure Among Africans: An Inverse Probability Treatment Weighted Analysis

Statin Treatment and Clinical Outcomes of Heart Failure Among Africans: An Inverse Probability Treatment Weighted Analysis

Dementia‐related adverse events in PARADIGM‐HF and other trials in heart failure with reduced ejection fraction

Cognitive Dysfunction in Heart Failure: Pathophysiology and Implications for Patient Management

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