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1.
Ann Pharmacother ; 54(5): 470-477, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31735059

RESUMEN

Objective: To review the pharmacology, efficacy, and safety of the selective transthyretin inhibitor tafamidis for transthyretin amyloid cardiomyopathy (ATTR-CM). Data Sources: A PubMed (1966 to October 2019) and ClinicalTrials. gov search was conducted using the keywords tafamidis, Fx-1006A, Vyndaqel, and Vyndamax. Additional articles were identified from references. Study Selection and Data Extraction: We included English-language clinical studies evaluating the pharmacology, efficacy, or safety of tafamidis in humans for ATTR-CM. Data Synthesis: Tafamidis binds to the thyroxine-binding sites of the transthyretin tetramer and inhibits its dissociation into monomers, which is the rate-limiting step in the amyloidogenic process. Treatment with tafamidis was significantly associated with a significant reduction in mortality, lowered cardiovascular-related hospitalizations, less functional decline, and improved transthyretin stabilization compared with placebo. Additionally, tafamidis was found to have fewer adverse events, with no difference found compared with placebo. Relevance to Patient Care and Clinical Practice: Historically, symptomatic management for ATTR-CM was the only option, and the treatment of the underlying disease was limited to liver or heart transplantation. Tafamidis is the first medication approved for the treatment of ATTR-CM and the only medication that showed a reduction in all-cause mortality and cardiovascular-related hospitalizations in patients with amyloidosis. However, the role of tafamidis in patients with the New York Heart Association class III/IV heart failure or mutated transthyretin remains unclear. Conclusion: Tafamidis is an effective and safe oral medication for the treatment of the cardiomyopathy of transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.


Asunto(s)
Neuropatías Amiloides Familiares/tratamiento farmacológico , Benzoxazoles/uso terapéutico , Cardiomiopatías/tratamiento farmacológico , Prealbúmina/metabolismo , Administración Oral , Adulto , Neuropatías Amiloides Familiares/complicaciones , Neuropatías Amiloides Familiares/metabolismo , Neuropatías Amiloides Familiares/mortalidad , Benzoxazoles/administración & dosificación , Benzoxazoles/efectos adversos , Cardiomiopatías/complicaciones , Cardiomiopatías/metabolismo , Cardiomiopatías/mortalidad , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Unión Proteica
2.
Clin Drug Investig ; 40(9): 799-808, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32661914

RESUMEN

BACKGROUND AND OBJECTIVES: Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) reduces the incidence of thrombotic events but increases the risk of bleeding, which is associated with a substantial and durable risk of death and could offset the benefits of a reduction in thrombotic events. P2Y12 inhibitor monotherapy after short-term DAPT could be an option to reduce the risk of bleeding. We carried out a meta-analysis comparing P2Y12 inhibitor monotherapy after short-term DAPT with standard-term DAPT in patients undergoing PCI. METHODS: We searched the PubMed and EMBASE databases through 11 April 2020. Two authors independently reviewed and selected eligible trials. The DerSimonian-Laird method with the binary random-effects model was used to calculate the relative risk (RR) with 95% confidence interval (CI). RESULTS: Five trials involving 23,762 patients were included in the final analyses; four were open-label trials, while the TWILIGHT trial was double-blinded. Ticagrelor was used in three trials, and the other two trials included several P2Y12 inhibitors. P2Y12 inhibitor monotherapy after short-term DAPT significantly reduced the bleeding events, defined as Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding, by 39% (RR 0.61, 95% CI 0.38-0.99; p = 0.045) and 46% (RR 0.56, 95% CI 0.42-0.73; p < 0.001), respectively. A significant reduction in cardiovascular death was associated with P2Y12 inhibitor monotherapy after short-term DAPT (RR 0.75, 95% CI 0.58-0.98; p = 0.037; I2 = 0). No significant difference in all-cause mortality, myocardial infarction, stroke, or definite or probable stent thrombosis was observed. CONCLUSIONS: This meta-analysis showed a significantly lowered risk of major bleeding and similar benefits of P2Y12 inhibitor monotherapy after short-term DAPT compared with standard-term DAPT in patients undergoing PCI.


Asunto(s)
Terapia Antiplaquetaria Doble , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Hemorragia/inducido químicamente , Humanos , Infarto del Miocardio/prevención & control , Inhibidores de Agregación Plaquetaria/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación
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