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Comment on: Revascularization Versus Medical Therapy in Patients Aged 80 Years and Older with Acute Myocardial Infarction

To the Editor: We have read the article entitled “Revascularization Versus Medical Therapy in Patients Aged 80 Years and Older with Acute Myocardial Infarction” by Phan et al. with great interest. In a cohort of 1,433 patients aged 80 years or older presenting with acute myocardial infarction (MI), the authors sought to evaluate the benefits of revascularization compared with medical therapy alone. From this retrospective monocentric observational study, the authors conclude that “revascularization is superior to medical therapy in reducing all-cause mortality and nonfatal MI in patients aged 80 years and older with acute MI.” We fully agree that older patients are underrepresented in clinical trials and that there is an urgent need for specific data in this population, and we applaud the authors for addressing such a major issue. However, we do not believe that this valuable retrospective study allows such a firm conclusion. Only a randomized clinical trial can support such a definite statement. Indeed, despite the epidemiological link, causality between revascularization and outcome improvement could not be demonstrated from this observational study. Aside from this methodological issue, several limitations further mitigate the conclusions drawn from the findings. First, this study focused only on patients who underwent cardiac catheterization. The frailest patients were de facto excluded because they are not eligible for such an invasive procedure. This highly limits the generalization of the results to the geriatric population. Second, as stated by the authors, frailty and comorbidities have to be considered by the clinician facing the decision of whether to perform revascularization during the acute phase of MI. However, reporting on such elements with coding data from a retrospective observational study is highly questionable because (1) the components of frailty are not part of the International Classification of Diseases; (2) no standardized geriatric evaluation was performed (patients were evaluated by cardiologists and cardiothoracic surgeons); and (3) only a prospective design adequately allows for the recording of frailty and comorbidities. These limitations probably explain why such low rates of comorbidities are reported (“dementia”: 4%, physical debilitation: 3%), suggesting they were underestimated in this older population. Failure to comprehensively record such data highly limits the validity of the propensity score adjustment. As mentioned by the authors, frailer comorbid patients are less likely to receive revascularization for acute MI, leading to a major indication bias. Regardless of the effect of revascularization, it is very likely that patients for whom such a procedure is decided will have a better prognosis. Third, the benefit of an invasive procedure may vary according to the pathophysiological type of MI. The fourth universal definition of MI distinguishes type 1 MI, due to an acute atherothrombotic event, from type 2 MI, defined as an imbalance between oxygen supply and demand without atherothrombosis. Type 2 MI is particularly frequent in older, comorbid patients and is associated with a doubled mortality risk. Invasive procedures are only rarely performed in type 2 MI patients, in the absence of proven benefit. Patients with type 2 MI are thus likely to be less represented in the invasive group, further worsening the indication bias in this study. Whether type 2 MI patients benefit from an invasive procedure is being evaluated in an on-going trial, the results of which should be of special interest for geriatricians. Kaura et al. have just published another observational study in the Lancet on the same issue and with a similar design in a large multicenter cohort of patients aged 80 years and older, but with a comprehensive report of comorbidities and frailty data, including more than 70 potentially confounding variables. Even with such an adjustment, the authors acknowledge that the results could be biased by unmeasured confounding due to factors such as frailty, which might not be well captured in routinely collected data. They prudently conclude that the survival advantage from invasive management might extend to patients aged 80 years or older with NSTEMI See the Reply by Phan et al.