Pharmacology/Pharmaceutical Industry
Randomized Controlled Trial: Mixed results with Andexanet Alfa for Factor Xa inhibitor-associated acute intracerebral hemorrhage – N Engl J Med
27 May, 2024 | 20:26h | UTCStudy Design and Population: This randomized controlled trial involved 530 patients with acute intracerebral hemorrhage who had taken factor Xa inhibitors within 15 hours before the event. They were randomly assigned to receive either andexanet alfa or usual care.
Main Findings: Hemostatic efficacy was achieved in 67% of patients receiving andexanet compared to 53.1% receiving usual care. Andexanet significantly reduced anti-factor Xa activity by 94.5%, compared to 26.9% with usual care. However, thrombotic events were more frequent in the andexanet group, including ischemic stroke.
Implications for Practice: Andexanet alfa is effective in controlling hematoma expansion in patients with factor Xa inhibitor-associated intracerebral hemorrhage but has an increased risk of thrombotic events. Further research is needed to balance efficacy and safety.
Reference (link to abstract – $ for full-text):
Randomized Clinical Trial: Dequalinium chloride demonstrates noninferiority to metronidazole in treating bacterial vaginosis – JAMA Netw Open
25 May, 2024 | 19:55h | UTCThis randomized clinical trial investigated the efficacy of dequalinium chloride compared to metronidazole for treating bacterial vaginosis in premenopausal women. Conducted across multiple centers from July 2021 to August 2022, the study involved 147 participants who were randomly assigned to receive either dequalinium chloride vaginal tablets or oral metronidazole. The primary outcome measured was the clinical cure rate shortly after treatment completion. Results showed that dequalinium chloride achieved a 92.8% cure rate, which was statistically noninferior to metronidazole’s 93.2% rate. Additionally, dequalinium chloride was better tolerated, with fewer adverse events reported compared to metronidazole. These findings suggest that dequalinium chloride is as effective as traditional antibiotic treatments for bacterial vaginosis and could be considered a viable non-antibiotic alternative due to its similar efficacy and enhanced tolerability.
Reference (link to free full-text):
Cohort Study: GLP1 receptor agonist use not associated with significant increase in thyroid cancer risk – The BMJ
25 May, 2024 | 19:51h | UTCA large Scandinavian cohort study investigated the association between glucagon-like peptide 1 (GLP1) receptor agonist use and thyroid cancer risk in Denmark, Norway, and Sweden from 2007 to 2021. The study compared 145,410 patients treated with GLP1 receptor agonists to 291,667 patients treated with dipeptidyl peptidase 4 (DPP4) inhibitors and included an additional analysis with sodium-glucose cotransporter 2 (SGLT2) inhibitors. Results showed no significant increase in thyroid cancer risk among GLP1 users over a mean follow-up of 3.9 years, with a hazard ratio of 0.93 (95% CI, 0.66 to 1.31) compared to DPP4 inhibitor users. The study utilized nationwide cancer registers and employed an active-comparator, new user design to minimize confounding, using Cox regression models adjusted by propensity score weighting. The findings suggest that while small risk increases cannot be definitively ruled out, the use of GLP1 receptor agonists does not substantially elevate thyroid cancer risk.
Reference (link to free full-text):
Cohort Study: Prenatal opioid exposure linked to modest increase in neuropsychiatric disorders – The BMJ
25 May, 2024 | 19:50h | UTCThis nationwide birth cohort study from South Korea investigated the impact of prenatal opioid exposure on the risk of neuropsychiatric disorders among children. The study followed 3,128,571 infants born between 2010 and 2017 until the end of 2020. Researchers found that infants exposed to opioids prenatally showed a slightly increased risk of developing neuropsychiatric disorders, including mood disorders, attention deficit hyperactivity disorder, and intellectual disability. The increased risk was more pronounced with higher opioid doses, longer duration of use, and exposure during the first trimester of pregnancy. However, this association was not significant in sibling comparison cohorts, indicating a modest overall clinical impact. The study emphasizes the need for cautious interpretation due to its observational design and the specific conditions under which risk increases.
Reference (link to free full-text):
APA workgroup update maintains skepticism on pharmacogenomic tools for depression – Am J Psychiatry
25 May, 2024 | 19:47h | UTCA recent review by the American Psychiatric Association (APA) Council of Research Workgroup on Biomarkers and Novel Treatments revisits the use of pharmacogenomic (PGx) tools for selecting depression treatments. The review assesses new clinical trials and meta-analyses conducted from 2017 to 2022. Of the studies analyzed, few demonstrated significant efficacy in treatment response using PGx tools, with many suffering from methodological flaws such as lack of full blinding and insufficient control measures. Despite some trials showing promise, the overall evidence remains insufficient to support the widespread clinical application of PGx tools in managing major depressive disorder. The Workgroup reaffirms the 2018 conclusions and aligns with the U.S. Food and Drug Administration’s stance, recommending that future research should focus on more rigorous study designs and explore other potential benefits of pharmacogenomics, such as predicting rare adverse drug reactions.
Reference (link to abstract – $ for full-text)
Retrospective Analysis: 7% of outpatients in Massachusetts experience adverse events, predominantly drug-related – Ann Intern Med
25 May, 2024 | 19:37h | UTCThis retrospective study reviewed electronic health records from 11 outpatient sites in Massachusetts during 2018 to assess the incidence and nature of adverse events (AEs) in 3,103 patients. AEs were identified in 7.0% of the patients, translating to 8.6 events per 100 patients annually. Adverse drug events were the most frequent type of AE, constituting 63.8% of events, followed by healthcare-associated infections (14.8%) and surgical or procedural events (14.2%). The severity of these events was notable, with 17.4% being serious and 2.1% life-threatening, though none were fatal. Notably, 23.2% of these events were deemed preventable. The risk of experiencing at least one AE varied significantly by age and race, with higher rates observed among older adults and Black patients compared to other demographics. The study highlights the pressing need for targeted interventions to reduce AEs in outpatient settings.
Reference (link to abstract – $ for full-text):
RCT: Ponatinib shows superior MRD-negative complete remission rates compared to Imatinib in newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia – JAMA
25 May, 2024 | 19:03h | UTCThis global phase 3 randomized clinical trial investigated the efficacy and safety of ponatinib versus imatinib in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). The study, conducted across 77 sites, enrolled 245 patients who were randomized in a 2:1 ratio to receive either ponatinib (30 mg/d) or imatinib (600 mg/d) alongside reduced-intensity chemotherapy. The primary endpoint of the trial was minimal residual disease–negative (MRD-negative) complete remission, assessed at the end of cycle 3. Results showed that ponatinib achieved a significantly higher MRD-negative complete remission rate of 34.4% compared to 16.7% with imatinib. Additionally, the safety profile between the two drugs was comparable, with arterial occlusive events being rare and similar across groups. These findings suggest ponatinib as a potentially preferable frontline therapy in this patient population due to its superior efficacy in achieving MRD-negative status without compromising safety.
Reference (link to abstract – $ for full-text):
Cohort Study: Impact of decreasing eGFR on serious adverse drug reactions in CKD patients – Am J Kidney Dis
25 May, 2024 | 18:48h | UTCThis prospective cohort study, part of the French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN), involved 3,033 outpatients with moderate to advanced chronic kidney disease (CKD). The study aimed to explore the correlation between estimated glomerular filtration rate (eGFR) and the incidence of serious adverse drug reactions (ADRs). Over a median follow-up of 4.7 years, 360 patients experienced 488 serious ADRs, predominantly kidney and urinary disorders, and hemorrhages, constituting 70% of cases. The study identified antithrombotics and renin-angiotensin system inhibitors as the most common medication classes leading to these ADRs. A significant finding was that a decrease in eGFR is associated with a higher risk of serious ADRs, specifically acute kidney injury and bleeding, which were largely preventable or potentially preventable. The outcomes highlight the critical need for careful drug prescription and monitoring in CKD patients to mitigate serious ADRs.
Reference (link to free full-text):
RCT: Triple combination of paracetamol, ibuprofen, and dexamethasone reduces morphine use post-hip arthroplasty – Lancet Rheumatol
11 May, 2024 | 14:18h | UTCStudy Design and Population: The RECIPE trial was a randomized, blinded, placebo-controlled multicenter study conducted across nine Danish hospitals to evaluate the effectiveness of non-opioid analgesic combinations in managing postoperative pain following total hip arthroplasty. A total of 1,060 adults scheduled for surgery were enrolled and randomly assigned to one of four treatment groups, receiving combinations of paracetamol, ibuprofen, and dexamethasone. The study’s primary endpoint was the 24-hour intravenous morphine consumption, with a predefined minimal important difference set at 8 mg.
Main Findings: The trial results indicated significant reductions in 24-hour morphine consumption in the group receiving paracetamol, ibuprofen, and dexamethasone combined, compared to other groups, though none reached the minimal important difference. Specifically, this group consumed a median of 15 mg morphine, which was less than the other groups ranging from 16 mg to 24 mg. However, the differences did not meet the study’s threshold for a clinically important effect. Adverse events were lowest in the combined treatment group, suggesting a better safety profile primarily characterized by fewer incidents of nausea, vomiting, and dizziness.
Implications for Practice: The findings support the use of a combined regimen of paracetamol, ibuprofen, and dexamethasone for reducing morphine consumption post-total hip arthroplasty, which could be significant in clinical settings aiming to minimize opioid use. The improved safety profile also highlights the potential benefits of multimodal analgesia. Further research may explore the optimization of dosing schedules and long-term outcomes to enhance patient recovery and satisfaction.
Reference (link to abstract – $ for full-text):
RCT: KarXT (xanomeline–trospium) demonstrates significant symptom reduction in schizophrenia compared to placebo – The Lancet
11 May, 2024 | 13:42h | UTCStudy Design and Population: The EMERGENT-2 study was a randomized, double-blind, placebo-controlled, flexible-dose, 5-week phase 3 trial conducted across 22 inpatient sites in the USA. It targeted adults aged 18–65 years diagnosed with schizophrenia, exhibiting a recent exacerbation in psychotic symptoms. A total of 252 participants, each with a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher and a Clinical Global Impression-Severity score of 4 or more, were enrolled and randomized equally into two groups to receive either the muscarinic receptor agonist KarXT (xanomeline–trospium) or a placebo.
Main Findings: KarXT significantly reduced the PANSS total scores from baseline to week 5, with a mean decrease of 21.2 points compared to 11.6 points in the placebo group (least squares mean difference -9.6; 95% CI -13.9 to -5.2; p<0.0001; Cohen’s d=0.61). All secondary endpoints were also met favorably for KarXT. Common adverse events for KarXT included constipation, dyspepsia, and nausea, but rates of extrapyramidal symptoms were similar between the two groups. The treatment was generally well tolerated with comparable discontinuation rates due to adverse events.
Implications for Practice: These results indicate that KarXT could represent a new class of antipsychotic treatment, diverging from traditional D2 dopamine receptor antagonists and instead leveraging muscarinic receptor activation. The promising outcomes observed in EMERGENT-2 suggest that KarXT has the potential to improve both positive and negative symptoms of schizophrenia while maintaining a favorable safety profile. Ongoing and future studies (EMERGENT-3, EMERGENT-4, and EMERGENT-5) will further elucidate the long-term efficacy and safety of KarXT.
Reference (link to abstract – $ for full-text):
RCT: Cytisinicline shows promising results in enhancing vaping cessation among adults – JAMA Intern Med
11 May, 2024 | 13:35h | UTCStudy Design and Population: The ORCA-V1 study was a double-blind, placebo-controlled randomized clinical trial conducted across five US clinical sites from July 2022 to February 2023. It enrolled 160 adults who used nicotine e-cigarettes daily and expressed a desire to quit, but were not current cigarette smokers. Participants were predominantly middle-aged (mean age 33.6 years), with a slight female majority (51.9%).
Main Findings: The trial assessed cytisinicline, a plant-based alkaloid, compared to placebo over a 12-week period with follow-up to 16 weeks. Results showed that cytisinicline significantly increased continuous abstinence from e-cigarette use during the last four weeks of treatment (31.8% vs 15.1% with placebo; odds ratio, 2.64; 95% CI, 1.06-7.10; P = .04). The effect was less pronounced but still present during the four weeks post-treatment (23.4% vs 13.2% with placebo; odds ratio, 2.00; 95% CI, 0.82-5.32; P = .15). The medication was well-tolerated, with only 3.8% of the cytisinicline group discontinuing due to adverse events.
Implications for Practice: Cytisinicline offers a promising pharmacotherapy option for adults seeking to quit vaping, demonstrating both efficacy and safety in this trial. Further research in larger populations and over longer periods is needed to confirm these findings and fully establish cytisinicline’s role in treating nicotine e-cigarette dependence.
Reference (link to abstract – $ for full-text):
Phase 2 RCT: Preventive subcutaneous L9LS monoclonal antibody reduces malaria incidence by 66-70% in Malian children – N Engl J Med
7 May, 2024 | 15:31h | UTCThis phase 2 randomized clinical trial investigated the safety and efficacy of the monoclonal antibody L9LS in preventing Plasmodium falciparum infection and clinical malaria in children aged 6 to 10 years in Mali. The trial was structured in two parts: initial dose assessment in adults followed by a randomized, placebo-controlled test in children over a 6-month malaria season. A total of 225 children participated, divided equally among three groups to receive either 150 mg of L9LS, 300 mg of L9LS, or a placebo. Results demonstrated a significant reduction in the rate of P. falciparum infection—66% efficacy with the 150-mg dose and 70% efficacy with the 300-mg dose. Similarly, efficacy against clinical malaria was 67% with the 150-mg dose and 77% with the 300-mg dose. Both doses were well-tolerated with no safety concerns reported, underscoring the potential of L9LS as a preventative treatment against malaria in endemic regions.
Reference (link to abstract – $ for full-text):
ACP Guidelines for the pharmacologic management of type 2 diabetes in adults – Ann Intern Med
3 May, 2024 | 14:05h | UTCThe American College of Physicians (ACP) has issued an updated guideline focusing on the pharmacological management of type 2 diabetes. This guideline reviews the efficacy and safety of new medications, including GLP-1 agonists, SGLT-2 inhibitors, and others, emphasizing a systematic evaluation using the GRADE methodology. Key recommendations advise the integration of SGLT-2 inhibitors or GLP-1 agonists with metformin and lifestyle changes for better glycemic control and reduction in mortality and major cardiovascular events. Conversely, the use of DPP-4 inhibitors in similar therapeutic contexts is not recommended due to insufficient evidence of benefit. This guideline targets healthcare providers managing nonpregnant adults with type 2 diabetes.
Reference (link to free full-text):
ACP cost-effectiveness analysis: Newer antidiabetic medications in type 2 diabetes – Ann Intern Med
3 May, 2024 | 13:57h | UTCThis systematic review evaluates the cost-effectiveness of newer antidiabetic medications for type 2 diabetes from U.S. clinical and economic perspectives. Analyzing non-industry funded cost-effectiveness analyses (CEAs) using GRADE and Drummond criteria, the study identifies varying cost per quality-adjusted life-year (QALY) values for medications such as GLP1a and SGLT2i. It concludes that while GLP1a and SGLT2i offer low value as primary therapies due to high costs, they may present intermediate value as adjunct treatments to metformin. The study highlights the methodological variability in CEAs and the influence of drug cost and effectiveness assumptions on outcomes. The results suggest cautious interpretation in clinical decision-making due to varied evidence quality and cost-effectiveness profiles among the reviewed medications.
Reference (link to free full-text):
ACP Meta-Analysis: Comparative efficacy of newer antidiabetic agents in type 2 diabetes management – Ann Intern Med
3 May, 2024 | 13:49h | UTCThis systematic review and network meta-analysis evaluates the effectiveness and safety of modern antidiabetic drugs in managing type 2 diabetes mellitus. The study analyzed 130 publications from 84 randomized controlled trials, using GRADE criteria for evidence assessment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) agonists demonstrated significant reductions in all-cause mortality and major adverse cardiovascular events when compared to usual care, with SGLT2 inhibitors also showing benefits in reducing chronic kidney disease progression and hospitalizations due to heart failure. In contrast, dipeptidyl peptidase-4 (DPP4) inhibitors, insulin, and tirzepatide showed no significant mortality benefits. The study identified limitations including sparse direct drug comparisons and inadequate data for certain patient subgroups. Overall, SGLT2 inhibitors and GLP1 agonists were associated with fewer serious adverse events and severe hypoglycemia compared to insulin and sulfonylureas.
Reference (link to free full-text):
Review: Key findings from the Women’s Health Initiative studies on postmenopausal interventions – JAMA
3 May, 2024 | 13:34h | UTCThe Women’s Health Initiative (WHI) studied the impact of various interventions on postmenopausal women aged 50-79, using data from 161,808 participants between 1993 and 2018. The findings suggest that hormone therapy, specifically with conjugated equine estrogens and medroxyprogesterone acetate, does not reduce the risk of cardiovascular diseases, dementia, or other chronic conditions in postmenopausal women. It is, however, effective for managing severe menopausal symptoms when initiated before age 60 in women without contraindications. The trials also concluded that universal supplementation of calcium and vitamin D does not effectively prevent fractures and should be limited to those not meeting dietary intake recommendations. Furthermore, a low-fat diet rich in fruits, vegetables, and grains did not reduce the incidence of breast or colorectal cancer, though it may decrease breast cancer mortality rates, indicating the need for further investigation.
Reference (link to free full-text for a limited period):
RCT: Beta-blockers post myocardial infarction showed no benefit in patients with preserved ejection fraction
30 Apr, 2024 | 13:40h | UTCThis randomized, open-label clinical trial conducted across 45 centers in Sweden, Estonia, and New Zealand examined the impact of long-term beta-blocker treatment in patients with acute myocardial infarction (AMI) who had undergone coronary angiography and had a preserved left ventricular ejection fraction (LVEF ≥ 50%). The study involved 5020 patients, predominantly from Sweden, with a median follow-up of 3.5 years. Participants were randomly assigned to receive either a beta-blocker (metoprolol or bisoprolol) or no beta-blocker. The primary endpoint was a composite of death from any cause or new myocardial infarction. The results showed no significant difference in the primary endpoint between the beta-blocker group (7.9%) and the no–beta-blocker group (8.3%) with a hazard ratio of 0.96 (95% CI, 0.79 to 1.16; P=0.64). Additionally, no significant differences were observed in secondary endpoints such as death from cardiovascular causes, myocardial infarction, or hospitalizations for atrial fibrillation and heart failure. Safety endpoints were also comparable between the groups. Overall, long-term beta-blocker treatment did not confer a reduction in risk for the primary composite endpoint or improve secondary outcomes in this patient population.
Commentary on X:
Original Article: Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction (REDUCE-AMI trial) https://t.co/z1NNeAK9Mm
Editorial: Routine Beta-Blockers in Secondary Prevention — On Injured Reserve https://t.co/NzlExH0LZm #ACC24 pic.twitter.com/8Jqpj2dM6E
— NEJM (@NEJM) April 17, 2024
Reference (link to abstract – $ for full-text):
RCT: Post-1 month ticagrelor monotherapy vs. dual antiplatelet therapy significantly reduces bleeding events in acute coronary syndromes
30 Apr, 2024 | 13:26h | UTCIn this randomized, placebo-controlled, double-blind clinical trial, 3400 patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI) were assessed to compare the effects of ticagrelor alone versus ticagrelor plus aspirin from 1 to 12 months post-PCI. The study aimed to determine if ticagrelor alone could reduce bleeding without increasing major adverse cardiovascular or cerebrovascular events (MACCE). The primary findings indicated that ticagrelor alone resulted in significantly lower clinically relevant bleeding (2.1% vs. 4.6%, p<0.0001) and demonstrated non-inferiority in MACCE rates compared to the dual therapy group (3.6% vs. 3.7%, pnon-inferiority<0.0001). These outcomes suggest that ticagrelor monotherapy, starting one month post-PCI, may be an effective alternative to standard dual antiplatelet therapy in reducing bleeding risks without compromising safety.
Commentary on X:
Ticagrelor, in combination with #aspirin for 1 month, followed by ticagrelor alone,
after #PCI (GLOBAL LEADERS): a randomised superiority trial https://t.co/Bo8gfHIZLeRegister now to freely access #ESCCongress #LancetCardiology content up to Sept 10! https://t.co/6wOSrV9yXM pic.twitter.com/8EV5d8s1c8
— The Lancet (@TheLancet) August 27, 2018
Reference (link to abstract – $ for full-text):
Phase 2 RCT: Lixisenatide slows progression of motor disability in early Parkinson’s disease, but with notable gastrointestinal side effects
30 Apr, 2024 | 13:00h | UTCIn a phase 2, double-blind, randomized, placebo-controlled trial, the effect of lixisenatide, a glucagon-like peptide-1 receptor agonist, was evaluated for its potential to slow the progression of motor disability in patients with early Parkinson’s disease. A total of 156 patients, diagnosed within the past three years and stable on symptom-managing medications, were enrolled and equally divided into lixisenatide and placebo groups. After 12 months, the lixisenatide group showed a slight improvement in motor disability (−0.04 point change) compared to a worsening in the placebo group (3.04 point change) on the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III. This difference was statistically significant (p=0.007). However, after a 2-month washout period, improvements were less distinct. Notably, 46% of lixisenatide-treated patients experienced nausea, and 13% reported vomiting. These findings suggest potential benefits of lixisenatide for motor symptoms in Parkinson’s disease, though further research is necessary to fully assess its efficacy and tolerability.
Commentary on X:
Original Article: Trial of Lixisenatide in Early Parkinson’s Disease (LIXIPARK phase 2 trial) https://t.co/2ancdAqO9i
Editorial: GLP-1, Parkinson’s Disease, and Neuroprotection https://t.co/ZaFfYyvEP9 #Neurology pic.twitter.com/h6Ds5wVSHu
— NEJM (@NEJM) April 5, 2024
Reference (link to abstract – $ for full-text):
RCT: No benefit of Apolipoprotein A1 infusions in preventing cardiovascular events post-myocardial infarction
29 Apr, 2024 | 12:42h | UTCThis international, double-blind, placebo-controlled trial investigated the effect of apolipoprotein A1 (CSL112) infusions on cardiovascular outcomes in patients with recent acute myocardial infarction and multivessel coronary disease. A total of 18,219 patients were randomized to receive either four weekly 6 g infusions of CSL112 or a placebo within five days of initial medical contact. Over 90, 180, and 365 days, the trial found no significant difference in the risk of myocardial infarction, stroke, or cardiovascular death between the two groups. Additionally, adverse events were similar across groups, though hypersensitivity was more common in the CSL112 group.
Reference (link to abstract – $ for full-text):
Cohort Study: No increased risk of autism, ADHD, or intellectual disability from acetaminophen use in pregnancy
29 Apr, 2024 | 12:34h | UTCThis cohort study investigated the association between acetaminophen use during pregnancy and the risk of autism, ADHD, and intellectual disability in children. The study utilized a population-based sample of nearly 2.5 million Swedish children born between 1995 and 2019, with data analyzed up to 2021. Initial findings without sibling controls suggested a marginal increase in the risks of autism and ADHD. However, sibling control analyses, which help adjust for familial confounding, showed no significant associations (HR for autism and ADHD at 0.98, and intellectual disability at 1.01). These results imply that earlier observed risks might be due to unaccounted familial factors, not acetaminophen exposure.
Reference (link to abstract – $ for full-text):
Cohort Study: Validation of a risk score for severe acute kidney injury in cisplatin treatment
27 Apr, 2024 | 16:24h | UTCStudy Design and Population:
This multicenter cohort study aimed to develop and validate a risk prediction model for severe cisplatin-associated acute kidney injury (CP-AKI). Conducted across six major academic cancer centers in the U.S., it included 24,717 adult participants (≥18 years) who received their first dose of intravenous cisplatin from 2006 to 2022. The study population was split into a derivation cohort of 11,766 and a validation cohort of 12,951.
Main Findings:
The study reported an incidence of CP-AKI of 5.2% in the derivation cohort and 3.3% in the validation cohort. Factors independently associated with CP-AKI included age, hypertension, diabetes, and baseline serum levels of creatinine, magnesium, and other relevant biomarkers. A novel, simple risk score was developed using nine covariates, demonstrating significant predictive capability for CP-AKI. The highest risk category had up to 24.00-fold increased odds of CP-AKI compared to the lowest risk category, with the primary model showing superior discrimination (C statistic 0.75) over previous models.
Implications for Practice:
The validated risk score offers a practical tool for clinicians to estimate the risk of severe CP-AKI in patients undergoing cisplatin chemotherapy. Its use could enhance monitoring strategies and potentially guide therapeutic decision-making to mitigate the risk of kidney injury and associated mortality.
Reference (free full-text):
Gupta et al. (2024). Derivation and external validation of a simple risk score for predicting severe acute kidney injury after intravenous cisplatin: cohort study. BMJ, 384, e077169. DOI: https://doi.org/10.1136/bmj-2023-077169
M-A Proportional increase in new-onset diabetes with different intensities of statin therapy
27 Apr, 2024 | 15:41h | UTCStudy Design and Population:
This research is a meta-analysis of individual participant data from large, long-term, randomized, double-blind controlled trials involving statins. The study encompasses 19 trials comparing statin use to placebo and four trials comparing varying intensities of statin therapy, involving a total of 154,664 participants over periods ranging from 4.3 to 4.9 years. Participants were adults enrolled in statin trials with a scheduled duration of at least two years and a participant count of at least 1000.
Main Findings:
The study revealed a dose-dependent increase in the incidence of new-onset diabetes when using statins. Participants receiving low to moderate-intensity statin therapy showed a 10% increase in new-onset diabetes annually compared to placebo, while those on high-intensity statin therapy exhibited a 36% increase. The absolute increases in new-onset diabetes were significantly influenced by the extent of HbA1c measurement. Notably, a large portion of new-onset diabetes cases occurred among participants with baseline glycaemic levels nearing the diabetes diagnostic threshold. Furthermore, the study found a moderate rise in mean glucose levels and HbA1c among those without baseline diabetes, and a significant worsening of glycemia among those with existing diabetes.
Implications for Practice:
The findings highlight a moderate, dose-dependent risk of new-onset diabetes associated with statin therapy, especially in individuals close to the diagnostic threshold for diabetes. These results should be considered in the clinical management of statin therapy, balancing the small increases in glycemia against the substantial benefits of statins in reducing cardiovascular risk. Healthcare providers should monitor glycaemic control in patients on statin therapy, particularly those prescribed high-intensity doses.
Reference (free full-text):
Cohort Study: Higher serious bleeding rates linked to diltiazem in elderly atrial fibrillation patients on anticoagulation
26 Apr, 2024 | 12:35h | UTCStudy Design and Population:
This retrospective cohort study analyzed data from 204,155 Medicare beneficiaries aged 65 years or older diagnosed with atrial fibrillation. The study focused on new users of the anticoagulants apixaban or rivaroxaban who commenced treatment with either diltiazem or metoprolol between January 2012 and November 2020, with follow-up extending up to 365 days.
Main Findings:
Patients treated with diltiazem exhibited a significantly increased risk of serious bleeding, including bleeding-related hospitalization and death, compared to those treated with metoprolol. The hazard ratio (HR) for serious bleeding events was 1.21, with a rate difference (RD) of 10.6 per 1000 person-years. Notably, the risk escalated with diltiazem doses exceeding 120 mg/day, indicating a dose-response relationship. Secondary outcomes, such as ischemic stroke or systemic embolism, did not show significant differences between the treatment groups.
Implications for Practice:
The findings suggest that in older adults with atrial fibrillation treated with apixaban or rivaroxaban, diltiazem increases the risk of serious bleeding, especially at higher doses. These results underscore the importance of cautious medication management and might influence clinical decisions regarding the choice of ventricular rate control in this population.
Reference (link to abstract – $ for full-text):
Cohort Study: Increased fracture risk linked with initiation of antihypertensive medication in older veterans
26 Apr, 2024 | 12:29h | UTCStudy Design and Population:
This retrospective cohort study evaluated the association between antihypertensive medication initiation and fracture risk among older long-term care nursing home residents within the Veterans Health Administration. Conducted from 2006 to 2019 with data analysis spanning 2021 to 2023, the study utilized target trial emulation techniques and included 29,648 residents. A 1:4 propensity score-matched method was employed to compare medication initiators with non-initiators.
Main Findings:
Out of the matched cohort of 64,710 residents, those who initiated antihypertensive medication showed a higher incidence of fractures (5.4 per 100 person-years) compared to controls (2.2 per 100 person-years). The adjusted hazard ratio for fractures was 2.42. Notably, higher risks were observed in subgroups with dementia or elevated blood pressure thresholds (systolic ≥140 mm Hg or diastolic ≥80 mm Hg). Risks for severe falls and syncope were also elevated in the medication-initiating group.
Implications for Practice:
The study indicates a significant association between the initiation of antihypertensive medications and increased fracture risks among older, frail nursing home residents. Given these findings, clinicians should exercise caution and consider enhanced monitoring and preventive strategies when prescribing these medications to this vulnerable population.
Reference (link to abstract – $ for full-text):
Dave, C. V. et al. (2024). Antihypertensive Medication and Fracture Risk in Older Veterans Health Administration Nursing Home Residents. JAMA Intern Med, Published online April 22, 2024. DOI:10.1001/jamainternmed.2024.0507.