Efficacy of same-day versus next-day administration of pegfilgrastim for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients receiving dose-dense doxorubicin and cyclophosphamide: A retrospective multi-site analysis.

INTRODUCTION: Administering pegfilgrastim on the same day as chemotherapy can improve patient satisfaction through convenience and may increase the utilization of cost-effective biosimilars compared to next-day administration, but the effect on clinical outcomes with commonly used breast cancer regimens is unclear. METHODS: This multi-site, retrospective cohort study included breast cancer patients age 18 years or older who received dose-dense doxorubicin and cyclophosphamide (ddAC) and pegfilgrastim between 1 June 2016 and 31 May 2020. Pegfilgrastim was given on the same day as chemotherapy at one site and the day after chemotherapy at the other two sites. The primary endpoint compared the incidence of febrile neutropenia associated with pegfilgrastim administration timing. RESULTS: A total of 360 patients were reviewed (146 same-day administration and 214 next-day administration). In the same-day group 36 patients (24.6%) developed FN compared to 25 patients (11.7%) in the next-day group (p = 0.002). Same-day administration also significantly increased the incidences of additional acute care visits (11.6% vs 2.8%, p = 0.0016), grade ≥ 3 neutropenia (38.4% vs 13.6%, p < 0.0001), chemotherapy dose reductions (21.2% vs 6.1%, p < 0.0001), and antibiotic use (26.7% vs 12.6%, p = 0.001). Same-day administration did not significantly increase the rate of hospitalization (15% vs 11.2%, p = 0.36) and delay of next chemotherapy cycle by ≥1 day (8.2% vs 6.1%, p = 0.57) due to neutropenic complications. CONCLUSIONS: Administering pegfilgrastim on the same day as ddAC led to a significant increase in neutropenic complications. This study confirms the need to administer pegfilgrastim the day after chemotherapy in breast cancer patients receiving ddAC.

Genotype-Guided Use of P2Y12 Inhibitors: A Review of Current State of the Art.

The pharmacodynamics of the purinergic receptor type Y, subtype 12 (P2Y12) inhibitors has evolved. Our understanding of the metabolism of P2Y12 inhibitors has revealed polymorphisms that impact drug metabolism and antiplatelet efficacy, leading to genetic testing guided therapy. In addition, assays of platelet function and biochemistry have provided insight into our understanding of the efficacy of "antiplatelet" therapy, identifying patients with high or low platelet reactivity on P2Y12 therapy. Despite the data, the implementation of these testing modalities has not gained mainstream adoption across hospital systems. Given differences in potency between the three clinically available P2Y12 inhibitors, the balance between thrombotic and bleeding complications must be carefully considered, especially for the large proportion of patients at higher risk for bleeding. Here we review the current data for genetic and functional testing, risk assessment strategies, and guidelines for P2Y12 inhibitors guided therapy.

COVID-19 pandemic: Challenges and solutions from the cardiology pharmacist's perspective.

The recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenges pharmacists worldwide. Alongside other specialized pharmacists, we re-evaluated daily processes and therapies used to treat COVID-19 patients within our institutions from a cardiovascular perspective and share what we have learned. To develop a collaborative approach for cardiology issues and concerns in the care of confirmed or suspected COVID-19 patients by drawing on the experiences of cardiology pharmacists across the country. On March 26, 2020, a conference call was convened composed of 24 cardiology residency-trained pharmacists (23 actively practicing in cardiology and 1 in critical care) from 16 institutions across the United States to discuss cardiology issues each have encountered with COVID-19 patients. Discussion centered around providing optimal pharmaceutical care while limiting staff exposure. The collaborative of pharmacists found for the ST-elevation myocardial infarction patient, many institutions were diverting COVID-19 rule-out patients to their Emergency Department (ED). Thrombolytics are an alternative to percutaneous coronary intervention (PCI) allowing for timely treatment of patients and decreased staff exposure. An emergency response grab and go kit includes initial drugs and airway equipment so the patient can be treated and the cart can be left outside the room. Cardiology pharmacists have developed policies and procedures to address monitoring of QT prolonging medications, the use of inhaled prostacyclins, and national drug shortages. Technology has allowed us to practice social distancing, while staying in close contact with our teams, patients, and colleagues and continuing to teach. Residents are engaged in unique decision-making processes with their preceptors and assist as pharmacist extenders. Cardiology pharmacists are in a unique position to work with other pharmacists and health care professionals to implement safe and effective practice changes during the COVID-19 pandemic. Ongoing monitoring and adjustments are necessary in rapidly changing times.

Risk Factors and Outcomes Associated with Prolonged Subtherapeutic Anticoagulation with Bivalirudin: A Retrospective Cohort Study.

BACKGROUND: Bivalirudin, a direct thrombin inhibitor, is a treatment option for the management of heparin-induced thrombocytopenia (HIT) and other coagulation disorders. To date, no published studies have identified patients at risk for or the consequence of subtherapeutic bivalirudin therapy. OBJECTIVES: The primary objective was to identify factors associated with failure to achieve early therapeutic anticoagulation (ETA) with bivalirudin, defined as achievement of two consecutive therapeutic activated partial thromboplastin times (aPTTs) within 24 hours. Secondary objectives included evaluating whether failure to achieve ETA was a risk factor for clinical outcomes of interest including thromboembolism, hemorrhage, and mortality. PATIENTS/METHODS: This was a retrospective cohort study. Patients between the ages of 18 and 89 years treated with bivalirudin for 24 hours or longer were identified and classified as either achieving or failing to achieve ETA. RESULTS: Nonadherence to the dosing protocol (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.07-2.71) and creatinine clearance (CrCl) of 60 ml/min or greater (OR 2.99, 95% CI 1.12-7.97) were significantly associated with failure to achieve ETA in univariate analyses. Conversely, increasing age (OR 0.98, 95% CI 0.97-0.99) was significantly associated with achievement of ETA. Failure to achieve ETA was associated with a 4-fold increase in the odds of thromboembolism. CONCLUSIONS: Younger age, normal renal function, and nonadherence to the dosing protocol when targeting therapeutic anticoagulation is associated with increased risk of failure to achieve ETA. This confers an elevated risk of thromboembolism when using bivalirudin for the management of HIT or other coagulation disorders.

Diagnosis, Treatment and Follow Up of Acute Pulmonary Embolism: Consensus Practice from the PERT Consortium.

Pulmonary embolism (PE) is a life-threatening condition and a leading cause of morbidity and mortality. There have been many advances in the field of PE in the last few years, requiring a careful assessment of their impact on patient care. However, variations in recommendations by different clinical guidelines, as well as lack of robust clinical trials, make clinical decisions challenging. The Pulmonary Embolism Response Team Consortium is an international association created to advance the diagnosis, treatment, and outcomes of patients with PE. In this consensus practice document, we provide a comprehensive review of the diagnosis, treatment, and follow-up of acute PE, including both clinical data and consensus opinion to provide guidance for clinicians caring for these patients.

Outcomes for Cancer Patients with Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND/PURPOSE: The incidence of cardiovascular disease in cancer patients is rising. The risk of in-hospital complications for cancer patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) is not well defined. METHODS/MATERIALS: A retrospective single-center cohort assessing STEMI patients with a history of cancer (n = 58) and without a history of cancer (n = 551) who underwent primary PCI between January 1, 2012 and June 30, 2017 was conducted. The primary outcome was a composite of in-hospital complications including reinfarction, cardiogenic shock, new heart failure, stroke, new atrial fibrillation, ventricular tachycardia/fibrillation, cardiac arrest, bleeding, new dialysis requirement, mechanical circulatory support, hospice requirement, and in-hospital mortality. RESULTS: Overall in-hospital complications occurred in 229 (37.6%) patients. There was no significant difference in overall complications in patients with a history of cancer (39.7%), compared to those without a cancer history (37.4%) (adjusted OR 0.84 [0.46-1.51], p = 0.58; unadjusted OR 1.10 [0.61-1.92], p = 0.73); there were no differences exhibited in any of the individual complications. Patients with a history of cancer were significantly more likely to be readmitted within 30 days (12.7% vs. 5%; p = 0.03) and receive bare metal stents (50% vs. 30.4%; p = 0.004) as compared to patients without a history of cancer. CONCLUSIONS: There was no significant difference for in-hospital complications in patients with a history of cancer and those without a history of cancer undergoing primary PCI for STEMI. Patients with a history of cancer were more likely to readmitted within 30 days and receive bare metal stents. SUMMARY: The risk of in-hospital complications for cancer patients with STEMI undergoing primary PCI is not well defined. In a single-center retrospective cohort, there was no significant difference for in-hospital complications between patients with a history of cancer and those without a history of cancer undergoing primary PCI for STEMI.

The effect of establishing pre-angiography thresholds on contrast utilization.

INTRODUCTION: Contrast induced nephropathy is linked to contrast utilization and strategies for minimizing renal injury are incorporated into many laboratories that perform coronary angiography. Contrast limits have been described, below which there is minimal incremental increase in the risk of renal injury. Whether a priori acknowledgement of these limits as part of a contrast "Time-Out" reduces contrast utilization has not been established. In this study, we investigate the effect of verbalizing pre-angiography and ½ time contrast thresholds on contrast utilization and associated clinical outcomes. METHODS: We retrospectively reviewed 5265 cases of coronary angiography (984 with contrast thresholds defined pre-procedure compared to 4281 without pre-defined contrast thresholds). There were two primary endpoints: (1) proportion of procedures that utilized an amount of contrast ≤ threshold, and (2) median difference between amount of contrast utilized and the contrast threshold. Secondary outcomes incorporated indices of renal function, and included changes in serum creatinine levels, eGFR, and CKD stage. RESULTS: Compared to pre-"Time-Out" group, the post-"Time-Out" group had a higher proportion of procedures with contrast ≤ stated contrast threshold (88% vs 84%, P < 0.002), and a lower amount of total contrast volume (88 mL [IQR 60-136] versus 78 mL [IQR 53-119]). The post-"Time-Out" group also had a lower incidence of any increase in post-procedure serum creatinine (45% vs 36%; P = 0.04), and a larger median decrease of pre- to post-procedure eGFR (P = 0.04). CONCLUSION: Acknowledgement of contrast threshold as part of a contrast "Time-Out" is associated with reduced overall contrast utilization, and likely minimizes risks of contrast-induced nephropathy.

Predictors of dexmedetomidine-associated hypotension in critically ill patients.

BACKGROUND: Dexmedetomidine is commonly used for sedation in the Intensive Care Unit (ICU), and its use may be associated with hypotension. We sought to determine predictors of dexmedetomidine-associated hypotension. METHODS: Retrospective, single-center study of 283 ICU patients in four adults ICUs over a 12 month period. Univariate analyses were performed to determine factors associated with dexmedetomidine-related hypotension. Risk factors significant at the 0.20 level in the univariate analysis were considered for inclusion into a step-wise multiple logistical regression model. RESULTS: Hypotension occurred in 121 (42.8%) patients with a median mean arterial pressure (MAP) nadir of 54 mmHg. Univariate analyses showed an association between hypotension and age (P = 0.03), Acute Physiology and Chronic Health Evaluation II (APACHE II) score (P = 0.02), baseline MAP (<0.001), admission to the cardiothoracic ICU (P = 0.05), history of coronary artery disease (P = 0.02), and postcardiac surgery (P = 0.0009). Admission to the medical ICU was associated with a decrease in development in hypotension (P = 0.03). There was a trend for hypotension with weight (P = 0.09) and history of congestive heart failure (P = 0.12) Only MAP prior to initiation (odds ratio [OR] 0.97, 95% confidence interval [95% CI] 0.95-0.99; P < 0.0001), APACHE II scores (OR 1.06, 95% CI 1.01-1.12; P = 0.017), and history of coronary artery disease (OR 0.48, 95% CI 0.26-0.90, P = 0.022) were independently associated with hypotension by multivariable analysis. CONCLUSIONS: Dexmedetomidine-associated hypotension is common. Preexisting low blood pressure, history of coronary artery disease, and higher acuity were identified as independent risk factors for dexmedetomidine-associated hypotension.

Statin desensitization in a patient with probable familial hypercholesterolemia.

PROBLEM OVERVIEW: With cardiovascular disease being the leading cause of morbidity and mortality in the United States, cholesterol-lowering medications have become a prominent focus of medical management and cardiovascular risk reduction, including the use of statins making them the most widely prescribed class of medications in the United States and are the cornerstone of management of hyperlipidemia. This case report describes a 29-year-old female with probable familial hypercholesterolemia (FH) who had allergic reactions to statin therapy on two separate occasions. She required statin therapy based on her elevated carotid intima media thickness test, historic LDL-C ≥ 190 mg/dL, elevated Lp(a), and family history significant for premature coronary heart disease. In this report, we document a case of successful oral desensitization to rosuvastatin and propose a replicable statin desensitization protocol. MAJOR MANAGEMENT: The patient was admitted for rosuvastatin desensitization following predetermined protocols, utilizing an interdisciplinary team, and monitored for 24 hours following completion of administration prior to discharge. She successfully completed desensitization to rosuvastatin 10mg by mouth daily without anaphylactic reaction. She continued to tolerate rosuvastatin 10mg daily through most recent follow-up, and with this addition, significant improvement in lipid levels was achieved. CONCLUSION: This case report presented a patient with probable FH who was previously intolerant to other statin therapies that underwent successful desensitization to rosuvastatin with subsequent achievement of therapy goals.

Innovative approach to preparing radial artery cocktails in response to manufacturer shortages of nitroglycerin and verapamil.

BACKGROUND: Transradial access has gained popularity over transfemoral access for cardiac catheterization, because of the decreased risk of bleeding, time to ambulation, and length of stay leading to improved patient satisfaction. One disadvantage of the radial artery approach is vasospasm, which can be prevented with the administration of verapamil and nitroglycerin in a pre- and postradial cocktail. Unfortunately, there have been manufacturer shortages for both of these medications. METHODS: The utilization of radial artery cocktails and other nitroglycerin compounding practices were evaluated in response to cost containment and waste reduction initiatives and to medication shortages. RESULTS: A modified process for supplying verapamil and nitroglycerin for the transradial approach via separate syringes enabled physicians to have quick access to the medications and to customize the cocktail based on the patient's needs. This process also decreased costs and minimized wastage. The change in practice decreased waste from 44% for preradial cocktail syringes and 66% for postradial cocktail syringes to 8.7%. DISCUSSION: This process for supplying the medications necessary to perform a radial artery catheterization and intracoronary nitroglycerin has allowed for conservation of commercial product supply.

Development and implementation of a nurse-driven, sliding-scale nomogram for bivalirudin in the management of heparin-induced thrombocytopenia.

PURPOSE: A simplified dosing nomogram to assist nurses in adjusting the rate of i.v. bivalirudin administration in cases of heparin-induced thrombocytopenia (HIT) is described. SUMMARY: To facilitate the availability of bivalirudin [corrected] as an alternative direct thrombin inhibitor (DTI) for patients with HIT at The Ohio State University Wexner Medical Center (OSUWMC), a team of clinical pharmacists developed a nomogram designed to simplify infusion dosage adjustments by nurses. In contrast to bivalirudin nomograms requiring patient-specific, percentage-based dose adjustments, the nomogram developed at OSUWMC specifies fixed adjustments (0.005 or 0.01 mg/kg/hr) according to the current activated partial thromboplastin time (aPTT) value relative to aPTT goals. During pilot testing over three years, the nomogram was used to guide dosage adjustments in 65 adult patients receiving continuous infusions of bivalirudin for suspected or confirmed HIT in intensive care units. Overall, the use of the nomogram resulted in adequate anticoagulation, with 53.7% of all measured aPTT values in the target range; 30.5% of aPTT values were below target, and 15.8% of values were above target. The median time to steady state was 11.0 hours (range, 5.0-31.8 hours), and bleeding rates were consistent with those reported in the literature. Nurse adherence to the nomogram was 100%, and no dosing errors occurred during a total of 487 dosage changes. Based on the pilot study results, the nomogram was refined to improve initial dosing for patients with creatinine clearance values of >30 mL/min; other refinements were made to enhance the safety of bivalirudin therapy for HIT in patients with severe renal impairment. CONCLUSION: A nurse-driven, sliding-scale nomogram for bivalirudin therapy in patients with HIT provided a simple dosing protocol and resulted in a high rate of adherence by nurses.

Bleeding outcomes associated with coronary artery bypass graft surgery and recent clopidogrel exposure.

BACKGROUND: Guidelines recommend discontinuing clopidogrel for at least 5 days before elective coronary artery bypass graft surgery (CABG) to limit blood transfusions and for at least 24 hours before urgent CABG to reduce major bleeding complications. Studies have produced conflicting results regarding whether recent exposure to clopidogrel increases bleeding, the need for intraoperative and postoperative blood products, postoperative complications, and hospital length of stay. We evaluated the effect of clopidogrel exposure on major bleeding at our institution within 5 days of CABG. METHODS: We conducted a retrospective review of patients who underwent CABG at a tertiary academic medical center. The primary outcome was major bleeding, defined as transfusion of 4 units of packed red blood cells (PRBCs) and/or a need for reexploration. Secondary outcomes included non-life-threatening bleeding, defined as transfusion of 2 units but <4 units of PRBCs; postoperative complications; hospital length of stay; readmission within 30 days of the procedure; and hospital mortality. Major bleeding events were analyzed with a logistic regression model that adjusted for covariates of bleeding risk factors. RESULTS: Of the 715 patients we reviewed, 169 patients received clopidogrel within 5 days before CABG, and 546 patients did not. A significantly higher incidence of major bleeding was observed in the clopidogrel group compared with the group not exposed to clopidogrel (32% versus 17%, P = .002). After adjusting for covariates, patients exposed to clopidogrel had significantly higher odds of major bleeding (odds ratio, 2.1; 95% confidence interval, 1.3-3.4; P = .003). The groups were similar with respect to postoperative complications, except for infection. The clopidogrel-exposed group had a significantly higher rate of leg site infections (3% versus 0.2%, P = .003). CONCLUSIONS: Clopidogrel exposure within 5 days of CABG is associated with an increased risk of major bleeding.

Stability of diluted adenosine solutions in polyolefin infusion bags.

BACKGROUND: Intravenous or intracoronary adenosine is used in the cardiac catherization lab to achieve maximal coronary blood flow and determine fractional flow reserve. OBJECTIVE: To determine the stability of adenosine 10 and 50 µg/mL in either 0.9% sodium chloride injection or 5% dextrose injection in polyolefin infusion bags stored at 2 temperatures, refrigeration (2°C-8°C) or controlled room temperature (20°C-25°C). METHODS: Adenosine 10 µg/mL and 50 µg/mL solutions were prepared in 50 mL polyolefin infusion bags containing 0.9% sodium chloride injection or 5% dextrose injection and stored at controlled room temperature or under refrigeration. Each combination of concentration, diluent, and storage was prepared in triplicate. Samples were assayed using stability-indicating, reversed-phase high-performance liquid chromatography immediately at time 0 and at 24 hours, 48 hours, 7 days, and 14 days. Stability was defined as retaining 90% to 110% of the initial adenosine concentration. The samples were also visually inspected against a light background for clarity, color, and the presence of particulate matter. RESULTS: After 14 days, all samples retained 99% to 101% of the initial adenosine concentration. No considerable change in pH or visual appearance was noted. The stability data indicated no significant loss of drug due to chemical degradation or physical interactions during storage. CONCLUSION: Adenosine solutions of 10 and 50 µg/mL were stable for at least 14 days in 50 mL polyolefin infusion bags of 0.9% sodium chloride injection or 5% dextrose injection stored at controlled room temperature and refrigerated conditions.

Drug-induced exanthem following dabigatran.

OBJECTIVE: To report an incident of a drug-induced exanthem during treatment with dabigatran in a patient without prior exposure to the drug. CASE SUMMARY: A 20-year-old white male was prescribed oral dabigatran 150 mg twice daily for thromboembolic prevention because of nonvalvular atrial fibrillation. After 2 weeks of dabigatran therapy, a raised, pruritic, erythematous rash developed on the patient's inner thigh and forearm. Upon discontinuation of dabigatran and initiation of oral corticosteroid treatment, the rash resolved. Dabigatran therapy was not readministered and thromboembolic prevention therapy with warfarin was instituted. DISCUSSION: The clinical evidence for efficacy of dabigatran was derived largely from the RE-LY trial, which provided an open-label comparison with warfarin for the reduction of stroke and systemic embolism in nonvalvular atrial fibrillation. The most frequent adverse reactions leading to discontinuation of dabigatran were bleeding and gastrointestinal events. In the RE-LY study, drug hyper-sensitivity, allergic edema, anaphylactic reaction, and anaphylactic shock were reported in <0.1% of patients receiving dabigatran. Despite the low incidence of hypersensitivity reported in the RE-LY trial, the use of the Naranjo probability scale indicated a probable relationship between the rash and dabigatran therapy in this patient. CONCLUSIONS: Upon initiation of dabigatran therapy, surveillance for hyper-sensitivity reactions should be included as part of routine drug monitoring.

Temporary extracorporeal circulatory support and pulmonary embolectomy for catastrophic amniotic fluid embolism.

Amniotic fluid embolism is usually a life-threatening complication of an otherwise healthy pregnancy. Medical management of the coagulopathy and cardiovascular collapse is challenging and is often unsuccessful. We present a case and advocate the use of temporary circulatory support and pulmonary embolectomy in what would otherwise have been a fatal scenario.

Superior vena cava bypass with cryopreserved ascending aorta allograft.

Initially superior vena cava obstruction is typically managed by an endovascular approach. However, in some patients, particularly those in whom angioplasty and stenting is not technically possible, or those who have recurrent disease after previous endovascular repair, an open surgical approach may be indicated. Conduit choices for caval reconstruction are less than ideal; hence we describe a case using a cryopreserved aortic allograft.

Postvaccination Influenza 2009 H1N1 Respiratory Failure Requiring Extracorporeal Membrane Oxygenation.

The spread of pandemic Influenza A (H1N1-2009) was believed to have been attenuated by the effectiveness of worldwide vaccination initiatives. Despite the immunogenicity of a safe vaccine, we report a case of vaccine failure resulting in catastrophic influenza-associated respiratory failure.

The use of extracorporeal membrane oxygenation in severe necrotizing soft tissue infections complicated by septic shock.

Necrotizing soft tissue infections remain a challenging clinical problem. Delays in diagnosis, incomplete débridement of necrotic tissues, and the hemodynamic instability and end-organ failure associated with overwhelming sepsis all contribute to significant mortality. Extracorporeal support is a well-established tool to support profound cardiopulmonary failure. To broaden the indications for use, we present two cases of young adults with necrotizing soft tissue infections who sustained sepsis-induced hemodynamic collapse and required extracorporeal support to facilitate adequate tissue débridement as a bridge to recovery.

Effect of body mass index and device type on infection in left ventricular assist device support beyond 30 days.

Infection as a complication of long-term left ventricular assist device (LVAD) support leads to significant morbidity and mortality. Obesity, a possible risk factor for other postoperative cardiovascular surgical site infections, is an increasingly prevalent condition among recipients of LVAD devices. We retrospectively analyzed 145 LVADs that remained in place beyond 30 days over a nine-year period at a single medical institution. Statistical analysis was carried out using univariate and multivariable logistic regression and chi(2)-testing where indicated. Body mass index (BMI) had no effect on the incidence of infectious outcomes regardless of age, gender, underlying pathogen or device type. This included the morbidly obese population as well (BMI >or=40). Independent of BMI, device type did have an effect, with the HeartMate XVE increasing the risk for infections [odds ratio (OR) 4.3 with 95% confidence interval (CI) 2.1-8.8, P=0.0001] and the HeartMate II reducing the risk (OR 0.21 with 95% CI 0.09-0.50, P=0.0001). The risk for infection after LVAD placement for long-term support is likely to be a multi-factorial phenomenon. BMI, including morbid obesity, does not appear to be a statistically significant relevant factor in determining that risk. Device type may have an effect, however, on risk of infection in long-term support.