Empagliflozin in Heart Failure and Preserved Ejection Fraction
EMPEROR-Preserved is the first trial to show unequivocal benefit of a medication for treatment of patients with heart failure with preserved ejection fraction (HFpEF). The sodium-glucose transporter-2 (SGLT2) inhibitor empagliflozin lowered the combined risk of cardiovascular (CV) death or hospitalization for heart failure in patients with HFpEF, regardless of the presence or absence of diabetes.
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The randomized, double-blind, parallel-group, placebo-controlled trial enrolled 5,988 patients with NYHA Class II to IV heart failure and left ventricular ejection fraction (LVEF) >40% (mean age, 72 years; 45% women; mean LVEF, 54%). Nearly half of all patients also had diabetes and nearly half had an eGFR (estimated glomerular filtration rate) of <60 mL/min/1.73 m2. They were randomized to empagliflozin 10 mg once daily (n = 2,997) or to placebo (n = 2,991).
SGLT2 inhibition with empagliflozin led to a 21% lower relative risk in the primary composite outcome of death from CV causes and hospitalization for heart failure. The composite outcome occurred in 415 patients (13.8%) in those receiving empagliflozin and in 511 patients (17.1%) in those on placebo. This reduction was mostly attributed to a lower number of hospitalizations for heart failure, with fewer admissions—407 in the empagliflozin arm vs. 514 in the placebo arm (hazard ratio, 0.73). Breaking the composite down into its parts, deaths from CV causes occurred in 219 patients (7.3%) in the empagliflozin arm and in 244 patients (8.2%) in the placebo arm (hazard ratio, 0.91); hospitalization for heart failure occurred in 259 patients (8.6%) in the empagliflozin arm and 352 patients (11.8%) in the placebo arm (hazard ratio, 0.7). The trial also showed a slower decline in renal function over time in those treated with empagliflozin. The rate of decline in eGFR was −1.25 mL/min/1.73 m2/yr in the empagliflozin arm vs. −2.62 mL/min/1.73 m2/yr in the placebo arm.
These results are likely to result in a change in clinical practice, as clinicians now have an option for treatment of patients with HFpEF. (Neale, T. (2021). EMPEROR-Preserved: Empagliflozin improves outcomes in HFpEF. Retrieved September 2021 from https://www.tctmd.com/news/emperor-preserved-empagliflozin-improves-outcomes-hfpef; New Engl J Med. 27 August 2021. Empagliflozin in heart failure with preserved ejection fraction. Retrieved September 2021 from https://www.nejm.org/doi/full/10.1056/NEJMoa2107038?query=recirc_curatedRelated_article)
Released: October 2021
Nursing Drug Handbook
© 2021 Wolters Kluwer
Maternal COVID-19 Vaccination
A cohort study published in the American Journal of Obstetrics and Gynecology provided data on maternal antibody generation and suggests that COVID-19 vaccination of women who are pregnant and lactating can confer robust maternal and neonatal immunity against SARS-CoV2 infection. Although the absolute risk of severe COVID-19 is low in women who are pregnant, pregnancy is a risk factor for severe disease. Mothers with severe COVID-19 infections and their neonates are at increased risk for a number of perinatal complications, including cesarean birth, hypertensive disease of pregnancy, venous thromboembolism, preterm birth, low birthweight, and NICU admission. COVID-19 infection in pregnancy is also associated with an increased risk for ICU admission, need for extracorporeal membrane oxygenation, and maternal death.
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The study enrolled 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, 16 nonpregnant). Researchers measured titers of SARS-CoV2 spike and reception-binding domain IgA, IgG, and IgM in the recipients’ blood and human milk at the time of the first vaccine dose, at the time of the second dose, 2 to 6 weeks after the second dose, and at delivery (for patients who were pregnant). Umbilical cord titers (n = 10) were assessed at delivery. These titers were then compared with those of women who were pregnant 4 to 12 weeks after a SARS-CoV2 infection (n = 37) by enzyme-linked immunosorbent assay.
The mRNA vaccine was highly effective in inducing antibody titers in women who were pregnant (median titer, 5.74) and lactating (median titer, 5.62), results similar to those in women who were not pregnant (median titer, 5.59). Higher levels of antibodies were observed in all women who were vaccinated compared to those of the women who were pregnant who had experienced natural SARS-CoV2 infection. Antibodies were also present in all umbilical cord blood and human milk samples. In particular, a boost in human milk IgG levels was observed, paralleling the boost seen in maternal IgG levels in serum after the second dose. Interestingly, IgA was not increased in the blood or human milk of the women in the study, an unexpected finding, as IgA is the largest component of the immune response in the human milk of women with natural SARS-CoV2 infection.
Vaccine-related fever and chills were reported by 32% of women who were pregnant (25/77) and by 50% of women who were not pregnant (8/16) after the second dose. Cumulative symptom score after the first dose was low in all groups, and there were no significant differences between groups in cumulative symptom score after the second dose (median score of 2 for women who were pregnant, 3 for women who were lactating, and 2.5 for women who were not pregnant).
Further research in larger populations is needed to support recommendations for vaccine administration in women who are pregnant, as well as providing a greater understanding of vaccine-induced and antibody transfer kinetics across all trimesters. (Pham, A., et al. (2021). Maternal COVID-19, vaccination safety in pregnancy, and evidence of protective immunity. J Allergy Clin Immunol, 148(3), 728–731. Retrieved September 2021 from https://www.jacionline.org/article/S0091-6749(21)01133-7/fulltext; Gray, K. J., et al. (2021). Coronavirus disease 2019 vaccine response in pregnant and lactating women: A cohort study. Am J Obstet Gynecol, 225(3), P303.E1–303.E17. Retrieved September 2021 from https://www.ajog.org/article/S0002-9378(21)00187-3/fulltext#secsectitle0060)
Released: October 2021
Nursing Drug Handbook
© 2021 Wolters Kluwer
Quadruple Pill for Hypertension
A study conducted by the University of Sydney and the George Institute for Global Health showed that a strategy of combining one-quarter doses of four antihypertensive medications into one pill (quadpill) as a first intervention against high blood pressure is more effective than the currently recommended single-drug therapy. This multicenter, double-blind, parallel-group, randomized, phase 3 trial, published in The Lancet and presented at the European Society of Cardiology Conference on August 29th, enrolled 591 patients across 10 Australian centers; participants had high blood pressure (BP) (baseline mean BP: 141/85 mm Hg) and were receiving no therapy or were receiving their first single antihypertensive treatment.
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The patients were assigned to the quadpill (n = 300), which contained 37.5 mg irbesartan, 1.25 mg amlodipine, 0.625 mg indapamide, and 2.5 mg bisoprolol, or to standard-dose monotherapy (n = 291) with 150-mg irbesartan. Patients who didn’t reach the target BP within 12 weeks could have additional medications added to the regimen, starting with amlodipine at 5 mg. A subgroup continued their randomly assigned treatment for 12 months to assess long-term effects.
Blood pressure was brought under control in 76% of participants receiving the quadpill in 12 weeks, compared to 58% in the control group. Mean BP at 12 weeks was 121/71 mm Hg on quadpill therapy versus 127/79 mm Hg on monotherapy; the mean difference in systolic BP was −6.9 mm Hg. The differences in outcome were sustained, with continued better BP control with the quadpill approach at 52 weeks. Mean systolic BP at that time remained lower on quadpill therapy (−7.7 mm Hg); rates of BP control remained higher in the quadpill group (81%) versus controls (62%).
Traditional medication treatment for hypertension starts with one antihypertensive and then adds other medications as needed, but this is not always successful; in some regions of the world, as few as 1 in 10 patients have their BP under control. These results could reduce risks of myocardial infarction or stroke by about 20% in areas with access to high levels of specialized treatment; in areas with little or no existing treatment, the benefits could be even greater. (George Institute for Global Public Health. News release. (2021, 30 August). Ground breaking study shows 4 in 1 blood pressure pill is more effective than current treatment. Retrieved September 2021 from https://www.georgeinstitute.org/media-releases/ground-breaking-study-shows-4-in-1-blood-pressure-pill-is-more-effective-than; University of Sydney. Media Release. (2021, 29 August). 4 in 1 blood pressure pill: Safe and much more effective than usual hypertension treatment. Retrieved September 2021 from https://cdn.georgeinstitute.org/sites/default/files/quartet_mr_final.pdf; Chow, C. K., et al. (2021). Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): A phase 3, randomised, double-blind, active-controlled trial. The Lancet, 398(10305), P1043–1052.)
Released: October 2021
Nursing Drug Handbook
© 2021 Wolters Kluwer
Ranibizumab against Retinopathy of Prematurity
Analysis of 2-year outcomes of the RAINBOW extension study, which compares results of intravitreal injection with the vascular endothelial growth factor (VEGF) inhibitor ranibizumab versus laser therapy for treatment of very-low-birthweight infants with retinopathy of prematurity (ROP), were published in Lancet Child and Adolescent Health. Because the retina develops late in fetal development, very premature babies can have incomplete development of the blood vessels needed to provide oxygen to the retina. After birth, blood vessels develop abnormally, causing the vision loss known as ROP. It’s known that an overabundance of VEGF can produce the abnormal blood vessels seen in ROP.
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Families of the 201 infants who completed the core RAINBOW study were approached for consent to enter an extension study through age 5; 180 infants were enrolled in the extension study, and 153 (85%) were evaluated at age 20 to 28 months for ophthalmic, developmental, and health outcomes, after correcting age for prematurity.
No child in this cohort developed new ocular abnormalities (the primary outcome). Structural abnormalities were present in 1 (2%) of the 56 infants in the ranibizumab 0.2-mg group, 1 (2%) of the 51 infants in the ranibizumab 0.1-mg group, and 4 (9%) of 44 infants in the laser therapy group. The odds ratio for structural abnormality was 5.68 for ranibizumab 0.2 mg versus laser therapy, 4.82 for ranibizumab 0.1 mg versus laser therapy, and 1.21 for ranibizumab 0.2 mg versus ranibizumab. 0.1 mg. High myopia, defined as −5 diopters or worse, was less frequent after the 0.2-mg dose of ranibizumab (5/110 eyes [5%]) than with laser therapy (16/82 eyes [20%]); odds ratio, 0.19. In addition, composite vision-related quality of life scores, based on parents’ reports using the Children’s Visual Function Questionnaire, were higher among patients receiving 0.2 mg ranibizumab (mean score, 84) compared with those receiving laser therapy (mean score, 77). Developmental scores, as assessed by the Mullen Scales of Early Learning, were similar across the three groups. (Marlow, N., et al. (2021). 2-year outcomes of ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW extension study): Prospective follow-up of an open label, randomised controlled trial. Lancet Child Adolesc Health. Advanced online publication. Retrieved September 2021 from https://www.thelancet.com/pdfs/journals/lanchi/PIIS2352-4642(21)00195-4.pdf)
Released: October 2021
Nursing Drug Handbook
© 2021 Wolters Kluwer