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Effects of Baseline Left Ventricular Hypertrophy and Decreased Renal Function on Cardiovascular and Renal Outcomes in Patients with Fabry Disease Treated with Agalsidase Alfa: A Fabry Outcome Survey Study.
Clin Ther. 2020 12; 42(12):2321-2330.e0.CT

Abstract

PURPOSE

The initiation of enzyme-replacement therapy prior to the occurrence of substantial and irreversible organ damage in patients with Fabry disease is of critical importance. The Fabry Outcome Survey is an international disease registry of patients with a confirmed diagnosis of Fabry disease. In this study, data from the Fabry Outcome Survey were used for the assessment of the risks for cardiovascular and renal events in patients who received agalsidase alfa treatment.

METHODS

Eligible patients were males and females aged ≥18 years with Fabry disease treated with agalsidase alfa. Cardiovascular events included myocardial infarction, left ventricular hypertrophy (LVH), heart failure, arrhythmia, conduction abnormality, and cardiac surgery. Renal events included dialysis, transplantation, and renal failure. Kaplan-Meier curves and log-rank tests were used for comparing event-free probabilities and time to first cardiovascular or renal event, from agalsidase alfa initiation to a maximum of 120 months, in patients with LVH versus normal left ventricular mass index (LVMI; ≤50 g/m2.7 in males and ≤48 g/m2.7 in females) at treatment initiation (baseline), and in patients with a low estimated glomerular filtration rate (eGFR; <90 mL/min/1.73 m2) versus normal eGFR at baseline. Multivariate Cox regression analysis was used for examining the association between key study variables and the risks for cardiovascular and renal events.

FINDINGS

Among the 560 patients (269 males; 291 females) with available LVMI data, 306 (55%) had LVH and 254 (45%) had normal LVMI at baseline. The risk for a cardiovascular event was higher in the subgroup with LVH versus normal LVMI at baseline (hazard ratio [HR] = 1.57; 95% CI, 1.21-2.05; P < 0.001), but the risk for a renal event was similar between the 2 subgroups (HR = 1.90; 95% CI, 0.94-3.85; P = 0.074). Among the 1093 patients (551 males; 542 females) with available eGFR data, 433 (40%) had a low eGFR and 660 (60%) had a normal eGFR at baseline. The subgroup with a low eGFR at baseline had a significantly higher risk for a cardiovascular event (HR = 1.33; 95% CI, 1.04-1.70; P = 0.021) or a renal event (HR = 5.88; 95% CI, 2.73-12.68; P < 0.001) compared with patients with a normal eGFR at baseline.

IMPLICATIONS

In the present study, the presence of LVH and/or reduced renal function at agalsidase alfa initiation was associated with a significantly higher risk for a cardiovascular or renal event, indicating that cardiovascular and renal pathologies in Fabry disease may be inter-related. Early initiation of agalsidase alfa treatment prior to the onset of severe organ damage may improve outcomes. ClinicalTrials.gov identifier: NCT03289065.

Authors+Show Affiliations

Nephrology and Dialysis Unit, Belcolle Hospital, Viterbo, Italy. Electronic address: sandro.feriozzi@gmail.com.General University Hospital, Prague, Czech Republic.Royal Free London NHS Foundation Trust, University College London, London, United Kingdom.Takeda Pharmaceutical Company, Zurich, Switzerland.Takeda Pharmaceutical Company, Zurich, Switzerland.Royal Free London NHS Foundation Trust, University College London, London, United Kingdom.No affiliation info available

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33218740

Citation

Feriozzi, Sandro, et al. "Effects of Baseline Left Ventricular Hypertrophy and Decreased Renal Function On Cardiovascular and Renal Outcomes in Patients With Fabry Disease Treated With Agalsidase Alfa: a Fabry Outcome Survey Study." Clinical Therapeutics, vol. 42, no. 12, 2020, pp. 2321-2330.e0.
Feriozzi S, Linhart A, Ramaswami U, et al. Effects of Baseline Left Ventricular Hypertrophy and Decreased Renal Function on Cardiovascular and Renal Outcomes in Patients with Fabry Disease Treated with Agalsidase Alfa: A Fabry Outcome Survey Study. Clin Ther. 2020;42(12):2321-2330.e0.
Feriozzi, S., Linhart, A., Ramaswami, U., Kalampoki, V., Gurevich, A., & Hughes, D. (2020). Effects of Baseline Left Ventricular Hypertrophy and Decreased Renal Function on Cardiovascular and Renal Outcomes in Patients with Fabry Disease Treated with Agalsidase Alfa: A Fabry Outcome Survey Study. Clinical Therapeutics, 42(12), 2321-e0. https://doi.org/10.1016/j.clinthera.2020.10.007
Feriozzi S, et al. Effects of Baseline Left Ventricular Hypertrophy and Decreased Renal Function On Cardiovascular and Renal Outcomes in Patients With Fabry Disease Treated With Agalsidase Alfa: a Fabry Outcome Survey Study. Clin Ther. 2020;42(12):2321-2330.e0. PubMed PMID: 33218740.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of Baseline Left Ventricular Hypertrophy and Decreased Renal Function on Cardiovascular and Renal Outcomes in Patients with Fabry Disease Treated with Agalsidase Alfa: A Fabry Outcome Survey Study. AU - Feriozzi,Sandro, AU - Linhart,Ales, AU - Ramaswami,Uma, AU - Kalampoki,Vasiliki, AU - Gurevich,Andrey, AU - Hughes,Derralynn, AU - ,, Y1 - 2020/11/17/ PY - 2020/05/20/received PY - 2020/09/04/revised PY - 2020/10/19/accepted PY - 2020/11/22/pubmed PY - 2021/5/21/medline PY - 2020/11/21/entrez KW - Fabry Outcome Survey KW - Fabry disease KW - agalsidase alfa KW - enzyme-replacement therapy KW - estimated glomerular filtration rate KW - left ventricular hypertrophy SP - 2321 EP - 2330.e0 JF - Clinical therapeutics JO - Clin Ther VL - 42 IS - 12 N2 - PURPOSE: The initiation of enzyme-replacement therapy prior to the occurrence of substantial and irreversible organ damage in patients with Fabry disease is of critical importance. The Fabry Outcome Survey is an international disease registry of patients with a confirmed diagnosis of Fabry disease. In this study, data from the Fabry Outcome Survey were used for the assessment of the risks for cardiovascular and renal events in patients who received agalsidase alfa treatment. METHODS: Eligible patients were males and females aged ≥18 years with Fabry disease treated with agalsidase alfa. Cardiovascular events included myocardial infarction, left ventricular hypertrophy (LVH), heart failure, arrhythmia, conduction abnormality, and cardiac surgery. Renal events included dialysis, transplantation, and renal failure. Kaplan-Meier curves and log-rank tests were used for comparing event-free probabilities and time to first cardiovascular or renal event, from agalsidase alfa initiation to a maximum of 120 months, in patients with LVH versus normal left ventricular mass index (LVMI; ≤50 g/m2.7 in males and ≤48 g/m2.7 in females) at treatment initiation (baseline), and in patients with a low estimated glomerular filtration rate (eGFR; <90 mL/min/1.73 m2) versus normal eGFR at baseline. Multivariate Cox regression analysis was used for examining the association between key study variables and the risks for cardiovascular and renal events. FINDINGS: Among the 560 patients (269 males; 291 females) with available LVMI data, 306 (55%) had LVH and 254 (45%) had normal LVMI at baseline. The risk for a cardiovascular event was higher in the subgroup with LVH versus normal LVMI at baseline (hazard ratio [HR] = 1.57; 95% CI, 1.21-2.05; P < 0.001), but the risk for a renal event was similar between the 2 subgroups (HR = 1.90; 95% CI, 0.94-3.85; P = 0.074). Among the 1093 patients (551 males; 542 females) with available eGFR data, 433 (40%) had a low eGFR and 660 (60%) had a normal eGFR at baseline. The subgroup with a low eGFR at baseline had a significantly higher risk for a cardiovascular event (HR = 1.33; 95% CI, 1.04-1.70; P = 0.021) or a renal event (HR = 5.88; 95% CI, 2.73-12.68; P < 0.001) compared with patients with a normal eGFR at baseline. IMPLICATIONS: In the present study, the presence of LVH and/or reduced renal function at agalsidase alfa initiation was associated with a significantly higher risk for a cardiovascular or renal event, indicating that cardiovascular and renal pathologies in Fabry disease may be inter-related. Early initiation of agalsidase alfa treatment prior to the onset of severe organ damage may improve outcomes. ClinicalTrials.gov identifier: NCT03289065. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/33218740/Effects_of_Baseline_Left_Ventricular_Hypertrophy_and_Decreased_Renal_Function_on_Cardiovascular_and_Renal_Outcomes_in_Patients_with_Fabry_Disease_Treated_with_Agalsidase_Alfa:_A_Fabry_Outcome_Survey_Study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(20)30475-6 DB - PRIME DP - Unbound Medicine ER -