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Atherosclerotic cardiovascular disease (ASCVD), a leading cause of mortality and morbidity, is associated with a substantial healthcare and economic burden. Reduction of low-density lipoprotein cholesterol (LDL-C) to guideline-recommended goals is crucial in the prevention or management of ASCVD, particularly in those at high risk. Despite the availability of several effective lipid-lowering therapies (LLTs), up to 80% of patients with ASCVD do not reach evidence-based LDL-C goals. This nonattainment may be due to poor adherence to, and lack of timely utilization of, LLTs driven by a range of variables, including polypharmacy, side effects, clinical inertia, costs, and access issues. Inclisiran was approved by the US Food and Drug Administration in 2021 as a novel, twice-yearly, healthcare provider (HCP)-administered LLT. In-office administration allows HCPs more control of drug acquisition, administration, and reimbursement, and may allow for more timely care and increased patient monitoring. In the USA, in-office administered drugs are considered a Medical Benefit and can be acquired and reimbursed using the "buy-and-bill" process. Buy-and-bill is a standard system for medication administration already established in multiple therapeutic areas, including oncology, vaccines, and allergy/immunology. Initiating in-office administration will involve new considerations for clinicians in the cardiovascular specialty, such as the implementation of new infrastructure and processes; however, it could ultimately increase treatment adherence and improve cardiovascular outcomes for patients with ASCVD. This article discusses the potential implications of buy-and-bill for the cardiology specialty and provides a practical guide to implementing HCP-administered specialty drugs in US clinical practice.
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PURPOSE: This review aims to summarize the evidence and pharmacological characteristics of treatment options for transthyretin amyloid cardiomyopathy (ATTR-CM). Additionally, this review highlights the role of clinical pharmacists in helping to secure newly introduced therapies. SUMMARY: ATTR-CM, a disease characterized by misfolded protein that is deposited in the myocardium and disrupts cardiac functioning, has historically been underdiagnosed due to the need for invasive biopsy and an illusion of rarity. Once diagnosed, limited treatment modalities for ATTR-CM have led providers to rely on nonpharmacological remedies or off-label use of medications with limited evidence of benefit. However, recent noninvasive diagnostic advancements and heightened disease state awareness have revealed increased prevalence of ATTR-CM. This has led to the introduction of several first-in-class pharmaceuticals with actions targeted at inhibiting the various phases of amyloidosis: TTR stabilizers include diflunisal and Food and Drug Administration (FDA)-approved tafamidis; TTR silencers include patisiran and inotersen; fibril disrupters include doxycycline with tauroursodeoxycholic acid; and alternative agents include green tea extract and curcumin. CONCLUSION: ATTR-CM treatments have emerged and, despite current limited data, are continuing to evolve. Tafamidis, the only agent approved by FDA for ATTR-CM, shows promise to improve survival and quality of life in patients with ATTR-CM. Pharmacists can play a key role in assisting with agent selection for this disease state, as well as providing knowledge about current and future clinical trials evaluating the safety and efficacy of the available treatment modalities.
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Neuropatías Amiloides Familiares , Neuropatías Amiloides Familiares/tratamiento farmacológico , Humanos , Prealbúmina , Calidad de Vida , Estados UnidosRESUMEN
Chronic angina pectoris is associated with considerable morbidity and mortality, especially if treated suboptimally. For many patients, aggressive pharmacologic intervention is necessary in order to alleviate anginal symptoms. The optimal treatment of stable ischemic heart disease (SIHD) should be the prevention of angina and ischemia, with the goal of maximizing both quality and quantity of life. In addition to effective risk factor modification with lifestyle changes, intensive pharmacologic secondary prevention is the therapeutic cornerstone in managing patients with SIHD. Current guidelines recommend a multifaceted therapeutic approach with ß-blockers as first-line treatment. Another important pharmacologic intervention for managing SIHD is nitrates. Nitrates can provide both relief of acute angina and can be used prophylactically before exposure to known triggers of myocardial ischemia to prevent angina. Additional therapeutic options include calcium channel blockers and ranolazine, an inhibitor of the late inward sodium current, that can be used alone or in addition to nitrates or ß-blockers when these agents fail to alleviate symptoms. Ranolazine appears to be particularly effective for patients with microvascular angina and endothelial dysfunction. In addition, certain antianginal therapies are approved in Europe and have been shown to improve symptoms, including ivabradine, nicorandil, and trimetazidine; however, these have yet to be approved in the United States. Ultimately, there are several different medications available to the physician for managing the patient with SIHD having chronic angina, when either used alone or in combination. The purpose of this review is to highlight the most important therapeutic approaches to optimizing contemporary treatment in response to individual patient needs.
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Antagonistas Adrenérgicos beta/administración & dosificación , Angina de Pecho/tratamiento farmacológico , Angina de Pecho/epidemiología , Isquemia Miocárdica/tratamiento farmacológico , Isquemia Miocárdica/epidemiología , Nitratos/administración & dosificación , Angina de Pecho/diagnóstico , Animales , Antiarrítmicos/administración & dosificación , Quimioterapia Combinada , Humanos , Isquemia Miocárdica/diagnóstico , Guías de Práctica Clínica como Asunto/normas , Vasodilatadores/administración & dosificaciónRESUMEN
Nitroglycerin is the oldest and most commonly prescribed short-acting anti-anginal agent; however, despite its long history of therapeutic usage, patient and health care provider education regarding the clinical benefits of the short-acting formulations in patients with angina remains under-appreciated. Nitrates predominantly induce vasodilation in large capacitance blood vessels, increase epicardial coronary arterial diameter and coronary collateral blood flow, and impair platelet aggregation. The potential for the prophylactic effect of short-acting nitrates remains an under-appreciated part of optimal medical therapy to reduce angina and decrease myocardial ischemia, thereby enhancing the quality of life. Short-acting nitroglycerin, administered either as a sublingual tablet or spray, can complement anti-anginal therapy as part of optimal medical therapy in patients with refractory and recurrent angina either with or without myocardial revascularization, and is most commonly used to provide rapid therapeutic relief of acute recurrent angina attacks. When administered prophylactically, both formulations increase angina-free walking time on treadmill testing, abolish or delay ST segment depression, and increase exercise tolerance. The sublingual spray formulation provides several clinical advantages compared to tablet formulations, including a lower incidence of headache and superiority to the sublingual tablet in terms of therapeutic action and time to onset, while the magnitude and duration of vasodilatory action appears to be comparable. Furthermore, the sublingual spray formulation may be advantageous to tablet preparations in patients with dry mouth. This review discusses the efficacy and utility of short-acting nitroglycerin (sublingual spray and tablet) therapy for both preventing and aborting an acute angina attack, thereby leading to an improved quality of life.
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Circulación Coronaria/efectos de los fármacos , Isquemia Miocárdica/tratamiento farmacológico , Nitroglicerina/uso terapéutico , Vasodilatación/efectos de los fármacos , Vasodilatadores/uso terapéutico , Administración Sublingual , Aerosoles , Animales , Química Farmacéutica , Tolerancia al Ejercicio/efectos de los fármacos , Humanos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatología , Nitroglicerina/administración & dosificación , Nitroglicerina/efectos adversos , Guías de Práctica Clínica como Asunto , Comprimidos , Factores de Tiempo , Resultado del Tratamiento , Vasodilatadores/administración & dosificación , Vasodilatadores/efectos adversosRESUMEN
Three factor Xa inhibitors have been studied in the treatment of venous thromboembolism, both for acute therapy and as extended therapy to prevent recurrent events. Rivaroxaban, apixaban, and edoxaban have all proven to be effective in Phase III clinical trials for this indication when compared to current standard of therapy with similar or less bleeding. Nevertheless, the agents all offer different pharmacological profiles, which have an impact on patient selection and potential advantages in clinical practice.
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Coagulación Sanguínea/efectos de los fármacos , Inhibidores del Factor Xa/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológico , Animales , Inhibidores del Factor Xa/efectos adversos , Hemorragia/inducido químicamente , Humanos , Morfolinas/uso terapéutico , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Piridonas/uso terapéutico , Factores de Riesgo , Rivaroxabán , Tiazoles/uso terapéutico , Tiofenos/uso terapéutico , Resultado del Tratamiento , Tromboembolia Venosa/sangreRESUMEN
Oral anticoagulation therapy is transforming with the advent of the target specific oral anticoagulants, particularly, the direct thrombin inhibitors and factor Xa inhibitors. These agents have demonstrated clinical efficacy and safety and offer several potential advantages over current standard of care therapy, warfarin. Nevertheless, the pharmacology between the newly approved oral anticoagulants differs and must be considered for appropriate management and patient selection. The pharmacodynamics and pharmacokinetics of dabigatran etexilate, rivaroxaban, apixaban and edoxaban are discussed in detail, which may translate into considerable clinical implications.
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Anticoagulantes/farmacocinética , Anticoagulantes/uso terapéutico , Sistemas de Liberación de Medicamentos , Inhibidores del Factor Xa , Trombina/antagonistas & inhibidores , Administración Oral , Animales , Anticoagulantes/efectos adversos , HumanosAsunto(s)
Bencimidazoles/efectos adversos , Hemorragia/etiología , Hemorragia/terapia , Piridinas/efectos adversos , Heridas no Penetrantes/terapia , Accidentes por Caídas , Anciano , Dabigatrán , Demencia/complicaciones , Femenino , Humanos , Neumotórax/complicaciones , Neumotórax/cirugía , Fracturas de las Costillas/complicaciones , Bazo/lesiones , Toracostomía/métodos , Vitamina K/uso terapéutico , Heridas no Penetrantes/complicacionesRESUMEN
Prothrombin complex concentrates (PCCs) offer a means for the rapid reversal of warfarin, particularly in the setting of life-threatening bleeding. We evaluated the effectiveness and safety of a PCC-based protocol in patients with warfarin-associated intracerebral hemorrhage (ICH), subdural hematoma (SDH), or subarachnoid hemorrhage (SAH). This was a retrospective case-series review of patients treated with an institution-approved warfarin reversal protocol. Patients with intracranial hemorrhage and known warfarin use with an international normalized ratio (INR)>1.4 received fresh frozen plasma (FFP), vitamin K (phytonadione), and weight-based, 3-factor PCC (Profilnine(®) SD) dose based on the initial INR. Demographic and clinical information, the degree of and time to INR normalization, and adverse events were recorded. The thirty study patients included 19 with primary ICH, 7 with SDH, and 4 with SAH. The mean age was 72.8 (±11) years, including 11 (37%) patients ≥80years old. The median presenting INR was 2.3 (IQR 2-3.3) and post-treatment INR was 1.4 (IQR 1.3-1.5, Z score 6.4, p<0.001). Median time from PCC administration to the first follow up INR was 95 (IQR 50-140) min. No patient's INR increased by more than 0.3 over 72h. Nine patients (30%) underwent neurosurgical procedures after PCC administration and no procedure-related bleeding complication was noted. Adverse events included 3 instances of early hematoma expansion, one ischemic stroke in a patient with endocarditis on post-PCC day 1, one pulmonary embolism 5weeks after PCC treatment, and one coronary in-stent thrombosis 60days after PCC treatment. 6 patients died prior to hospital discharge of anticipated complications of their initial event, and none from identifiable thrombotic complications of PCC. A 3-factor PCC preparation (Profilnine(®) SD), administered with FFP and vitamin K to patients with acute warfarin-associated intracranial bleeding is a reasonable approach to urgent warfarin reversal. However, randomized, prospective trials are needed to verify the safety and clinical effectiveness of PCC administration in this population.
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Anticoagulantes/efectos adversos , Anticoagulantes/antagonistas & inhibidores , Trastornos de la Coagulación Sanguínea/inducido químicamente , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Factores de Coagulación Sanguínea/uso terapéutico , Hemorragias Intracraneales/tratamiento farmacológico , Warfarina/efectos adversos , Warfarina/antagonistas & inhibidores , Anciano , Anciano de 80 o más Años , Algoritmos , Trastornos de la Coagulación Sanguínea/mortalidad , Factores de Coagulación Sanguínea/efectos adversos , Femenino , Hemostáticos/uso terapéutico , Humanos , Relación Normalizada Internacional , Hemorragias Intracraneales/etiología , Hemorragias Intracraneales/mortalidad , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Plasma , Resultado del Tratamiento , Vitamina K/uso terapéuticoRESUMEN
Safe and effective stroke prevention in atrial fibrillation (AF) is crucial as the number of patients with this condition continues to increase. Several novel oral anticoagulants are being developed as replacements for warfarin for this indication. Direct factor Xa inhibitors comprise the largest class of oral anticoagulants in development; the inhibition of factor Xa is recognized to be a promising target for therapeutic anticoagulation, partly because of its location in the coagulation cascade. Apixaban, betrixaban, edoxaban, and rivaroxaban are small-molecule, selective inhibitors that directly and reversibly bind to the active site of factor Xa. Their pharmacokinetic and pharmacodynamic profiles vary, which might allow patient-specific therapy. Several of these agents have been tested in clinical trials for various indications, including AF, with favorable results. In particular, apixaban and rivaroxaban have shown superiority and noninferiority, respectively, to warfarin in phase III clinical trials for stroke prevention in AF. These agents have also been shown to be safe in terms of bleeding risk. Despite these advantages, factor Xa inhibitors have several characteristics, such as potential interactions with other drugs (inhibitors of cytochrome P450 and P-glycoprotein) and the inability to reverse their anticoagulant effects, as well as concerns about poor patient compliance, which must be considered when initiating patients on a novel factor Xa inhibitor.
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Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Coagulación Sanguínea/efectos de los fármacos , Inhibidores del Factor Xa , Accidente Cerebrovascular/prevención & control , Administración Oral , Animales , Anticoagulantes/efectos adversos , Fibrilación Atrial/sangre , Fibrilación Atrial/complicaciones , Interacciones Farmacológicas , Medicina Basada en la Evidencia , Factor Xa/metabolismo , Hemorragia/inducido químicamente , Humanos , Cumplimiento de la Medicación , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
STUDY OBJECTIVES: To evaluate steady-state bivalirudin dosing requirements in patients with a wide range of kidney function who were being treated for heparin-induced thrombocytopenia (HIT)-related disorders. DESIGN: Retrospective medical record review. SETTING: Academic medical center. PATIENTS: Sixty-four adults with varying degrees of renal function who were receiving bivalirudin for at least 48 hours for HIT-related disorders between March 2007 and May 2010. MEASUREMENTS AND MAIN RESULTS: Steady-state conditions were defined as a constant bivalirudin infusion dose for at least 12 hours, with serum creatinine concentration varying less than 20% for 48 hours (for patients not receiving renal replacement therapy) and at least two therapeutic activated partial thromboplastin time (aPTT) values (60-80 sec). Patients were assigned to five groups based on Cockcroft-Gault-estimated creatinine clearance (Clcr) of less than 30, 30-60, or greater than 60 ml/minute, or by type of renal replacement therapy-intermittent hemodialysis or continuous venovenous hemofiltration (CVVH). For Clcr greater than 60 ml/minute, the median bivalirudin dose was 0.15 mg/kg/hour (interquartile range [IQR] 0.11-0.15 mg/kg/hr), which was greater than median doses for Clcr 30-60 ml/minute (0.10 mg/kg/hr, IQR 0.06-0.13 mg/kg/hr, p=0.004), Clcr less than 30 ml/minute (0.08 mg/kg/hr, IQR 0.04-0.1 mg/kg/hr, p=0.001), CVVH (0.06 mg/kg/hr, IQR 0.03-0.10 mg/kg/hr, p=0.046), and hemodialysis (0.04 mg/kg/hr, IQR 0.03-0.05 mg/kg/hr, p=0.0001). Bivalirudin doses correlated with Clcr (Spearman r = 0.58, p<0.01). The median aPTT value of 70 seconds (IQR 63-74 sec) was similar in all groups. Thrombosis was present before bivalirudin therapy in 18 (28%) of 64 patients, and two patients (3%) developed thromboemboli during bivalirudin therapy. Clinically significant bleeding related to bivalirudin and leading to discontinuation of bivalirudin occurred in four patients (6%). The median international normalized ratio increased from 1.5 (IQR 1.3-1.7) before bivalirudin therapy to 1.9 (IQR 1.8-2.1) during bivalirudin therapy (p=0.002) in 11 patients who were not receiving warfarin. CONCLUSION: Bivalirudin dosing requirements increased with increasing Clcr values. The high degree of variability suggests that dosing in individual patients will require careful titration to achieve adequate anticoagulation.
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Antitrombinas/administración & dosificación , Antitrombinas/uso terapéutico , Creatinina/sangre , Heparina/efectos adversos , Hirudinas/administración & dosificación , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/uso terapéutico , Trombocitopenia/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antitrombinas/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Hirudinas/efectos adversos , Humanos , Infusiones Intravenosas , Relación Normalizada Internacional/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial/estadística & datos numéricos , Fragmentos de Péptidos/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Terapia de Reemplazo Renal/métodos , Estudios Retrospectivos , Trombocitopenia/sangre , Trombocitopenia/inducido químicamenteRESUMEN
Therapeutic anticoagulation with heparins, warfarin, and anti-Xa inhibitors carry an inherent risk of complications due to their multifaceted pharmacokinetic and pharmacodynamic properties as well as narrow therapeutic ranges. When an anticoagulated patient presents with a major or life-threatening bleed, immediate and effective therapy may be necessary to reverse the effects of the anticoagulant, minimize blood loss, and reduce patient morbidity and mortality. Optimal agents and strategies for anticoagulant reversal are limited, particularly for newer anticoagulants. The literature describing such strategies available to reverse the effects of anticoagulants in the setting of a bleed is limited, and therefore many controversies exist. Thus, as new anticoagulants become available, without a specific agent for reversal, the concerns and controversies related to this topic must be addressed. The purpose of this review is to discuss the management of major or life-threatening bleeds by addressing the following controversies: (1) the use of recombinant factor VIIa for rapid reversal of warfarin in patients with intracerebral hemorrhage, (2) the role of prothrombin complex concentrate in emergent warfarin reversal, and (3) the optimal approach to reverse newer anticoagulants such as low molecular weight heparins, fondaparinux, and direct thrombin inhibitors.