RESUMO
ABSTRACT: The incretin hormone system is the target of multiple type 2 diabetes mellitus (T2DM) treatments because defects in this system play major roles in the pathogenesis of diabetes. Currently, the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended for patients with atherosclerotic cardiovascular (CV) disease and those at high risk for atherosclerotic CV disease. In addition to the favorable CV effects, GLP-1 RAs also provide robust lowering of hemoglobin A1c and weight. Although these factors make GLP-1 RAs attractive options for T2DM, the currently available agents have no effect on glucose-dependent insulinotropic polypeptide (GIP). Patients with T2DM are known to have GIP defect which is significant due to its profound insulinotropic effects. Tirzepatide is a novel incretin agent currently recently approved by the Food and Drug Administration for the treatment of T2DM. This first-in-class agent serves as a coagonist for both the GLP-1 and GIP receptors. In this review, we report on the pharmacologic mechanism of GLP-1, GIP, and coagonist effects on the cardiometabolic system. In addition, we review the glycemic lowering, weight loss effects, and other cardiometabolic outcomes of tirzepatide based on phase 2 and 3 data. The safety profile of tirzepatide is consistent across all phase 3 trials. The most common adverse effects are gastrointestinal symptoms, but they generally have a low risk for discontinuation. Overall, preliminary data suggest that tirzepatide is an efficacious and safe agent for the treatment of T2DM.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico , Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Incretinas/efeitos adversosRESUMO
PURPOSE OF REVIEW: Atherosclerotic cardiovascular disease (ASCVD) is caused by elevated levels of low-density lipoprotein cholesterol (LDL-C). Although statins significantly reduce ASCVD risk, there remains a high degree of residual risk in statin-treated patients. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition has emerged as a significant therapeutic target for further lowering of LDL-C when used in combination with statins. The purpose of this review is to provide an update on recent evidence supporting the use of PCSK9 inhibitors in patients with ASCVD. RECENT FINDINGS: Alirocumab and evolocumab were approved by the US Food and Drug Administration in 2015. Multiple phase II and III studies have demonstrated that these agents reduce LDL-C levels by up to 60% and are relatively safe, with the exception of injection site reactions. Additionally, two randomized controlled clinical trials have demonstrated that both alirocumab and evolocumab reduce ASCVD events when used in combination with statin therapy compared to statin alone. In light of this evidence, the 2018 Cholesterol Guideline incorporated PCSK9 inhibitors into the treatment algorithm for select secondary prevention patients unable to achieve an LDL-C below 70 mg/dL despite maximally tolerated statin plus ezetimibe. Although PCSK9 inhibitors provide substantial reductions in LDL-C levels and reduce ASCVD events in secondary prevention populations, the cost-effectiveness of alirocumab and evolocumab limit widespread use. Additional research is needed to explore the role of PCSK9 inhibitors in other populations, including primary prevention, patients unable to tolerate statins, and acute myocardial infarction.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Inibidores de PCSK9 , Idoso , Anticorpos Monoclonais Humanizados/farmacologia , Aterosclerose/prevenção & controle , LDL-Colesterol/sangue , Quimioterapia Combinada , Ezetimiba/uso terapêutico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prevenção Primária , Fatores de Risco , Prevenção SecundáriaRESUMO
BACKGROUND AND PURPOSE: Effective communication skills are essential for all pharmacists, regardless of practice setting. An implicit need in pharmacy education is to emphasize direct application of these skills to future healthcare practice prior to experiential rotations. The aim of this article is to describe how we revised a required first professional year (P1) doctor of pharmacy course to achieve two main goals: 1) improve the course relevance by connecting content to real-world skills; and 2) qualify all pharmacy students at our institution as certified National Diabetes Prevention Program (DPP) lifestyle coaches upon course completion. EDUCATIONAL ACTIVITY AND SETTING: Lifestyle coach training approved by the Centers for Disease Control and Prevention (CDC) was integrated into a P1 communications course consisting of 14 modules that include: review of diabetes pathophysiology, group facilitation skills, social determinants of health, food tracking, action planning, participant retention and program administration. This content serves as a direct application of pre-existing course objectives related to knowledge (evidence-based theory) and skills (technical and counseling) required for effective communication with patients, families, and health professionals. FINDINGS: Between 2019 and 2022, the redesigned course was offered to 373 P1 students. Course evaluations during this time were consistently positive. The average evaluation score since DPP activities were integrated into the course was 3.41 (on a 4-point scale). Based upon course evaluations, students appreciated three main benefits of incorporating lifestyle coach certification into the pharmacy curriculum: 1) a certified skill that can differentiate them in the job market; 2) practice of skills on real patients under faculty supervision in the community setting; 3) early exposure to pharmacy patient care topics, thus contributing to professional identity. SUMMARY: Integration of lifestyle coach training into an existing core P1 pharmacy course increased application and assessment of communications skills and allowed wider availability of trained coaches to deliver DPP in the community.
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Currículo , Diabetes Mellitus , Promoção da Saúde , Humanos , Promoção da Saúde/métodos , Promoção da Saúde/normas , Diabetes Mellitus/terapia , Currículo/tendências , Currículo/normas , Educação em Farmácia/métodos , Educação em Farmácia/normas , Estilo de Vida , Comunicação , Estudantes de Farmácia/estatística & dados numéricosRESUMO
BACKGROUND: Therapeutic inertia (TI), failure to intensify antihypertensive medication when blood pressure (BP) is above goal, remains prevalent in hypertension management. The degree to which self-reported antihypertensive adherence is associated with TI with intensive BP goals remains unclear. METHODS AND RESULTS: Cross-sectional analysis was performed of the 12-month visit of participants in the intensive arm of SPRINT (Systolic Blood Pressure Intervention Trial), which randomized adults to intensive (<120 mm Hg) versus standard (<140 mm Hg) systolic BP goals. TI was defined as no increase in antihypertensive regimen intensity score, which incorporates medication number and dose, when systolic BP is ≥120 mm Hg. Self-reported adherence was assessed using the 8-Item Morisky Medication Adherence Scale (MMAS-8) and categorized as low (MMAS-8 score <6), medium (MMAS-8 score 6 to <8), and high (MMAS-8 score 8). Poisson regressions estimated prevalence ratios (PRs) and 95% CIs for TI associated with MMAS-8. Among 1009 intensive arm participants with systolic BP >120 mm Hg at the 12-month visit (mean age, 69.6 years; 35.2% female, 28.8% non-Hispanic Black), TI occurred in 50.8% of participants. Participants with low adherence (versus high) were younger and more likely to be non-Hispanic Black or smokers. The prevalence of TI among patients with low, medium, and high adherence was 45.0%, 53.5%, and 50.4%, respectively. After adjustment, neither low nor medium adherence (versus high) were associated with TI (PR, 1.11 [95% CI, 0.87-1.42]; PR, 1.08 [95% CI, 0.84-1.38], respectively). CONCLUSIONS: Although clinician uncertainty about adherence is often cited as a reason for why antihypertensive intensification is withheld when above BP goals, we observed no evidence of an association between self-reported adherence and TI.
Assuntos
Anti-Hipertensivos , Hipertensão , Adulto , Humanos , Feminino , Idoso , Masculino , Pressão Sanguínea , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Autorrelato , Estudos Transversais , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Adesão à MedicaçãoRESUMO
Lipoprotein(a), or Lp(a), is structurally like low-density lipoprotein (LDL) but differs in that it contains glycoprotein apolipoprotein(a) [apo(a)]. Due to its prothrombotic and proinflammatory properties, Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. Lp(a) levels are genetically determined, and it is estimated that 20%-25% of the global population has an Lp(a) level ≥50 mg/dL (or ≥125 nmol/L). Diet and lifestyle interventions have little to no effect on Lp(a) levels. Lipoprotein apheresis is the only approved treatment for elevated Lp(a) but is time-intensive for the patient and only modestly effective. Pharmacological approaches to reduce Lp(a) levels and its associated risks are of significant interest; however, currently available lipid-lowering therapies have limited effectiveness in reducing Lp(a) levels. Although statins are first-line agents to reduce LDL cholesterol levels, they modestly increase Lp(a) levels and have not been shown to change Lp(a)-mediated ASCVD risk. Alirocumab, evolocumab, and inclisiran reduce Lp(a) levels by 20-25%, yet the clinical implications of this reduction for Lp(a)-mediated ASCVD risk are uncertain. Niacin also lowers Lp(a) levels; however, its effectiveness in mitigating Lp(a)-mediated ASCVD risk remains unclear, and its side effects have limited its utilization. Recommendations for when to screen and how to manage individuals with elevated Lp(a) vary widely between national and international guidelines and scientific statements. Three investigational compounds targeting Lp(a), including small interfering RNA (siRNA) agents (olpasiran, SLN360) and an antisense oligonucleotide (pelacarsen), are in various stages of development. These compounds block the translation of messenger RNA (mRNA) into apo(a), a key structural component of Lp(a), thereby substantially reducing Lp(a) synthesis in the liver. The purpose of this review is to describe current recommendations for screening and managing elevated Lp(a), describe the effects of currently available lipid-lowering therapies on Lp(a) levels, and provide insight into emerging therapies targeting Lp(a).
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Aterosclerose , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , Humanos , Lipoproteína(a)/genética , Lipoproteína(a)/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Aterosclerose/tratamento farmacológico , Fatores de Risco , Oligonucleotídeos Antissenso/uso terapêutico , Hiperlipidemias/complicaçõesRESUMO
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are highly effective at lowering hemoglobin A1c (HbA1c) and facilitating weight loss. Four agents in the GLP-1 RA class, albiglutide, liraglutide, dulaglutide, and semaglutide, also have cardioprotective effects. However, subcutaneous administration of these agents remains a major reason for their underutilization. A new coformulation of semaglutide with sodium N-[8-(2-hydroxybenzoyl) amino caprylate (SNAC) is the first oral GLP-1 RA reviewed by the U.S. Food and Drug Administration (FDA). The SNAC technology prevents destruction of semaglutide in the stomach and facilitates transcellular absorption through the gastric membrane enabling semaglutide to reach systemic circulation intact. The oral formulation of semaglutide was studied in the PIONEER trials, demonstrating similar efficacy to the presently available GLP-1 RAs with regard to HbA1c lowering and weight loss. Although the PIONEER 6 trial suggests positive effects on cardiovascular mortality with oral semaglutide, these benefits may not fully be appreciated until the completion of the SOUL trial.
Assuntos
Caprilatos/farmacocinética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Hipoglicemiantes/administração & dosagem , Administração Oral , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Sistemas de Liberação de Medicamentos , Peptídeos Semelhantes ao Glucagon/farmacocinética , Humanos , Hipoglicemiantes/farmacocinética , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/prevenção & controleRESUMO
BACKGROUND: National treatment guidelines recommend glucagon-like peptide receptor agonists (GLP-1 RAs) as add-on therapy to oral agents. However, GLP-1 RAs in combination with dipeptidyl peptidase-4 (DPP-4) inhibitors is not recommended due to a lack of evidence. OBJECTIVE: This case series aims to describe the efficacy and safety of once-weekly GLP-1 RAs administered concomitantly with DPP-4 inhibitors in patients with type 2 diabetes. METHODS: A retrospective chart review of electronic medical records at a free health clinic was conducted between July 2014 and September 2016. Patients 18 years and older with type 2 diabetes were included if they received concomitant DPP-4 inhibitor and once-weekly GLP-1 RA therapy with at least one glycated hemoglobin A1c (HbA1c) measurement within three to six months of starting the combination. The primary and secondary outcomes included change in HbA1c and weight, and patient reported adverse events. RESULTS: Out of forty-three patients that received combination DPP-4 inhibitor plus GLP-1 RA therapy, only eighteen received once-weekly GLP-1 RA. At 3 months, the median (IQR) HbA1c and weight change was -0.8% (-4.3 to 2%) and -0.4kg (-4.2 to 5.8 kg) respectively. No patients reached an HbA1c below 7% and only three patients (17%) reached a HbA1c less than 8%. Patient reported adverse effects included gastrointestinal disturbances (28%), hypoglycemic symptoms (17%), and injection site reactions (0.6%). CONCLUSIONS: Concomitant use of once-weekly GLP-1 RAs and DPP-4 inhibitors provides only modest improvement in glycemic control with minimal weight loss benefits, which is similar to monotherapy with either agent. The combination is unlikely to provide synergistic effects and is not cost effective. These data support the current recommendations against use of combined incretin therapy.
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BACKGROUND: Clinical pharmacists are frequently involved in the management of dyslipidemia, yet clinical pharmacists' knowledge, awareness, and the level of agreement with the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guideline are unknown. OBJECTIVE: The objective of the study was to examine clinical pharmacists' knowledge, awareness, and the level of agreement with the 2013 ACC/AHA cholesterol guideline. METHODS: We administered a validated questionnaire via an online survey that was electronically mailed to clinical pharmacists. We compared responses between those in practice for ≤ 10 and those in practice for > 10 years, and according to practice specialty. RESULTS: The response rate was 11% (314 of 2845). Most respondents were from the Midwestern and Southeastern US, in practice for ≤ 10 years, and practiced in family practice/primary care. Nearly all (92%) respondents had read the guideline and 72% were able to identify the 4 statin benefit groups. Notable knowledge gaps included recalling the 4 outcomes of the 10-year atherosclerotic cardiovascular disease (ASCVD) risk estimator (41.4%), understanding differences between the Framingham Risk Score and the ASCVD risk estimator (33.7%), and monitoring lipids after initiating a statin (41.1%). More knowledge gaps were identified in those practicing for > 10 years and who specialized in internal medicine. The use of the ASCVD risk estimator was high; yet nearly half (44.2%) were concerned whether the ASCVD risk estimator would overestimate 10-year ASCVD risk. CONCLUSION: Although most clinical pharmacists had read the 2013 ACC/AHA cholesterol guideline, several knowledge gaps were identified, especially among those with more experience and those practicing in internal medicine. Targeted education efforts are needed to address these gaps.
Assuntos
American Heart Association , Doenças Cardiovasculares/sangue , Guias como Assunto/normas , Farmacêuticos/normas , Inquéritos e Questionários , Adulto , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/prevenção & controle , Cardiologia/métodos , Cardiologia/normas , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Fidelidade a Diretrizes , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Prevenção Primária/métodos , Medição de Risco , Fatores de Risco , Estados UnidosRESUMO
Hypertriglyceridemia, defined as serum triglyceride (TG) levels >150 mg/dL, now affects over one-quarter of the US adult population and is associated with an increased risk of atherosclerotic cardiovascular disease. Available guidelines for managing hypertriglyceridemia vary with respect to TG thresholds and severity of disease. Lifestyle modifications and management of secondary causes (eg, diabetes) remain the first step in managing hypertriglyceridemia, with pharmacotherapy reserved to reduce the risk of pancreatitis and/or further reduce TG levels. Several classes of lipid-lowering agents are available with variable TG-lowering efficacy. Although there is no consensus regarding the choice of initial TG-lowering pharmacotherapy, there is general agreement that the decision depends on the degree of hypertriglyceridemia and atherosclerotic cardiovascular disease risk. This review will discuss available and emerging lipid-lowering therapies for the management of moderately elevated TG, defined as TG 150 to 499 mg/dL.
Assuntos
Hipolipemiantes/farmacologia , Triglicerídeos/sangue , Humanos , Guias de Prática Clínica como AssuntoRESUMO
The Society of Healthcare Epidemiology of America, the Centers for Disease Control and Prevention, and the President's Council of Advisors on Science and Technology recognize the need to combat antimicrobial resistance through the promotion of antimicrobial stewardship programs. Health care facilities in Virginia were surveyed using a 23-item survey focused on facility characteristics and antimicrobial stewardship strategies. Antimicrobial stewardship activities were highly variable and many are missing key personnel and resources.
Assuntos
Antibacterianos/uso terapêutico , Uso de Medicamentos/normas , Política de Saúde , Política Organizacional , Resistência Microbiana a Medicamentos , Humanos , Inquéritos e Questionários , VirginiaRESUMO
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of antihyperglycemic agents that improve glycemic control by increasing glycosuria. Additional benefits beyond glucose lowering include significant improvements in seated clinic blood pressure (BP), partly attributed to their diuretic-like actions. Less known are the effects of this class on 24-hour ambulatory BP, which is a better predictor of cardiovascular risk than seated clinic BP. METHODS AND RESULTS: We performed a meta-analysis of randomized, double-blind, placebo-controlled trials to investigate the effects of SGLT2 inhibitors on 24-hour ambulatory BP. We searched all studies published before August 17, 2016, which reported 24-hour ambulatory BP data. Mean differences in 24-hour BP, daytime BP, and nighttime BP were calculated by a random-effects model. SGLT2 inhibitors significantly reduce 24-hour ambulatory systolic and diastolic BP by -3.76 mm Hg (95% CI, -4.23 to -2.34; I2=0.99) and -1.83 mm Hg (95% CI, -2.35 to -1.31; I2=0.76), respectively. Significant reductions in daytime and nighttime systolic and diastolic BP were also found. No association between baseline BP or change in body weight were observed. CONCLUSIONS: This meta-analysis shows that the reduction in 24-hour ambulatory BP observed with SGLT2 inhibitors is a class effect. The diurnal effect of SGLT2 inhibitors on 24-hour ambulatory BP may contribute to their favorable effects on cardiovascular outcomes.
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Pressão Sanguínea/efeitos dos fármacos , Ritmo Circadiano , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Túbulos Renais Proximais/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Idoso , Compostos Benzidrílicos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Canagliflozina/uso terapêutico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatologia , Feminino , Glucosídeos/uso terapêutico , Humanos , Hipoglicemiantes/efeitos adversos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Transportador 2 de Glucose-Sódio/metabolismo , Resultado do TratamentoRESUMO
PURPOSE: A case of a patient who received ceftaroline fosamil as salvage therapy for a methicillin-resistant Staphylococcus aureus (MRSA) epidural abscess is reported. SUMMARY: A 48-year-old white woman arrived at the emergency department (ED) with an altered mental status. She had been to the ED two days prior with complaints of sudden-onset and worsening neck pain. She had a history of compacted disks in her neck secondary to a motor vehicle accident that occurred three years prior but that did not require surgical intervention. Computed tomography and magnetic resonance imaging scans confirmed an epidural abscess with wound cultures growing MRSA. The admitting physician indicated that the patient was severely septic. Acyclovir, ceftriaxone, and vancomycin were initiated for empirical treatment due to suspected meningitis. Paired blood cultures also continued to grow MRSA in four of four bottles collected four days after admission. This indicated that antimicrobial therapy was not successfully eradicating the MRSA found in the blood and the patient's clinical status was deteriorating. Ceftaroline was used as salvage therapy, resulting in rapid clearance of MRSA from the blood and the patient becoming afebrile in 24 hours. Blood culture tests on hospital day 11-one day after ceftaroline initiation-were clear of MRSA. The patient was discharged to a long-term-care facility and ordered ceftaroline fosamil 600 mg i.v. every 12 hours for four weeks. CONCLUSION: A MRSA epidural abscess in a 48-year-old woman was successfully treated with ceftaroline fosamil 600 mg every 12 hours as salvage therapy.