Background Studies of sex differences in long-term mortality after acute myocardial infarction (AMI) have reported mixed results. A systematic review is needed to characterize what is known about sex differences in long-term outcomes and to define gaps in knowledge. Methods and Results We searched the Medline database from 1966 to December 2012 to identify all studies that provided sex-based comparisons of mortality after AMI. Only studies with at least five years of follow-up were reviewed. Of the 1,877 identified abstracts, 52 studies met inclusion criteria, of which 39 were included in this review. Most studies included less than one-third women. There was significant heterogeneity across studies in patient populations, methodology, and risk adjustment, which produced substantial variability in risk estimates. In general, most studies reported higher unadjusted mortality for women compared with men at both 5 and 10 years after AMI; however, many of the differences in mortality became attenuated after adjustment for age. Multivariable models varied between studies; however, most reported a further reduction in sex differences after adjustment for covariates other than age. Few studies examined sex-by-age interactions; however several studies reported interactions between sex and treatment, whereby women have similar mortality risk as men after revascularization. Conclusions Sex differences in long-term mortality after AMI are largely explained by differences in age, comorbidities, and treatment utilization between women and men. Future research should aim to clarify how these differences in risk factors and presentation contribute to the sex gap in mortality.

Background While some studies have found an association between delayed graft function (DGF) after kidney transplantation and worse long-term outcomes, a causal relationship remains controversial. We investigated this relationship using an instrumental variables model (IVM), a quasi-randomization technique for drawing causal inferences. Methods We identified 80,690 adult, deceased-donor, kidney-only transplant recipients from the Scientific Registry of Transplant Recipients between 1997 and 2010. We used cold ischemia time (CIT) as an instrument to test the hypothesis that DGF causes death-censored graft loss and mortality at 1 and 5 years post-transplant, controlling for an array of characteristics known to affect patient and graft survival. We compared our IVM results to a multivariable linear probability model (LPM). Results DGF occurred in 27% of our sample. Graft loss rates at 1 and 5 years were 6% and 22%, respectively, and 1-year and 5-year mortality rates were 5% and 20%, respectively. In the LPM, DGF was associated with increased risk of both graft loss and mortality at 1 and 5 years (p<0.001). In the IVM, we found evidence suggesting a causal relationship between DGF and death-censored graft loss at both 1 year (13.5% increase; p<0.001) and 5 years (16.2% increase; p<0.001), and between DGF and mortality at both 1 year (7.1% increase; p<0.001) and 5 years (11.0% increase; p<0.01). Results were robust to exclusion of lower-quality as well as pumped kidneys and use of a creatinine-based definition for DGF. Conclusion Instrumental variables analysis supports a causal relationship between DGF and both graft loss and mortality.

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Background: Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), which has persisted despite refinements in technique and increased operator experience. While cerebral embolic protection devices (EPDs) have been developed to mitigate this risk, data regarding their impact on stroke and other outcomes after TAVR are limited. Methods: We performed an observational study using data from the STS/ACC-TVT Registry. Patients were included if they underwent elective or urgent transfemoral TAVR between January 2018 and December 2019. The primary outcome was in-hospital stroke. To adjust for confounding, the association between EPD use and clinical outcomes was evaluated using instrumental variable (IV) analysis, a technique designed to support causal inference from observational data, with site-level preference for EPD use within the same quarter of the procedure as the instrument. We also performed a propensity score-based secondary analysis using overlap weights. Results: Our analytic sample included 123,186 patients from 599 sites. The use of EPD during TAVR increased over time, reaching 28% of sites and 13% of TAVR procedures by December 2019. There was wide variation in EPD use across hospitals, with 8% of sites performing >50% of TAVR procedures with an EPD and 72% performing zero procedures with an EPD in the last quarter of 2019. In our primary analysis using the IV model, there was no association between EPD use and in-hospital stroke (adjusted relative risk (0.90 [95% CI: 0.68, 1.13], absolute risk difference -0.15% [95% CI: -0.49, 0.20]). However, in our secondary analysis using the propensity score-based model, EPD use was associated with 18% lower odds of in-hospital stroke (adjusted OR 0.82 [95% CI 0.69, 0.97], absolute risk difference -0.28% [95% CI: -0.52, -0.03]). Results were generally consistent across the secondary endpoints as well as subgroup analyses. Conclusions: In this nationally-representative observational study, we did not find an association between EPD use for TAVR and in-hospital stroke in our primary IV analysis, and found only a modestly lower risk of in-hospital stroke in our secondary propensity-weighted analysis. These findings provide a strong basis for large-scale RCTs to test whether EPDs provide meaningful clinical benefit for patients undergoing TAVR.