Evidence from clinical research indicates that men and women can differ in response to drug treatment. The knowledge database Janusmed Sex and Gender was developed to illuminate potential sex and gender differences in drug therapy and, therefore, achieve a better patient safety. The database contains non-commercial evidence-based information on drug substances regarding sex and gender aspects in patient treatment. Here, we describe our experiences and reflections from collecting, analyzing, and evaluating the evidence.Substances have been systematically reviewed and classified in a standardized manner. The classification considers clinically relevant sex and gender differences based on available evidence. Mainly biological sex differences are assessed except for gender differences regarding adverse effects and compliance. Of the 400 substances included in the database, clinically relevant sex differences were found for 20%. Sex-divided data were missing for 22% and no clinically relevant differences were found for more than half of the substances (52%). We noted that pivotal clinical studies often lack sex analyses of efficacy and adverse effects, and post-hoc analyzes are performed instead. Furthermore, most pharmacokinetic analyses use weight correction, but medicines are often prescribed in standard doses. In addition, few studies have sex differences as a primary outcome and some pharmacokinetic analyses are unpublished, which may complicate the classification of evidence.Our work underlines the need of sex and gender analyses, and sex-divided data in drug treatment, to increase the knowledge about these aspects in drug treatment and contribute to a more individualized patient treatment. 

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Sex and gender differences in drug treatment: experiences from the knowledge database Janusmed Sex and Gender

In patients with heart failure (HF), randomized controlled trials (RCTs) of sodium-glucose transporter-2 inhibitors (SGLT-2is) have proven to be effective in decreasing the primary composite outcome of cardiovascular death and hospitalizations for HF. A recently published meta-analysis showed that the use of SGLT-2is among women with diabetes resulted in less reduction in primary composite outcomes compared with men. This study aims to explore potential sex differences in primary composite outcomes among patients with HF treated with SGLT-2is.We systematically searched the medical database from 2017 to 2022 and retrieved all the RCTs using SGLT-2is with specified cardiovascular outcomes. We used the PRISMA (Preferred Reporting Items for a Review and Meta-analysis) method to screen for eligibility. We evaluated the quality of studies using the Cochrane Risk of Bias tool. We pooled the hazard ratio (HR) of the primary composite outcomes in both sexes, performed a meta-analysis, and calculated the odds ratio (OR) of the primary composite outcomes based on sex.We included 5 RCTs with a total number of 21,947 patients. Of these, 7837 (35.7 %) were females. Primary composite outcomes were significantly lower in males and females taking SGLT-2is compared to placebo (males - HR 0.77; 95 % CI 0.72 to 0.84; p = 0.00001; females - HR 0.75; 95 % CI 0.67 to 0.84; p = 0.00001). Pooled data from four of the RCTs (n = 20,725) revealed a greater occurrence of the primary composite outcomes in females compared with males (OR 1.32; 95 % CI 1.17 to 1.48; p = 0.0002).SGLT-2is reduce the risk of primary composite outcomes in patients with HF, regardless of sex; however, the benefits were less pronounced in women. Further research needs to be done to better explain these observed differences in outcomes. 

https://doi.org/10.1016/j.ahjo.2023.100261

Sex differences in cardiovascular outcomes of SGLT-2 inhibitors in heart failure randomized controlled trials: A systematic review and meta-analysis

BACKGROUND
Transcatheter Aortic Valve Replacement (TAVR) is a relatively novel minimally invasive procedure for the treatment of symptomatic patients with severe aortic stenosis. Although it has been proven effective in improving mortality and quality of life, TAVR is associated with serious complications, such as acute kidney injury (AKI).


SUMMARY
TAVR-associated AKI is likely due to several factors such as sustained hypotension, transapical approach, volume of contrast use and baseline low GFR. This narrative review aims to present an overview of the latest literature and evidence regarding the definition of TAVR-associated AKI, its risk factors, and its impact on morbidity and mortality. The review used a systematic search strategy with multiple health-focused databases (Medline, EMBASE), and identified 8 clinical trials and 27 observational studies concerning TAVR-associated AKI. Results showed that TAVR-associated AKI is linked to several modifiable and non-modifiable risk factors, and is associated with higher mortality. A variety of diagnostic imaging modalities have the potential to identify patients at high-risk for development of TAVR-AKI; however, there are no existing consensus recommendations regarding their use as of this time. The implications of these findings highlight the importance of identifying high-risk patients for which preventive measures may play a crucial role, and should be maximized.


KEY MESSAGE
This study reviews the current understanding of TAVR-associated AKI including its pathophysiology, risk factors, diagnostic modalities, and preventative management for patients.

/pdf/transcatheter-aortic-valve-replacement-tavr-associated-acute-fo5qjvx7.pdf

V. Tang

Papers

Sex differences in cardiovascular outcomes of SGLT-2 inhibitors in heart failure randomized controlled trials: A systematic review and meta-analysis

Transcatheter Aortic Valve Replacement (TAVR)-associated Acute Kidney Injury: An Update.

The impact of hypertensive disorders on shock index in deliveries complicated by postpartum hemorrhage