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1.
N Engl J Med ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32197277

RESUMO

BACKGROUND: Familial hypercholesterolemia is characterized by an elevated level of low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascular disease. Monoclonal antibodies directed against proprotein convertase subtilisin-kexin type 9 (PCSK9) have been shown to reduce LDL cholesterol levels by more than 50% but require administration every 2 to 4 weeks. In a phase 2 trial, a twice-yearly injection of inclisiran, a small interfering RNA, was shown to inhibit hepatic synthesis of PCSK9 in adults with heterozygous familial hypercholesterolemia. METHODS: In this phase 3, double-blind trial, we randomly assigned, in a 1:1 ratio, 482 adults who had heterozygous familial hypercholesterolemia to receive subcutaneous injections of inclisiran sodium (at a dose of 300 mg) or matching placebo on days 1, 90, 270, and 450. The two primary end points were the percent change from baseline in the LDL cholesterol level on day 510 and the time-adjusted percent change from baseline in the LDL cholesterol level between day 90 and day 540. RESULTS: The median age of the patients was 56 years, and 47% were men; the mean baseline level of LDL cholesterol was 153 mg per deciliter. At day 510, the percent change in the LDL cholesterol level was a reduction of 39.7% (95% confidence interval [CI], -43.7 to -35.7) in the inclisiran group and an increase of 8.2% (95% CI, 4.3 to 12.2) in the placebo group, for a between-group difference of -47.9 percentage points (95% CI, -53.5 to -42.3; P<0.001). The time-averaged percent change in the LDL cholesterol level between day 90 and day 540 was a reduction of 38.1% (95% CI, -41.1 to -35.1) in the inclisiran group and an increase of 6.2% (95% CI, 3.3 to 9.2) in the placebo group, for a between-group difference of -44.3 percentage points (95% CI, -48.5 to -40.1; P<0.001). There were robust reductions in LDL cholesterol levels in all genotypes of familial hypercholesterolemia. Adverse events and serious adverse events were similar in the two groups. CONCLUSIONS: Among adults with heterozygous familial hypercholesterolemia, those who received inclisiran had significantly lower levels of LDL cholesterol than those who received placebo, with an infrequent dosing regimen and an acceptable safety profile. (Funded by the Medicines Company; ORION-9 ClinicalTrials.gov number, NCT03397121.).

2.
N Engl J Med ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32187462

RESUMO

BACKGROUND: Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing. METHODS: We enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540. RESULTS: A total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean (±SD) LDL cholesterol levels at baseline were 104.7±38.3 mg per deciliter (2.71±0.99 mmol per liter) and 105.5±39.1 mg per deciliter (2.73±1.01 mmol per liter), respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval [CI], 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo). Adverse events were generally similar in the inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo (2.6% vs. 0.9% in the ORION-10 trial and 4.7% vs. 0.5% in the ORION-11 trial); such reactions were generally mild, and none were severe or persistent. CONCLUSIONS: Reductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo. (Funded by the Medicines Company; ORION-10 and ORION-11 ClinicalTrials.gov numbers, NCT03399370 and NCT03400800.).

3.
PLoS One ; 15(2): e0229098, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32084179

RESUMO

Non-communicable diseases, including cardiovascular diseases (CVDs), are increasing in African populations. High serum low density lipoprotein cholesterol (LDL-cholesterol) levels are a known risk factor for CVDs in European populations, but the link remains poorly understood among Africans. This study investigated the associations between serum LDL-cholesterol levels and selected variants in the low density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9) and low density lipoprotein receptor adaptor protein 1 (LDLRAP1) genes in some selected African populations. Nineteen SNPs were selected from publicly available African whole genome sequence data based on functional prediction and allele frequency. SNPs were genotyped in 1000 participants from the AWI-Gen, study selected from the extremes of LDL-cholesterol level distribution (500 with LDL-cholesterol>3.5 mmol/L and 500 with LDL-cholesterol<1.1 mmol/L). The minor alleles at five of the six associated SNPs were significantly associated (P<0.05) with lower LDL-cholesterol levels: LDLRAP1 rs12071264 (OR 0.56, 95% CI: 0.39-0.75, P = 2.73x10-4) and rs35910270 (OR 0.78, 95% CI: 0.64-0.94, P = 0.008); APOB rs6752026 (OR 0. 55, 95% CI: 0.41-0.72, P = 2.82x10-5); LDLR: rs72568855 (OR 0.47, 95% CI: 0.27-0.82, P = 0.008); and PCSK9 rs45613943 (OR = 0.72, 95% CI: 0.58-0.88, P = 0.001). The minor allele of the sixth variant was associated with higher LDL-cholesterol levels: APOB rs679899 (OR 1.41, 95% CI: 1.06-1.86, P = 0.016). A replication analysis in the Africa America Diabetes Mellitus (AADM) study found the PCSK9 variant to be significantly associated with low LDL-cholesterol levels (Beta = -0.10). Since Africans generally have lower LDL-cholesterol levels, these LDL-cholesterol associated variants may be involved in adaptation due to unique gene-environment interactions. In conclusion, using a limited number of potentially functional variants in four genes, we identified significant associations with lower LDL-cholesterol levels in sub-Saharan Africans.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32053090

RESUMO

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.

6.
J Am Coll Cardiol ; 75(6): 565-574, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32057369

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitor therapy is a treatment option for patients with familial hypercholesterolemia (FH) who are unable to reach low-density lipoprotein cholesterol (LDL-C) goals. OBJECTIVES: The aim of this study was to provide long-term safety and efficacy data for evolocumab in patients with homozygous FH (HoFH) and severe heterozygous FH (HeFH). METHODS: In this open-label, single-arm study, patients with HoFH or severe HeFH ≥12 years of age and on stable lipid-lowering therapy began subcutaneous evolocumab 420 mg monthly or 420 mg every 2 weeks if on lipoprotein apheresis. After 12 weeks, those not on apheresis could be up-titrated to 420 mg every 2 weeks. The primary endpoint was the incidence of treatment-emergent adverse events; secondary endpoints were changes in LDL-C and other lipids. RESULTS: In total, 300 patients (106 with HoFH, including 14 <18 years of age at enrollment) received evolocumab for a median of 4.1 years. Adverse events occurred in 89.3% of patients, the most common of which were nasopharyngitis, influenza, upper respiratory tract infection, and headache. Mean change in LDL-C from baseline to week 12 was -21.2% (-59.8 mg/dl) in patients with HoFH and -54.9% (-104.4 mg/dl) in those with severe HeFH and was sustained over time. Of 48 patients with HoFH who were up-titrated, mean change in LDL-C improved from -19.6% at week 12 to -29.7% after 12 weeks of 420 mg every 2 weeks. The adjudicated cardiovascular event rate was 2.7% per year. Of 61 patients receiving apheresis at enrollment, 16 discontinued apheresis. CONCLUSIONS: Evolocumab was well tolerated and effectively reduced plasma LDL-C levels in patients with HoFH and severe HeFH over a median of 4.1 years.

7.
Nat Rev Cardiol ; 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974482

RESUMO

Optimal care for familial hypercholesterolaemia (FH) requires patient-centred management, multidisciplinary teamwork, involvement of primary care practitioners, patient networks, support groups and high-quality clinical registries, implemented through models of care adapted to FH. Models of care - evidence-based and context-specific frameworks that aim to deliver the highest quality of care for patients and their families - allow the application of precision and multidisciplinary medicine to FH care and can serve as paradigms for the prevention of premature atherosclerotic cardiovascular disease in all at-risk patients and families worldwide. The exponential growth in the number of publications on diverse aspects of FH has provided new knowledge for developing essential elements of existing models of care. These elements include clinical diagnostic criteria and genetic testing; risk restratification strategies; LDL-cholesterol treatment targets; management protocols for children; care of women in pregnancy; use of pharmacotherapies, including ezetimibe and PCSK9 inhibitors; use of lipoprotein apheresis for severe FH; and addressing barriers to care. However, substantial gaps remain that need to be addressed by a broad research agenda, implementation strategies and global collaboration and advocacy, aimed at improving the uptake, cost-effectiveness and routine implementation of evidence-based standards. In this Review, we summarize the dramatic increase in knowledge that informs adaptive models of care, with an emphasis on articles published since 2014.

8.
Lancet Diabetes Endocrinol ; 8(1): 50-67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31582260

RESUMO

Genome sequencing and gene-based therapies appear poised to advance the management of rare lipoprotein disorders and associated dyslipidaemias. However, in practice, underdiagnosis and undertreatment of these disorders are common, in large part due to interindividual variability in the genetic causes and phenotypic presentation of these conditions. To address these challenges, the European Atherosclerosis Society formed a task force to provide practical clinical guidance focusing on patients with extreme concentrations (either low or high) of plasma low-density lipoprotein cholesterol, triglycerides, or high-density lipoprotein cholesterol. The task force also recognises the scarcity of quality information regarding the prevalence and outcomes of these conditions. Collaborative registries are needed to improve health policy for the care of patients with rare dyslipidaemias.

9.
Curr Atheroscler Rep ; 21(12): 48, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31741187

RESUMO

PURPOSE OF REVIEW: The goal of this review is to evaluate the role of inhibiting the synthesis of lipoproteins when there is no or little residual LDL-receptor function as in patients with homozygous familial hypercholesterolaemia. Lomitapide is administered orally once a day while mipomersen is given by subcutaneous injection once a week. Lomitapide inhibits microsomal triglyceride transfer protein while mipomersen is an antisense oligonucleotide directed against apoB100. RECENT FINDINGS: The pivotal registration trials for lomitapide and mipomersen were published in 2013 and 2010, respectively. More recently published data from extension trials and cohort studies provides additional information on long-term safety and efficacy. The mean LDL cholesterol reduction was 50% with lomitapide in its single-arm open-label registration trial. Mipomersen reduced LDL cholesterol by approximately 25% in its double-blind, placebo-controlled registration study. Both lomitapide and mipomersen therapy are associated with variable increases in hepatic fat content. The long-term safety of increased hepatic fat content in patients receiving these therapies is uncertain and requires further study. Both drugs may cause elevated transaminase in some patients, but no cases of severe liver injury have been reported. Lomitapide may also cause gastrointestinal discomfort and diarrhoea, especially if patients consume high-fat meals and patients are advised to follow a low-fat diet supplemented with essential fatty acids and fat-soluble vitamins. Mipomersen may cause injection-site and influenza-like reactions. The effect of lomitapide and mipomersen on cardiovascular outcomes has not been studied, but circumstantial evidence suggests that the LDL cholesterol lowering achieved with these two agents may reduce cardiovascular event rates.

11.
AIDS ; 33(13): 2049-2059, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577571

RESUMO

OBJECTIVE: Obesity is a major long-term concern in HIV-positive patients due to the pathogenic link between obesity and noncommunicable chronic diseases (NCDs). We aim to characterize changes in BMI over time on antiretroviral therapy (ART) and investigate the association between weight gain and survival in South Africa. DESIGN AND METHODS: A prospective cohort study among HIV-positive adults on first-line ART between April 2004 and 2015 in Johannesburg, South Africa. We used latent-class growth modelling (adjusted for age, sex and CD4 cell count) to identify groups of individuals with similar patterns of change in BMI over time. RESULTS: Eleven thousand, two hundred and sixty-three patients were included. The best fit model involved two linear and two quadratic trajectories. Thirty-five percent of patients were categorized into group one (mean BMI at ART initiation, 20.4 kg/m; mean BMI after 8 years of follow-up, 20.9 kg/m), 38% into group two (24.5-26.2 kg/m), 21% into group three (29.5-32.6 kg/m) and 6% into group four (36.5-40.0 kg/m). Over the 8 years of follow-up, 6% of our cohort went down in BMI standard category, while 45% went up. The largest increase occurred in the first 12 months on ART. In years 2 through 8, we saw a more gradual increase in BMI. CONCLUSION: The largest gain in BMI in HIV patients occurred in the first year on ART. During follow-up, over 50% of our population changed BMI categories putting them at an increased risk for NCDs. Consistent counselling on nutritional and lifestyle changes could help improve ART patients' long-term health outcomes.

12.
J Am Coll Cardiol ; 74(17): 2132-2146, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31648705

RESUMO

BACKGROUND: Evolocumab and other anti-PCSK9 antibodies reduced adverse cardiovascular outcomes in clinical trials of high-risk patients over <3 years median treatment duration. OBJECTIVES: The OSLER-1 trial (Open Label Study of Long Term Evaluation Against LDL-C Trial) evaluated longer-term effects of evolocumab during open-label hypercholesterolemia treatment for up to 5 years. METHODS: Patients randomized to standard of care (SOC) or evolocumab 420 mg monthly (evolocumab + SOC) for year 1. After year 1, patients could enter the all-evolocumab period and receive evolocumab + SOC for an additional 4 years. The authors analyzed the persistence of lipid effects and exposure-dependent safety focusing on yearly rates of adverse events (AEs) and anti-drug antibodies over 4.951 patient-years of observation. RESULTS: A total of 1,255 patients (safety analysis population) randomized into the year 1 SOC-controlled period and received ≥1 evolocumab dose (mean ± SD age 57 ± 12 years; 53% female). A total of 1,151 patients (efficacy analysis population) progressed to the all-evolocumab period (year 2 and beyond). Evolocumab + SOC persistently lowered mean ± SE low-density lipoprotein cholesterol (LDL-C) by 56% ± 0.6% (n = 1,071), 57% ± 0.8% (n = 1,001), 56% ± 0.8% (n = 943), and 56% ± 0.8% (n = 803) after approximately 2, 3, 4, and 5 years, respectively, from randomization. Mean baseline LDL-C decreased from 140 to 61 mg/dl on treatment. Yearly serious AE rates during evolocumab + SOC ranged from 6.9% to 7.9%, comparable to the 6.8% rate in SOC patients during year 1. Evolocumab discontinuation due to AEs occurred in 5.7% of patients. Two SOC and 2 evolocumab + SOC patients developed new, transient, binding anti-drug antibodies; no neutralizing antibodies were observed. CONCLUSIONS: The OSLER-1 trial demonstrated consistently excellent LDL-C-lowering efficacy, tolerance, and safety of evolocumab, with no neutralizing antibodies detected, throughout the longest-duration study of a PCSK9 inhibitor reported to date. (Open Label Study of Long Term Evaluation Against LDL-C Trial [OSLER-1]; NCT01439880).

13.
Cardiovasc J Afr ; 30(5): 279-284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31512717

RESUMO

BACKGROUND: Alirocumab reduces low-density lipoprotein cholesterol (LDL-C) levels by up to 61%. The ODYSSEY Open-Label Extension study investigated the effect of alirocumab in patients with heterozygous familial hypercholesterolaemia (HeFH) over 144 weeks. METHODS: Eligible patients with HeFH had completed an earlier double-blind, randomised, placebo-controlled parent study. Patients were initiated on 75 mg alirocumab Q2W subcutaneous (SC) unless baseline LDL-C was > 8.9 mmol/l, in which case they received 150 mg alirocumab Q2W. Dose titration to 150 mg Q2W was at the investigator's discretion. RESULTS: The study enrolled 167 patients and the parent study mean (± SD) baseline LDL-C level was 3.65 ± 1.9 mmol/l. Mean LDL-C level was reduced by 48.7% at week 144; mean on-treatment LDL-C was 2.30 ± 1.24 mmol/l. Eight patients reported injection-site reactions, with one treatment discontinuation. Treatment emergent anti-drug antibodies were identified in five patients but these did not affect the efficacy. CONCLUSIONS: Alirocumab effectively and safely reduced LDL-C in these patients.

14.
J Clin Lipidol ; 13(5): 735-743, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31377052

RESUMO

BACKGROUND: Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease. OBJECTIVE: We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status. METHODS: Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24-104 weeks' duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non-familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75 mg every 2 weeks (Q2W) to 150 mg Q2W at Week 12 if predefined risk-based LDL-C goals were not achieved at Week 8 (≥70 mg/dL in very high cardiovascular risk; ≥100 mg/dL in moderate or high cardiovascular risk). Two trials compared alirocumab 150 mg Q2W vs placebo. The efficacy and safety of alirocumab were assessed post hoc in subgroups stratified by age (<65, ≥65 to <75, ≥75 years) and baseline hypertension or smoking status. RESULTS: Alirocumab reduced LDL-C by 23.7% (75/150 mg vs ezetimibe + statin) to 65.4% (150 mg vs placebo + statin) from baseline to Week 24 vs control. Subgroup analyses confirmed no significant interactions in response to alirocumab between age group, hypertension, or smoking status. Overall rates of treatment-emergent adverse events were similar between alirocumab and control groups. CONCLUSIONS: In this pooled analysis from 10 trials, alirocumab led to substantial LDL-C reductions vs control in every age group and regardless of hypertension or smoking status. Alirocumab was well tolerated in all subgroups.

15.
16.
AIDS ; 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31274536

RESUMO

OBJECTIVE: Obesity is a major long-term concern in HIV-positive patients due to the pathogenic link between obesity and non-communicable chronic diseases (NCD). We aim to characterize changes in body mass index (BMI) over time on antiretroviral therapy (ART) and investigate the association between weight gain and survival in South Africa. DESIGN & METHODS: Prospective cohort study among HIV-positive adults on first-line ART between April 2004-2015 in Johannesburg, South Africa. We used latent-class growth modelling (adjusted for age, gender, and CD4 count) to identify groups of individuals with similar patterns of change in BMI over time. RESULTS: 11,263 patients were included. The best fit model involved two linear and two quadratic trajectories. 35% of patients categorized into group one (mean BMI at ART initiation, 20.4 kg/m; mean BMI after 8 years of follow-up, 20.9 kg/m), 38% into group two (24.5 to 26.2 kg/m), 21% into group three (29.5 to 32.6 kg/m)and 6% into group four (36.5 to 40.0 kg/m). Over the 8 years of follow-up, 6% of our cohort went down in BMI standard category, while 45% went up. The largest increase occurred in the first 12 months on ART. In years two through eight, we saw a more gradual increase in BMI. CONCLUSION: The largest gain in BMI in HIV patients occurred in the first year on ART. During follow-up, over 50% of our population changed BMI categories putting them at increased risk for NCDs. Consistent counselling on nutritional and lifestyle changes could help improve ART patients' long term health outcomes.

17.
BMC Cardiovasc Disord ; 19(1): 61, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30876390

RESUMO

BACKGROUND: With development of cholesterol management guidelines by the American College of Cardiology/American Heart Association (ACC/AHA), more individuals at risk of cardiovascular disease may be eligible for statin therapy. It is not known how this affects statin eligibility in the Africa and Middle East Region. METHODS: Data were used from the Africa Middle East Cardiovascular Epidemiological (ACE) study. The percentage of subjects eligible for statins per the ACC/AHA 2013 cholesterol guidelines and the 2002 National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP III) recommendations were compared. Analyses were carried out according to age, gender, community (urban/rural), and country income categories based on World Bank definitions. RESULTS: According to the ACC/AHA recommendations, 1695 out of 4378 subjects (39%; 95% confidence interval [CI], 37-40%) satisfied statin eligibility criteria vs. 1043/4378 (24%; 95% CI, 23-25%) per NCEP-ATP recommendations, representing a 63% increase in statin eligibility. Consistent increases in eligibility for statin therapy were seen according to the ACC/AHA vs. NCEP-ATP guidelines across sub-groups of age, gender, community, and country income. Notable increases for statin eligibility according to ACC/AHA vs. NCEP-ATP were seen, respectively, in subjects aged ≥65 years (86% vs. 39%), in males (46% vs. 25%), in low-income countries (28% vs. 14%), and rural communities (37% vs. 19%). CONCLUSION: An increase in statin eligibility was seen applying ACC/AHA cholesterol guidelines compared with previous NCEP-ATP recommendations in the Africa Middle East region. The economic consequences of these guideline recommendations will need further research. TRIAL REGISTRATION: The ACE trial is registered under NCT01243138 .


Assuntos
Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Dislipidemias/tratamento farmacológico , Definição da Elegibilidade/normas , Fidelidade a Diretrizes/normas , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Adolescente , Adulto , África/epidemiologia , Fatores Etários , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Renda , Masculino , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Medição de Risco , Fatores de Risco , Saúde da População Rural/normas , Fatores Sexuais , Resultado do Tratamento , Saúde da População Urbana/normas , Adulto Jovem
18.
Cardiovasc J Afr ; 30(1): 15-23, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30720848

RESUMO

The International Cholesterol Management Practice Study (ICLPS) South Africa investigated achievement of European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline low-density lipoprotein cholesterol (LDL-C) targets in real-world clinical practice. Demographic data, clinical characteristics, cardiovascular risk factors, lipid-modifying medications, lipid values and investigator's assessment of cardiovascular risk were recorded for 396 patients on stable lipid-modifying therapy. Most (98.7%) patients received statins; 25.1% of statin-treated patients were receiving high-intensity statins. Overall, 41.4% of patients achieved their LDL-C target; among 354 (89.4%) patients in whom cardiovascular disease risk, based on ESC Systematic Coronary Risk Estimation (SCORE) was calculated, achievement rate was 14.3% for moderate-risk (n = 7), 59.3% for high-risk (n = 123) and 32.3% for very high-risk patients (n = 223). Half of Asian (54.7%) and black African (53.2%) patients were at LDL-C target compared with 29.8% of European/Caucasian and 27.3% of 'other' patients. Improved guideline adherence and greater use of combination therapy may increase LDL-C goal achievement.


Assuntos
Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Padrões de Prática Médica , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Fidelidade a Diretrizes , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Medição de Risco , Fatores de Risco , África do Sul/epidemiologia , Fatores de Tempo , Resultado do Tratamento
19.
Cardiovasc Drugs Ther ; 33(1): 69-76, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30734207

RESUMO

PURPOSE: This post-hoc analysis examined whether age modified the efficacy and safety of alirocumab, a PCSK9 inhibitor, in patients with heterozygous familial hypercholesterolemia (HeFH), using pooled data from four 78-week placebo-controlled phase 3 trials (ODYSSEY FH I, FH II, LONG TERM, and HIGH FH). METHODS: Data from 1257 patients with HeFH on maximally tolerated statin ± other lipid-lowering therapies were analyzed by an alirocumab dose regimen and by age subgroups (18 to < 45, 45 to < 55, 55 to < 65, and ≥ 65 years). In the FH I and II trials, patients received 75 mg subcutaneously every 2 weeks (Q2W), with dose increase to 150 mg Q2W at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥ 70 mg/dl. In HIGH FH and LONG TERM, patients received 150 mg alirocumab Q2W. RESULTS: Baseline characteristics were similar between treatment groups across all age groups; the proportion of males decreased whereas the proportion of patients with coronary heart disease, diabetes, hypertension, and declining renal function increased with increasing age. Mean LDL-C reductions at week 24 were consistent across age groups (50.6-61.0% and 51.1-65.8% vs. placebo for the 75/150 and 150 mg alirocumab dose regimens, respectively; both non-significant interaction P-values). Treatment-emergent adverse events occurred in similar frequency in alirocumab- and placebo-treated patients regardless of age, except for injection-site reactions, which were more common in alirocumab than placebo but declined in frequency with age. CONCLUSIONS: Alirocumab treatment resulted in significant LDL-C reductions at weeks 12 and 24 and was generally well tolerated in patients with HeFH across all age groups studied.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Heterozigoto , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Adolescente , Adulto , Fatores Etários , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Ensaios Clínicos Fase III como Assunto , Regulação para Baixo , Feminino , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Pró-Proteína Convertase 9/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Atherosclerosis ; 277: 234-255, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30270054

RESUMO

BACKGROUND AND AIMS: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. METHODS: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. RESULTS: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited. CONCLUSIONS: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.


Assuntos
Anticolesterolemiantes/uso terapêutico , Remoção de Componentes Sanguíneos , Saúde Global , Hiperlipoproteinemia Tipo II/terapia , Cooperação Internacional , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Remoção de Componentes Sanguíneos/efeitos adversos , LDL-Colesterol/sangue , Comportamento Cooperativo , Predisposição Genética para Doença , Pesquisas sobre Serviços de Saúde , Acesso aos Serviços de Saúde , Disparidades em Assistência à Saúde , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Fenótipo , Valor Preditivo dos Testes , Prevalência , Fatores de Risco , Resultado do Tratamento
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