ABSTRACT

This point of view explores the safety concerns of Janus kinase inhibitors (JAK-Is), used in treating rheumatoid arthritis (RA) and other rheumatologic conditions. Increasing evidence shows that JAK-Is may elevate the risk of venous thromboembolism (VTE), especially pulmonary embolism. This fact has prompted the European Medicines Agency to advise cautious use of these drugs in patients over 65, smokers, and those at risk of cardiovascular issues or cancer. The paper analyses the evidence on the association between VTE risk and RA and whether different JAK-Is pose different risks. It also probes the link between VTE, lipids, and JAK inhibition, noting that JAK-Is can alter HDL and LDL levels. On the other hand, some evidence indicates that tighter LDL-cholesterol control could mitigate VTE risk, particularly pulmonary embolism. Moreover, data from trials show little attention to treating this main cardiovascular and VTE risk factor in rheumatological patients. Although the lipid paradox theory emphasizes the U-shaped relationship between LDL cholesterol and cardiovascular risk in patients with RA, uncontrolled levels of clinically relevant LDL cholesterol remain closely linked to cardiovascular and VTE risk. In conclusion, high-potency statins could help to manage the increased cardiovascular and VTE risk concomitant to JAK-Is treatment in rheumatologic patients without depriving them of the best therapeutic choice and, in addition, reducing the inherent risk associated with the disease.

PMID:37898967 | DOI:10.1007/s11739-023-03426-1

19:48

PubMed articles on: Cardio-Oncology

Prospective, Multicenter Phase II Trial of Non-Pegylated Liposomal Doxorubicin Combined with Ifosfamide in First-Line Treatment of Advanced/Metastatic Soft Tissue Sarcomas

Cancers (Basel). 2023 Oct 18;15(20):5036. doi: 10.3390/cancers15205036.

ABSTRACT

Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with higher doses, poses a significant challenge to its safe and effective application. To try to overcome these undesired effects, encapsulation of doxorubicin in liposomes has been proposed. Caelyx and Myocet are different formulations of pegylated (PLD) and non-pegylated liposomal doxorubicin (NPLD), respectively. Both PLD and NPLD have shown similar activity compared with free drugs but with reduced cardiotoxicity. While the hand-foot syndrome exhibits a high occurrence among patients treated with PLD, its frequency is notably reduced in those receiving NPLD. In this prospective, multicenter, one-stage, single-arm phase II trial, we assessed the combination of NPLD and ifosfamide as first-line treatment for advanced/metastatic soft tissue sarcoma (STS). Patients received six cycles of NPLD (50 mg/m2) on day 1 along with ifosfamide (3000 mg/m2 on days 1, 2, and 3 with equidose MESNA) administered every 3 weeks. The overall response rate, yielding 40% (95% CI: 0.29-0.51), resulted in statistical significance; the disease control rate stood at 81% (95% CI: 0.73-0.90), while only 16% (95% CI: 0.08-0.24) of patients experienced a progressive disease. These findings indicate that the combination of NPLD and ifosfamide yields a statistically significant response rate in advanced/metastatic STS with limited toxicity.

PMID:37894403 | PMC:PMC10605752 | DOI:10.3390/cancers15205036

19:48

PubMed articles on: Cancer & VTE/PE

Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis

Medicina (Kaunas). 2023 Oct 20;59(10):1867. doi: 10.3390/medicina59101867.

ABSTRACT

Background and Objectives: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. Materials and Methods: We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). Results: It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I2 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I2 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I2 0%). Conclusions: Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, but without statistical significance. No statistical significance was observed in clinically relevant major or non-major bleeding.

PMID:37893585 | DOI:10.3390/medicina59101867

19:48

PubMed articles on: Cardio-Oncology

The Protective Effect of Citronellol against Doxorubicin-Induced Cardiotoxicity in Rats

Biomedicines. 2023 Oct 18;11(10):2820. doi: 10.3390/biomedicines11102820.