Pharmacology/Pharmaceutical Industry
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.
RCT: Lack of significant effect of Paxlovid (nirmatrelvir–ritonavir) on symptom alleviation in Covid-19
26 Apr, 2024 | 11:49h | UTCStudy Design and Population:
This phase 2–3 randomized clinical trial investigated the efficacy of nirmatrelvir in combination with ritonavir for treating mild-to-moderate Covid-19 in adults. Participants, both vaccinated and unvaccinated, were enrolled based on their risk factors for severe Covid-19. The study included 1296 adults who had confirmed Covid-19 with symptom onset within the past 5 days. They were randomly assigned to receive either nirmatrelvir–ritonavir or placebo every 12 hours for 5 days.
Main Findings:
The primary endpoint was the time to sustained alleviation of all targeted Covid-19 signs and symptoms. Results showed that the median time to alleviation was 12 days for the treatment group and 13 days for the placebo group, a difference that was not statistically significant (P=0.60). Hospitalizations and deaths were slightly lower in the treatment group (0.8%) compared to the placebo group (1.6%), but this difference was also not statistically significant. Adverse events were similar across both groups, with dysgeusia and diarrhea being the most common in the treatment group.
Implications for Practice:
The findings indicate that nirmatrelvir–ritonavir treatment does not significantly reduce the time to symptom alleviation for Covid-19 compared to placebo among vaccinated or unvaccinated adults. These results suggest that further research is needed to explore the potential benefits of this treatment in specific subpopulations or in combination with other interventions.
Reference (free full-text):
FDA approves antibiotic Zevtera (ceftobiprole medocaril sodium) for three indications
26 Apr, 2024 | 11:39h | UTCThe FDA has granted approval for Zevtera (ceftobiprole medocaril sodium), an antibiotic formulated for injection, targeting three key bacterial infections. This includes treatment for adults with Staphylococcus aureus bloodstream infections (SAB) with or without right-sided infective endocarditis, acute bacterial skin and skin structure infections (ABSSSI), and community-acquired bacterial pneumonia (CABP) in both adults and pediatric patients aged three months to under 18 years.
The approval follows rigorous clinical trials demonstrating Zevtera’s efficacy. In a multicenter study for SAB, Zevtera achieved a 69.8% success rate, slightly outperforming the comparator drug. For ABSSSI, Zevtera showed a 91.3% early clinical response, and for CABP, it had a clinical cure rate of 76.4% in adults. Pediatric efficacy for CABP was extrapolated from adult data and supported by a smaller pediatric trial.
Common side effects include anemia, nausea, and increased liver enzyme levels, with specific reactions varying by infection treated. Contraindications include severe hypersensitivity to ceftobiprole or other cephalosporins. Zevtera also carries warnings about potential hypersensitivity reactions, central nervous system effects, and Clostridioides difficile-associated diarrhea.
This approval, supported by Priority Review and Fast Track designations, offers a new treatment option for clinicians managing these serious infections.
Source: FDA NEWS RELEASE: FDA Approves New Antibiotic for Three Different Uses
High efficacy of exagamglogene autotemcel in achieving transfusion independence in β-Thalassemia
25 Apr, 2024 | 23:29h | UTCStudy Design and Population:
This open-label, single-group, phase 3 trial investigated the efficacy of exagamglogene autotemcel (exa-cel), a nonviral CRISPR-Cas9 gene-edited cell therapy, in patients aged 12 to 35 with transfusion-dependent β-thalassemia. Various genotypes were included, and participants underwent myeloablative conditioning followed by exa-cel infusion. The primary endpoint was to achieve and maintain transfusion independence.
Main Findings:
Of the 52 patients treated, 35 with sufficient follow-up showed that 32 (91%) achieved transfusion independence for at least 12 months, significantly surpassing the study’s efficacy threshold. The average total hemoglobin during this period was 13.1 g/dL, with fetal hemoglobin averaging 11.9 g/dL and widely distributed across red cells. The treatment’s safety profile was compatible with the expected outcomes of myeloablative conditioning and autologous hematopoietic stem cell transplantation, with no reported deaths or cancer developments.
Implications for Practice:
The successful achievement of transfusion independence in a high percentage of patients suggests that exa-cel is a promising treatment option for transfusion-dependent β-thalassemia. This study supports the potential for gene-edited cell therapies to significantly improve outcomes in genetic blood disorders. Continued monitoring and further research are recommended to fully understand the long-term implications and safety of such treatments.
Reference:
CRISPR-Cas9 gene editing in sickle cell disease shows high efficacy in preventing vaso-occlusive crises
25 Apr, 2024 | 23:21h | UTCStudy Design and Population: This phase 3, single-group, open-label randomized clinical trial investigated the efficacy of exagamglogene autotemcel (exa-cel), a nonviral CRISPR-Cas9 gene-edited therapy, in patients aged 12 to 35 years with severe sickle cell disease. The study included patients who experienced at least two severe vaso-occlusive crises annually in the two years prior to screening. The therapeutic intervention involved editing CD34+ hematopoietic stem and progenitor cells (HSPCs) and administering a myeloablative conditioning regimen with busulfan.
Main Findings: Of the 44 participants treated, 30 with sufficient follow-up demonstrated a significant response. Ninety-seven percent (29 of 30) remained free from severe vaso-occlusive crises for at least 12 consecutive months, and 100% (30 of 30) avoided hospitalization for these crises over the same period. The intervention showed a high safety profile, consistent with myeloablative busulfan conditioning and autologous HSPC transplantation, with no cancers reported during the follow-up.
Implications for Practice: The results suggest that exa-cel can effectively eliminate severe vaso-occlusive crises in patients with sickle cell disease, marking a substantial advance in treatment options. These findings may pave the way for broader application of gene-editing therapies in hematologic diseases, pending further research on long-term outcomes and safety.
Pragmatic Cluster-Randomised Trial: Efficacy of a Fixed-Dose Polypill in Reducing Cardiovascular Disease Risk in Rural Iran
21 Apr, 2024 | 21:05h | UTCStudy Design and Population: The PolyPars Study was structured as a two-arm pragmatic cluster-randomised trial within the larger PARS cohort study. It targeted residents aged over 50 in a district in southern Iran, dividing 91 villages into two groups: one receiving a once-daily polypill (containing two antihypertensives, a statin, and aspirin) alongside non-pharmacological interventions, and the other receiving only the non-pharmacological interventions. The trial included 4,415 participants aged 50-75 years, with the primary endpoint being the first occurrence of major cardiovascular events.
Main Findings: Over a median follow-up of 4.6 years, adherence to the polypill was high at 86%. The intervention arm showed a significant reduction in the incidence of the primary outcome, with only 4.0% (88 participants) experiencing major cardiovascular events compared to 8.0% (176 participants) in the control arm. This translates to a hazard ratio of 0.50, indicating a 50% reduction in risk, and an absolute risk reduction of 4.0%.
Implications for Practice: The study demonstrates the significant potential of fixed-dose combination therapy with the polypill to halve the risk of major cardiovascular diseases in a population-level intervention. This finding supports the polypill as a safe and effective strategy for both primary and secondary prevention of cardiovascular diseases, particularly in settings where access to individual medications and consistent medical supervision might be limited.
Nested Case-Control Study: Increased risk of major bleeding in atrial fibrillation patients with concomitant SSRI and oral anticoagulant use
23 Mar, 2024 | 20:48h | UTCStudy Design and Population
This nested case-control study investigated the association between the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and oral anticoagulants (OACs) on the risk of major bleeding among patients with atrial fibrillation. Conducted within the UK’s Clinical Practice Research Datalink, the study included 42,190 cases of major bleeding matched to 1,156,641 controls based on age, sex, cohort entry date, and follow-up duration. Patients initiating OACs between January 2, 1998, and March 29, 2021, were included, with risk-set sampling utilized for control selection.
Main Findings
The study found that concomitant use of SSRIs and OACs was associated with a 33% increased risk of major bleeding compared to OAC use alone, with the highest risk observed within the first 30 days of concurrent use. The increased risk was consistent across different ages, sexes, and patient histories, including those with chronic kidney disease or previous bleeding events. Notably, the elevated risk of bleeding extended up to 6 months of concomitant use but did not vary significantly with the potency of SSRIs or the type of OAC used (direct OACs or vitamin K antagonists).
Implications for Practice
These findings underscore the need for healthcare professionals to closely monitor patients with atrial fibrillation who are prescribed SSRIs in addition to OACs, particularly during the initial months of treatment. This study highlights the importance of managing bleeding risk factors and suggests reconsidering the necessity and duration of concomitant SSRI and OAC use. Future research should focus on strategies to mitigate this bleeding risk and explore alternative treatments for managing depression in patients requiring anticoagulation.
Reference
Observational Study: Association of antiarrhythmic drug use with increased risk of pacemaker implantation and syncope in new-onset atrial fibrillation patients
23 Mar, 2024 | 20:08h | UTCStudy Design and Population
This observational study utilized data from the Korean National Health Insurance Service to evaluate the impact of antiarrhythmic drugs (AADs) on the risk of pacemaker implantation or syncope in patients diagnosed with new-onset atrial fibrillation (AF) between 2013 and 2019. A total of 770,977 new-onset AF cases were identified, with 142,141 patients prescribed AADs within one year of diagnosis. The study compared the risk of these outcomes between AAD users and nonusers.
Main Findings
The study found that the use of AADs was associated with a significantly increased risk of pacemaker implantation or syncope, with adjusted risks being 3.5 times higher for either outcome, 2.0 times higher for syncope alone, and 5.0 times higher for pacemaker implantation. These associations were consistent across various patient subgroups, and propensity score-matched analysis supported these findings. Notably, women were found to be more susceptible to the adverse effects of AADs than men.
Implications for Practice
The findings suggest a need for careful evaluation of the risks associated with AAD use in patients with new-onset AF, particularly regarding the potential for pacemaker implantation or syncope. These results highlight the importance of individualized patient assessment before prescribing AADs to mitigate these risks effectively. Further research is needed to explore the mechanisms behind these associations and to develop strategies to minimize adverse outcomes in this patient population.
Reference
M-A: Cardiovascular benefits of SGLT2 inhibitors in patients without diabetes
22 Mar, 2024 | 11:07h | UTCStudy Design and Population: This meta-analysis investigated the cardiovascular (CV) outcomes associated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients without diabetes mellitus (DM). By systematically reviewing online databases, the authors identified and included six randomized controlled trials (RCTs) in their analysis. These trials compared SGLT2i with placebo/control in a total of 12,984 participants, who were followed for an average duration of 17.7 months. The study population comprised mainly patients with heart failure (HF), chronic kidney disease, or myocardial infarction, with a mean age of 64 years, where 72% were men and the mean hemoglobin A1C level was 5.7%.
Main Findings: The use of SGLT2i was associated with a significant reduction in composite CV death or hospitalization for HF, with an odds ratio (OR) of 0.77 (95% confidence interval [CI], 0.68 to 0.87, p < 0.0001), primarily due to a decrease in hospitalization for HF (OR 0.70, 95% CI 0.60 to 0.81, p < 0.00001). No significant differences were observed in CV death, all-cause death, or major adverse CV events when comparing SGLT2i to placebo. Notably, serious adverse events were lower with the use of empagliflozin compared to placebo.
Implications for Practice: This meta-analysis highlights the significant CV benefits of SGLT2i treatment in reducing CV death or hospitalization for HF in patients without DM, compared with placebo. These findings suggest the potential for broader use of SGLT2i in populations without diabetes to improve cardiovascular outcomes.
Reference: Sahib Singh et al. (2024). Cardiovascular Outcomes With Empagliflozin and Dapagliflozin in Patients Without Diabetes. The American Journal of Cardiology, Published: February 29, 2024. DOI: https://doi.org/10.1016/j.amjcard.2024.02.039. Access the study here: [Link]
Cohort Study: Elevated autism spectrum disorder risk in children exposed to valproate during pregnancy
21 Mar, 2024 | 13:16h | UTCStudy Design and Population: This cohort study utilized two health care utilization databases in the United States, covering the period from 2000 to 2020, to investigate the association between prenatal exposure to antiseizure medications and the risk of autism spectrum disorder (ASD) in children. The study compared children exposed to topiramate, valproate, or lamotrigine during the second half of pregnancy to those unexposed to any antiseizure medication, specifically focusing on a population-based cohort of pregnant women and their offspring.
Main Findings: The cumulative incidence of ASD at 8 years of age was found to be higher in children exposed to these medications compared to the general population. Notably, the incidence was 6.2% for children exposed to topiramate, 10.5% for valproate, and 4.1% for lamotrigine among children born to mothers with epilepsy. However, after adjusting for potential confounders, the increased risk of ASD remained significant only for valproate exposure, with a hazard ratio of 2.67, indicating a substantial risk compared to unexposed children. Topiramate and lamotrigine showed no significant increase in risk after adjustment.
Implications for Practice: The findings underscore the importance of carefully considering the risks and benefits of using antiseizure medications during pregnancy. Specifically, valproate should be used with caution, if at all, given its significant association with an increased risk of ASD in offspring. This study supports the need for targeted counseling and monitoring of pregnant women with epilepsy and highlights the necessity for further research to fully understand the neurodevelopmental impact of prenatal exposure to antiseizure medications.
Reference: Sonia Hernández-Díaz et al. (2024). Cohort Study: Assessing Autism Spectrum Disorder Risk in Children Exposed to Antiseizure Medications During Pregnancy. N Engl J Med, 390(13), 1069-1079. DOI: 10.1056/NEJMoa2309359. Access the study here: [Link]
RCT: Quadruple quarter-dose hypertension medication versus monotherapy for ambulatory blood pressure control
20 Mar, 2024 | 18:00h | UTCStudy Design and Population: This randomized clinical trial investigated the efficacy of a combination of four ultra-low-dose blood pressure medications (quadpill) compared to standard monotherapy in adults with hypertension. A total of 591 participants, either untreated or currently on monotherapy for hypertension, were enrolled and randomly assigned to receive either the quadpill (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or a monotherapy control (irbesartan 150 mg).
Main Findings: At 12 weeks, the quadpill group demonstrated significantly lower mean 24-hour ambulatory systolic and diastolic blood pressure (SBP and DBP) by 7.7 mmHg and 5.3 mmHg, respectively, compared to the monotherapy group, with similar reductions observed during daytime and night-time. Additionally, the rate of blood pressure control (24-hour average BP < 130/80 mmHg) was significantly higher in the quadpill group (77% vs. 50%). The study highlighted the quadpill’s effectiveness in reducing blood pressure variability and enhancing control rates across a 24-hour period.
Implications for Practice: The findings from this study support the superior efficacy of an ultra-low-dose quadruple medication strategy over monotherapy in managing ambulatory blood pressure among hypertensive patients. These results suggest that a quadpill approach could offer a more effective means for clinicians to achieve and maintain blood pressure control in hypertensive patients, potentially improving cardiovascular outcomes.
Reference: Janis M Nolde et al. (2024). Ambulatory blood pressure after 12 weeks of quadruple combination of quarter doses of blood pressure medication vs. standard medication. J Hypertens, 2024 Feb 29. DOI: 10.1097/HJH.0000000000003683. Access the study here: [Link]
Presented at ASRS Meeting | Studies link GLP-1 agonists to progression of diabetic retinopathy
11 Aug, 2023 | 15:38h | UTCStudies link GLP-1 agonists to progression of diabetic retinopathy – MDedge
M-A | Pharmacist-led home BP telemonitoring enhances control over usual care
11 Aug, 2023 | 15:29h | UTC
Review | Adverse effects of antidepressant medications and their management in children and adolescents
9 Aug, 2023 | 15:25h | UTC
M-A | Absence of evidence for antipsychotics in youth unipolar depression; limited evidence in bipolar depression
9 Aug, 2023 | 15:23h | UTC
M-A | Nearly 37% of elderly outpatients are at risk due to potentially inappropriate medication use
8 Aug, 2023 | 13:37h | UTC
Perspective | Will unpredictable side effects dim the promise of new Alzheimer’s drugs?
8 Aug, 2023 | 13:30h | UTCWill unpredictable side effects dim the promise of new Alzheimer’s drugs? – Science (a few articles per month are free)
Related:
RCT | Donanemab slows early symptomatic Alzheimer’s progression, but raises serious safety concerns
RCT | Lecanemab slows cognitive decline in early Alzheimer’s disease but raises safety concerns
Cohort Study | Habitual calcium supplementation linked to higher CVD incidence and mortality in diabetics
8 Aug, 2023 | 13:24h | UTCAssociations of Habitual Calcium Supplementation With Risk of Cardiovascular Disease and Mortality in Individuals With and Without Diabetes – Diabetes Care (link to abstract – $ for full-text)
Commentary on Twitter
Habitual Ca supplementation was associated with higher risks of CVD in diabetics but not non-diabetics, suggesting that diabetics may need to be cautious about the long-term use of Ca supplements. @ADA_Pubs
Read Here➡️https://t.co/wUBy6KJhaw pic.twitter.com/6FXmwBwnMS
— Diabetes Care, a research journal of the ADA ? (@DiabetesCareADA) July 28, 2023
Opinion Video | Critical analysis of the data behind Covid-19 booster shots
31 Jul, 2023 | 14:40h | UTCOriginal Publication: Correspondence | Potential “healthy vaccinee bias” in a study of BNT162b2 vaccine against Covid-19
New WHO lists of essential medicines
28 Jul, 2023 | 14:23h | UTCNews Release: WHO endorses landmark public health decisions on Essential Medicines for Multiple Sclerosis – World Health Organization
Lists of Essential Medicines
Model Lists of Essential Medicines – World Health Organization
Model Lists of Essential Medicines for Children – World Health Organization
Commentary on Twitter
OUT TODAY: New editions of the WHO Model Lists of Essential Medicines and Essential Medicines for Children which include important new medicines for the treatment of multiple sclerosis, cancer, infectious diseases and cardiovascular conditions, among others… pic.twitter.com/RZYdgc0i65
— World Health Organization (WHO) (@WHO) July 26, 2023
Study | Only 11% of sports supplements listing botanical ingredients accurately declare contents, 12% contain FDA-prohibited stimulants
28 Jul, 2023 | 14:21h | UTCCommentaries:
Ensuring the Safety and Value of Supplements – JAMA Network Open
BMJ Investigation | Medical royal colleges receive millions from drug and medical devices companies
28 Jul, 2023 | 14:19h | UTCMedical royal colleges receive millions from drug and medical devices companies – The BMJ
News Release: Medical royal colleges receive millions from drug/medical device companies – BMJ Newsroom
Commentary on Twitter
Drug and medical device companies have given £9m to UK royal colleges in recent years.
Scroll through our series of #BMJInfographics to see how much individual companies have paid each college ? https://t.co/s03xSl18BP pic.twitter.com/PX1Lzmtb4N
— The BMJ (@bmj_latest) July 27, 2023
Position Paper | Prioritizing deprescribing in fall prevention strategies
28 Jul, 2023 | 14:12h | UTCOriginal Guideline: World guidelines for falls prevention and management for older adults: a global initiative – Age and Ageing
RCT | Vitamin D supplementation shows no cognitive benefit in mild cognitive impairment intervention
25 Jul, 2023 | 14:00h | UTCCommentary: Exercise and Cognitive Training Slow Thinking Declines. Vitamin D? Not So Much – HealthDay
Related:
RCT | No statistically significant impact of vitamin D on major cardiovascular events
2ry analysis of a RCT | Vitamin D supplementation does not affect cognitive function in older adults
Randomized Trial: Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease
Meta-Analysis: Vitamin D Not Effective for Cardiovascular Disease Prevention
Vitamin D, calcium, other vitamins, and supplements do not prevent cardiovascular diseases