Trending Topics in Health-System Pharmacy
APhA Staff
Use of premade clevidipine shortens time to goal BP for patients with acute stroke
Patients admitted to the hospital with acute cardiovascular accident (CVA or stroke) often exhibit increased BP, and managing this hypertensive response is critical to treatment of these patients. Continuous infusion of calcium channel blockers such as nicardipine and clevidipine are often used for such treatment because they can be rapidly titrated for acute BP reduction. Both nicardipine and clevidipine are available as premade infusions, which are more expensive than pharmacy-compounded infusions but can possibly be administered more quickly.
The authors of a recent retrospective, observational study, published in the May issue of the American Journal of Health-System Pharmacy, sought to determine if the difference in product availability of premade clevidipine or pharmacy-compounded nicardipine affects the time to goal systolic BP in patients with acute CVA who experienced acute hypertension. Secondary objectives included time from order to administration, time from administration to goal systolic BP, percentage of systolic BP readings below goal, total volume administered, hospital and intensive care unit lengths of stay, inpatient mortality, and adverse events.
The study, conducted by Bethany Martini, PharmD, and Amber Schalk, PharmD, MBA, BCPS, at Sparrow Hospital in Lansing, MI, included 71 patients, 37 in the nicardipine group and 34 in the clevidipine group. A significant difference was found in mean time to goal systolic BP (150.9 minutes in the nicardipine group compared with 69.3 minutes in the clevidipine group). Time from order to administration was 80.1 minutes in the nicardipine group and 35.2 minutes in the clevidipine group, while mean time from administration to goal systolic BP was 70.9 minutes in the nicardipine group and 42.3 minutes in the clevidipine group. No difference was observed between groups in percentage of systolic BP readings below goal, total volume administered, length of stay, or inpatient mortality. Adverse events occurred in 13 (35.1%) of the nicardipine-treated patients and 17 (50%) of the clevidipine-treated patients.
The researchers concluded that the use of premade clevidipine should be considered over pharmacy-prepared nicardipine when rapid BP lowering is warranted in patients with acute CVA. ■
Predicting antibiotic effectiveness in treating uncomplicated acute appendicitis
Recent research suggests that patients who have been diagnosed with uncomplicated acute appendicitis could avoid surgery using antibiotic treatment. According to a study published in JAMA Surgery on January 11, 2022, understanding the associations between clinical and radiographic characteristics and the risk of surgery within 30 days of beginning antibiotics is critical for decision making related to treatment of acute appendicitis.
To assess these patient factors, researchers with the CODA Collaborative used data from the CODA randomized clinical trial conducted at 25 U.S. medical centers to compare characteristics of the patients in the trial who had been randomized to receive antibiotics based on whether the patient required an appendectomy within 30 days of beginning antibiotic treatment.
Of the 776 participants who initially received antibiotics, 154 participants (21%) required an appendectomy within 30 days. After adjustment for other factors, the researchers found that appendicitis severity was not associated with risk of appendectomy within 30 days, but presence of appendicolith was associated with a nearly twofold increased risk of appendectomy.
The authors suggest that these findings will be useful in developing patient-facing tools to support informed decision making for the treatment of appendicitis. ■
Should phosphodiesterase type 5 inhibitors and oral nitrates be prescribed for patients with IHD?
Because muscle relaxation is a known side effect of PDE5 inhibitors, concomitant use of with oral nitrates could result in low blood pressure, causing fainting, strokes, or heart problems. A recent study by Holt and colleagues at the Copenhagen University Hospital–Herlev and Gentofte (Denmark) measured the association between cardiovascular outcomes and such concomitant use of the two medications in real-world situations and found that unlike results from clinical trials, such use did not cause unwanted outcomes.
The study, published on April 19, 2022, in the Annals of Internal Medicine, identified over 42,000 Danish patients with ischemic heart disease (IHD) who had a continuing prescription for nitrates and a new, filled prescription for PDE5 inhibitors between 2000 and 2018. The researchers measured two composite outcomes: cardiac arrest, shock, myocardial infarction, ischemic stroke, or acute coronary arteriography; and syncope, angina pectoris, or a drug-related adverse event. During the study period, the prescription rate for PDE5 inhibitors in patients with IHD who were taking nitrates increased from an average of 0.9 prescriptions to 19.5 prescriptions/100 persons/year in 2018. No statistically significant association was found between the coprescription of nitrates with PDE5 inhibitors and the risk for either composite outcome.
The researchers concluded that while unwanted outcomes from concomitant use have been observed in laboratory studies and clinical trials, such adverse effects may occur only infrequently when the two medications drugs are used in ordinary medical practice. They suggested that clinicians may be advising patients to take the medications at different times of the day, and that this routine may be alleviating the possible cardiovascular outcomes. ■
Very low-dose edoxaban may be beneficial for older patients with AFib
Clinical guidelines recommend the use of oral anticoagulants to prevent cardioembolic stroke in patients with AFib, even in older patients, but many clinicians are reluctant to prescribe standard DOAC doses to older patients due to the increased risk of bleeding.
Researchers in Japan led by Masaru Kuroda, MD, PhD, at the Akashi Medical Center used a subanalysis of the results from the randomized Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients clinical trial to investigate the use of low-dose edoxaban in 3 groups of older patients (80–84 years, 85–89 years, and ≥ 90 years). Eligible patients were recruited randomly from 164 hospitals in Japan and were randomly assigned 1:1 to receive edoxaban or placebo.
The study, published on April 13, 2022, in JAMA Cardiology, showed that 15 mg of edoxaban daily reduced the incidence of stroke or systemic embolism consistently across these three age groups, with a numerically higher risk of major or clinically relevant nonmajor bleeding that did not reach statistical significance. ■
Seeking better guidance for treating severe inpatient hypertension
Hypertension often develops in hospitalized patients admitted for other reasons, but treatment guidelines are lacking. According to the authors of a recent study published on February 17, 2022, in the Journal of Clinical Hypertension, increased BP in hospitalized patients is associated with increased risk of CVD-related outcomes, including stroke, myocardial in-
farction, and coronary artery disease increases, but treatment of severe inpatient hypertension in the absence of acute target organ injury is currently not directed by clinical guidelines.
Researchers led by F. Perry Wilson, MD, MSCE, of the Department of Internal Medicine at Yale University conducted a multi-hospital retrospective cohort study characterize hospitalized patients who develop severe hypertension and assess BP response to treatment as the time to a mean arterial pressure (MAP) drop of ≥ 30%. The authors defined severe inpatient hypertension as the first documented BP elevation (systolic BP > 180 or diastolic BP > 110) at least one hour after admission. Treatment was defined as receiving I.V. or oral antihypertensive medications within 6 hours of BP elevation.
Results of the study showed that 10% of hospitalized patients developed severe hypertension, of which 40% were treated with antihypertensive medications. Patients who developed severe hypertension were older, more commonly women and black, and had more comorbidities. Overall, the authors found that clinically significant MAP drop is observed among inpatients with severe hypertension irrespective of treatment, with greater rates observed among patients treated only with I.V. antihypertensive medications.
The researchers concluded that treating severe inpatient hypertension with I.V. antihypertensive medications should be done conservatively. Future research will focus on assessing BP reduction following treatment with specific antihypertensive drug classes and types and the effect of treatment on clinical outcomes, such as stroke, myocardial infarction, and acute kidney injury, specifically among those with a significant MAP drop. Given that both untreated and treated patients with severe hypertension had a significant reduction in MAP, a one-size-fits-all approach is not appropriate to treating severe hypertension, and additional research is needed to phenotype hospitalized patients with severe hypertension based on adverse outcome risk to help establish personalized treatment guidelines. ■