Abstract
The long-term clinical benefits of myocardial revascularization in a contemporary, nationwide cohort of acute myocardial infarction (AMI) survivors are unclear. We aimed to compare the mortality rates and clinical outcomes at 8 years of patients admitted in Italy for a first AMI managed with or without myocardial revascularization during the index event. This is a national retrospective cohort study that enrolled patients admitted for a first AMI in 2012 in all Italian hospitals who survived at 30 days. The outcomes of interest were all-cause mortality, major cardio-cerebrovascular events (MACCE), and re-hospitalization for heart failure (HF) at 8 years. Time to events was analysed using a Cox and Fine and Gray multivariate regression model. A total of 127 431 patients with AMI were admitted to Italian hospitals in 2012. The study cohort consisted of 62 336 AMI events, of whom 63.8% underwent percutaneous or surgical revascularization ≤30 days of the index hospital admission. At 8 years, the cumulative incidence of all-cause death was 36.5% (24.6% in revascularized and 57.6% in not revascularized patients). After multiple corrections, the hazard ratio (HR) for all-cause mortality in revascularized vs. not revascularized patients was 0.61 (P < 0.0001). The rate of MACCE was 45.7% and 65.8% (adjusted HR 0.83; P < 0.0001), while re-hospitalizations for HF occurred in 17.6% and 29.8% (adjusted HR 0.97; P = 0.16) in AMI survivors revascularized and not revascularized, respectively. In our contemporary nationwide cohort of patients at their first AMI episode, those who underwent myocardial revascularization within 1 month from the index event compared to those not revascularized presented an adjusted 39% risk reduction in all-cause mortality and 17% in MACCE at 8-year follow-up.
Keywords: Acute myocardial infarction, Percutaneous coronary intervention, Coronary artery bypass grafting, Secondary prevention, Conservative management
Introduction
Care for patients with acute myocardial infarction (AMI) has advanced substantially during the past decades, with novel pharmacological therapies and rapid access to successful myocardial revascularization facilitated by AMI networks of care.1–4 The early benefits of these interventions include lower mortality and a better quality of life.1–4 In contrast, less is known about the long-term impact of myocardial revascularization in AMI, and few nationwide studies providing unbiased estimates of clinical events have been reported in contemporary series.5–10
We aimed at analysing the clinical impact of myocardial revascularization at long-term follow-up in AMI survivors using a nationwide, comprehensive, and universal administrative database of AMI events.
Methods
Study design
This was a retrospective cohort study that enrolled all patients admitted to all public and private hospitals in Italy for an AMI event from 1 January to 31 December 2012. The Italian National Registry of Hospital Discharge Records (HDR), provided by the Italian Ministry of Health, and other administrative databases available through a collaboration with the Italian National Program for Outcome Evaluation (PNE-AGENAS) were used as sources of data.
Study population
The Italian HDR database was used as the source of data to identify the study population. All HDR of patients aged 18–100 years, resident in Italy, admitted in 2012 and reporting a primary diagnosis of AMI [International Classification of Disease, 9th Revision, Clinical Modification (ICD 9 CM) 410] or a secondary diagnosis of AMI with any concomitant AMI complication within the primary diagnosis (ICD-9-CM codes 411, 413, 414, 426, 427, 428, 423.0, 429.5, 429.6, 429.71, 429.79, 429.81, 518.4, 518.81, 780.01, 780.2, 785.51, 799.1, 997.02, and 998.2) were selected (Outcomes evaluation National program [PNE] Ed. 2020; available at https://pne.agenas.it/).
Patients discharged to home within 2 days from admission (probable false AMI cases) and AMI patients who died within 30 days from the index hospital admission were excluded. Furthermore, to avoid the inclusion of multiple admissions due to the same event, duplicate records and records concerning both transfers of patients to another hospital and patients with a previous AMI admission within 30 days of the index admission were excluded.11
For the purpose of this analysis, to define a cohort of first AMI events, all patients having had an AMI event or a percutaneous coronary intervention (PCI; ICD-9-CM codes 00.66, 36.01, 36.02, 36.05, 36.06, 36.07) and/or coronary artery bypass grafting procedure (CABG; ICD-9CM codes 36.10–36.19) in the previous 5 years were excluded. Patients meeting the cohort definition criteria were classified as having myocardial revascularization if they underwent PCI or CABG during the index admission for AMI or within the subsequent 30 days.
Hospital Discharge Records from 1 January 2007 were used to detect previous hospitalizations for the study population. Data on patient risk factors and comorbidities, according to the ICD9-CM codes reported in Supplementary material online, Table S1, were retrieved either from the index admission or the previous 5-year hospitalizations.
Outcomes
All-cause mortality at 8-year follow-up represented the main adverse outcome. We also evaluated the long-term incidence of major adverse cardio-cerebrovascular events (MACCE), defined as all-cause death or re-hospitalizations for MI, stroke, and/or myocardial revascularization, and the rate of new admissions for heart failure (HF) at 8 years, as secondary endpoints.
Statistical analysis
The prevalence of risk factors and comorbidities were presented as counts and percentages; age was expressed as the mean ± standard deviation. Cox regression models were used to analyse time to death and MACCE, while Fine and Gray models were used to analyse time to re-hospitalization for HF, AMI, stroke, and myocardial revascularization, with death as a competing risk.
To provide adjusted outcome data, age, gender, and patients’ risk factors and comorbidities were included in the multivariate models as potential confounding factors; stepwise procedures were used to identify independent associations with each of the considered outcomes. Since some chronic comorbidities recorded in the index hospitalization show a paradoxical protective effect,12 the same comorbidities recorded in the previous hospitalizations were also forced into the models.
All-cause mortality was also analysed by stratifying by gender (male or female) and age (< or ≥75 years old).
All assumptions of statistical methods were explicitly checked. Statistical analyses were performed using SAS 9.4 (Cary, NC, USA).
Results
Out of the overall 127 431 AMI hospitalizations that occurred in Italy in 2012, our study cohort consisted of 62 336 AMI events (Figure 1): 63.8% treated with myocardial revascularization (92.7% with PCI only, 4.6% with CABG only and 2.7% with PCI and CABG) and the remaining 36.2% managed without revascularization. Among the study cohort, 35.5% were females and 36.3% were aged ≥75 years (Table 1).
Figure 1.
Study flowchart. AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention.
Table 1.
Baseline characteristics of the enlisted population
| Not revascularized | Revascularized | P value | |
|---|---|---|---|
| (n = 22 553) | (n = 39 783) | ||
| Age (years), mean ± SD | 74.98 ± 13.66 | 65.41 ± 12.50 | <0.0001 |
| Age ≥ 75, n (%) | 12 922 (57.3) | 9731 (24.5) | <0.0001 |
| Gender (F), n (%) | 11 994 (53.2) | 10 218 (25.7) | <0.0001 |
| Hypertension, n (%) | 5756 (25.5) | 5204 (13.1) | <0.0001 |
| Diabetes, n (%) | 3001 (13.3) | 3076 (7.7) | <0.0001 |
| Heart failure, n (%) | 2125 (9.4) | 801 (2.0) | <0.0001 |
| Ill-defined descriptions and complications of heart disease, n (%) | 479 (2.1) | 226 (0.6) | <0.0001 |
| Cerebrovascular disease, n (%) | 2568 (11.4) | 1912 (4.8) | <0.0001 |
| Cerebrovascular disease (ind. adm.), n (%) | 1520 (6.7) | 1162 (2.9) | <0.0001 |
| Vascular disease, n (%) | 1386 (6.2) | 1312 (3.3) | <0.0001 |
| Vascular disease (ind. adm.), n (%) | 839 (3.7) | 1047 (2.6) | <0.0001 |
| Chronic coronary syndromes, n (%) | 2598 (11.5) | 1896 (4.8) | <0.0001 |
| Arrhythmias, n (%) | 2630 (11.7) | 1494 (3.8) | <0.0001 |
| Anaemia, n (%) | 1323 (5.9) | 656 (1.7) | <0.0001 |
| Anaemia (ind. adm.), n (%) | 1419 (6.3) | 651 (1.6) | <0.0001 |
| Blood clotting defects, n (%) | 67 (0.3) | 49 (0.1) | <0.0001 |
| Blood clotting defects (ind. adm.), n (%) | 15 (0.1) | 9 (0.02) | 0.0073 |
| Other hematological diseases, n (%) | 167 (0.7) | 154 (0.4) | <0.0001 |
| Other hematological diseases (ind. adm.), n (%) | 99 (0.4) | 125 (0.3) | 0.0124 |
| Cardiomyopathy, n (%) | 406 (1.8) | 186 (0.5) | <0.0001 |
| Cardiomyopathy (ind. adm.), n (%) | 586 (2.6) | 346 (0.9) | <0.0001 |
| Rheumatic heart disease, n (%) | 325 (1.4) | 155 (0.4) | <0.0001 |
| Rheumatic heart disease (ind. adm.), n (%) | 489 (2.2) | 286 (0.7) | <0.0001 |
| Endocarditis and acute myocarditis, n (%) | 30 (0.1) | 18 (0.05) | 0.0001 |
| Other chronic heart conditions, n (%) | 390 (1.7) | 167 (0.4) | <0.0001 |
| Other chronic heart conditions (ind.adm.), n (%) | 592 (2.6) | 383 (1.0) | <0.0001 |
| Chronic kidney disease, n (%) | 1575 (7.0) | 961 (2.4) | <0.0001 |
| Chronic kidney diseases (ind. adm.), n (%) | 2728 (12.1) | 1972 (5.0) | <0.0001 |
| Other chronic disease (liver, pancreas, intestine), n (%) | 544 (2.4) | 714 (1.8) | <0.0001 |
| Other chronic disease (liver, pancreas, intestine) (ind. adm.), n (%) | 199 (0.9) | 152 (0.4) | <0.0001 |
| Obesity, n (%) | 419 (1.9) | 467 (1.2) | <0.0001 |
| Obesity (ind. adm.), n (%) | 529 (2.4) | 1107 (2.8) | 0.0010 |
| Chronic obstructive pulmonary disease, n (%) | 2056 (9.1) | 1406 (3.5) | <0.0001 |
| Malignant neoplasms, n (%) | 2295 (10.2) | 2465 (6.2) | <0.0001 |
| Previous vascular surgery, n (%) | 1068 (4.7) | 1235 (3.1) | <0.0001 |
| Previous cerebral revascularization, n (%) | 209 (0.9) | 261 (0.7) | 0.0002 |
| Other previous cardiac surgery than CABG, n (%) | 256 (1.1) | 137 (0.3) | <0.0001 |
ind. adm, comorbidity information retrieved at the index admission.
At an 8-year follow-up, the cumulative incidence of all-cause mortality was 36.5% (24.6% in revascularized and 57.6% in not revascularized patients). After multiple corrections, the hazard ratio (HR) for all-cause mortality in revascularized vs. not revascularized patients was 0.61 (P < 0.0001) (Table 2 and Figure 2). Acute myocardial infarction patients who received myocardial revascularization within 48 h from hospital admission had a 45% reduced risk of all-cause death as compared to not revascularized patients (HR 0.55; P < 0.0001), while those revascularized from 48 h to 30 days had a 29% reduced risk (HR 0.71; P < 0.0001) (Figure 2).
Table 2.
Cox regression analyses for primary and secondary endpoints at 8 years
| Death |
MACCE |
HF |
||||
|---|---|---|---|---|---|---|
| HR | P value | HR | P value | HR | P value | |
| Myocardial revascularization | 0.61 | <0.0001 | 0.83 | <0.0001 | 0.97 | 0.1641 |
| Age (years) | 1.09 | <0.0001 | 1.04 | <0.0001 | 1.05 | <0.0001 |
| Gender (F) | 0.87 | <0.0001 | 0.86 | <0.0001 | 1.03 | 0.2099 |
| Hypertension | — | — | — | — | 1.16 | <0.0001 |
| Diabetes | 1.43 | <0.0001 | 1.35 | <0.0001 | 1.38 | <0.0001 |
| Heart failure | 1.36 | <0.0001 | 1.29 | <0.0001 | — | — |
| Cerebrovascular disease | 1.19 | <0.0001 | 1.16 | <0.0001 | 0.93 | 0.0502 |
| Cerebrovascular disease (ind. adm.) | 1.28 | <0.0001 | 1.22 | <0.0001 | — | — |
| Vascular disease | 1.20 | <0.0001 | 1.17 | <0.0001 | 1.23 | <0.0001 |
| Vascular disease (ind. adm.) | 1.15 | <0.0001 | 1.09 | 0.0025 | — | — |
| Chronic coronary syndromes | — | — | 1.07 | 0.0013 | 1.20 | <0.0001 |
| Arrhythmias | 1.04 | 0.1066 | 1.04 | 0.0516 | 1.22 | <0.0001 |
| Anaemia | 1.23 | <0.0001 | 1.15 | <0.0001 | 0.93 | 0.1523 |
| Anaemia (ind. adm.) | 1.29 | <0.0001 | 1.27 | <0.0001 | 1.19 | <0.0001 |
| Other hematological diseases | 1.22 | 0.0092 | 1.13 | 0.0786 | — | — |
| Other hematological diseases (ind. adm.) | 1.37 | 0.0009 | 1.19 | 0.0428 | — | — |
| Cardiomyopathy | 1.15 | 0.0066 | 1.04 | 0.4751 | 1.20 | 0.0996 |
| Cardiomyopathy (ind. adm.) | 1.29 | <0.0001 | 1.18 | <0.0001 | 2.10 | <0.0001 |
| Rheumatic heart disease | 1.06 | 0.3319 | 1.06 | 0.2463 | 1.26 | 0.0272 |
| Rheumatic heart disease (ind. adm.) | 1.14 | 0.0043 | 1.13 | 0.0054 | 1.55 | <0.0001 |
| Other chronic heart conditions | 1.08 | 0.1895 | — | — | 1.13 | 0.2268 |
| Other chronic heart conditions (ind.adm.) | 1.07 | 0.1037 | — | — | 1.21 | 0.0062 |
| Chronic kidney disease | 1.23 | <0.0001 | 1.17 | <0.0001 | 1.07 | 0.1711 |
| Chronic kidney diseases (ind. adm.) | 1.34 | <0.0001 | 1.26 | <0.0001 | 1.38 | <0.0001 |
| Other chronic disease (liver, pancreas, intestine) | 1.23 | <0.0001 | 1.12 | 0.0027 | — | — |
| Other chronic disease (liver, pancreas, intestine) (ind. adm.) | 1.54 | <0.0001 | 1.27 | 0.0003 | — | — |
| Obesity | — | — | — | — | 1.23 | 0.0047 |
| Obesity (ind. adm.) | — | — | — | — | 1.23 | 0.0005 |
| Chronic obstructive pulmonary disease | 1.20 | <0.0001 | 1.12 | <0.0001 | 1.21 | <0.0001 |
| Malignant neoplasms | 1.56 | <0.0001 | 1.30 | <0.0001 | 0.89 | 0.0004 |
| Previous vascular surgery | 1.39 | <0.0001 | 1.19 | <0.0001 | — | — |
| Previous cerebral revascularization | 0.90 | 0.0931 | — | — | 1.51 | <0.0001 |
| Other previous cardiac surgery than CABG | 1.16 | 0.0346 | — | — | — | — |
HF, heart failure; ind. adm, comorbidity information retrieved at the index admission; MACCE, major averse cardiac and cerebrovascular events.
Figure 2.
Adjusted survival curves for 8-year all-cause death in patients revascularized (red line) and not revascularized (blue line) (A) and in patients revascularized ≤48 h (red line) or >48 h to <30 days from the index hospitalization (green line) and not revascularized (blue line) (B).
Myocardial revascularization was performed in 73.7% and 46.0% of males and females, and in 75.7% and 43.0% of patients aged < and ≥75 years, respectively. Table 3 and Figure 3 show the HR for all-cause death according to gender (male or female) and age (≥ or <75 years) in revascularized and not revascularized AMI survivors. Acute myocardial infarction patients aged ≥75 years and not revascularized presented the highest mortality rate, regardless of gender.
Table 3.
Adjusted hazard ratios of revascularized vs. not revascularized patients for 8-year all-cause mortality (females aged 75 years not revascularized as reference), according to gender and age
| HR Revasc vs. No-Revasc | P value | |
|---|---|---|
| Males, <75 years, No Revasc | 0.23 | <0.0001 |
| Males, <75 years, Revasc | 0.12 | <0.0001 |
| Males, >75 years, No Revasc | 1.01 | 0.5372 |
| Males, >75 years, Revasc | 0.53 | <0.0001 |
| Females, <75 years, No Revasc | 0.21 | <0.0001 |
| Females, <75 years, Revasc | 0.14 | <0.0001 |
| Females, >75 years, No Revasc | REF | REF |
| Females, >75 years, Revasc | 0.51 | <0.0001 |
No Revasc, no myocardial revascularization; Revasc, myocardial revascularization.
Figure 3.
Adjusted survival curves for 8-year all-cause death in men, women, patients ≥ or <75 years old revascularized (red line) and not revascularized (blue line).
At 8 years, the cumulative incidence of MACCE was 45.7% and 65.8% in revascularized and not revascularized AMI patients, respectively (adjusted HR 0.83; P < 0.0001), while re-hospitalizations for HF occurred in 17.6% of revascularized and in 29.8% of not revascularized patients (adjusted HR 0.97; P = 0.16) (Table 2 and Figure 4). The adjusted HR for the single components of MACCE in revascularized vs. not revascularized AMI survivors are shown in Table 4.
Figure 4.
Cumulative incidence function of major cardio-cerebrovascular events (A) and heart failure (B) in patients revascularized (red line) and not revascularized (blue line) at 8-year follow-up.
Table 4.
Adjusted hazard ratios of revascularized vs. not revascularized patients for 8-year major cardio-cerebrovascular events and its components
| HR | P value | |
|---|---|---|
| MACCE | 0.83 | <0.0001 |
| Death | 0.61 | <0.0001 |
| Stroke | 1.05 | 0.2388 |
| AMI | 0.93 | 0.0056 |
| Re-PCI | 2.40 | <0.0001 |
| Re-CABG | 3.67 | <0.0001 |
Discussion
The main findings of this analysis of contemporary, nationwide administrative data are the following: (i) two-thirds of first AMI survivors hospitalized in Italy in 2012 received myocardial revascularization within 1 month from the index admission; (ii) patients revascularized presented a risk reduction of ∼40% in 8-year overall mortality compared to patients not revascularized, with a more pronounced survival benefit in elderly patients.
The use of myocardial revascularization in the contemporary management of AMI may vary according to randomized clinical trials and real-world data.11,13–17 Recent trials conducted in all-comers AMI populations showed that approximately one-third of patients were managed without revascularization.18 Similarly, recent surveys have suggested that ∼30–40% of AMI cases do not receive myocardial revascularization during hospitalization.11,13,14 Data of this study are in accordance with these percentages and confirm that the medical management of AMI is still relatively frequent in clinical practice. Notably, patients not revascularized seem to receive suboptimal pharmacological treatment at the time of hospital discharge, which may contribute to their worse prognosis.19 Possible reasons for not undergoing in-hospital revascularization include multiple and serious comorbidities, resource availability, organizational issues, socioeconomic disparities, absence of significant coronary stenoses, patient refusal, or unfavourable coronary anatomy.
There are few population studies of long-term survival after AMI.1–4 In a cohort study conducted in the USA during 2003–06, 3-year mortality rate among patients aged ≥65 years with non-ST-elevation myocardial infarction (NSTEMI) was reported to be 40%.20 In another study conducted in England from 2004 to 2010, 7-year mortality was 31% for men and 47% for women after a first AMI.9 In a more recent analysis of data from Sweden (2013–14), the 7-year survival was about 70% for patients with ST-elevation myocardial infarction (STEMI) and 60% for those with NSTEMI.7,8 Accordingly, in a cohort of AMI patients hospitalized in Australia and New Zealand from 2009 to 2015, the survival rate was 62% at 7 years.21 An increased use of efficient secondary preventive strategies, high levels of access to timely reperfusion and changes in lifestyle are probably responsible for the improved survival rates observed in recent decades. Our data are in accordance with the recent literature: the crude 8-year survival rate was ∼64% in the overall population, reaching 75% in revascularized patients and 85% in those revascularized within 48 h from hospital admission. On the other hand, in elderly patients, long-term survival was approximately 50% in revascularized and 20% in non-revascularized AMI survivors, regardless of gender. In this regard, our data solicits the planning of educational campaigns and guidelines’ adherence programmes focused on the acute management of elderly patients with AMI. Indeed, dedicated randomized clinical trials22–24 and observational nationwide studies25–27 documented a clear benefit of myocardial revascularization even in older and frail AMI patients. Based upon this evidence, the recent European guidelines on AMI recommend that elderly patients apply the same interventional strategies used for younger ones, considering on an individual case basis ischaemic and bleeding risks, estimated life expectancy, quality of life, patient values, and preferences.28 Therefore, in daily practice, improving post-AMI care for older patients should require a multidisciplinary approach, carefully balancing the risks and benefits of secondary prevention strategies.
Limitations
There are several limitations of using an administrative health claims database. One is that the lack of specific clinical information may have affected the accuracy of the diagnosis and risk stratification of AMI. In addition, we cannot clearly classify from ICD‐9 CM codes the type and severity of AMI. Another limitation is the deficiencies in the ICD‐9 CM code descriptions that provide comprehensive data on in-hospital complications. Furthermore, we cannot determine the extent to which misclassification and coding errors may be present.
Conclusions
In the present contemporary, nationwide cohort of first AMI survivors, those who underwent myocardial revascularization within 1 month of the index event presented an adjusted 39% relative risk reduction in all-cause mortality and 17% in MACCE at 8-year follow-up compared to those not revascularized. These data further confirm the key role of appropriate, timely, and effective myocardial revascularization in the contemporary management of AMI, particularly in older patients.
Supplementary material
Supplementary material is available at European Heart Journal Supplements online.
Conflict of interest: none declared.
Data availability
The data underlying this article were provided by AGENAS/ISS with permission. Data will be shared on request to the corresponding author with the permission of AGENAS/ISS.
Supplementary Material
References
- 1. Anderson JL, Morrow DA.. Acute myocardial infarction. N Engl J Med 2017;376:2053–2064. [DOI] [PubMed] [Google Scholar]
- 2. Fox KAA, Clayton TC, Damman P, Pocock SJ, de Winter RJ, Tijssen JGP, Lagerqvist B, Wallentin L; FIR Collaboration. Long-term outcome of a routine versus selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome a meta-analysis of individual patient data. J Am Coll Cardiol 2010;55:2435–2445. [DOI] [PubMed] [Google Scholar]
- 3. Keeley EC, Boura JA, Grines CL.. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13–20. [DOI] [PubMed] [Google Scholar]
- 4. Bradley EH, Herrin J, Wang Y, Barton BA, Webster TR, Mattera JA, Roumanis SA, Curtis JP, Nallamothu BK, Magid DJ, McNamara RL, Parkosewich J, Loeb JM, Krumholz HM.. Strategies for reducing the door-to-balloon time in acute myocardial infarction. N Engl J Med 2006;355:2308–2320. [DOI] [PubMed] [Google Scholar]
- 5. Ellis CJ, Gamble GD, Williams MJA, Matsis P, Elliott JM, Devlin G, Mann S, French JK, White HD; Regional Cardiac Society NZ ACS Audit Group. All-cause mortality following an acute coronary syndrome: 12-year follow-up of the comprehensive 2002 New Zealand acute coronary syndrome audit. Heart Lung Circ 2019;28:245–256. [DOI] [PubMed] [Google Scholar]
- 6. Ranasinghe I, Barzi F, Brieger D, Gallagher M.. Long-term mortality following interhospital transfer for acute myocardial infarction. Heart 2015;101:1032–1040. [DOI] [PubMed] [Google Scholar]
- 7. Szummer K, Wallentin L, Lindhagen L, Alfredsson J, Erlinge D, Held C, James S, Kellerth T, Lindahl B, Ravn-Fischer A, Rydberg E, Yndigegn T, Jernberg T.. Relations between implementation of new treatments and improved outcomes in patients with non-ST-elevation myocardial infarction during the last 20 years: experiences from SWEDEHEART registry 1995 to 2014. Eur Heart J 2018; 39:3766–3776. [DOI] [PubMed] [Google Scholar]
- 8. Szummer K, Wallentin L, Lindhagen L, Alfredsson J, Erlinge D, Held C, James S, Kellerth T, Lindahl B, Ravn-Fischer A, Rydberg E, Yndigegn T, Jernberg T.. Improved outcomes in patients with ST-elevation myocardial infarction during the last 20 years are related to implementation of evidence-based treatments: experiences from the SWEDEHEART registry 1995–2014. Eur Heart J 2017;38:3056–3065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Smolina K, Wright FL, Rayner M, Goldacre MJ.. Long-term survival and recurrence after acute myocardial infarction in England, 2004 to 2010. Circ Cardiovasc Qual Outcomes 2012;5:532–540. [DOI] [PubMed] [Google Scholar]
- 10. De Luca L, Cicala SD, D'Errigo P, Cerza F, Mureddu GF, Rosato S, Badoni G, Seccareccia F, Baglio G.. Impact of age, gender and heart failure on mortality trends after acute myocardial infarction in Italy. Int J Cardiol 2022;348:147–151. [DOI] [PubMed] [Google Scholar]
- 11. Roe MT, White JA, Kaul P, Tricoci P, Lokhnygina Y, Miller CD, van't Hof AW, Montalescot G, James SK, Saucedo J, Ohman EM, Pollack CV, Hochman JS, Armstrong PW, Giugliano RP, Harrington RA, Van de Werf F, Califf RM, Newby LK.. Regional patterns of use of a medical management strategy for patients with non-ST-segment elevation acute coronary syndromes: insights from the EARLY-ACS Trial. Circ Cardiovasc Qual Outcomes 2012;5:205–213. [DOI] [PubMed] [Google Scholar]
- 12. Romano PS, Mark DH.. Bias in the coding of hospital discharge data and its implications for quality assessment. Med Care 1994;32:81–90. [DOI] [PubMed] [Google Scholar]
- 13. Amsterdam EA, Peterson ED, Ou F-S, Newby LK, Pollack CV, Gibler WB, Ohman EM, Roe MT.. Comparative trends in guidelines adherence among patients with non-ST-segment elevation acute coronary syndromes treated with invasive versus conservative management strategies: results from the CRUSADE quality improvement initiative. Am Heart J 2009;158:748–754. [DOI] [PubMed] [Google Scholar]
- 14. Bagnall AJ, Goodman SG, Fox KAA, Yan RT, Gore JM, Cheema AN, Huynh T, Chauret D, Fitchett DH, Langer A, Yan AT; Canadian Acute Coronary Syndrome Registry I and II Investigators; Canadian Global Registry of Acute Coronary Events (GRACE/GRACE2) Investigators. Influence of age on use of cardiac catheterization and associated outcomes in patients with non-ST-elevation acute coronary syndromes. Am J Cardiol 2009;103:1530–1536. [DOI] [PubMed] [Google Scholar]
- 15. Swanson N, Montalescot G, Eagle KA, Goodman SG, Huang W, Brieger D, Devlin G; GRACE Investigators. Delay to angiography and outcomes following presentation with high-risk, non-ST-elevation acute coronary syndromes: results from the Global Registry of Acute Coronary Events. Heart 2009;95:211–215. [DOI] [PubMed] [Google Scholar]
- 16. O'Donoghue M, Boden WE, Braunwald E, Cannon CP, Clayton TC, de Winter RJ, Fox KAA, Lagerqvist B, McCullough PA, Murphy SA, Spacek R, Swahn E, Wallentin L, Windhausen F, Sabatine MS.. Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction: a meta-analysis. JAMA 2008;300:71–80. [DOI] [PubMed] [Google Scholar]
- 17. Poole-Wilson PA, Pocock SJ, Fox KAA, Henderson RA, Wheatley DJ, Chamberlain DA, Shaw TRD, Clayton TC; Randomised Intervention Trial of unstable Angina Investigators. Interventional versus conservative treatment in acute non-ST elevation coronary syndrome: time course of patient management and disease events over one year in the RITA 3 trial. Heart 2006;92:1473–1479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Tricoci P, Huang Z, Held C, Moliterno DJ, Armstrong PW, Van de Werf F, White HD, Aylward PE, Wallentin L, Chen E, Lokhnygina Y, Pei J, Leonardi S, Rorick TL, Kilian AM, Jennings LHK, Ambrosio G, Bode C, Cequier A, Cornel JH, Diaz R, Erkan A, Huber K, Hudson MP, Jiang L, Jukema JW, Lewis BS, Lincoff AM, Montalescot G, Nicolau JC, Ogawa H, Pfisterer M, Prieto JC, Ruzyllo W, Sinnaeve PR, Storey RF, Valgimigli M, Whellan DJ, Widimsky P, Strony J, Harrington RA, Mahaffey KW; TRACER Investigators. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 2012;366:20–33. [DOI] [PubMed] [Google Scholar]
- 19. De Luca L, Leonardi S, Smecca IM, Formigli D, Lucci D, Gonzini L, Tuccillo B, Olivari Z, Gulizia MM, Bovenzi FM, De Servi S; EYESHOT Investigators. Contemporary antithrombotic strategies in patients with acute coronary syndromes managed without revascularization: insights from the EYESHOT study. Eur Heart J Cardiovasc Pharmacother 2015;1:168–178. [DOI] [PubMed] [Google Scholar]
- 20. Roe MT, Chen AY, Thomas L, Wang TY, Alexander KP, Hammill BG, Gibler WB, Ohman EM, Peterson ED.. Predicting long-term mortality in older patients after non-ST-segment elevation myocardial infarction: the Crusade long-term mortality model and risk score. Am Heart J 2011;162:875–883. [DOI] [PubMed] [Google Scholar]
- 21. Nadlacki B, Horton D, Hossain S, Hariharaputhiran S, Ngo L, Ali A, Aliprandi-Costa B, Ellis CJ, Adams RJ, Visvanathan R, Ranasinghe I.. Long term survival after acute myocardial infarction in Australia and New Zealand, 2009-2015: a population cohort study. Med J Aust 2021;214:519–525. [DOI] [PubMed] [Google Scholar]
- 22.Morici N, De Servi S, De Luca L, Crimi G, Montalto C, De Rosa R, De Luca G, Rubboli A, Valgimigli M, Savonitto S. Management of acute coronary syndromes in older adults. Eur Heart J 2022, in press; doi:10.1093/eurheartj/ehab391. [DOI] [PubMed] [Google Scholar]
- 23. Bueno H, Betriu A, Heras M, Alonso JJ, Cequier A, Garcia EJ, Lopez-Sendon JL, Macaya C, Hernandez-Antolin R, Bueno H, Hernandez-Antolin R, Alonso JJ, Betriu A, Cequier A, Garcia EJ, Heras M, Lopez-Sendon JL, Macaya C, Azpitarte J, Sanz G, Chamorro A, Lopez-Palop R, Sionis A, Aros F, Garcia-Fernandez E, Rubio R, Hernandez F, Tascon JC, Moreu J, Betriu A, Heras M, Hernandez-Antolin R, Fernandez-Ortiz A, Moris C, de Posada IS, Cequier A, Esplugas E, Melgares R, Bosa F, Garcia-Gonzalez MJ, Lezaun R, Carmona JR, Vazquez JM, Castro-Beiras A, Picart JG, de Rozas JD, Fernandez JD, Vazquez FF, Alonso N, Zueco JJ, San Jose JM, San Roman A, Hernandez C, Garcia JMH, Alcantara AG, Bethencourt A, Fiol M, Mancisidor X, Mancisidor X, Ruiz R, Hidalgo R, Sobrino N, Maqueda IG, Torres A, Aros F, Amaro A, Jaquet M; on behalf of the TRIANA Investigators. Primary angioplasty vs. fibrinolysis in very old patients with acute myocardial infarction: TRIANA (TRatamiento del Infarto Agudo de miocardio eN Ancianos) randomized trial and pooled analysis with previous studies. Eur Heart J 2011;32:51–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Savonitto S, Cavallini C, Petronio AS, Murena E, Antonicelli R, Sacco A, Steffenino G, Bonechi F, Mossuti E, Manari A, Tolaro S, Toso A, Daniotti A, Piscione F, Morici N, Cesana BM, Jori MC, De Servi S; Italian Elderly ACS Trial Investigators. Early aggressive versus initially conservative treatment in elderly patients with non-ST-segment elevation acute coronary syndrome: a randomized controlled trial. JACC Cardiovasc Interv 2012;5:906–916. [DOI] [PubMed] [Google Scholar]
- 25. De Luca L, Olivari Z, Bolognese L, Lucci D, Gonzini L, Di Chiara A, Casella G, Chiarella F, Boccanelli A, Di Pasquale G, Bovenzi FM, Savonitto S.. A decade of changes in clinical characteristics and management of elderly patients with non-ST elevation myocardial infarction admitted in Italian cardiac care units. Open Heart 2014;1:e000148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.De Luca L, Marini M, Gonzini L, Boccanelli A, Casella G, Chiarella F, De Servi S, Di Chiara A, Di Pasquale G, Olivari Z, Caretta G, Lenatti L, Gulizia MM, Savonitto S. Contemporary trends and age-specific sex differences in management and outcome for patients with ST-segment elevation myocardial infarction. J Am Heart Assoc 2016;5:e004202. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Kaura A, Sterne JAC, Trickey A, Abbott S, Mulla A, Glampson B, Panoulas V, Davies J, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Melikian N, Johnson T, Francis DP, Shah AM, Perera D, Kharbanda R, Patel RS, Mayet J.. Invasive versus non-invasive management of older patients with non-ST elevation myocardial infarction (SENIOR-NSTEMI): a cohort study based on routine clinical data. Lancet 2020;396:623–634. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Collet J-P, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Jüni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM; ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2021;42:1289–1367. [DOI] [PubMed] [Google Scholar]
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Data Availability Statement
The data underlying this article were provided by AGENAS/ISS with permission. Data will be shared on request to the corresponding author with the permission of AGENAS/ISS.