Editor's Note: Commentary based on Turk J, Fourny M, Yayehd K, et al. Age-related differences in reperfusion therapy and outcomes for ST-segment elevation myocardial infarction. J Am Geriatr Soc 2018.

Rationale for Study: Contemporary data on timely access to reperfusion therapy and in-hospital outcomes according to the age of older adults presenting with ST-elevation myocardial infarction (STEMI) is limited.

Funding: This study was supported by a grant from the French Ministry of Health (PREPS 2014 14-00040) and was developed within the framework of the Grenoble Alpes Data Institute (ANR-14-IDEX-02).

Study Design: Retrospective cohort study of adults (≥18 years old) presenting with STEMI to 23 public and private hospitals in the northern Alps in France. Individuals were enrolled prospectively in a clinical registry from January 2009 to December 2015.

Inclusion Criteria: All adults with symptoms of myocardial infarction (MI) <12 hours from symptom onset with persistent ST segment elevation, new or presumed new left bundle branch block or paced rhythm.

Exclusion Criteria: None.

Exposure: Age was categorized into three groups: <75 years old, 75-84 years old and ≥85 years old.

Primary Outcome: Receipt of timely reperfusion therapy, defined as IV fibrinolysis within 30 minutes of first medical contact (FMC), primary PCI within 60 minutes of FMC for early presenters (<2 hours of symptom onset) or patients presenting directly to a PCI-capable facility or primary PCI within 90 minutes for all other patients.

Secondary Outcomes: Delivery of any reperfusion therapy (primary PCI or fibrinolysis), delivery of primary PCI, in-hospital all-cause mortality, non-fatal reinfarction, stroke, acute heart failure and major bleeding events. All in-hospital events were adjudicated by independent chart review by cardiologists and emergency physicians with experience in treating STEMI.

Statistical Analysis: Multivariable logistic regression was performed separately modeling both in-hospital mortality and provision of timely reperfusion, additionally evaluating the statistical interaction of age by timely reperfusion. Causal mediation analysis was used to decompose the effect of age on in-hospital mortality. Multiple imputation used for missing covariate information. A meta-analysis of published literature on age and reperfusion was used to compute summary estimates for comparison.

Results: A total of 4,813 were included of which 3,716 (77.2%) were <75 years old, 782 (16.2%) were 75-84 years old and 315 (6.5%) were ≥85 years old. The percentage of females and individuals with diabetes, prior coronary artery disease, new left bundle branch block, cardiogenic shock, time for symptom onset to FMC and presentation to a PCI-capable hospital increased with age. Individuals older than 75 years old were less likely to present with cardiac arrest at the time of FMC.

Overall, 91.3% of participants received any perfusion (65.4% primary PCI; 26% fibrinolysis). Rates of reperfusion decreased and primary PCI was more common on a relative basis with increasing age (p < 0.001). Rates of any perfusion, primary PCI, and timely reperfusion respectively by age groups were:

• 92.9%, 63.7%, 44.6% for participants <75 years old.
• 89.0%, 70.3%, 36.8% for participants 75-84 years old.
• 78.7%, 72.4%, 29.9% for individuals 85 years old and older.

In-hospital mortality increased with age (<75 years old: 3.4%; 75-84 years old: 10.2%; 19.8% ≥85 years old) with a 37% relative reduction in the odds of in-hospital mortality with timely reperfusion therapy (OR 0.63; 95% CI 0.46-0.85) with a non-significant interaction by age (p = 0.45). Compared to those <75 years old, failure to provide timely reperfusion explained 3.1% (95% CI 0.5-5.7, p = 0.02) and 3.6% (95% CI 0.4-6.8%, p = 0.03) of in-hospital mortality for participants 75-84 and ≥85 years old respectively. Sensitivity analyses were robust to exclusion of those <65 years old from the study or to exclusion of those who died prior to receipt of reperfusion.

Limitations of Study:

• Non-randomized observational data may be subject to residual confounding.
• Age considered as a categorical rather than continuous variable in analyses.
• Use of standard logistic regression does not account for clustering of outcomes by hospital.
• Limited information on comorbidities, pre-existing frailty or disability, living situation prior to admission, arterial access site, and long-term outcomes was available.

Conclusion: Individuals 75 years and older with STEMI who met contemporary eligibility criteria for reperfusion in a STEMI system still received delayed reperfusion which contributed partly to higher in-hospital mortality in older participants.

Geriatric Perspective for the Cardiovascular Clinician: It is well known that age is an independent risk factor for mortality in STEMI patients,¹ with those ≥75 having nearly four times the mortality risk of those younger than age 75,^2,3 and that primary PCI and prompt coronary reperfusion improves survival of older adults¹ in this setting.^4,5 Despite these data, a substantial proportion of older adults still undergo delayed reperfusion.^6,7 The impact of regional and national networks of STEMI care on timely reperfusion timing and optimal outcomes for older adults is unknown. This is particularly relevant given that 25% of all STEMI patients in Western countries are ≥75 years old.⁸

In the current analysis, using a retrospective cohort of STEMI patients in France, Turk et al.⁹ demonstrate that while overall reperfusion rates are high (91.3%), rates of any reperfusion and timely reperfusion (i.e., IV fibrinolysis within 30 minutes or primary PCI within 60 minutes of FMC for early presenters, or primary PCI within 90 minutes for all others) still decline with age. There is an increasing use of primary PCI in older age groups (72% of age ≥85 vs. 64% age <65 years) and less use of fibrinolysis. Among those undergoing fibrinolysis, there is no apparent reperfusion delay. Rather, overall delay with age is noted among those undergoing PCI (average of 82 min for age ≥85 vs. 72 min age <65 years) with delays noted in early PCI at <30 min and in the delayed PCI delivery >90 min from FMC. Overall, less than one-third of patients older than age 85 received timely reperfusion. The authors cite many potential reasons for this gap in reperfusion including relative or absolute contraindications to fibrinolysis,¹⁰ atypical clinical presentations,¹⁰ delayed clinical presentations,¹⁰ cognitive status,² individual preference,³ earlier time to death among older adults and concerns among providers about age-related risks surrounding treatment.^1,11,12

Nevertheless, even in those receiving timely reperfusion, there was an age-related increase in in-hospital mortality. Older individuals were more likely to present with cardiogenic shock, were more likely to have diabetes and prior coronary disease, have lower vessel patency rates and had a longer time from symptom onset to FMC. Thus, older individuals demonstrate a higher-risk phenotype that may attenuate some of the benefit received from timely reperfusion. Thus, the current analysis confirms that age-related discrepancies in optimal reperfusion and outcomes remain prevalent despite improvements in PCI network coordination and supports intrinsic features to biological aging that complicate care of older individuals.

In summary, this study supports effectiveness of reperfusion in older adults and further reinforces the need for improvements in processes of care to allow for timely reperfusion with PCI of older adults presenting with STEMI. As detailed reasons for the delay observed in reperfusion are not provided in the current work, future research defining the primary contributors to delay is necessary to develop evidence-based strategies to reduce this discrepancy. Decision-making and unclear patient preferences for acute care in the oldest subgroups may contribute to early and late term delays in PCI in those centers where delivery in younger patients is timelier. More consideration of ways to ensure those who need and are eager to receive emergent care past age 85 are able to get the benefits from its timely delivery.

References

1. Alexander KP, Newby LK, Armstrong PW, et al. Acute coronary care in the elderly, part II: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology. Circulation 2007;115:2570-89.
2. Guagliumi G, Stone GW, Cox DA, et al. Outcome in elderly patients undergoing primary coronary intervention for acute myocardial infarction: results from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Circulation 2004;110:1598-604.
3. Forman DE, Chen AY, Wiviott SD, Wang TY, Magid DJ, Alexander KP. Comparison of outcomes in patients aged <75, 75 to 84, and ≥ 85 years with ST-elevation myocardial infarction (from the ACTION Registry-GWTG). Am J Cardiol 2010;106:1382-8.
4. Anderson JL, Adams CD, Antman EM, et al. 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:e179-347.
5. Steg PG, James SK, Gersh BJ. 2012 ESC STEMI guidelines and reperfusion therapy: evidence-based recommendations, enduring optimal patient management. Heart 2013;99:1156-7.
6. Puymirat E, Aissaoui N, Cayla G, et al. Changes in one-year mortality in elderly patients admitted with acute myocardial infarction in relation with early management. Am J Med 2017;130:555-63.
7. Schoenenberger AW, Radovanovic D, Windecker S, et al. Temporal trends in the treatment and outcomes of elderly patients with acute coronary syndrome. Eur Heart J 2016;37:1304-11.
8. Puymirat E, Simon T, Steg PG, et al. Association of changes in clinical characteristics and management with improvement in survival among patients with ST-elevation myocardial infarction. JAMA 2012;308:998-1006.
9. Turk J, Fourny M, Yayehd K, et al. Age-related differences in reperfusion therapy and outcomes for ST-segment elevation myocardial infarction. J Am Geriatr Soc 2018.
10. Sappa R, Grillo MT, Cinguetti M, et al. Short and long-term outcome in very old patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention. Int J Cardiol 2017;249:112-8.
11. Schoenenberger AW, Radovanovic D, Stauffer JC, et al. Age-related differences in the use of guideline-recommended medical and interventional therapies for acute coronary syndromes: a cohort study. J Am Geriatr Soc 2008;56:510-6.
12. Newell MC, Henry JT, Henry TD, et al. Impact of age on treatment and outcomes in ST-elevation myocardial infarction. Am Heart J 2011;161:664-72.

Keywords: Geriatrics, Myocardial Infarction, Myocardial Reperfusion, Coronary Artery Disease, Risk Factors, Bundle-Branch Block, Shock, Cardiogenic, Fibrinolysis, Heart Arrest, Stroke, Heart Failure, Diabetes Mellitus, Percutaneous Coronary Intervention, Aging

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