Evening Dosing of Antihypertensive Not Superior to Morning Dosing
A randomized UK trial in more than 21,000 patients with hypertension has challenged the long-standing belief that evening doses of antihypertensive medications lead to better outcomes. Results of the trial TIME (Treatment In Morning vs. Evening), a large, prospective, randomized trial that tested whether evening doses of antihypertensives improved major CV outcomes compared with morning dosing, were presented at the European Society of Cardiology Congress in Barcelona.
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Adults taking antihypertensive medications in the UK who had a valid e-mail address were recruited and followed for more than 5 years. After signing up on the trial website, participants were randomized, 10,503 to evening dosing and 10,601 to morning dosing. Average age of patients was 65; 58% were men and 98% were white. Information on outcomes was obtained from e-mail contact with participants and through record linkages to national databases. Further data was gathered from family doctors and hospitals in the UK and was adjudicated by a blinded committee.
The composite endpoint for the study was hospitalization for nonfatal MI, nonfatal stroke, or vascular death. This occurred at similar frequencies regardless of the time of medication administration: 362 participants (3.4%) in the evening dosing group and 390 participants (3.7%) in the morning dosing group experienced these outcomes, for an unadjusted hazard ratio (HR) of 0.95. Other outcomes also showed that neither time of antihypertensive dosing was superior to the other. These outcomes include:
- Nonfatal stroke: HR, 0.93
- Nonfatal MI: HR, 0.92
- CV death: HR, 1.1
- All-cause mortality: HR, 1.04
During the presentation, researchers concluded that patients can take their regular antihypertensive medications at a time of day that is convenient and works for them. (Practical Cardiology. (2022). TIME study: No added benefit from nighttime dosing of blood pressure medications. Retrieved August 2022 from https://www.practicalcardiology.com/view/time-study-no-added-benefit-from-nighttime-dosing-of-blood-pressure-medications; European Society of Cardiology. (2022). Evening dosing of blood pressure medication not better than morning dosing. Press release. Retrieved August 2022 from https://www.escardio.org/The-ESC/Press-Office/Press-releases/Evening-dosing-of-blood-pressure-medication-not-better-than-morning-dosing)
Released: September 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer
CDC Report Details Safety of COVID-19 Booster Doses for Children Ages 5 to 11
A report from the Centers for Disease Control and Prevention (CDC) published in MMWR detailed the findings of safety monitoring of COVID-19 vaccine booster doses administered to children ages 5 to 11. On May 17, 2022, the FDA authorized a booster dose of the Pfizer-BioNTech COVID-19 vaccine under Emergency Use Authorization for children ages 5 to 11 years, to be given 5 months after receipt of the second primary series dose. Approximately 650,000 booster doses were administered to individuals in this age group in the first 10 weeks of rollout (May 17 to July 31).
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Safety data were obtained from v-safe, a voluntary smartphone-based safety surveillance system established to monitor adverse events after COVID-19 vaccination, and from VAERS (Vaccine Adverse Event Reporting System), a national passive vaccine safety surveillance system comanaged by the CDC and FDA. Through v-safe, health surveys are sent daily to registrants during the first week after vaccine administration, with questions about potential local injection-site reactions and systemic reactions as well as health inputs. If parents indicate on the survey that they sought medical care for their child after vaccination, the CDC’s v-safe call center contacts them and encourages completion of a VAERS report. VAERS was developed to monitor adverse events after vaccination; it accepts reports from health care providers, vaccine manufacturers, and members of the public. Serious events that are included in the report include hospitalization, life-threatening illness, permanent disability, congenital anomalies/birth defects, or death.
During those first 10 weeks, approximately 657,302 U.S. children received a third (booster) dose of the Pfizer-BioNTech vaccine; 3,249 reports were made to v-safe for children in this age group. Both local injection-site reactions (n = 2,224) and systemic reactions (n = 1,483) were reported; the prevalence of both was similar to that seen after the second dose of the vaccine:
- Local reactions: 68.5% booster, 68.0% second dose
- Systemic reactions: 45.6% booster, 45.8% second dose
The most frequently reported adverse events were injection-site pain (n = 2,166), fatigue (n = 938), and headache (n = 647); most were mild and were most frequently reported the day after vaccination. In the week after receiving the booster, 225 enrolled children were unable to attend school, and 392 were unable to complete daily activities. The inability to attend school was reported less frequently than after the second dose (6.9% vs. 10.0%), but inability to complete daily activities was reported more frequently (12.1% vs. 7.5%).
VAERS received 581 reports of adverse events after receipt of the booster by children ages 5 to 11; 578 (99.5%) of these reports were considered nonserious. The most commonly reported events (71.1%) were vaccine administration errors (such as preparation errors, incorrect dose, and inappropriate age). Local and systemic reactions were common among the VAERS reports, but no reports of myocarditis or death were received. Only three serious reports were made to VAERS: new-onset diabetes 10 days after vaccination, facial swelling 3 days after vaccination, and pain, fatigue, and malaise 5 days after vaccination.
These findings may change somewhat over time, as safety monitoring continues, more school-age children receive boosters, and as vaccine providers gain additional experience with pediatric doses of COVID-19 vaccines. Continued education of vaccine providers might reduce the errors reported to VAERS. (Hause, A. M., et al. (2022). Safety monitoring of Pfizer-BioNTech COVID-19 vaccine booster doses among children aged 5-11 years – United States, May 17 – July 31, 2022. MMWR, 71(33): 1047–1051. Retrieved August 2022 from https://www.cdc.gov/mmwr/volumes/71/wr/mm7133a3.htm)
Released: September 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer
Olokizumab Effectiveness Expands Treatment Options for Rheumatoid Arthritis
A new drug for rheumatoid arthritis (RA) has been shown to be at least as effective as the current gold standard treatment. Currently, if a patient’s disease progresses on initial therapy with the folic acid antagonist methotrexate, combination therapy with the tumor necrosis inhibitor adalimumab plus methotrexate is administered. Olokizumab is a monoclonal antibody that targets IL-6, which is known to play a role in the inflammatory process and in the progression of joint damage in RA.
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CREDO2 (Clinical Rheumatoid Arthritis Development of Olokizumab) was a Phase III, double-blind, randomized, placebo- and active-controlled, international trial conducted from May 2016 through November 2019 at 209 sites worldwide. Results of the multicenter study, published in the New England Journal of Medicine, compared treatment with olokizumab plus methotrexate to placebo and to the gold standard, adalimumab plus methotrexate, testing for superiority to placebo and for noninferiority to adalimumab.
The study randomly assigned patients with RA and inadequate response to initial methotrexate treatment to receive olokizumab 64 mg every 2 weeks (n = 464), olokizumab 64 mg every 4 weeks (n = 479), adalimumab 40 mg every 2 weeks (n = 462), or placebo (n = 243). All patients continued receiving methotrexate. Patients were followed to determine if they met the criteria for an American College of Rheumatology 20 (ACR20) response by week 12. Such a response entails at least 20% fewer tender or swollen joints and an improvement of at least 20% in 3 of 5 treatment domains:
- Patient’s global assessment of disease activity
- Patient’s assessment of pain
- Provider’s global assessment of disease activity
- Patient function according to score on Health Assessment Question-Disability Index
- C-reactive protein level.
Results demonstrated that, in patients with RA who were receiving maintenance methotrexate, olokizumab was superior to placebo and noninferior to adalimumab in producing ACR20 response at week 12. The proportion of patients who reached ACR20 response at 12 weeks was 44.4% with placebo, 70.3% with olokizumab every 2 weeks, 71.4% with olokizumab every 4 weeks, and 66.9% with adalimumab. Both dosages of olokizumab were considered noninferior to adalimumab on this measure.
The percentage of patients with a Disease Activity Score 28 of less than 3.2 (a measure of acute inflammation) at week 12 was 12.8% of those receiving placebo, 45.3% of those receiving olokizumab every 2 weeks, 45.7% of those receiving olokizumab every 4 weeks, and 38.3% of those receiving adalimumab. The percentage of patients who achieved remission, as assessed by Clinical Disease Activity Index score of 2.8 or less at week 24, was 41.4% with placebo, 11.2% with olokizumab every 2 weeks, 12.1% with olokizumab every 4 weeks, and 13.0% with adalimumab. Adverse events occurred in approximately 70% of patients and were most commonly infections that were mild to moderate in severity.
These results offer another option for treatment for patients with RA, up to 25% of whom don’t respond well to current treatment options. Larger and longer trials are needed to further elucidate the safety and efficacy of olokizumab in RA. (Smolen, J. S., et al. (2022). Olokizumab versus placebo or adalimumab in rheumatoid arthritis. New Engl J Med, 387: 715–726. Retrieved August 2022 from https://www.nejm.org/doi/full/10.1056/NEJMoa2201302)
Released: September 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer
Updated Recommendations for Statin Use for Primary Prevention of Cardiovascular Disease
Updated recommendations for use of statins as primary prevention of atherosclerotic cardiovascular disease (CVD) in adults have been published by the U.S. Preventive Services Task Force (USPSTF) in JAMA. These recommendations were based on review of evidence on the benefits and harms of statins for reducing CVD-related morbidity or mortality and all-cause mortality in adults age 40 and older without a previous history of CVD and no signs or symptoms of CVD who were considered at risk.
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In pooled analysis, statins were associated with a decreased risk of all-cause mortality (18 trials), relative risk (RR), 0.92; of fatal or nonfatal stroke (15 trials), RR, 0.78; of fatal or nonfatal MI (12 trials), RR, 0.67; and with a decreased risk of composite CV outcomes (15 trials), RR, 0.72. No significant harm was associated with statin use in these studies, suggesting a significant overall benefit to their use as primary prevention.
Based on this analysis, USPSTF makes the following clinical recommendations:
- Clinicians should prescribe statins as preventive for CVD in adults ages 40 to 75 who have at least one risk factor for CVD and a 10-year CVD event risk of 10% or greater; the analysis showed with moderate certainty that use of statins in this population had at least a moderate net benefit.
- Clinicians can selectively offer statins to those ages 40 to 75 with at least one CVD risk factor and a 10-year CVD event risk between 7.5% and 10%, taking the patient’s values and preference into account, as well as the presence of factors not included in the original risk assessment; the analysis showed with moderate certainty that use of statins in this population had a smaller net benefit.
- Evidence is insufficient to determine how beneficial it would be to prescribe statins as primary prevention for CVD events and mortality in adults age 76 or older with no history of CVD. Such use would be at the discretion of the clinician, taking other factors into consideration.
The analysis also demonstrates directions for research, including improving the accuracy of CVD risk prediction in all racial, ethnic, and socioeconomic groups, gaining a clearer picture of the benefits and harms of statins as primary prevention in older adults, and determining the efficacy and safety of long-term statin use in younger adults, as well as examining the effects of early versus delayed initiation of statin therapy for primary prevention of CVD disease. (US Preventive Services Task Force. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force recommendation statement. (2022). JAMA, 328(8): 746-753. Retrieved August 2022 from https://jamanetwork.com/journals/jama/fullarticle/2795521)
Released: September 2022
Nursing Drug Handbook
© 2022 Wolters Kluwer