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1.
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.

2.
Eur Heart J ; 41(2): 218-220, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31605128
3.
Diabetes Obes Metab ; 22(1): 16-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31407866

RESUMO

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have been shown to mitigate the risks of cardiovascular (CV) and renal complications in patients with type 2 diabetes (T2D) and CV risk factors or CV disease (CVD). In CV outcomes trials (CVOTs) of patients with T2D and established CVD or multiple CV risk factors, empagliflozin and canagliflozin were associated with significant reductions in the risks of major adverse CV events (MACE), hospitalization for heart failure (HF) and kidney disease progression. In the DECLARE-TIMI 58 study, in which the majority of patients did not have established CVD, dapagliflozin was associated with significant reductions in the composite end point of CV death or hospitalization for HF and was noninferior to placebo with regard to MACE; although patients had relatively good renal function, dapagliflozin also showed renal benefits similar to those seen with empagliflozin and canagliflozin. This article reviews the increased risk of CVD and renal disease in patients with T2D and discusses the potential mechanisms of the cardioprotective and renoprotective effects of SGLT-2i therapy. The observed improvements in CV and renal outcomes with SGLT-2is in CVOTs suggest a class effect in this patient population and have influenced treatment guidelines for the way add-on therapy to metformin is initiated in patients with T2D and high CV risk. The overall cardioprotective and renoprotective effects of SGLT-2is in patients with T2D and high CV risk are most likely attributable to multiple mechanisms, including cardiac, haemodynamic, metabolic, anti-inflammatory and renal effects.

4.
Prim Care Diabetes ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704161

RESUMO

Cardiovascular disease (CVD) is the primary cause of morbidity and mortality in patients with type 2 diabetes (T2D). This review examines the impact of cardiovascular outcome trials (CVOTs) on clinical practice. To date, all CVOTs have shown non-inferiority versus placebo (both added to standard of care) against a primary endpoint of 3- or 4-point major adverse cardiovascular event (MACE), confirming CV safety of these treatments. Additionally, some CVOTs have shown superiority to placebo against the same MACE endpoint, suggesting a cardioprotective action for these treatments. This is reflected in guideline updates, which primary care physicians should consider when personalizing treatments.

5.
J Diabetes ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31688975

RESUMO

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of drugs that were primarily developed for the treatment of type 2 diabetes mellitus. However, these agents have shown to provide additional beneficial effects. We will discuss three main topics regarding the use of SGLT2 inhibitors: noncardiovascular effects, cardiovascular benefits, and novel clinical indications. Multiple clinical trials and preliminary studies across varying disciplines have shown that these agents exhibit cardiorenal-protective benefits, retinoprotective benefits, and may aid in weight loss without causing marked hypoglycemia. Therefore, these agents represent an avenue in clinical practice to manage comorbid conditions in the hyperglycemic patient. Because of their multifaceted effects and robust action, SGLT2 inhibitors represent therapy options for providers that not only provide beneficial clinical results but also reduce total patient drug burden.

6.
Curr Cardiol Rev ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31657680

RESUMO

The incidence of symptomatic atrial thrombi involving the right atrium is considerably lower than the left atrium. Left atrial thrombus is a well-recognized and studied condition; however, there is a significant knowledge gap regarding the optimal management of right atrial thrombi. The relatively low prevalence and incidence of right atrial thrombi directly contribute to the lack of available clinical guidelines. In general, there are two main types of atrial thrombi: type A and type B. Type A thrombi are likely embolic in nature while type B thrombi are formed within the right atrium and are associated with conditions such as atrial fibrillation or right-sided valvular heart disease. We present a narrative review of a patient found to have a right atrial thrombus and a review of the pertinent literature investigating all 3 major treatments arms including embolectomy, thrombolysis, and anticoagulation.

7.
Diabetol Metab Syndr ; 11: 80, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572499

RESUMO

The recent American Diabetes Association and the European Association for the Study of Diabetes guideline mentioned glycaemia management in type 2 diabetes mellitus (T2DM) patients with cardiovascular diseases (CVDs); however, it did not cover the treatment approaches for patients with T2DM having a high risk of CVD, and treatment and screening approaches for CVDs in patients with concomitant T2DM. This consensus guideline undertakes the data obtained from all the cardiovascular outcome trials (CVOTs) to propose approaches for the T2DM management in presence of CV comorbidities. For patients at high risk of CVD, metformin is the drug of choice to manage the T2DM to achieve a patient specific HbA1c target. In case of established CVD, a combination of glucagon-like peptide-1 receptor agonist with proven CV benefits is recommended along with metformin, while for chronic kidney disease or heart failure, a sodium-glucose transporter proteins-2 inhibitor with proven benefit is advised. This document also summarises various screening and investigational approaches for the major CV events with their accuracy and specificity along with the treatment guidance to assist the healthcare professionals in selecting the best management strategies for every individual. Since lifestyle modification and management plays an important role in maintaining the effectiveness of the pharmacological therapies, authors of this consensus recommendation have also briefed on the patient-centric non-pharmacological management of T2DM and CVD.

8.
Cardiovasc Diabetol ; 18(1): 84, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234885

RESUMO

Heart disease continues to affect health outcomes globally, accounting for a quarter of all deaths in the United States. Despite the improvement in the development and implementation of guideline-directed medical therapy, the risk of adverse cardiac events remains substantially high. Historically, it has been debated whether omega-3 polyunsaturated fatty acids provide clinical benefit in cardiac disease. The recently published REDUCE-IT trial demonstrated a statistically significant absolute risk reduction of 4.8% in its primary endpoint (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina) with the use of icosapent ethyl, which is a highly purified eicosapentaenoic acid (EPA) ethyl ester. However, the mechanism of action of omega-3 fatty acids is not commonly discussed. Moreover, the use of EPA was not without risk, as the incidence of atrial fibrillation was increased along with a trend towards increased bleeding risk. Thus, our aim is to help explain the function of purified EPA ethyl ester, especially at the molecular level, which will ultimately lead to a better understanding of their clinically observable effects.

11.
Curr Diab Rep ; 18(12): 144, 2018 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-30406850

RESUMO

PURPOSE OF REVIEW: To evaluate the treatment of type 2 diabetes from a cardiologist's view. RECENT FINDINGS: A new era in the treatment of type 2 diabetes began for the cardiologist in 2015 with the publication of the EMPA-REG outcome trial finding a significant reduction in CV death with empagliflozin (oral sodium-glucose co-transporter-2 [SGLT2] inhibitor) in patients with type 2 diabetes at increased cardiovascular risk. Shortly thereafter, the injectable glucagon-like peptide agonists (GLP-1) liraglutide and semaglutide found a significant reduction in composite major cardiovascular events (CV death, non-fatal MI, or stroke). Both classes have demonstrated significant renal protection when added to usual care. Moreover, there may be some exciting new benefits of SGLT2 inhibitors for patients with heart failure. These research studies are underway. These two new classes of cardiovascular drugs for type 2 diabetes usher in a new era for the cardiologist who sees greater than 50% of patients with diabetes. The off-target effect of these agents is different as with all new cardiovascular compounds. While safety profiles in these populations are consistent with the known effects of these classes, new off-target effects have been seen with some agents in this class. Ongoing collaboration between cardiologists and other care providers remains important in the implementation of the evidence and care of patients with type 2 diabetes.


Assuntos
Cardiologistas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos como Assunto , Humanos , Fatores de Risco
13.
Vasc Health Risk Manag ; 14: 137-143, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29950852

RESUMO

Paraoxonase-1 (PON1) is a high-density lipoprotein-associated esterase and is speculated to play a role in several human diseases including diabetes mellitus and atherosclerosis. Low PON1 activity has been associated with increased risk of major cardiovascular events, therefore a variety of studies have been conducted to establish the cardioprotective properties and clinical relevance of PON1. The major aim of this review was to highlight the important studies and to subsequently assess if PON1 has clinical relevance. A review of the literature showed that there is currently insufficient data to suggest that PON1 has clinical relevance. It is our opinion that robust studies are required to clarify the clinical relevance of PON1.


Assuntos
Arildialquilfosfatase/genética , Doenças Cardiovasculares/genética , Polimorfismo Genético , Animais , Arildialquilfosfatase/química , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/enzimologia , Predisposição Genética para Doença , Humanos , Fenótipo , Conformação Proteica , Medição de Risco , Fatores de Risco , Relação Estrutura-Atividade
14.
Diabetes Ther ; 9(2): 551-564, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29397532

RESUMO

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycemia in patients with type 2 diabetes, but heart rate increases have been observed. METHODS: A pooled post hoc analysis of 11 randomized clinical trials (N = 4595) of 10-30 weeks' duration from the exenatide once-weekly (QW) development program evaluated heart rate with exenatide QW (intervention group) and exenatide twice daily (BID), liraglutide, and non-GLP-1RAs (insulin, metformin, pioglitazone, and sitagliptin) (comparison groups). The time course and size of heart rate changes from baseline and the relationship of heart rate change with baseline heart rate were studied. A multivariate analysis (9 studies; N = 3903) examined associations between patient characteristics or treatments and heart rate increases. RESULTS: Mean baseline heart rate ± standard deviation was 75.0 ± 8.5 beats per minute (bpm) with exenatide QW (n = 2096), 75.8 ± 8.7 bpm with exenatide BID (n = 606), 75.2 ± 8.9 bpm with liraglutide (n = 450), and 74.5 ± 8.6 bpm with non-GLP-1RAs (n = 1443). Least-squares mean ± standard error changes from baseline to final heart rate were + 2.7 ± 0.2, + 1.0 ± 0.3, and + 3.0 ± 0.4 bpm with exenatide QW, exenatide BID, and liraglutide, respectively, and - 0.8 ± 0.2 bpm with non-GLP-1RAs. The size and direction of heart rate changes in individual patients varied within each treatment group at all time points. At posttreatment follow-up, heart rate reverted to the baseline level after GLP-1RA discontinuation. Heart rate changes correlated negatively with baseline heart rate for all therapies (r = - 0.3 to - 0.4). Baseline heart rate was the strongest predictor of increased heart rate. CONCLUSIONS: Small increases in heart rate were associated with exenatide QW, exenatide BID, and liraglutide treatments but reverted to baseline after discontinuation. Increases were more likely in patients with a low baseline heart rate. The clinical relevance of these heart rate increases is unknown but will be clarified by several ongoing and recently completed cardiovascular outcome studies.

16.
Endocrinol Diabetes Metab ; 1(2): e00014, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30815550

RESUMO

Background: Left ventricular (LV) diastolic dysfunction commonly is observed in individuals with type 2 diabetes mellitus (T2DM). We employed transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMRI) to investigate the hypothesis that LV diastolic dysfunction in T2DM is associated with poor glycemic control. Methods: Forty subjects, 21 with normal glucose tolerance (NGT) and 19 with T2DM, were studied with CMRI and TTE to assess LV function. Early-to-late transmitral flow ratio (E/A) and deceleration time (DecT) were assessed with both modalities. Normalized (to body surface area) end-diastolic volume (EDV/BSA) and normalized peak LV filling rate (pLVFR/BSA) were assessed with CMRI. Early transmitral flow velocity to septal velocity (E/e') and isovolumetric relaxation time (IVRT) were measured using TTE. Dimensional parameters were normalized to body surface area (BSA). Results: CMRI measurements demonstrated impaired E/A (1.13 ± 0.34 vs 1.62 ± 0.42, P < .001), increased DecT (174 ± 46 ms vs 146 ± 15, P = .005), as well as lower EDV/BSA (63 ± 10 vs 72 ± 9 mL/m2, P < .01) and pLVFR/BSA (189 ± 46 vs 221 ± 48 mL s-1 m-2, P < .05) in T2DM subjects. TTE measurements revealed lower E/A (1.1 ± 0.4 vs 1.4 ± 0.2, P < .001) and E/e' (6.8 ± 1.5 vs 8.7 ± 2.0, P < .0001) with higher DecT (203 ± 22 ms vs 179 ± 18, P < .001) and IVRT (106 ± 14 ms vs 92 ± 10, P < .001) in T2DM. Multiple parameters of LV function: E/ACMRI (r = -.50, P = .001), E/ATTE (r = -.46, P < .005), pLVFR/BSA (r = -.35, P < .05), E/e' (r = -.46, P < .005), EDV/BSACMRI (r = -.51, P < .0001), EDV/BSATTE (r = -.42, P < .01) were negatively correlated with HbA1c. All but E/e' also were inversely correlated with fasting plasma glucose (FPG). Conclusions: Impaired LV diastolic function (DF) was found in T2DM subjects with both CMRI and TTE, and multiple LVDF parameters correlated negatively with HbA1c and FPG. These results indicate that impaired LVDF is inversely linked to glycemic control in T2DM patients.

17.
Endocrinol Diabetes Metab ; 1(4): e00034, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30815562

RESUMO

Objective: To determine the glucose-lowering mechanism of action and the effects of a quick-release bromocriptine-QR, a D2-dopamine agonist (Cycloset) on vascular function in patients with type 2 diabetes (T2D). Study design and methods: Fifteen poorly controlled T2D treated with metformin plus glucagon-like peptide-1 receptor agonists (GLP-1RA) were studied after 4 months of Cycloset, 3.2 mg/d. Subjects received a 5-hour double-tracer (iv 3-3H-glucose and oral 14C-glucose) mixed meal test (MMT) to quantitate rates of endogenous glucose production (EGP), oral glucose appearance (RaO) and disappearance (Rd) pre- and post-Cycloset. Vascular assessments included 2-day continuous BP monitoring, reactive hyperaemia index (RHI) and arterial stiffness (AS). Results: HbA1c decreased from 8.3 ± 0.3% to 7.7 ± 0.2% (P < 0.05), fasting plasma glucose did not change (143 ± 4 vs 147 ± 5) and mean plasma glucose during MTT decreased from 223 ± 3 to 210 ± 4 mg/dL (P < 0.05) after Cycloset. Basal EGP (2.2 ± 0.2 vs 2.1 ± 0.2 mg/kg min) was unchanged, but there was greater MMT suppression (1.1 ± 0.1 vs 0.7 ± 0.1, P < 0.05). After Cycloset, RaO declined from 2.0 ± 0.1 to 1.7 ± 0.2 mg/kg min and peripheral oral glucose appearance from 53.1 ± 3.2 to 44.4 ± 3.1 g (P < 0.01). There were no changes in plasma insulin or glucagon concentration. Systolic (134 ± 4 vs 126 ± 6), diastolic (78 ± 3 vs 73 ± 4), mean BP (97 ± 5 vs 90 ± 4) and pulse pressure (54 ± 2 vs 51 ± 2 mm Hg) were reduced; RHI increased from 1.4 ± 0.1 to 1.9 ± 0.3 au and AS decreased modestly (19.8 ± 4.1 to 16.2 ± 3.7 au, P = NS). Conclusions: Addition of Cycloset to GLP-1 RA improved vascular indices and postprandial hyperglycaemia in T2DM primarily by lowering oral glucose appearance, suggesting that hepatic glucose uptake was enhanced. Improved vascular indices may explain the reduction in cardiovascular events observed with Cycloset therapy in patients with T2DM.

18.
Diabetes Obes Metab ; 20(4): 786-799, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29171700

RESUMO

T2DM is a complex disease underlined by multiple pathogenic defects responsible for the development and progression of hyperglycaemia. Each of these factors can now be tackled in a more targeted manner thanks to glucose-lowering drugs that have been made available in the past 2 to 3 decades. Recognition of the multiplicity of the mechanisms underlying hyperglycaemia calls for treatments that address more than 1 of these mechanisms, with more emphasis placed on the earlier use of combination therapies. Although chronic hyperglycaemia contributes to and amplifies cardiovascular risk, several trials have failed to show a marked effect from intensive glycaemic control. During the past 10 years, the effect of specific glucose-lowering agents on cardiovascular risk has been explored with dedicated trials. Overall, the cardiovascular safety of the new glucose-lowering agents has been proven with some of the trials summarized in this review, showing significant reduction of cardiovascular risk. Against this background, pioglitazone, in addition to exerting a sustained glucose-lowering effect, also has ancillary metabolic actions of potential interest in addressing the cardiovascular risk of T2DM, such as preservation of beta-cell mass and function. As such, it seems a logical agent to combine with other oral anti-hyperglycaemic agents, including dipeptidyl peptidase-4 inhibitors (DPP4i). DPP4i, which may also have a potential to preserve beta-cell function, is available as a fixed-dose combination with pioglitazone, and could, potentially, attenuate some of the side effects of pioglitazone, particularly if a lower dose of the thiazolidinedione is used. This review critically discusses the potential for early combination of pioglitazone and DPP4i.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Pioglitazona/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Humanos , Avaliação de Resultados da Assistência ao Paciente , Melhoria de Qualidade , Resultado do Tratamento
20.
Diabetes Care ; 40(11): 1530-1536, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28847910

RESUMO

OBJECTIVE: To examine the effect of pioglitazone on myocardial insulin sensitivity and left ventricular (LV) function in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Twelve subjects with T2D and 12 with normal glucose tolerance received a euglycemic insulin clamp. Myocardial glucose uptake (MGU) and myocardial perfusion were measured with [18F]fluoro-2-deoxy-d-glucose and [15O]H2O positron emission tomography before and after 24 weeks of pioglitazone treatment. Myocardial function and transmitral early diastolic relation/atrial contraction (E/A) flow ratio were measured with magnetic resonance imaging. RESULTS: Pioglitazone reduced HbA1c by 0.9%; decreased systolic and diastolic blood pressure by 7 ± 2 and 7 ± 2 mmHg, respectively (P < 0.05); and increased whole-body insulin-stimulated glucose uptake by 71% (3.4 ± 1.3 to 5.8 ± 2.1 mg/kg · min; P < 0.01) in subjects with T2D. Pioglitazone enhanced MGU by 75% (0.24 ± 0.14 to 0.42 ± 0.13 µmol/min · g; P < 0.01) and myocardial perfusion by 16% (0.95 ± 0.16 to 1.10 ± 0.25 mL/min · g; P < 0.05). Measures of diastolic function, E/A ratio (1.04 ± 0.3 to 1.25 ± 0.4) and peak LV filling rate (349 ± 107 to 433 ± 99 mL/min), both increased (P < 0.01). End-systolic volume, end-diastolic volume, peak LV ejection rate, and cardiac output trended to increase (P not significant), whereas the ejection fraction (61 ± 6 to 66 ± 7%) and stroke volume increased significantly (71 ± 20 to 80 ± 20 L/min; both P < 0.05). CONCLUSIONS: Pioglitazone improves whole-body and myocardial insulin sensitivity, LV diastolic function, and systolic function in T2D. Improved myocardial insulin sensitivity and diastolic function are strongly correlated.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diástole/efeitos dos fármacos , Tiazolidinedionas/administração & dosagem , Função Ventricular Esquerda/efeitos dos fármacos , Adulto , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Colesterol/sangue , Feminino , Técnica Clamp de Glucose , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Pioglitazona , Volume Sistólico/efeitos dos fármacos , Sístole/efeitos dos fármacos , Triglicerídeos/sangue
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