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

15:16

PubMed articles on: Cardio-Oncology

Cardiac Toxicities in Oncology: Elucidating the Dark Box in the Era of Precision Medicine

Curr Issues Mol Biol. 2023 Oct 15;45(10):8337-8358. doi: 10.3390/cimb45100526.

ABSTRACT

Despite current advancements in chemotherapy, immunotherapy and targeted treatments, the potential for major adverse cardiovascular events, regardless of previous cardiac history, persists. Scoring systems, such as the Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) risk assessment tool, can be utilized to evaluate several factors including prior cardiac history, risk factors and cardiac biomarkers to categorize patients into low, moderate, high, and very high-risk groups. Common cardiotoxicity complications include new or worsening left ventricular ejection fraction (LVEF), QT interval prolongation, myocardial ischaemia, hypertension, thromboembolic disease, cardiac device malfunction and valve disease. Baseline electrocardiogram (ECG) and transthoracic echocardiogram (TTE) are routinely performed for all patients commenced on cardiotoxic treatment, while other imaging modalities and biochemical markers have proven useful for monitoring. Management mainly includes early risk stratification and prompt identification of cardiovascular complications, with patient-specific surveillance throughout treatment. A multidisciplinary approach is crucial in determining the relationship between potential treatment benefits and cardiotoxicity, and whether the continuation of treatment is appropriate on a case-by-case basis. Early risk stratification, optimizing the patient's cardiovascular status prior to treatment, and prompt identification of suspected cardiotoxicity are key in significantly reducing risk. This article provides a comprehensive review of the various types of treatment-related cardiotoxicity, offering guidance on identifying high-risk patients, recognizing early signs of cardiotoxicity, and outlining appropriate treatment approaches and follow-up care for such cases.

PMID:37886969 | PMC:PMC10605822 | DOI:10.3390/cimb45100526

15:16

PubMed articles on: Cardio-Oncology

The (pro)renin Receptor - A Regulatory Nodal Point in Disease Networks

Curr Drug Targets. 2023 Oct 25. doi: 10.2174/0113894501250617231016052930. Online ahead of print.

ABSTRACT

Experimental inhibition of the (pro)renin receptor [(P)RR] is a promising therapeutic strategy in different disease models ranging from cardiorenal to oncological entities. Here, we briefly review the direct protein-protein interaction partners of the (P)RR and the plethora of distinct diseases in which the (P)RR is involved. The first structural work on the (P)RR using AlphaFold, which was recently published by Ebihara et al., is the center of this mini-review since it can mechanistically link the protein-protein interaction level with the pathophysiological level. More detailed insights into the 3D structure of the (P)RR and its interaction domains might guide drug discovery on this novel target. Finally, antibody- and small molecule-based approaches to inhibit the (P)RR are shortly discussed.

PMID:37885110 | DOI:10.2174/0113894501250617231016052930

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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

15:16

PubMed articles on: Cancer & VTE/PE

Risk and timing of venous thromboembolism after surgery for lung cancer: a nationwide cohort study

Ann Thorac Surg. 2023 Oct 25:S0003-4975(23)01073-1. doi: 10.1016/j.athoracsur.2023.10.015. Online ahead of print.