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Artigo em Inglês | MEDLINE | ID: mdl-32053090


BACKGROUND: Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel class of non-statin lipid lowering therapy that reduce LDL-cholesterol by 50 - 60%. PCSK9 inhibitors decrease LDL-cholesterol by preventing intracellular degradation of LDL receptors; subsequently, a greater number of LDL-receptors are available on the cell surface to extract circulating LDL. OBJECTIVE: To describe the origins of PCSK9 inhibitors and their current use in clinical practice. METHODS: We performed a narrative review of the PCSK9 inhibitor class of drugs Results: Current data indicates that PCSK9 inhibitors effectively reduce LDL-cholesterol and are well tolerated and safe. PCSK9 inhibitors have also been shown to reduce cardiovascular event rates in patients with stable atherosclerotic cardiovascular disease and in patients with a recent (up to one year) acute coronary syndrome. Given the costs, chronicity of the treatment and the potential budget impact, PCSK9 inhibitors are often limited to patients with the highest absolute risk for major adverse cardiovascular events despite optimal treatment with high-intensity statin and ezetimibe. CONCLUSION: PCSK9 inhibitors have a favorable safety, efficacy and tolerability profile. Post-marketing safety surveillance and real-world studies are needed to further support the long-term safety profile of this class of medicine.

Medicine (Baltimore) ; 95(9): e2844, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26945366


Efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. We explored the association between efavirenz exposure and incident diabetes in a large Southern African cohort commencing NNRTI-based first-line ART. Our cohort included HIV-infected adults starting NNRTI-based ART in a private sector HIV disease management program from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. We included 56,298 patients with 113,297 patient-years of follow-up (PYFU) on first-line ART. The crude incidence of diabetes was 13.24 per 1000 PYFU. Treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval (CI): 1.10-1.46)) in a multivariate analysis adjusting for age, sex, body mass index, baseline CD4 count, viral load, NRTI backbone, and exposure to other diabetogenic medicines. Zidovudine and stavudine exposure were also associated with an increased risk of developing diabetes. We found that treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programs, and use of antiretrovirals with lower risk of metabolic complications should be encouraged.

Benzoxazinas/efeitos adversos , Infecções por HIV , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Benzoxazinas/administração & dosagem , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Incidência , Masculino , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Fatores de Risco , África do Sul/epidemiologia , Estatística como Assunto