Concerns Raised about Cardiovascular Safety of Therapeutic Cannabis Use
Recreational use of cannabis has been linked with cardiovascular adverse effects. In response to the rise in use of medical cannabis to treat chronic pain, Danish researchers designed a study, published in the European Heart Journal, to investigate whether these associations with new-onset arrhythmias would hold true for medical cannabis use.
READ MORE...
The nationwide cohort study identified 5,391 patients with a prescription for medical cannabis (63.2% women, median age 59) and matched them 1:5 to 26,941 controls based on age, sex, chronic pain diagnosis, and concomitant use of other pain medications. The patients were followed from the index date of the initial prescription (or corresponding date for control patients) until either new-onset arrhythmia, death, or 180 days of observation. The study, based on 4 years of nationwide data from an established cannabis pilot program that allowed any Danish health care provider to prescribe it for chronic pain, allowed use of a combination product containing both cannabidiol (CBD) and tetrahydrocannabinol (THC), as well as products containing only CBD or THC as an option. Of the patients who initiated medical cannabis treatment, 29% received a CBD/THC combination product, 24% CBD only, and 47% THC only. The study reported the absolute risk of first-time arrhythmia, including atrial fibrillation or flutter, conduction disorder, paroxysmal tachycardia, and ventricular arrhythmia, and of acute coronary syndrome; these findings were determined from hospitalizations or outpatient visits coded with any of the arrhythmias.
Arrhythmia was observed in 42 of the 5,391 patients on medical cannabis and in 104 of the 26,941 control individuals. The new-onset arrhythmias observed included atrial fibrillation or flutter (76%), paroxysmal tachycardia (12%), and other arrythmias (12%) in the users of medical cannabis and atrial flutter or fibrillation (79%), conduction disorders (14%), and other arrythmias (7%) in the control group. Medical cannabis use was associated with an elevated risk of new-onset arrhythmia. The 180-day absolute risk was 0.8% compared with 0.4% in control individuals (absolute risk difference, 0.4%), with a risk ratio of 2.07. No significant association was found between use of medical cannabis and risk of hospitalization for acute coronary syndrome (180-day absolute risk difference of 0.04% and 180-day risk ratio of 1.20). Including concomitant treatment with opioids, antiepileptics, and NSAIDs yielded similar results: risk ratios of 1.97 and 1.14 for new-onset arrhythmias and acute coronary syndrome, respectively.
The interest in new treatments for chronic pain, including medical cannabis, is substantial. This study provides evidence of an elevated risk of new-onset arrhythmias, although the incidence is relatively small. Further studies can better identify those at most risk. (Holt, A., et al. (2024). Cannabis for chronic pain: Cardiovascular safety in a nationwide Danish study. Eur Heart J, 45(6), 475–484. Retrieved March 2024 from https://academic.oup.com/eurheartj/article/45/6/475/7500071; Page, II, R. L. (2024). Cannabis by any name does not smell as sweet: Potential cardiovascular events with medical cannabis. Eur Heart J, 45(6), 485–487. Retrieved March 2024 from https://academic.oup.com/eurheartj/article/45/6/485/7500073)
Released: March 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer
Zinc Supplementation Decreases Hand-Foot Skin Reaction in Patients Treated With Regorafenib
Hand-foot skin reaction (HFSR), characterized by abnormalities of the skin on the palms of the hands and soles of the feet, occurs in approximately 35% of cancer patients treated with vascular endothelial growth factor receptor—tyrosine kinase inhibitors (VEGFR-TKIs). But despite its prevalence, effective interventions for HFSR are lacking.
READ MORE...
Because zinc deficiency has been associated with the dermatologic toxicity related to these agents, a phase 2 randomized trial published in the Journal of the American Academy of Dermatology investigated whether zinc supplementation could reduce the severity of HFSR induced by the oral multikinase inhibitor regorafenib within the first 8 weeks of treatment. The trial enrolled 65 patients with metastatic colorectal cancer being treated with regorafenib from March 2016 to March 2019 into a zinc supplementation group (n = 32; zinc gluconate, 78 mg PO twice daily) or a control group (n = 33).
The median serum zinc concentrations at baseline were similar between the zinc supplementation (67.75 mcg/dL) and control groups (65.7 mcg/dL). After 4 weeks of regorafenib treatment, both zinc supplementation and control groups had a similar incidence of grade 2/3 HFSR (21.8% [n = 7 of 32] and 30.3% [n = 10 of 33], respectively). But after 4 weeks, the incidence of grade 2/3 HFSR dropped in the zinc supplementation group, to 12.5% (n = 4 of 23) while remaining similar in the control group (33.3% [n = 11 of 33]). The researchers noted that 6 of the 7 patients who had grade 2/3 HFSR at 4 weeks had improved to grade 0/1 by week 8.
The researchers note the limitations of the study, including the small sample size, lack of data on the patients' quality of life, and the potential influence of skin care measures taken during the study period on the severity of the HFSR. To combat that final problem, patients were assigned to the same dermatologist to minimize differences in the management of skin toxicity. The underlying mechanism of the serum zinc decrease in patients with HSFR caused by VEGFR-TKI treatment remains unclear; it's possible that GI side effects of the treatment may influence zinc intake or that the VEGFR-TKI may directly chelate zinc ions.
Based on this data and other cohort data, clinicians should consider zinc supplementation for those undergoing VEGFR-TKI therapy who develop HFSR. This approach can facilitate quicker recovery from HFSR and allow cancer patients to continue treatment with VEGFR-TKI at optimal doses. (Huang, W-K., et al. (2024). Zinc supplementation decreased incidence of grade ≥2 hand-foot skin reaction induced by regorafenib: A phase II randomized clinical trial. J Am Acad Dermatol, 90(2), 368—369. Retrieved March 2024 from https://www.jaad.org/article/S0190-9622(23)02383-6/fulltext; Lu, C-W. (2023). Zinc supplementation is associated with improvement in hand-foot skin reaction in patients on vascular endothelial growth factor receptor-tyrosine kinase inhibitors: A cohort study. J Am Acad Dermatol. Advanced online publication. Retrieved March 2024 from https://www.jaad.org/article/S0190-9622(23)03272-3/fulltext)
Released: March 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer
Resmetirom Helps Resolve Nonalcoholic Steatohepatitis and Improves Liver Fibrosis
Nonalcoholic steatohepatitis (NASH) is a progressive liver disease, with a global prevalence of 4% to 6%. NASH is characterized by 5% or greater hepatic steatosis with hepatocellular damage and inflammation. Once it progresses to clinically meaningful fibrosis, the risk of adverse outcomes increases, especially among patients with type 2 diabetes. MAESTRO-NASH is an ongoing phase 3 trial evaluating the safety and efficacy of resmetirom, an oral, liver-directed thyroid hormone receptor beta (THRβ)-selective agonist, in adults with biopsy-confirmed NASH and fibrosis. In NASH, THRβ formation in the liver is impaired, which leads to a reduction in mitochondrial function and beta oxidation of fatty acids in association with increasing fibrosis. The double-blind, placebo-controlled trial is being conducted at 245 sites in 15 countries with a planned duration of 54 months. A report in the New England Journal of Medicine describes results of the primary biopsy end points at week 52.
READ MORE...
The trial included 966 patients who were randomized to 80-mg (n = 322) or 100-mg (n = 323) resmetirom or placebo (n = 321). Patients were age 18 or older and had three of five risk factors for metabolic syndrome. Baseline biopsies and repeat biopsies at week 52 were used to determine NASH resolution and improvement in fibrosis. NASH resolution was shown by a hepatocellular ballooning score of 0, lobular inflammation score of 0 to 1, and reduction in nonalcoholic fatty liver disease (NAFLD) activity score by at least 2 points with no worsening of fibrosis. Improvement in fibrosis was indicated by a reduction by at least one stage (scale F0 for no fibrosis to F4 for cirrhosis) with no worsening of the NAFLD activity score.
Demographic and clinical characteristics were similar across groups; 89.3% were white, with a high incidence of metabolic risk factors (78.1% had hypertension, 71.3% dyslipidemia, and 67.0% type 2 diabetes). The mean age of patients was 56.6 years, and the mean body mass index was 35.7. On baseline biopsy, 83.5% of patients had an NAFLD activity score of 5 or more, 5.1% had F1B fibrosis, 33.0% had F2 fibrosis, and 61.9% had F3 fibrosis. NASH resolution with no worsening of fibrosis was achieved in significantly more patients receiving resmetirom than placebo: 25.9% in the 80-mg group and 29.9% in the 100-mg group, compared with 9.7% in the placebo group. Improvement in fibrosis with no worsening of NAFLD score was also achieved in significantly more patients receiving resmetirom than placebo: 24.2% in the 80-mg group and 25.9% in the 100-mg group, compared with 14.2% in the placebo group.
The percentage change from baseline in LDL cholesterol level at week 24, a key secondary endpoint, was −1.36% in the 80-mg resmetirom group, −16.3% in the 100-mg resmetirom group and 0.1% in the placebo group; the decreases with resmetirom use seemed to be maintained at week 52. Most adverse events were mild to moderate and were most frequently GI events; diarrhea and nausea were more frequent with resmeritom. The incidence of serious adverse events was similar across all trial groups: 10.9% in the 80-mg group, 12.7% in the 100-mg group, and 11.5% in the placebo group. (Harrison, S. A., et al. (2024). A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. New Engl J Med, 390, 497–509. Retrieved March 2024 from https://www.nejm.org/doi/full/10.1056/NEJMoa2309000)
Released: March 2024
Nursing Drug Handbook
© 2024 Wolters Kluwer