Abstract
Background
As treatment of coronary artery disease improved over the last years, management of elder patients remained a matter of debate since this age group has been underrepresented in most trials. The study aimed to evaluate a population of patients with ≥ 85 years old with non-ST-segment elevation myocardial infarction (NSTEMI) and compare the prognosis according to coronary revascularization execution.
Methods
We retrospectively studied 324 patients included in a national multicenter registry between October 2010 and October 2018, who underwent coronary angiography and had at least one stenosis ≥ 50%.
Results
In this population, 73.1% of the patients underwent percutaneous coronary intervention (PCI) and 26.9% of the patients underwent optimized medical treatment (OMT). The OMT group had more past history of diabetes, stroke and dementia. On coronary angiography, the PCI group used more often the femoral artery access and single-vessel lesions were also more common. Three-vessel disease was more common in the OMT group. During hospitalization, there were more major bleeding events and death in the PCI group. During the one-year follow-up, there were no significant differences in all-cause mortality rate.
Conclusions
Very old patients with NSTEMI submitted to OMT had more comorbidities and more three-vessel disease, factors that could have influenced the therapeutic decision. Patients undergoing PCI had more in-hospital major bleeding events and mortality, with no significant differences after one year.
Keywords: Coronary artery disease, Revascularization, The elderly
1. Introduction
Age is a major classic unmodifiable cardiovascular risk factor. As the population got older, ischemic heart disease became one of the most prevalent diseases and the leading cause of death worldwide. For this reason, it is fundamental that we know how to deal with elderly patients, who frequently offer a complex clinical challenge. Not only ischemic events have more clinical impact on the elderly, but also coronary lesions become more complex with age.
Old patients are less likely to receive evidence-based therapies and, at the same time, are at a higher risk for procedural and other in-hospital complications.[1, 2] Several registries have proven that the elderly have less coronary angiographies than their younger counterparts during the acute coronary syndrome. However, observational studies and subanalysis tend to show a survival benefit of an early invasive strategy when compared to a conservative one.[3] This evidence is stronger in patients with ST-segment elevation myocardial infarction.
In this study, we sought to evaluate if percutaneous coronary intervention (PCI) affected the prognosis of a population of very old patients with ≥ 85 years old and with non-ST-segment elevation myocardial infarction (NSTEMI). However, all patients went through the coronary angiography, which means coronary anatomy also took part on the decision of the therapeutic strategy.
2. Methods
2.1. Study population
We retrospectively studied a population of patients with NSTEMI included periodically in a national multicenter registry between October 2010 and October 2018 (Figure 1). The NSTEMI was defined according to the existing myocardial infarction guidelines.[4] We selected subjects aged ≥ 85 years old, who underwent coronary angiography and had at least one coronary stenosis ≥ 50%. We therefore excluded patients who didn't perform the coronary angiography and who had the coronary artery bypass grafting performed during hospitalization or planned at discharge. Thus, we ended up studying 324 patients fulfilling these criteria.
1.
The flowchart diagram.
CA: coronary angiography; CABG: coronary artery bypass grafting; NSTEMI: non-ST-segment elevation myocardial infarction; OMT: optimized medical treatment; PCI: percutaneous coronary intervention.
Two groups were designated according to revascularization execution: the PCI group and the optimized medical treatment (OMT) group without PCI.
2.2. Clinical variables
All data on demographics, previous medical history, clinical presentation, laboratory findings, in-hospital procedures, coronary artery disease extent, culprit artery, medication given and in-hospital complications were collected and analysed from the registry database.
2.3. Follow-up and endpoints
During the one-year follow-up, we defined all-cause mortality as major endpoint. There was available follow-up data in 164 patients, 120 patients from the PCI group and 44 patients from the OMT group.
2.4. Statistical analysis
Baseline and admission characteristics, laboratory findings, in-hospital procedures, coronary artery disease extent, in-hospital complications, medication prescribed during hospitalization and at discharge and follow-up endpoints were compared between patients from both groups.
Continuous variables with normal distribution were expressed as mean ± SD or otherwise, if they did not have a normal distribution, as median (interquartile range). Categorical variables were presented as frequencies. Comparison between continuous variables was computed with Student's t-test if they had a normal distribution or with Mann-Whitney U test if they did not have a normal distribution. The Pearson's chi-squared test was used to compare categorical variables.
The log-rank test was used to compare all-cause mortality during follow-up. Multivariate Cox regression analysis was used to assess the independent association between coronary revascularization and all-cause mortality. Variables associated with the endpoint in univariate analysis were included in the models.
Two-tailed tests were used to calculate P-value. A P- value of < 0.05 was considered statistically significant. All statistics were performed using version 23.0 of IBM SPSS software (SPSS Inc., Chicago, IL, USA).
3. Results
Out of a total of 324 patients, 73.1% of patients underwent PCI and 26.9% of patients underwent OMT. The OMT group had more comorbidities, namely higher body mass index, more past history of diabetes mellitus, cerebrovascular disease, atrial fibrillation and dementia (Table 1). Killip classification at admission was similar between groups and laboratory findings only revealed significant differences in platelet count, this time in favour of the OMT group.
1.
Baseline and admission characteristics.
| Variable | Total | PCI group | OMT group | P-value |
| Data are presented as means ± SD or %. *Presented as median (interquartile range). BMI: body mass index; CABG: coronary artery bypass grafting; OMT: optimized medical treatment; PCI: percutaneous coronary intervention. | ||||
| Baseline characteristics | ||||
| Age, yrs | 87 ± 2 | 87 ± 2 | 87 ± 2 | 0.685 |
| Male gender | 55.9% | 54.0% | 60.9% | 0.267 |
| BMI, kg/m2 | 26.1 ± 3.6 | 25.8 ± 3.4 | 26.9 ± 3.8 | 0.033 |
| Hypertension | 87.5% | 86.4% | 90.7% | 0.300 |
| Dyslipidaemia | 59.0% | 58.8% | 59.5% | 0.905 |
| Diabetes mellitus | 33.4% | 29.6% | 43.7% | 0.018 |
| Active smoker | 1.3% | 1.3% | 1.2% | 0.940 |
| Previous myocardial infarction | 28.5% | 27.7% | 31.0% | 0.566 |
| Previous PCI | 15.6% | 16.6% | 12.9% | 0.426 |
| Previous CABG | 7.2% | 6.4% | 9.4% | 0.349 |
| Previous stroke | 12.2% | 9.4% | 20.0% | 0.011 |
| Peripheral arterial disease | 5.4% | 4.7% | 7.1% | 0.403 |
| Atrial fibrillation | 12.1% | 9.8% | 18.4% | 0.036 |
| Dementia | 2.2% | 0.9% | 6.0% | 0.007 |
| Chronic kidney disease | 12.9% | 14.1% | 9.4% | 0.268 |
| Chronic obstructive pulmonary disease | 9.7% | 8.9% | 11.9% | 0.430 |
| Previous major bleeding | 2.6% | 1.7% | 4.9% | 0.121 |
| Admission characteristics | ||||
| Killip class Ⅰ | 75.7% | 75.3% | 76.7% | 0.792 |
| Killip class Ⅳ | 0.3% | 0.4% | 0 | 0.545 |
| Haemoglobin, g/dL | 12.6 ± 1.6 | 12.4 ± 1.6 | 13.1 ± 1.8 | 0.296 |
| Platelet count, ×103/mm3 | 201 (163.5-251.5)* | 196 (161-243)* | 208 (176-258.5)* | 0.045 |
| Creatinine, mg/dL | 1.0 (1.0-1.2)* | 1.0 (1.0-1.3)* | 1.0 (0.9-1.0)* | 0.393 |
On coronary angiography, the PCI group used more often the femoral artery access compared to the OMT group (Table 2). While the presence of single vessel lesions was more common in the PCI group, three-vessel disease was more common in the OMT group. Moreover, significant stenosis of the left main coronary artery was more common in the latter group, which added more complexity to the degree of coronary disease extent. During hospitalization, 5.9% of the patients in the PCI group underwent the second staged coronary angioplasty. All patients in this group had TIMI grade 3 flow of the revascularized coronary artery at the end of the procedure. Although there was a tendency to a lower left ventricular ejection fraction (LVEF) in the OMT group, it didn't achieve statistical significance.
2.
Coronary angiography and echocardiography findings.
| Variable | Total | PCI group | OMT group | P-value |
| Data are presented as means ± SD or %. LAD: left anterior descending coronary artery; LCX: left circumflex coronary artery; LM: left main coronary artery; LVEF: left ventricular ejection fraction; OMT: optimized medical treatment; PCI: percutaneous coronary intervention; RCA: right coronary artery. | ||||
| Coronary angiography | ||||
| Femoral artery access | 31.2% | 35.5% | 19.3% | 0.006 |
| One-vessel disease | 26.2% | 29.2% | 18.8% | 0.047 |
| Three-vessel disease | 37.6% | 33.2% | 48.8% | 0.015 |
| LM stenosis ≥ 50% | 14.7% | 10.7% | 25.0% | 0.002 |
| LAD stenosis ≥ 50% | 80.4% | 78.8% | 84.9% | 0.224 |
| LCX stenosis ≥ 50% | 66.2% | 62.4% | 76.2% | 0.023 |
| RCA stenosis ≥ 50% | 65.6% | 64.9% | 67.5% | 0.670 |
| Echocardiography | ||||
| LVEF | 51% ± 11% | 52% ± 11% | 49% ± 12% | 0.171 |
Beta-blocker, angiotensin-converting enzyme inhibitor/ angiotensin Ⅱ receptors antagonist (ACEI/ARA Ⅱ) and statin prescription during hospitalization and at discharge was similar in both groups (supplemental material, Table 1S). The same happened for antiplatelet agents during hospitalization. However, at discharge, prescription of aspirin (90.7% vs. 96.4%, P = 0.042) and clopidogrel (74.1% vs. 85.2%, P = 0.023) was lower in the OMT group, at the cost of a higher prescription of vitamin K antagonists (7.0% vs. 2.3%, P = 0.046).
During hospitalization, there were more major bleeding events and death in the PCI group (Table 3). We haven't found more significant differences for other complications. In the secondary analysis, we realized that the group of patients that died during hospitalization had lower LVEF (45.4% ± 10.5%), 10% of patients had re-infarction, 10% of patients had mechanical complication, 20% of patients had new-onset atrial fibrillation and 20% of patients had major bleeding events. All of them were under double antiplatelet therapy, half of patients was medicated with beta-blockers and 70% of patients was medicated with ACEI/ARA Ⅱ.
3.
In-hospital major complications.
| Variable | Total | PCI group | OMT group | P-value |
| Data are presented as %. *Presented as median (interquartile range). OMT: optimized medical treatment; PCI: percutaneous coronary intervention. | ||||
| Re-infarction | 3.1% | 3.4% | 2.3% | 0.612 |
| Cardiogenic shock | 2.5% | 3.0% | 1.1% | 0.344 |
| New-onset atrial fibrillation | 8.1% | 7.2% | 10.3% | 0.363 |
| Mecanical complication | 0.3% | 0.4% | 0 | 0.542 |
| Resuscitated cardiac arrest | 0.6% | 0.4% | 1.1% | 0.461 |
| Stroke | 0.3% | 0 | 1.1% | 0.100 |
| Major bleeding | 3.1% | 4.2% | 0 | 0.041 |
| Death | 3.1% | 4.2% | 0 | 0.042 |
| Length of hospital stay, days | 5 (3-8)* | 5 (3-8)* | 6 (4-8)* | 0.282 |
After the one-year follow-up, we found a lower mortality rate among the PCI group, but it didn't reach statistical significance (HR = 0.645, 95% CI: 0.245–1.698, P = 0.375). Kaplan-Meier survival curves also haven't shown significant differences between groups (Figure 2).
2.
One-year mortality comparison between PCI and OMT.
OMT: optimized medical treatment; PCI: percutaneous coronary intervention.
4. Discussion
As treatment of coronary artery disease improved over the last years, management of elder patients remained a matter of debate and controversy since this age group has traditionally been set apart or underrepresented in the vast majority of the most important trials in the cardiovascular area. Probably this is one of the main reasons why many old patients still receive less frequently evidence-based treatment when compared with their counterparts. In this study, we decided to go further by establishing a higher age threshold in order to have a better clue at the true impact of age in therapy decision making. Furthermore, patients > 85 years old are the group of patients where more data is lacking regarding coronary revascularization.[4]
We found that the OMT group generally had more comorbidities which may have influenced the decision to perform angioplasty. Moreover, coronary artery disease in this group had a higher level of complexity, raising the risk/benefit ratio too high for an invasive strategy. A lower prescription of antiplatelet agents at the cost of a higher prescription of vitamin K antagonists at discharge was probably associated with a higher prevalence of atrial fibrillation in the OMT group.
Usually, the incidence of major bleeding events in invasive strategy groups are related to access sites.[5, 6] In this study, not only the common use of the femoral artery access during coronary angiography, but also the presence of a lower platelet count at admission could have been the main reasons for the higher rate of bleeding events in the PCI group. In-hospital mortality was also significantly higher in this group, however it wasn't necessarily and directly related to bleeding complications since only a minor part of the group had major bleeding events.
The majority of previous studies considering elderly patients with NSTEMI focused on trying to understand if the adoption of an invasive strategy, defined as routine early coronary angiography, was better than a conservative strategy, with no coronary angiography or with one only after recurrent ischemia. While most of the observational registries, which are prone to selection bias, defend the invasive strategy, many small randomized trials don't show any survival benefit of this strategy.[7-13] A large observational study of octogenarians with a non-ST-segment elevation coronary syndrome showed that an early invasive strategy reduced in-hospital mortality at the cost of a higher incidence of cardiogenic shock.[14] Saraswat, et al.[15] in their meta-analysis consisting of 523 studies and 19788 patients, found that observational studies showed a significant reduction in the one-year mortality with an invasive approach (OR = 0.38, P < 0.001), while no survival benefit in randomized studies data was found (OR = 0.77, P = 0.20). European guidelines suggest the consideration for an invasive strategy based on careful evaluation of potential risks and benefits and patients' comorbidities and quality of life.[16] American Heart Association/American College of Cardiology guidelines go further giving a class I-A recommendation for revascularization in patients with ≥ 75 years old, although also with a patient-centered decision.[17]
However, in most trials, a considerable amount of patients allocated in the invasive strategy group do not perform coronary revascularization. Therefore, we think that this study might be of great clinical importance, since we not only included patients that did coronary angiography and had obstructive coronary artery disease, but also guaranteed that every single patient in the invasive strategy group had coronary angioplasty and none in the conservative strategy group had this procedure.
Mortality rates during the one-year follow-up were high in this study, but consistent with what we were expecting considering previous registries.[18, 19] Rates between groups didn't differ significantly which, in the end, didn't confer a long-term survival benefit for angioplasty against OMT.
4.1. Limitations
This study has some particular limitations. It is a retrospective observational study, thus associated with its inherent information and selection bias and the possibility of residual confounding after adjustment cannot be excluded. The number of major adverse events may have been underrepresented given the relatively small population number and the considerable difference in sample size between both groups. Despite being a multicenter national study, the small sample size could be justified by the strict selection criteria, namely the higher age threshold and the need of having performed a coronary angiography. Still, we believe that this way all possible patient related clinical factors were weighted in the decision to revascularize the patient, which allowed us to better assess the true impact of PCI in these older patients.
4.2. Conclusions
In summary, this study reassures that very old patients are in fact one of the hardest population to manage during the myocardial infarction. We urge for bigger randomized trials that can clearly define better guidelines for the treatment of these patients, who will probably comprise an important proportion of the patients we see in our daily practice in the future years. For now, the best strategy is to collectively evaluate each case on an individual basis.
Acknowledgments
All authors had no conflicts of interest to disclose.
SUPPLEMENTARY DATA
Supplementary data to this article can be found online.
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Supplementary Materials
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