We thank Dr. Watanabe for his comment but respectfully disagree that our approach was “inadequate.”
While coronary revascularization is an important consideration when examining associations with outcomes after myocardial infarction, we intentionally did not include it in the estimation of the propensity score, which was used to balance baseline characteristics between men and women, because revascularization is not a baseline characteristic but, rather, a future event.
An introduction to propensity score methods for reducing the effects of confounding in observational studies.
Moreover, adjusting for revascularization in models predicting outcomes is problematic because of confounding by indication (ie, the selection of patients for coronary intervention vs medical management only is largely influenced by the severity of myocardial infarction and by coronary anatomy, which ultimately determines the clinical outcome).
The benefit of an invasive strategy in women with non-ST-elevation acute coronary syndrome remains somewhat unclear. Despite an overall benefit for patients treated with revascularization in the FRISC II and RITA 3 trials,
- Mehta SR
- Cannon CP
- Fox KA
- et al.
Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials.
subgroup analyses showed that revascularization may be associated with a higher risk of death or myocardial infarction in women.
- Lagerqvist B
- Safstrom K
- Stahle E
- Wallentin L
- Swahn E.
Is early invasive treatment of unstable coronary artery disease equally effective for both women and men? FRISC II Study Group Investigators.
- Clayton TC
- Pocock SJ
- Henderson RA
- et al.
Do men benefit more than women from an interventional strategy in patients with unstable angina or non-ST-elevation myocardial infarction? The impact of gender in the RITA 3 trial.
A meta-analysis by O'Donoghue et al
- O'Donoghue M
- Boden WE
- Braunwald E
- et al.
Early invasive vs conservative treatment strategies in women and men with unstable angina and non–ST-segment elevation myocardial infarction: a meta-analysis.
found that both men and high-risk women have a comparable benefit from an invasive strategy in non-ST-elevation acute coronary syndrome for reducing the odds of death, myocardial infarction, or rehospitalization with acute coronary syndrome. In contrast, an invasive strategy does not appear to substantially benefit low-risk women and may potentially increase the risk of death or myocardial infarction, possibly because of an increased prevalence of nonsignificant epicardial coronary artery disease and different coronary physiology. A more recent large prospective, multicenter myocardial infarction registry has shown that in-hospital revascularization after acute myocardial infarction, as well as female sex, were independent predictors of rehospitalization for acute coronary syndrome.
- Arnold SV
- Smolderen KG
- Kennedy KF
- et al.
Risk factors for rehospitalization for acute coronary syndromes and unplanned revascularization following acute myocardial infarction..
Importantly, most studies involving patients with myocardial infarction have focused on the benefit of coronary revascularization in decreasing the composite of death, myocardial infarction, and rehospitalization for acute coronary syndrome without providing clear evidence of reduction for recurrent myocardial infarction. Regardless of sex, the benefit of invasive strategy observed in most studies was largely driven by reduction in rehospitalizations, with modest effects on death or recurrent myocardial infarction.
Our study shows that after incident myocardial infarction, women experienced a markedly increased risk of recurrent myocardial infarction as compared with men, after using propensity scores to equalize the most important and clinically relevant baseline characteristics between men and women.
- Asleh R
- Manemann SM
- Weston SA
- et al.
Sex differences in outcomes after myocardial infarction in the community.
Our findings of an excess risk of recurrent myocardial infarction in women were in distinct contrast with the risk of heart failure, all-cause mortality, and cardiovascular death, which did not differ by sex after propensity score adjustment. Although we could not, by design, account for unmeasured confounders, our findings suggest that the increased risk of recurrent myocardial infarction in women may be attributed to specific sex-mediated differences in the pathophysiology of coronary artery disease. Indeed, studies have shown that women experience more microvascular and nonobstructive coronary artery disease, coronary vasospasm, spontaneous coronary artery dissection, and higher susceptibility to thrombotic occlusions following revascularization.
- Lansky AJ
- Ng VG
- Maehara A
- et al.
Gender and the extent of coronary atherosclerosis, plaque composition, and clinical outcomes in acute coronary syndromes.
As patients without significant epicardial disease are unlikely to benefit from coronary intervention, the benefit of revascularization in decreasing recurrent myocardial infarction might be more challenging to determine in women. These data emphasize the need for further research to elucidate the underlying mechanisms and potential benefit from revascularization to improve outcomes for women after myocardial infarction.
Conflicts of Interest: The authors have no conflicts of interest to disclose.
Authorship: All authors have participated in the preparation of the manuscript.
© 2021 Elsevier Inc. All rights reserved.