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This prospective ex vivo and in vitro pharmacodynamic (PD)/pharmacokinetic investigation was conducted in patients with diabetes mellitus with (n = 31) and without chronic kidney disease (n = 30). PD assessments included platelet reactivity index, maximum platelet aggregation, and P2Y12 reaction units. Ex vivo pharmacokinetic assessments included plasma levels of clopidogrel and its active metabolite. In vitro PD assessments were conducted on baseline samples incubated with escalating concentrations of clopidogrel and its active metabolite. Among patients with diabetes mellitus treated with clopidogrel, impaired renal function was associated with increased maximum platelet aggregation. This finding could be attributed partially to upregulation of the P2Y12 activity without differences in drug absorption or metabolism. (Impact of Chronic Kidney Disease on Clopidogrel Effects in Diabetes Mellitus; NCT03774394).
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There is a direct relationship between the duration and level of exposure to low density lipoprotein cholesterol (LDL-C) levels over one's lifespan and cardiovascular events. Early treatment to lower elevated LDL-C is crucial for better outcomes with multiple therapies currently available to reduce atherogenic lipoproteins. Statins remain the foundation of LDL-C lowering therapy as one of the most cost-effective drugs to reduce atherosclerotic events (ASCVD) and mortality. Nonetheless, LDL-driven goal attainment remains suboptimal globally, highlighting a considerable need for non-statin therapies to address residual risk related to statin intolerance, non-adherence, and inherited lipoprotein disorders. LDL-C lowering interventions beyond statins include ezetimibe, PCSK9 monoclonal antibodies, inclisiran and bempedoic acid with specific guideline recommendations as to when to consider each. For patients with homozygous familial hypercholesterolemia requiring more advanced therapy, lomitapide and evinacumab are available, providing mechanisms that are not LDL receptor dependent. Lipoprotein apheresis remains an effective option for clinical familial hypercholesterolemia as well as elevated lipoprotein (a). There are investigational therapies being explored to add to our current armamentarium including CETP inhibitors, a third-generation PCSK9 inhibitor (small recombinant fusion protein oral PCSK9 inhibitor) and gene editing which aims to directly restore or disrupt genes of interest at the DNA level. This article is a brief review of the pharmacotherapy options beyond statins for lowering LDL-C and their impact on ASCVD risk reduction. Our primary aim is to guide physicians on the role these therapies play in achieving appropriate LDL-C goals, with an algorithm of when to consider each based on efficacy, safety and outcomes.
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National guidelines define psoriasis as a risk enhancer for cardiovascular disease and recommend increased monitoring and more intense management of cardiovascular risk factors in these patients, who face an increased burden of cardiovascular disease morbidity and mortality. Screening for modifiable cardiovascular risk factors, including blood pressure, weight, cholesterol, glucose, and smoking, can be efficiently incorporated into routine dermatology clinical practice. Partnerships with primary care providers and preventive cardiologists are essential to improving management of cardiovascular risk in patients with psoriasis.
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Doenças Cardiovasculares , Fatores de Risco de Doenças Cardíacas , Guias de Prática Clínica como Assunto , Psoríase , Humanos , Psoríase/complicações , Psoríase/terapia , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco , Atenção Primária à SaúdeRESUMO
Triglycerides play a crucial role in the efficient storage of energy in the body. Mild and moderate hypertriglyceridemia (HTG) is a heterogeneous disorder with significant association with atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, ischemic stroke, and peripheral artery disease and represents an important component of the residual ASCVD risk in statin treated patients despite optimal low-density lipoprotein cholesterol reduction. Individuals with severe HTG (>1,000 mg/dL) rarely develop atherosclerosis but have an incremental incidence of acute pancreatitis with significant morbidity and mortality. HTG can occur from a combination of genetic (both mono and polygenic) and environmental factors including poor diet, low physical activity, obesity, medications, and diseases like insulin resistance and other endocrine pathologies. HTG represents a potential target for ASCVD risk and pancreatitis risk reduction, however data on ASCVD reduction by treating HTG is still lacking and HTG-associated acute pancreatitis occurs too rarely to effectively demonstrate treatment benefit. In this review, we address the key aspects of HTG pathophysiology and examine the mechanisms and background of current and emerging therapies in the management of HTG.
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BACKGROUND: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (ie, known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel. OBJECTIVES: The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score. METHODS: This was a prospective, randomized PD study of NOAC-treated patients undergoing PCI. Patients with an ABCD-GENE score ≥10 (n = 39), defined as having impaired clopidogrel response, were randomized to low-dose ticagrelor (n = 20; 60 mg twice a day) or clopidogrel (n = 19; 75 mg once a day). Patients with an ABCD-GENE score <10 (n = 42) were treated with clopidogrel (75 mg once a day; control cohort). PD assessments at baseline and 30 days post-randomization (trough and peak) were performed to assess P2Y12 signaling (VerifyNow P2Y12 reaction units [PRU], light transmittance aggregometry, and vasodilator-stimulated phosphoprotein); makers of thrombosis not specific to P2Y12 signaling were also assessed. The primary endpoint was PRU (trough levels) at 30 days. RESULTS: At 30 days, PRU levels were reduced with ticagrelor-based DAT compared with clopidogrel-based DAT at trough (23.0 [Q1-Q3: 3.0-46.0] vs 154.5 [Q1-Q3: 77.5-183.0]; P < 0.001) and peak (6.0 [Q1-Q3: 4.0-14.0] vs 129.0 [Q1-Q3: 66.0-171.0]; P < 0.001). Trough PRU levels in the control arm (104.0 [Q1-Q3: 35.0-167.0]) were higher than ticagrelor-based DAT (P = 0.005) and numerically lower than clopidogrel-based DAT (P = 0.234). Results were consistent by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. Markers measuring other pathways leading to thrombus formation were largely unaffected. CONCLUSIONS: In NOAC-treated patients undergoing PCI with an ABCD-GENE score ≥10, ticagrelor-based DAT using a 60-mg, twice-a-day regimen reduced platelet P2Y12 reactivity compared with clopidogrel-based DAT. (Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI [SWAP-AC-2]; NCT04483583).
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Anticoagulantes , Clopidogrel , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Antagonistas do Receptor Purinérgico P2Y , Receptores Purinérgicos P2Y12 , Ticagrelor , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Ticagrelor/efeitos adversos , Ticagrelor/administração & dosagem , Masculino , Estudos Prospectivos , Feminino , Idoso , Pessoa de Meia-Idade , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Administração Oral , Resultado do Tratamento , Fatores de Tempo , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Receptores Purinérgicos P2Y12/sangue , Testes de Função Plaquetária , Agregação Plaquetária/efeitos dos fármacos , Fosfoproteínas/sangue , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Proteínas dos Microfilamentos/sangue , Proteínas dos Microfilamentos/genética , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Moléculas de Adesão Celular/sangue , Resistência a Medicamentos , Terapia Antiplaquetária Dupla/efeitos adversosRESUMO
Since the 2019 National Lipid Association (NLA) Scientific Statement on Use of Lipoprotein(a) in Clinical Practice was issued, accumulating epidemiological data have clarified the relationship between lipoprotein(a) [Lp(a)] level and cardiovascular disease risk and risk reduction. Therefore, the NLA developed this focused update to guide clinicians in applying this emerging evidence in clinical practice. We now have sufficient evidence to support the recommendation to measure Lp(a) levels at least once in every adult for risk stratification. Individuals with Lp(a) levels <75â¯nmol/L (30â¯mg/dL) are considered low risk, individuals with Lp(a) levels ≥125â¯nmol/L (50â¯mg/dL) are considered high risk, and individuals with Lp(a) levels between 75 and 125â¯nmol/L (30-50â¯mg/dL) are at intermediate risk. Cascade screening of first-degree relatives of patients with elevated Lp(a) can identify additional individuals at risk who require intervention. Patients with elevated Lp(a) should receive early, more-intensive risk factor management, including lifestyle modification and lipid-lowering drug therapy in high-risk individuals, primarily to reduce low-density lipoprotein cholesterol (LDL-C) levels. The U.S. Food and Drug Administration approved an indication for lipoprotein apheresis (which reduces both Lp(a) and LDL-C) in high-risk patients with familial hypercholesterolemia and documented coronary or peripheral artery disease whose Lp(a) level remains ≥60â¯mg/dL [â¼150â¯nmol/L)] and LDL-Câ¯≥â¯100â¯mg/dL on maximally tolerated lipid-lowering therapy. Although Lp(a) is an established independent causal risk factor for cardiovascular disease, and despite the high prevalence of Lp(a) elevation (â¼1 of 5 individuals), measurement rates are low, warranting improved screening strategies for cardiovascular disease prevention.
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Doenças Cardiovasculares , Lipoproteína(a) , Humanos , Lipoproteína(a)/sangue , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/sangue , Fatores de Risco , Hipolipemiantes/uso terapêuticoRESUMO
BACKGROUND: To date, there are no data on switching to dual pathway inhibition (DPI) patients who have completed a guideline-recommended dual antiplatelet therapy (DAPT) regimen. OBJECTIVES: To assess the feasibility of switching from DAPT to DPI and to compare the pharmacodynamic (PD) profiles of these treatments. METHODS: This was a prospective, randomized, PD study conducted in 90 patients with chronic coronary syndrome (CCS) on DAPT with aspirin (81 mg/qd) plus a P2Y12 inhibitor (clopidogrel [75 mg/qd; n = 30], ticagrelor [90 mg/bid; n = 30], or prasugrel [10 mg/qd; n = 30]). Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81 mg/qd plus rivaroxaban 2.5 mg/bid). PD assessments included: VerifyNow P2Y12 reaction units; light transmittance aggregometry following stimuli with adenosine diphosphate (ADP), tissue factor (TF), and a combination of collagen, ADP, and TF (maximum platelet aggregation %); thrombin generation (TG). Assays were performed at baseline and 30 days postrandomization. RESULTS: Switching from DAPT to DPI occurred without major side effects. DAPT was associated with enhanced P2Y12 inhibition, while DPI with reduced TG. Platelet-mediated global thrombogenicity (primary endpoint) showed no differences between DAPT and DPI in the ticagrelor (14.5% [0.0-63.0] vs. 20.0% [0.0-70.0]; p = 0.477) and prasugrel (20.0% [0.0-66.0] vs. 4.0% [0.0-70.0]; p = 0.482), but not clopidogrel (27.0% [0.0-68.0] vs. 53.0% [0.0-81.0]; p = 0.011), cohorts. CONCLUSION: In patients with CCS, switching from different DAPT regimens to DPI was feasible, showing enhanced P2Y12 inhibition with DAPT and reduced TG with DPI, with no differences in platelet-mediated global thrombogenicity between DPI and ticagrelor- and prasugrel-, but not clopidogrel-, based DAPT. CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov Unique Identifier: NCT04006288.
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Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Aspirina/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/uso terapêutico , Rivaroxabana/efeitos adversos , Cloridrato de Prasugrel , Estudos Prospectivos , Adenosina/efeitos adversos , Clopidogrel/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/etiologia , Difosfato de Adenosina , Antagonistas do Receptor Purinérgico P2Y , Intervenção Coronária Percutânea/efeitos adversosRESUMO
BACKGROUND: A drug-drug interaction (DDI) may occur when transitioning from intravenous P2Y12 inhibition with cangrelor to oral P2Y12 inhibition with prasugrel. However, this has never been tested in patients undergoing percutaneous coronary intervention (PCI). OBJECTIVES: This study sought to rule out a DDI when cangrelor and prasugrel are concomitantly administered in PCI patients. METHODS: SWAP-6 (Switching Antiplatelet-6) was a prospective, randomized, 3-arm, open-label pharmacokinetic (PK) and pharmacodynamic (PD) study. Patients (N = 77) were randomized to 1) prasugrel only at the start of PCI, 2) cangrelor plus prasugrel concomitantly at the start of PCI, or 3) cangrelor at the start of PCI plus prasugrel at the end of infusion. Cangrelor infusion was maintained for 2 hours. PK/PD assessments were performed at baseline and 6 time points postrandomization. The primary endpoint was noninferiority in VerifyNow (Werfen) P2Y12 reaction units measured at 4 hours after randomization between cangrelor plus prasugrel concomitantly administered vs prasugrel only. PK assessments included plasma levels of the active metabolite of prasugrel. RESULTS: Compared with prasugrel, cangrelor further enhances P2Y12 inhibitory effects. At 4 hours postrandomization, P2Y12 reaction unit levels were significantly lower with prasugrel only compared to cangrelor and prasugrel concomitantly administered (least squares means difference = 130; 95% CI: 85-176), failing to meet the prespecified noninferiority margin. Findings were corroborated by multiple PD assays. The active metabolite of prasugrel levels were not affected by concomitant administration of cangrelor and were low at the end of cangrelor infusion. CONCLUSIONS: In patients undergoing PCI, concomitant administration of prasugrel with cangrelor leads to a marked increase in platelet reactivity after stopping cangrelor infusion, supporting the presence of a DDI. (Switching Antiplatelet Therapy-6 [SWAP-6]; NCT04668144).
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Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Cloridrato de Prasugrel , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y , Testes de Função Plaquetária , Resultado do TratamentoRESUMO
Background Dyslipidemia is an important risk factor for atherosclerotic cardiovascular disease, especially when disease presents at a young age. Despite national screening guidelines to perform a lipid profile test in children and young adults, many reproductive-age women have not undergone lipid screening. Our objective was to assess the feasibility of lipid screening during the first trimester of pregnancy as a strategy to increase lipid screening rates among women receiving prenatal care. Methods and Results A nonfasting lipid panel was incorporated into routine prenatal care among obstetricians at a single academic clinic. Educational materials and a clinical referral pathway were developed for patients with abnormal results. Over 6 months, 445 patients had a first prenatal care visit. Of the 358 patients who completed laboratory testing, 236 (66%) patients completed lipid testing. Overall, 59 (25%) patients had abnormal results. One patient with previously undiagnosed suspected familial hypercholesterolemia was identified. Barriers to ordering lipid tests included the burden of reviewing additional laboratory results and uncertainty about patient counseling. Conclusions Implementation of nonfasting lipid screening as part of routine prenatal care during the first trimester is feasible and may play a crucial role in timely diagnosis and management of lipid disorders in women of reproductive age. Future work should focus on optimizing health system workflow to minimize burden on clinical staff and facilitate follow-up with appropriate specialists.
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Dislipidemias , Cuidado Pré-Natal , Gravidez , Adulto Jovem , Criança , Humanos , Feminino , Primeiro Trimestre da Gravidez , Estudos de Viabilidade , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , LipídeosRESUMO
The prevalence of lipid-related risk for atherosclerotic cardiovascular disease surpasses half the population as individuals age, and thus generalists and primary care providers manage by far the bulk of treatment of lipid disorders. It should come as no surprise that many individuals who practice clinical lipidology, focusing on the care of patients with resistant or perplexing lipid disorders, come from a background of general or primary care medicine. Among 429 providers responding to a survey of National Lipid Association (NLA) members in 2010, 50% were internal medicine or family medicine practitioners, 32% cardiologists, 11% endocrinologists, and 7% with a variety of other specialty training. This JCL Roundtable brings together 3 NLA physician leaders who came from primary care. We discuss their career pathways, their blend of practice, teaching, research, and administration, and the settings in which they carry out the lipidology mission.
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Transtornos do Metabolismo dos Lipídeos , Humanos , LipídeosRESUMO
Hypertriglyceridemia (HTG) is a prevalent medical condition in patients with cardiometabolic risk factors and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), if left undiagnosed and undertreated. Current guidelines identify HTG as a risk-enhancing factor and, as a result, recommend clinical evaluation and lifestyle-based interventions to address potential secondary causes of elevated triglyceride (TG) levels. For individuals with mild to moderate HTG at risk of ASCVD, statin therapy alone or in combination with other lipid-lowering medications known to decrease ASCVD risk are guideline-endorsed. In addition to lifestyle modifications, patients with severe HTG at risk of acute pancreatitis may benefit from fibrates, mixed formulation omega-3 fatty acids, and niacin; however, evidence does not support their use for ASCVD risk reduction in the contemporary statin era. Novel therapeutics including those that target apoC-III and ANGPTL3 have shown to be safe, well-tolerated, and effective for lowering TG levels. Given the growing burden of cardiometabolic disease and risk factors, public health and health policy strategies are urgently needed to enhance access to effective pharmacotherapies, affordable and nutritious food options, and timely health care services.
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BACKGROUND: The impact of intense low-density lipoprotein cholesterol (LDL-C) reduction using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor on profiles of platelet reactivity has yet to be explored. AIMS: Our aim was to investigate the effects of the PCSK9 inhibitor, evolocumab, on platelet reactivity in patients with atherosclerotic cardiovascular disease (ASCVD) on clopidogrel treatment. METHODS: This was a prospective, randomised, double-blind, placebo-controlled pharmacodynamic study in patients with ASCVD on clopidogrel treatment and with LDL-C levels ≥70 mg/dL despite a maximally tolerated statin dose. Patients were stratified according to levels of platelet reactivity using VerifyNow P2Y12 reactivity units (PRU) into high platelet reactivity (HPR; PRU >208) or normal platelet reactivity (NPR; PRU >85 and ≤208). Each cohort was randomised to receive evolocumab 420 mg or placebo. The primary endpoint was the difference in PRU at 30 days. RESULTS: A total of 84 patients (HPR, n=37 [19 evolocumab vs 18 placebo]; NPR, n=47 [22 evolocumab vs 25 placebo]) were included. Evolocumab significantly reduced LDL-C compared to placebo at 14 (p<0.001) and 30 (p=0.001) days. At 14 days, PRU levels were significantly lower with evolocumab compared to placebo in the HPR (218.2±29.7 vs 246.6±35.2; p=0.017), but not in the NPR cohort (141.2±42.8 vs 148.2±41.7; p=0.578). At 30 days, there were no significant differences in PRU in the HPR (219.3±38.3 vs 240.9±51.8; p=0.161) or NPR (141.5±54.3 vs 158.6±40.8; p=0.229) cohorts. CONCLUSIONS: Compared to placebo, evolocumab in adjunct to statin therapy did not significantly reduce platelet reactivity at 30 days in ASCVD patients on clopidogrel treatment despite intense LDL-C reduction. ClinicalTrials.gov: NCT03096288.
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Anticolesterolemiantes , Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Pró-Proteína Convertase 9 , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , LDL-Colesterol/uso terapêutico , Clopidogrel/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Estudos Prospectivos , Aterosclerose/tratamento farmacológico , Resultado do Tratamento , Método Duplo-CegoRESUMO
BACKGROUND: There are no studies specifically designed to rule out a drug-drug interaction (DDI) when cangrelor is used among patients who have been pretreated with ticagrelor. OBJECTIVES: This study sought to rule out a DDI among cangrelor-treated patients who have been pretreated with ticagrelor. METHODS: In this prospective, randomized, double-blind, placebo-controlled, crossover, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (N = 20) were pretreated with a 180-mg ticagrelor loading dose and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours). Patients crossed over after 1 to 4 weeks of washout. PK analysis included ticagrelor plasma levels and its active metabolite. PD assessments included VerifyNow P2Y12 reaction units (PRU), light transmittance aggregometry, vasodilator-stimulated phosphoprotein, and Total Thrombus-Formation Analysis System. PK/PD assessments were performed at 7 time points. RESULTS: Compared with placebo, adding cangrelor to patients pretreated with ticagrelor resulted in a significant reduction in PRU at 30 minutes and 1 hour after starting infusion. At 2 hours after stopping cangrelor/placebo infusion, PRU were low and similar in both groups (16.9 vs 12.6; mean difference: 4.3; 95% CI: -28.6 to 37.3), meeting the noninferiority primary endpoint (predefined noninferiority margin 45 PRU). Consistent findings were shown with all PD assays. PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite. CONCLUSIONS: Compared with placebo, the use of cangrelor in patients pretreated with ticagrelor results in enhanced platelet inhibition with no differences in PK/PD profiles after discontinuation of drug infusion indicating the absence of a DDI. (PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment [SWAP-5]; NCT04634162).
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Doença da Artéria Coronariana , Humanos , Ticagrelor , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores da Agregação Plaquetária , Estudos Prospectivos , Resultado do Tratamento , Plaquetas/metabolismo , Antagonistas do Receptor Purinérgico P2Y , Testes de Função PlaquetáriaRESUMO
Despite the development of new therapies to lower cardiovascular disease (CVD) risk in recent decades, the trend of reductions in CVD mortality has reversed. New therapies are essential for the prevention of first and recurrent CVD. The importance of lowering low-density lipoprotein cholesterol (LDL-C) in the management and prevention of atherosclerotic CVD (ASCVD) is widely reflected in clinical treatment guidelines; however, most patients with established ASCVD do not achieve guideline-recommended LDL-C targets. Common reasons include adherence challenges, public disinformation, statin tolerability issues, access barriers, and clinical inertia. Inclisiran is a novel small interfering ribonucleic acid (RNA) that lowers circulating LDL-C by â¼50% when added to maximally tolerated statins by mimicking the body's natural pathway of RNA interference to specifically prevent proprotein convertase subtilisin/kexin type 9 synthesis. The unique dosing regimen of inclisiran (initial, at 3 months, and then every 6 months) has the advantage of allowing for healthcare provider administration during recommended routine visits for patients with established ASCVD, which can circumvent adherence issues associated with currently available LDL-C-lowering therapies. Inclisiran has demonstrated favorable tolerability and safety for up to 3 years, and evidence from longer-term use is accumulating in ongoing studies. This review discusses the novel mechanism of action of inclisiran and its potential position in the clinical armamentarium.
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Anticolesterolemiantes , Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , LDL-Colesterol , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , RNA Interferente Pequeno/uso terapêutico , Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Aterosclerose/tratamento farmacológico , Anticolesterolemiantes/uso terapêuticoRESUMO
BACKGROUND: Estimation of atherosclerotic cardiovascular disease (ASCVD) risk is a key step in cardiovascular disease (CVD) prevention, but it requires entering additional risk factor information into a computer. We developed a simplified ASCVD risk score that can be automatically calculated by the clinical laboratory when a fasting standard lipid panel is reported. METHODS: Equations for an estimated ASCVD (eASCVD) risk score were developed for 4 race/sex groups (non-Hispanic White/Black, men/women), using the following variables: total cholesterol, high-density lipoprotein cholesterol, triglycerides, and age. The eASCVD score was derived using regression analysis to yield similar risk estimates as the standard ASCVD risk equations for non-diabetic individuals not on lipid-lowering therapy in the National Health and Nutrition Examination Survey (NHANES) (n = 6027). RESULTS: At a cutpoint of 7.5%/10-year, the eASCVD risk score had an overall sensitivity of 69.1% and a specificity of 97.5% for identifying statin-eligible patients with at least intermediate risk based on the standard risk score. By using the sum of other risk factors present (systolic blood pressure >130 mmHg, blood pressure medication use, and cigarette use), the overall sensitivity of the eASCVD score improved to 93.7%, with a specificity of 92.3%. Furthermore, it showed 90% concordance with the standard risk score in predicting cardiovascular events in the Atherosclerosis Risk in Communities (ARIC) study (n = 14 742). CONCLUSIONS: Because the automated eASCVD risk score can be computed for all patients with a fasting standard lipid panel, it could be used as an adjunctive tool for the primary prevention of ASCVD and as a decision aid for statin therapy.
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Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/tratamento farmacológico , Colesterol , Técnicas de Apoio para a Decisão , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipoproteínas HDL , Masculino , Inquéritos Nutricionais , Medição de Risco , Fatores de Risco , TriglicerídeosRESUMO
AIMS: Dual pathway inhibition (DPI) by adding a vascular dose of rivaroxaban to a single antiplatelet agent has emerged as a promising antithrombotic strategy. However, in most studies the antiplatelet agent of choice used in adjunct to a vascular dose of rivaroxaban was aspirin, and data on a P2Y12 inhibitor and how this DPI regimen compares with standard dual antiplatelet therapy (DAPT) are limited. METHODS AND RESULTS: This investigation was a substudy analysis conducted in selected cohorts of patients with stable atherosclerotic disease enrolled from a larger prospective, open-label, parallel-group pharmacodynamic (PD) study. We analysed data from 40 patients treated with either clopidogrel- or ticagrelor-based DAPT first, and clopidogrel- or ticagrelor-based DPI thereafter. PD measures explored key pathways involved in thrombus formation and included markers of (1) P2Y12 reactivity, (2) platelet-mediated global thrombogenicity, (3) cyclooxygenase-1 activity, (4) thrombin receptor-activating peptide (TRAP)-induced platelet aggregation, (5) tissue factor (TF)-induced platelet aggregation, and (6) thrombin generation. Compared with DAPT, on a background of the same P2Y12 inhibitor (clopidogrel or ticagrelor), DPI was associated with reduced thrombin generation, increased markers of cyclooxygenase-1 activity and TRAP-induced platelet aggregation, and no differences in markers of P2Y12 signalling, platelet-mediated global thrombogenicity, and TF-induced platelet aggregation. In an analysis according to P2Y12 inhibitor type, ticagrelor reduced markers of platelet-mediated global thrombogenicity, P2Y12 signalling, and rates of high platelet reactivity compared with clopidogrel. CONCLUSION: Compared with DAPT with aspirin and a P2Y12 inhibitor, the use of a P2Y12 inhibitor in adjunct to a vascular dose of rivaroxaban as part of a DPI strategy is associated with similar effects on platelet-mediated global thrombogenicity but reduced thrombin generation. A DPI strategy with ticagrelor is associated with enhanced antithrombotic efficacy, the clinical implications of which warrant larger scale investigations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03718429.
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Aspirina , Inibidores da Agregação Plaquetária , Clopidogrel/efeitos adversos , Ciclo-Oxigenase 1 , Fibrinolíticos/uso terapêutico , Humanos , Peptídeos , Estudos Prospectivos , Receptores de Trombina , Rivaroxabana/efeitos adversos , Trombina , Tromboplastina , Ticagrelor/efeitos adversosRESUMO
Genetic lipid disorders, ranging from common dyslipidemias such as familial hypercholesterolemia, lipoprotein (a), and familial combined hyperlipidemia to rare disorders including familial chylomicronemia syndrome and inherited hypoalphalipoproteinemias (ie, Tangier and fish eye diseases), affect millions of individuals in the United States and tens of millions around the world and are often undiagnosed in the general population. Clinicians should take into consideration the potential of inherited lipid disorders or syndromes when severe derangements in lipid parameters are observed. Patients' combined genotype and phenotype should be evaluated in conjunction with a host of environmental factors impacting their risk of atherosclerotic cardiovascular disease.