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1.
Rev Med Liege ; 76(2): 128-133, 2021 Feb.
Artículo en Francés | MEDLINE | ID: mdl-33543860

RESUMEN

Fixed combination atorvastatin-perindopril (Lipercosyl®) for substitution treatment of cardiovascular risk management Lipercosyl® is a fixed combination of atorvastatin and perindopril, a cholesterol-lowering and an antihypertensive agent, which allows blood pressure and cholesterol levels to be controlled in hypertensive patients with dyslipidemia : atorvastatin, an inhibitor of HMG-CoA reductase, and perindopril, an angiotensin converting enzyme inhibitor. Six presentations with different dosages of each molecule are available so the treatment can be individualized. Specific precautions of use to each medication must obviously be observed. The use of such a combination helps to ensure a good level of cholesterol while controlling blood pressure.


Asunto(s)
Enfermedades Cardiovasculares , Hipertensión , Amlodipino , Antihipertensivos/farmacología , Atorvastatina , Presión Sanguínea , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Combinación de Medicamentos , Humanos , Hipertensión/tratamiento farmacológico , Perindopril/farmacología , Factores de Riesgo
4.
Cardiovasc Ther ; 2021: 8886210, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33505518

RESUMEN

Direct oral anticoagulants (DOACs) are widely used for the prevention of stroke in nonvalvular atrial fibrillation, treatment of deep venous thrombosis and pulmonary embolism, and as prophylaxis after hip and knee surgery after approval by the Food and Drug Administration. In the last decade, DOACs were studied for various indications; this review is focused on rivaroxaban, a factor Xa inhibitor, which is used in an expanded evidence-based fashion for coronary artery disease, peripheral artery disease, heart failure, malignancy, and prophylaxis of deep venous thrombosis in acute medical illnesses.


Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Inhibidores del Factor Xa/administración & dosificación , Rivaroxabán/administración & dosificación , Enfermedades Cardiovasculares/diagnóstico , Toma de Decisiones Clínicas , Inhibidores del Factor Xa/efectos adversos , Hemorragia/inducido químicamente , Humanos , Selección de Paciente , Factores de Riesgo , Rivaroxabán/efectos adversos , Resultado del Tratamiento
5.
Mol Pharmacol ; 99(1): 29-38, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32321734

RESUMEN

Bone marrow-derived hematopoietic stem/progenitor cells are vasculogenic and play an important role in endothelial health and vascular homeostasis by participating in postnatal vasculogenesis. Progenitor cells are mobilized from bone marrow niches in response to remote ischemic injury and migrate to the areas of damage and stimulate revascularization largely by paracrine activation of angiogenic functions in the peri-ischemic vasculature. This innate vasoprotective mechanism is impaired in certain chronic clinical conditions, which leads to the development of cardiovascular complications. Members of the renin-angiotensin system-angiotensin-converting enzymes (ACEs) ACE and ACE2, angiotensin II (Ang II), Ang-(1-7), and receptors AT1 and Mas-are expressed in vasculogenic progenitor cells derived from humans and rodents. Ang-(1-7), generated by ACE2, is known to produce cardiovascular protective effects by acting on Mas receptor and is considered as a counter-regulatory mechanism to the detrimental effects of Ang II. Evidence has now been accumulating in support of the activation of the ACE2/Ang-(1-7)/Mas receptor pathway by pharmacologic or molecular maneuvers, which stimulates mobilization of progenitor cells from bone marrow, migration to areas of vascular damage, and revascularization of ischemic areas in pathologic conditions. This minireview summarizes recent studies that have enhanced our understanding of the physiology and pharmacology of vasoprotective axis in bone marrow-derived progenitor cells in health and disease. SIGNIFICANCE STATEMENT: Hematopoietic stem progenitor cells (HSPCs) stimulate revascularization of ischemic areas. However, the reparative potential is diminished in certain chronic clinical conditions, leading to the development of cardiovascular diseases. ACE2 and Mas receptor are key members of the alternative axis of the renin-angiotensin system and are expressed in HSPCs. Accumulating evidence points to activation of ACE2 or Mas receptor as a promising approach for restoring the reparative potential, thereby preventing the development of ischemic vascular diseases.


Asunto(s)
Angiotensina I/metabolismo , Enfermedades Cardiovasculares/metabolismo , Sistemas de Liberación de Medicamentos/tendencias , Células Madre Hematopoyéticas/metabolismo , Fragmentos de Péptidos/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animales , Fármacos Cardiovasculares/administración & dosificación , Fármacos Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Células Madre/efectos de los fármacos , Células Madre/metabolismo
6.
Complement Ther Clin Pract ; 42: 101291, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33321447

RESUMEN

BACKGROUND: The objective of this systematic review is to assess the relationship between chromium supplementation and inflammatory biomarkers levels (hs-CRP, TNF-α, IL-6) as risk factor for cardiovascular diseases. Recent studies raise questions regarding the potential of chromium supplementation to decrease the blood-levels of inflammatory markers, lowering cellular oxidative stress as markers of myocardial infarction; however, the results of the researches are inconclusive. METHODS: The following databases including PubMed, Scopus, Cochran Library and Embase databases were systematically searched until April 2020. Analysis was performed using random-effect model. RESULTS: The pooled findings for biomarkers of inflammation showed that chromium supplementation significantly reduced serum high-sensitivity C-reactive protein (hs-CRP) (WMD: -0.87 mg/dL, 95% CI: -1.49, -0.26), and tumor necrosis factor-alpha (TNF-α) (WMD: -0.97 pg/ml; 95% CI: -1.92, -0.01) and chromium insignificantly reduced interleukin -6 (IL-6) (WMD: -0.45 pg/ml, 95% CI: -1.18, 0.29). CONCLUSION: Overall, the results of this systematic review and meta-analysis imply that chromium supplementation may help to improve biomarkers of inflammation as markers of myocardial infarction.


Asunto(s)
Proteína C-Reactiva , Enfermedades Cardiovasculares , Cromo , Suplementos Dietéticos , Proteína C-Reactiva/análisis , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Cromo/uso terapéutico , Humanos , Inflamación/tratamiento farmacológico , Interleucina-6 , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Factor de Necrosis Tumoral alfa
7.
Acta Pharm ; 71(2): 175-184, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-33151168

RESUMEN

Recently, an outbreak of a fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. Possible interaction of SARS-CoV-2 with DPP4 peptidase may partly contribute to the viral pathogenesis. An integrative bioinformatics approach starting with mining the biomedical literature for high confidence DPP4-protein/gene associations followed by functional analysis using network analysis and pathway enrichment was adopted. The results indicate that the identified DPP4 networks are highly enriched in viral processes required for viral entry and infection, and as a result, we propose DPP4 as an important putative target for the treatment of COVID-19. Additionally, our protein-chemical interaction networks identified important interactions between DPP4 and sitagliptin. We conclude that sitagliptin may be beneficial for the treatment of COVID-19 disease, either as monotherapy or in combination with other therapies, especially for diabetic patients and patients with pre-existing cardiovascular conditions who are already at higher risk of COVID-19 mortality.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Dipeptidil Peptidasa 4/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Fosfato de Sitagliptina/farmacología , Fosfato de Sitagliptina/uso terapéutico , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/tratamiento farmacológico , Biología Computacional , Infecciones por Coronavirus/complicaciones , Cristalografía por Rayos X , Minería de Datos , Complicaciones de la Diabetes/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Reposicionamiento de Medicamentos , Redes Reguladoras de Genes , Humanos , Estructura Molecular , Pandemias , Neumonía Viral/complicaciones
8.
Medicine (Baltimore) ; 99(46): e22987, 2020 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-33181661

RESUMEN

To investigate the frequency and degree of azole antifungal agents that influence the anticoagulant activity of warfarin to reduce the potential bleeding risk and provide a reference for rational administration of warfarin in clinics.Patients with an abnormal international normalized ratio (INR; INR ≥ 4.5) and treated with warfarin plus azole antifungal agents were screened from February 2011 to July 2016, and their data were extracted.Thirty-two patients treated with warfarin plus azole antifungal agents were included. The INR of all the included patients increased by more than 20% of the INR of warfarin alone, and the warfarin sensitivity index showed an upward trend. The INRs of 21 patients treated with fluconazole (FLCZ) and warfarin was closely monitored for 1 week after the combination treatment, and the interaction between warfarin and the azole antifungal agents peaked on the seventh day. The INRs when warfarin was coadministered with azoles (Y) correlated significantly with those in the absence of azoles (X): FLCZ: Y = 1.2515X + 2.1538, R = 0.8128; and voriconazole Y = 2.4144 X + 2.6216, R2 = 0.7828.The combination of FLCZ and voriconazole will enhance the anticoagulant effect of warfarin. Therefore, it is recommended to detect the genotype of CYP2C9 in patients and evaluate the interaction between the 2 drugs to adjust the warfarin dose. It is also recommended to closely monitor INR within 1 week of the addition of azole antifungal agents.


Asunto(s)
Anticoagulantes/farmacología , Antifúngicos/farmacología , Azoles/farmacología , Warfarina/farmacología , Adulto , Anciano , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/genética , Citocromo P-450 CYP2C9/efectos de los fármacos , Citocromo P-450 CYP2C9/genética , Resistencia a Medicamentos/efectos de los fármacos , Quimioterapia Combinada , Femenino , Genotipo , Humanos , Relación Normalizada Internacional , Masculino , Errores Innatos del Metabolismo , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
9.
Kardiologiia ; 60(8): 130-140, 2020 Sep 17.
Artículo en Ruso | MEDLINE | ID: mdl-33164724

RESUMEN

The article discusses results of secondary analysis of the data obtained in the SPRINT study and published in recent years. Unresolved issues in the tactics of managing patients with arterial hypertension are discussed. One of such issues is choosing an optimum level of blood pressure (BP) for a subgroup of patients with certain characteristics, including elderly and senile patients, patients with chronic kidney disease, and patients with arterial hypertension who continue smoking. The article discusses calculation of a threshold of risk for complications of cardiovascular diseases, at which a maximum advantage of intensified regimens of antihypertensive therapy could be achieved. In addition, the article addresses approaches to selection of antihypertensive drugs in the current conditions. The authors discussed the role of candesartan in the treatment of arterial hypertension, a sartan most studied in a broad range of patients. The issue of a rapid increase in BP without a damage to target organs is addressed; evidence for the role of captopril in such clinical situation is provided.


Asunto(s)
Enfermedades Cardiovasculares , Hipertensión , Anciano , Antihipertensivos/uso terapéutico , Presión Sanguínea , Captopril/farmacología , Enfermedades Cardiovasculares/tratamiento farmacológico , Humanos , Hipertensión/tratamiento farmacológico
10.
Kardiologiia ; 60(7): 103-107, 2020 Aug 11.
Artículo en Ruso | MEDLINE | ID: mdl-33155948

RESUMEN

The article discusses issues of lipid-lowering therapy in elderly and senile patients. Major statements of actual clinical guidelines are provided. Issues of statin therapy in patients older than 65 and new data on statin safety in such patients are discussed in detail. The authors presented results of clinical studies 2019 on the use of ezetimibe in patients older than 75 as a part of primary and secondary prevention of cardiovascular diseases.


Asunto(s)
Anticolesterolemiantes , Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Anciano , Anticolesterolemiantes/efectos adversos , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Quimioterapia Combinada , Ezetimiba/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Lípidos , Prevención Secundaria
12.
Pharmacol Res Perspect ; 8(6): e00666, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33084232

RESUMEN

Conflicting evidence exists about the effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on COVID-19 clinical outcomes. We aimed to provide a comprehensive/updated evaluation of the effect of ACEIs/ARBs on COVID-19-related clinical outcomes, including exploration of interclass differences between ACEIs and ARBs, using a systematic review/meta-analysis approach conducted in Medline (OVID), Embase, Scopus, Cochrane library, and medRxiv from inception to 22 May 2020. English studies that evaluated the effect of ACEIs/ARBs among patients with COVID-19 were included. Studies' quality was appraised using the Newcastle-Ottawa Scale. Data were analyzed using the random-effects modeling stratified by exposure (ACEIs/ARBs, ACEIs, and ARBs). Heterogeneiity was assessed using I2 statistic. Several subgroup analyses were conducted to explore the impact of potential confounders. Overall, 27 studies were eligible. The pooled analyses showed nonsignificant associations between ACEIs/ARBs and death (OR:0.97, 95%CI:0.75,1.27), ICU admission (OR:1.09;95%CI:0.65,1.81), death/ICU admission (OR:0.67; 95%CI:0.52,0.86), risk of COVID-19 infection (OR:1.01; 95%CI:0.93,1.10), severe infection (OR:0.78; 95%CI:0.53,1.15), and hospitalization (OR:1.15; 95%CI:0.81,1.65). However, the subgroup analyses indicated significant association between ACEIs/ARBs and hospitalization among USA studies (OR:1.59; 95%CI:1.03,2.44), peer-reviewed (OR:1.93, 95%CI:1.38,2.71), good quality and studies which reported adjusted measure of effect (OR:1.30, 95%CI:1.10,1.50). Significant differences were found between ACEIs and ARBs with the latter being significantly associated with lower risk of acquiring COVID-19 infection (OR:0.24; 95%CI: 0.17,0.34). In conclusion, high-quality evidence exists for the effect of ACEIs/ARBs on some COVID-19 clinical outcomes. For the first time, we provided evidence, albeit of low quality, on interclass differences between ACEIs and ARBs for some of the reported clinical outcomes.


Asunto(s)
Antagonistas de Receptores de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Betacoronavirus/efectos de los fármacos , Enfermedades Cardiovasculares/tratamiento farmacológico , Infecciones por Coronavirus/mortalidad , Neumonía Viral/mortalidad , Adulto , Anciano , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enfermedades Cardiovasculares/complicaciones , Comorbilidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Femenino , Mortalidad Hospitalaria/tendencias , Hospitalización/estadística & datos numéricos , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Evaluación de Resultado en la Atención de Salud , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/virología , Medición de Riesgo , Ventiladores Mecánicos/efectos adversos , Ventiladores Mecánicos/estadística & datos numéricos
14.
Drug Discov Ther ; 14(5): 256-258, 2020 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-33116037

RESUMEN

In the ongoing coronavirus diseases-2019 (COVID-19) crisis that caused immense suffering and deaths, the choice of therapy for the prevention and life-saving conditions must be based on sound scientific evidence. Uncertainty and apprehension are exacerbated in people using angiotensin-converting enzyme (ACE) inhibitors to control their comorbidities such as hypertension and diabetes. These drugs are reported to result in unfavorable outcome as they tend to increase the levels of ACE2 which mediates the entry of SARS-CoV-2. Amiloride, a prototypic inhibitor of epithelial sodium channels (ENaC) can be an ideal candidate for COVID-19 patients, given its ACE reducing and cytosolic pH increasing effects. Moreover, its potassium-sparing and anti-epileptic activities make it a promising alternative or a combinatorial agent.


Asunto(s)
Amilorida/farmacología , Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Bloqueadores del Canal de Sodio Epitelial/farmacología , Neumonía Viral/tratamiento farmacológico , Mucosa Respiratoria/efectos de los fármacos , Internalización del Virus/efectos de los fármacos , Células A549 , Betacoronavirus/patogenicidad , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/enzimología , Infecciones por Coronavirus/enzimología , Infecciones por Coronavirus/virología , Regulación hacia Abajo , Interacciones Huésped-Patógeno , Humanos , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Neumonía Viral/enzimología , Neumonía Viral/virología , Receptores Virales/metabolismo , Mucosa Respiratoria/enzimología , Mucosa Respiratoria/virología
15.
Medicine (Baltimore) ; 99(40): e22572, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33019469

RESUMEN

RATIONALE: Atorvastatin is the most common drug used in therapy for cardiovascular diseases. The most common adverse side effects associated with statins are myopathy and hypertransaminasemia. Here, we report a rare case of gamma glutamyl transpeptidase (GGT) elevation induced by atorvastatin. PATIENT CONCERNS: A 47-year-old male was admitted to our hospital with dyslipidemia, he had been taking pitavastatin 2 mg/day for 2 months. The levels of total cholesterol (265.28 mg/dL) and low-density lipoprotein-cholesterol (LDL) (179.15 mg/dL) were also high. DIAGNOSIS: Blood lipid test showed mixed dyslipidemia. INTERVENTION: Atorvastatin 10 mg/day was given to the patient. OUTCOMES: The patient came back to our hospital for blood tests after 4 weeks. Although no symptoms were detectable, the patient's GGT level was markedly elevated (up to 6-fold over normal level) with less marked increases in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). The serum GGT level returned to normal within 6 weeks of cessation of atorvastatin. LESSONS: This is a case of GGT elevation without hyperbilirubinemia, hypertransaminasemiam, or serum creatine phosphokinase (CPK) abnormalities despite an atorvastatin regimen. This case highlights GGT elevation caused by atorvastatin, a rare but serious condition. Clinicians should be aware of these possible adverse effects and monitor liver function tests in patients on statin therapy.


Asunto(s)
Atorvastatina/efectos adversos , Dislipidemias/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Quinolinas/efectos adversos , gamma-Glutamiltransferasa/efectos de los fármacos , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Atorvastatina/administración & dosificación , Atorvastatina/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dislipidemias/diagnóstico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lípidos/sangre , Masculino , Persona de Mediana Edad , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Privación de Tratamiento , gamma-Glutamiltransferasa/sangre
16.
Int J Mol Sci ; 21(18)2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32899833

RESUMEN

Coronavirus disease 2019 (COVID-19) is usually more severe and associated with worst outcomes in individuals with pre-existing cardiovascular pathologies, including hypertension or atherothrombosis. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can differentially infect multiple tissues (i.e., lung, vessel, heart, liver) in different stages of disease, and in an age- and sex-dependent manner. In particular, cardiovascular (CV) cells (e.g., endothelial cells, cardiomyocytes) could be directly infected and indirectly disturbed by systemic alterations, leading to hyperinflammatory, apoptotic, thrombotic, and vasoconstrictive responses. Until now, hundreds of clinical trials are testing antivirals and immunomodulators to decrease SARS-CoV-2 infection or related systemic anomalies. However, new therapies targeting the CV system might reduce the severity and lethality of disease. In this line, activation of the non-canonical pathway of the renin-angiotensin-aldosterone system (RAAS) could improve CV homeostasis under COVID-19. In particular, treatments with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) may help to reduce hyperinflammation and viral propagation, while infusion of soluble ACE2 may trap plasma viral particles and increase cardioprotective Ang-(1-9) and Ang-(1-7) peptides. The association of specific ACE2 polymorphisms with increased susceptibility of infection and related CV pathologies suggests potential genetic therapies. Moreover, specific agonists of Ang-(1-7) receptor could counter-regulate the hypertensive, hyperinflammatory, and hypercoagulable responses. Interestingly, sex hormones could also regulate all these RAAS components. Therefore, while waiting for an efficient vaccine, we suggest further investigations on the non-canonical RAAS pathway to reduce cardiovascular damage and mortality in COVID-19 patients.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Cardiotónicos/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Sistema Renina-Angiotensina , Animales , Enfermedades Cardiovasculares/etiología , Infecciones por Coronavirus/complicaciones , Humanos , Pandemias , Neumonía Viral/complicaciones
17.
Adv Exp Med Biol ; 1274: 71-99, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32894508

RESUMEN

Bioactive lipid mediators resulting from the metabolism of polyunsaturated fatty acids (PUFA) are controlled by many pathways that regulate the levels of these mediators and maintain homeostasis to prevent disease. PUFA metabolism is driven primarily through three pathways. Two pathways, the cyclooxygenase (COX) and lipoxygenase (LO) enzymatic pathways, form metabolites that are mostly inflammatory, while the third route of metabolism results from the oxidation by the cytochrome P450 enzymes to form hydroxylated PUFA and epoxide metabolites. These epoxygenated fatty acids (EpFA) demonstrate largely anti-inflammatory and beneficial properties, in contrast to the other metabolites formed from the degradation of PUFA. Dysregulation of these systems often leads to chronic disease. Pharmaceutical targets of disease focus on preventing the formation of inflammatory metabolites from the COX and LO pathways, while maintaining the EpFA and increasing their concentration in the body is seen as beneficial to treating and preventing disease. The soluble epoxide hydrolase (sEH) is the major route of metabolism of EpFA. Inhibiting its activity increases concentrations of beneficial EpFA, and often disease states correlate to mutations in the sEH enzyme that increase its activity and decrease the concentrations of EpFA in the body. Recent approaches to increasing EpFA include synthetic mimics that replicate biological activity of EpFA while preventing their metabolism, while other approaches focus on developing small molecule inhibitors to the sEH. Increasing EpFA concentrations in the body has demonstrated multiple beneficial effects in treating many diseases, including inflammatory and painful conditions, cardiovascular disease, neurological and disease of the central nervous system. Demonstration of efficacy in so many disease states can be explained by the fundamental mechanism that EpFA have of maintaining healthy microvasculature and preventing mitochondrial and endoplasmic reticulum stress. While there are no FDA approved methods that target the sEH or other enzymes responsible for metabolizing EpFA, current clinical efforts to test for efficacy by increasing EpFA that include inhibiting the sEH or administration of EpFA mimics that block metabolism are in progress.


Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Estrés del Retículo Endoplásmico , Ácidos Grasos/metabolismo , Inflamación/tratamiento farmacológico , Mitocondrias/patología , Terapia Molecular Dirigida , Manejo del Dolor , Enfermedades Cardiovasculares/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Inflamación/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Dolor
18.
Cochrane Database Syst Rev ; 9: CD008294, 2020 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-32990945

RESUMEN

BACKGROUND: Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed for preventing or treating various chronic conditions associated with oxidative stress. This is an update of a previously published review. OBJECTIVES: To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders. SEARCH METHODS: We searched three databases and three trial registries; latest search: 30 September 2019. We contacted the manufacturers of pine bark extracts to identify additional studies and hand-searched bibliographies of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted data and assessed risk of bias. Where possible, we pooled data in meta-analyses. We used GRADE to evaluate the certainty of evidence. Primary outcomes were participant- and investigator-reported clinical outcomes directly related to each disorder and all-cause mortality. We also assessed adverse events and biomarkers of oxidative stress. MAIN RESULTS: This review included 27 RCTs (22 parallel and five cross-over designs; 1641 participants) evaluating pine bark extract supplements across 10 chronic disorders: asthma (two studies; 86 participants); attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), cardiovascular disease (CVD) and risk factors (seven studies; 338 participants), chronic venous insufficiency (CVI) (two studies; 60 participants), diabetes mellitus (DM) (six studies; 339 participants), erectile dysfunction (three studies; 277 participants), female sexual dysfunction (one study; 83 participants), osteoarthritis (three studies; 293 participants), osteopenia (one study; 44 participants) and traumatic brain injury (one study; 60 participants). Two studies exclusively recruited children; the remainder recruited adults. Trials lasted between four weeks and six months. Placebo was the control in 24 studies. Overall risk of bias was low for four, high for one and unclear for 22 studies. In adults with asthma, we do not know whether pine bark extract increases change in forced expiratory volume in one second (FEV1) % predicted/forced vital capacity (FVC) (mean difference (MD) 7.70, 95% confidence interval (CI) 3.19 to 12.21; one study; 44 participants; very low-certainty evidence), increases change in FEV1 % predicted (MD 7.00, 95% CI 0.10 to 13.90; one study; 44 participants; very low-certainty evidence), improves asthma symptoms (risk ratio (RR) 1.85, 95% CI 1.32 to 2.58; one study; 60 participants; very low-certainty evidence) or increases the number of people able to stop using albuterol inhalers (RR 6.00, 95% CI 1.97 to 18.25; one study; 60 participants; very low-certainty evidence). In children with ADHD, we do not know whether pine bark extract decreases inattention and hyperactivity assessed by parent- and teacher-rating scales (narrative synthesis; one study; 57 participants; very low-certainty evidence) or increases the change in visual-motoric coordination and concentration (MD 3.37, 95% CI 2.41 to 4.33; one study; 57 participants; very low-certainty evidence). In participants with CVD, we do not know whether pine bark extract decreases diastolic blood pressure (MD -3.00 mm Hg, 95% CI -4.51 to -1.49; one study; 61 participants; very low-certainty evidence); increases HDL cholesterol (MD 0.05 mmol/L, 95% CI -0.01 to 0.11; one study; 61 participants; very low-certainty evidence) or decreases LDL cholesterol (MD -0.03 mmol/L, 95% CI -0.05 to 0.00; one study; 61 participants; very low-certainty evidence). In participants with CVI, we do not know whether pine bark extract decreases pain scores (MD -0.59, 95% CI -1.02 to -0.16; one study; 40 participants; very low-certainty evidence), increases the disappearance of pain (RR 25.0, 95% CI 1.58 to 395.48; one study; 40 participants; very low-certainty evidence) or increases physician-judged treatment efficacy (RR 4.75, 95% CI 1.97 to 11.48; 1 study; 40 participants; very low-certainty evidence). In type 2 DM, we do not know whether pine bark extract leads to a greater reduction in fasting blood glucose (MD 1.0 mmol/L, 95% CI 0.91 to 1.09; one study; 48 participants;very low-certainty evidence) or decreases HbA1c (MD -0.90 %, 95% CI -1.78 to -0.02; 1 study; 48 participants; very low-certainty evidence). In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence). In men with erectile dysfunction, we do not know whether pine bark extract supplements increase International Index of Erectile Function-5 scores (not pooled; two studies; 147 participants; very low-certainty evidence). In women with sexual dysfunction, we do not know whether pine bark extract increases satisfaction as measured by the Female Sexual Function Index (MD 5.10, 95% CI 3.49 to 6.71; one study; 75 participants; very low-certainty evidence) or leads to a greater reduction of pain scores (MD 4.30, 95% CI 2.69 to 5.91; one study; 75 participants; very low-certainty evidence). In adults with osteoarthritis of the knee, we do not know whether pine bark extract decreases composite Western Ontario and McMaster Universities Osteoarthritis Index scores (MD -730.00, 95% CI -1011.95 to -448.05; one study; 37 participants; very low-certainty evidence) or the use of non-steroidal anti-inflammatory medication (MD -18.30, 95% CI -25.14 to -11.46; one study; 35 participants; very low-certainty evidence). We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence). In individuals with traumatic brain injury, we do not know whether pine bark extract decreases cognitive failure scores (MD -2.24, 95% CI -11.17 to 6.69; one study; 56 participants; very low-certainty evidence) or post-concussion symptoms (MD -0.76, 95% CI -5.39 to 3.87; one study; 56 participants; very low-certainty evidence). For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events. AUTHORS' CONCLUSIONS: Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.


Asunto(s)
Antioxidantes/uso terapéutico , Enfermedad Crónica/tratamiento farmacológico , Flavonoides/uso terapéutico , Corteza de la Planta/química , Extractos Vegetales/uso terapéutico , Adolescente , Adulto , Asma/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Sesgo , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Enfermedades Cardiovasculares/tratamiento farmacológico , Niño , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Disfunción Eréctil/tratamiento farmacológico , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Osteoartritis/tratamiento farmacológico , Pinus , Ensayos Clínicos Controlados Aleatorios como Asunto , Disfunciones Sexuales Psicológicas/tratamiento farmacológico , Insuficiencia Venosa/tratamiento farmacológico
19.
Am J Cardiol ; 134: 62-68, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32933754

RESUMEN

The reduction of cardiovascular events with icosapent ethyl-intervention (REDUCE-IT) trial showed in persons with prior cardiovascular disease (CVD) or diabetes mellitus (DM) that icosapent ethyl (IPE) reduced CVD events by 25%. We projected the preventable initial and total CVD events if REDUCE-IT trial eligibility criteria were applied to US adults. We identified US adults with available REDUCE-IT inclusion criteria from NHANES Surveys 1999-2016 and estimated primary (CVD death, nonfatal myocardial infarction, stroke, revascularization, or unstable angina) and secondary composite (CVD death, nonfatal MI or stroke) events using REDUCE-IT published event rates in the IPE and placebo groups, the difference being the number of preventable events. From 11,445 adults aged ≥45 years (representing 111.1 million [M]), a total of 319 persons (3.0 M) fit key REDUCE-IT eligibility criteria: triglycerides of 135 to 499 mg/dL, HbA1c <10%, blood pressure <200/100 mm Hg, and on a statin with LDL-C of 40 to 99 mg/dL. 63% had prior CVD and 37% had DM + ≥1 risk factor (primary prevention cohort). If these persons are given IPE for the REDUCE-IT median trial period of 4.9 years, we estimated preventing a total 349,817 (71,391/year) primary CVD outcomes of which 146,011 (29,798/year) were initial events. Most (24,151) preventable events were from the secondary prevention cohort. Using FDA eligibility criteria, an estimated 4.6 million persons would be eligible for IPE, with 60,544 preventable primary CVD outcomes annually from REDUCE-IT USA event rates. In conclusion, many CVD events in US adults with known CVD or DM and well-controlled LDL-C on statin therapy can be prevented with IPE.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus/tratamiento farmacológico , Ácido Eicosapentaenoico/análogos & derivados , Determinación de la Elegibilidad , Reguladores del Metabolismo de Lípidos/uso terapéutico , Revascularización Miocárdica/estadística & datos numéricos , Anciano , Angina Inestable/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/mortalidad , Ácido Eicosapentaenoico/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Encuestas Nutricionales , Prevención Primaria , Prevención Secundaria , Accidente Cerebrovascular/prevención & control
20.
Value Health ; 23(9): 1163-1170, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32940234

RESUMEN

OBJECTIVES: The cardiovascular outcomes challenge examined the predictive accuracy of 10 diabetes models in estimating hard outcomes in 2 recent cardiovascular outcomes trials (CVOTs) and whether recalibration can be used to improve replication. METHODS: Participating groups were asked to reproduce the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) and the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program. Calibration was performed and additional analyses assessed model ability to replicate absolute event rates, hazard ratios (HRs), and the generalizability of calibration across CVOTs within a drug class. RESULTS: Ten groups submitted results. Models underestimated treatment effects (ie, HRs) using uncalibrated models for both trials. Calibration to the placebo arm of EMPA-REG OUTCOME greatly improved the prediction of event rates in the placebo, but less so in the active comparator arm. Calibrating to both arms of EMPA-REG OUTCOME individually enabled replication of the observed outcomes. Using EMPA-REG OUTCOME-calibrated models to predict CANVAS Program outcomes was an improvement over uncalibrated models but failed to capture treatment effects adequately. Applying canagliflozin HRs directly provided the best fit. CONCLUSIONS: The Ninth Mount Hood Diabetes Challenge demonstrated that commonly used risk equations were generally unable to capture recent CVOT treatment effects but that calibration of the risk equations can improve predictive accuracy. Although calibration serves as a practical approach to improve predictive accuracy for CVOT outcomes, it does not extrapolate generally to other settings, time horizons, and comparators. New methods and/or new risk equations for capturing these CV benefits are needed.


Asunto(s)
Modelos Económicos , Evaluación de Resultado en la Atención de Salud/métodos , Compuestos de Bencidrilo/uso terapéutico , Calibración , Canagliflozina/uso terapéutico , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Humanos , Medición de Riesgo , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
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