Shannon W. Finks

Hydralazine-induced lupus: Maintaining vigilance with increased use in patients with heart failure

Objective: To review data concerning the incidence and danger of hydralazine-induced systemic lupus erythematosus (SLE) and review how best to monitor patients placed on chronic hydralazine therapy. Data Sources: Literature was sought utilizing PUBMED (1960 to present) and MEDLINE (1966 to present). Search terms included hydralazine, drug-induced systemic lupus erythematosus, congestive heart failure, and antinuclear antibody. Data Synthesis: A major adverse effect of hydralazine therapy is drug-induced SLE. An evaluation of case reports and review of the literature was undertaken to determine the significance of this major adverse effect and stress the importance of close monitoring of patients placed on chronic hydralazine therapy for heart failure. Risk factors are discussed including high daily doses, slow acetylator and HLA-DRw4 phenotypes, therapy longer than 3 months, and female gender. Conclusions: Following the publication of A-HeFT, an increase in the amount of hydralazine prescribed in patients with heart failure has been noted. Patients should be closely monitored when initiating hydralazine and during chronic therapy. Although dose limitation of hydralazine reduces risk, low doses are well documented to be associated with SLE. A baseline antinuclear antibody level should be determined on initiation of hydralazine, but it is not recommended to regularly check antinuclear antibody levels because a positive result does not necessarily indicate SLE is present. Patients should be monitored at each visit for signs and symptoms of SLE, and, if any signs and symptoms of the syndrome develop while the patient is on hydralazine therapy, the drug should be discontinued immediately because complications from the syndrome can be potentially fatal.

Key articles of dietary interventions that influence cardiovascular mortality.

Lifestyle modifications, particularly diet, are a key component to the reduction of cardiovascular events. Diets high in carbohydrates and saturated fat have been shown to negatively affect blood cholesterol, thereby increasing the risk for cardiovascular disease (CVD). Dietary interventions that emphasize the consumption of whole grains, fruits, and vegetables have been shown to be successful in reducing cardiovascular risk. Clinical pharmacist practitioners need to be knowledgeable regarding lifestyle modifications, specifically dietary issues, to develop a comprehensive, effective, and evidence‐based plan for patients who are either at risk for or who have established CVD. Numerous studies have been published over the past few years with regard to the rapidly growing field of dietary interventions that influence cardiovascular risk, and the amount of literature can be overwhelming. Thus we chose to focus our review on articles that assess changes in dietary patterns that affect overall mortality risk from CVD. As such, literature describing the impact of dietary factors that influence weight, lipid changes, or other risk factors alone were not included in this review. A group of practitioners with expertise and interest in CVD were involved in the compilation of this article.

Clinical Efficacy and Safety of Cilostazol: A Critical Review of the Literature

Cilostazol is a unique antiplatelet agent that has been commercially available for over two decades. As a phosphodiesterase III inhibitor, it reversibly inhibits platelet aggregation yet also possesses vasodilatory and antiproliferative properties. It has been widely studied in a variety of disease states, including peripheral arterial disease, cerebrovascular disease, and coronary artery disease with percutaneous coronary intervention. Overall, cilostazol appears to be a promising agent in the management of these disease states with a bleeding profile comparable to placebo; even when combined with other antiplatelet agents, cilostazol does not appear to increase the rate of bleeding. Despite the possible benefit of cilostazol, its use is limited by tolerability as some patients often report drug discontinuation due to headache, diarrhea, dizziness, or increased heart rate. To date, it has been predominantly studied in the Asian population, making it difficult to extrapolate these results to a more diverse patient population. This paper discusses the evolving role of cilostazol in the treatment of vascular diseases.

Bivalirudin for Patients with Heparin-Induced Thrombocytopenia Undergoing Cardiovascular Surgery:

Objective To evaluate the uso of bivalirudin in patients with heparin-induced thrombocytopenia (HIT) undergoing cardiovascular surgery. Data Sources: Relevant information was identified through a search of MEDLINE (1966–April 2008), international Pharmaceutical Abstracts (1960–April 2008), and Cochrane Databases (publications archived until April 2008) using the terms bivalirudin, heparin-induced thrombocytopenia, and cardiovascular surgery. Study Selection And Data Extraction: Prospective and retrospective studies, case reports, and case series in adults were eligible for inclusion if bivalirudin had been used in a patient with known HIT undergoing any cardiovascular surgical procedure other than percutaneous coronary intervention. Data Synthesis: Two small, open-label, multicenter clinical trials were identified that evaluated treatment with bivalirudin in patients with HIT undergoing coronary artery bypass graft surgery. Ono looked at on-pump cardiopulmonary bypass (CPB), while the other looked at off-pump CPB. Procedural success was achieved at day 7 in 94% (n = 46) of patients in the on-pump CPB study and in 92% (n = 47) of patients in the off-pump CPB study. Dosing strategies varied between the 2 trials, with the on-pump study using a 1-mg/kg bivalirudin bolus followed by a 2.5-mg/kg/h infusion; the off-pump study used a 0.75-mg/kg bolus followed by a 1.75-mg/kg/h infusion. In addition, 10 case reports met the criteria to be included in the review and are summarized. In these cases, procedural success was reported using various bivalirudin doses in valve repair and replacement, right ventricular assist device implantation, and heart transplantation. Conclusions: Growing data demonstrate procedural success with bivalirudin in patients with HIT undergoing cardiovascular surgery. However, bivalirudin dosing and goal-activated clotting times varied between the studies and case reports. Bivalirudin represents a viable alternative to heparin in patients with HIT undergoing cardiovascular surgery; however, further trials are warranted to identify optimal dosing and monitoring parameters.

Use of Cilostazol in Percutaneous Coronary Interventions

OBJECTIVE: To evaluate the addition of cilostazol to standard dual antiplatelet therapy (DAT) with aspirin and clopidogrel in patients receiving coronary stenting. DATA SOURCES: Relevant information was identified through a search of MEDLINE (1966-November 2011), International Pharmaceutical Abstracts (1960-2011), and Cochrane Databases (publications archived until November 2011) using the terms cilostazol, percutaneous coronary intervention, triple therapy, and antiplatelet agents. STUDY SELECTION AND DATA EXTRACTION: English-language prospective and retrospective studies, including registry data in adults, were eligible for inclusion if triple therapy with cilostazol was compared with DAT with aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) with stenting. Article bibliographies were also reviewed. DATA SYNTHESIS: Cilostazol uniquely possesses antiproliferative properties in addition to its antiplatelet effects. Several prospective and retrospective clinical trials evaluated it as a third agent in standard antiplatelet regimens after PCI with both bare metal and drug-eluting stents. Both angiographic and clinical outcomes, including major adverse cardiac events (MACEs), have been improved with the addition of cilostazol to DAT in most trials, without increasing bleeding risk. Higher-risk patients, such as elderly individuals and patients with diabetes, long lesions, or small vessels, seem to benefit the most from triple therapy. Patients who are poor responders to clopidogrel also appear to benefit from the addition of cilostazol by improving platelet reactivity with standard DAT. CONCLUSIONS: Triple therapy with cilostazol has been shown to reduce MACEs by providing increased inhibition of platelet aggregation and reducing the rates of in-stent thrombosis compared to DAT without increasing the risk of bleeding complications. Further studies are needed to identify proper patient selection based on risk factors for the addition of cilostazol. Additionally, studies comparing cilostazol with newer antiplatelet therapies, such as prasugrel and ticagrelor, are needed.

Aspirin Resistance: Disparities and Clinical Implications

Aspirin is one of the most widely prescribed drugs for the prevention of thrombosis in patients with vascular disease. Yet, aspirin is unable to prevent thrombosis in all patients. The term “aspirin resistance” has been used to broadly define the failure of aspirin to prevent a thrombotic event. Whether this is directly related to aspirin itself through biochemical aspirin resistance or treatment failure, or if it is because of aspirins inability to overcome the thrombogenic aspects of the disease process itself, has not been elucidated. This can have dramatic clinical implications for a variety of vascular disease subsets and is cause for concern, considering the high prevalence of aspirin use for both primary and secondary prevention. Disparities exist in the rates of aspirin resistance among certain patient populations, such as women, patients with diabetes mellitus, and those with heart failure, and across clinical conditions, such as cardiovascular and cerebrovascular disease. Clinical trial data from studies observing resistance have revealed that regardless of study size, dose of aspirin, control for drug interactions and adherence, or assay used to measure platelet function, aspirin resistance is associated with an increased risk for adverse events. Although the evidence is mounting, there has yet to be a consensus on the appropriate clinical response to aspirin resistance.

Reversal Agents for Direct Oral Anticoagulants: Understanding New and Upcoming Options.

Direct oral anticoagulants (DOACs), originally developed as an alternative for vitamin K antagonists, are shifting the landscape of antithrombotic therapy. DOACs such as dabigatran, rivaroxaban, apixaban, and edoxaban offer enhancements in safety, convenience, and efficacy compared with warfarin. However, as choices for oral anticoagulation therapy have increased, so has the need for effectual antidotes before urgent surgical procedures and for the reversal of serious adverse events caused by DOACs. To date, one antidote has been FDA approved in the United States for the reversal of dabigatran, and two antidotes are undergoing phase 2and 3clinical trials. This review will summarize currently available and developing data for DOAC antidotes: idarucizumab, exanet alfa, and ciraparantag.

Management of Venous Thromboembolism Recent Advances in Oral Anticoagulation Therapy

Objective: To review clinical data on direct oral anticoagulants (DOACs) used in the acute treatment of venous thromboembolism (VTE) as well as practical considerations when using these products. Data Sources: Searches of PubMed and Google Scholar for VTE, deep vein thrombosis, pulmonary embolism, and relevant drug international nonproprietary names were conducted. Additional online searches were conducted for prescribing information. Study Selection and Data Extraction: Relevant articles on dabigatran, rivaroxaban, apixaban, and edoxaban for the management of VTE compared with oral vitamin K antagonists (VKAs; published between 1966 and December 2015) were reviewed and summarized, together with information on dosing, pharmacokinetics/pharmacodynamics, and drug-drug interactions. Data Synthesis: The DOACs have the potential to circumvent many of the disadvantages of VKAs. At a minimum, they greatly increase the available therapeutic options, thus providing a greater opportunity for clinicians to select a management option that best fits the needs of individual patients. Despite the significant advance that DOACs represent, they are not without risk and require careful consideration of a number of clinical issues to optimize safety and efficacy. Conclusions: The emergence of DOACs for the management of thromboembolic disorders represents a paradigm shift from oral VKAs. The DOACs provide similar efficacy and improved safety in selected patients as compared with VKAs. Clinicians treating VTE need to be familiar with the intricacies involved in using these agents, including the appropriate dose selection for the relevant indication, avoidance of drug-drug and drug-disease interactions, and consideration of dose adjustments in specific clinical situations, such as organ dysfunction.

Role of the Pharmacist in Achieving Performance Measures to Improve the Prevention and Treatment of Venous Thromboembolism

Current prescribing practices for venous thromboembolism (VTE) prophylaxis and treatment are suboptimal, particularly regarding the use of appropriate prophylaxis in accordance with evidence‐based guidelines. Failure to prevent avoidable VTE is associated with a substantial clinical and economic burden, due not only to the initial event, but also to VTE recurrence and long‐term sequelae. Quality improvement initiatives such as the Surgical Care Improvement Project, the Centers for Medicare and Medicaid Services, the National Quality Forum, and The Joint Commission have developed performance measures to address the shortfall and improve adherence with best‐practice recommendations. Several studies have highlighted the benefits of pharmacist‐led anticoagulation services for reducing the occurrence of VTE and bleeding complications while reducing excess hospitalization and health care costs. By assuming responsibility for anticoagulation management, pharmacists can ensure that at‐risk patients receive the correct drug at the correct dose for the correct duration, from initial presentation to outpatient follow‐up. Increasing continuity of care in this manner will ultimately improve patient outcomes and reduce costs. Pharmacists can also play a key role in helping hospitals achieve performance measures by aiding in the development and implementation of local VTE guidelines, policies, and other quality improvement initiatives; by helping to establish critical pathways with protocols; and by providing valuable education for other health care professionals and patients alike. Pharmacists are in an ideal position to facilitate achievement of VTE‐related performance measures and can thus substantially contribute to the much‐needed improvement in current VTE prevention and care.

Annual Influenza Vaccination: Offering Protection Beyond Infection

Abstract Cardiovascular disease (CVD), the leading cause of death in the world, is largely preventable. An increasing amount of evidence suggests that annual vaccination with inactivated influenza vaccine reduces morbidity and mortality associated with CVD; however, immunization rates in patients with CVD fall consistently below the goals established by Healthy People 2020. This review outlines the importance of vaccination and summarizes the available literature on the role of seasonal influenza vaccination and the incidence of coronary artery disease and stroke.