Academic Editor: Peter A. McCullough
The benefit of complete revascularization in elderly patients with non-ST
elevation myocardial infarction (NSTEMI), and multivessel disease remains debated
(MVD). The aim of our study was to determine the current long-term prognostic
benefit of complete revascularization in this population. A retrospective cohort
study of 1722 consecutive elderly NSTEMI patients was performed. Among the study
participants 30.4% (n = 524) were completed revascularizated and in 69.6% (n =
1198) culprit vessel only revascularization was performed. A propensity score
analysis was performed and we divided the study population into two groups:
complete revascularization (n = 500) and culprit vessel only revascularization (n
= 500). The median follow-up was 45.7 months, the all cause mortality (44.5% vs
30.5%, p
Nowadays, non-ST elevation myocardial infarction (NSTEMI) is the most frequent manifestation of acute coronary syndrome (ACS) [1]. Current guidelines recommend an invasive strategy in patients with NSTEMI in order to improves mortality and reduce long term clinical events [2, 3].
Half of NSTEMI patients have multivessel disease (MVD) in the coronary angiography [4, 5]. Recent studies have suggested that in NSTEMI patients with MVD, complete coronary revascularization (CCR) appears to be superior to culprit vessel only (CV) PCI in NSTEMI patients with MVD [6]. However, both the European Society of Cardiology and the American College of Cardiology guidelines do not specify the extent of revascularization giving a class IIa for complete revascularization in STEMI patients [3, 4, 7].
The proportion of elderly with NSTEMI will grow up in the next years and their management will become daily clinical practice challenge. Currently, 30% of the patients included in the European NSTEMI-ACS registries [8, 9] are older than 75 years. However, those patients are underrepresented in randomized clinical trials (i.e., 13% in the TRITON-TIMI 38 study and 15% in the PLATO study) [10, 11]. Also, due to a selection bias, elderly individuals enrolled in clinical trial may not be representative of the population treated in everyday clinical practice.
Elderly patients are less likely to receive evidence-based therapies and undergo an invasive strategy compared with younger patients despite of their benefits [12, 13, 14, 15].
Indeed, the current guidelines recommend that elderly patients should be considered for an invasive strategy and, if appropriate, revascularization after careful evaluation of potential risks and benefits, estimated life expectancy, comorbidities, quality of life, and patient values and preferences [3].
Our study aims to analyze the long-term prognosis of complete revascularization (CCR) compared with culprit vessel only (CV) in a cohort of elderly patients with NSTEMI and MVD in a real life registry.
A retrospective study of all consecutive patients
Flowchart of the patients of the study.
NSTEMI was defined according to current clinical practical guidelines [3, 4]. A standard definition of MVD was used as the presence of at least one angiographically significant non- infarct-related (non-culprit) lesion (stenosis at least 70% of the vessel diameter) that was amenable to successful treatment with PCI and was located in a vessel with a diameter of at least 2.5 mm that was not stented as part of the index culprit-lesion PCI.
CV revascularization was defined as revascularization of only the infarct-related artery, and complete revascularization was performed as a routine staged PCI (i.e., PCI during a procedure separate from the index PCI procedure for NSTEMI) of all suitable non-culprit lesions, regardless of whether there were clinical symptoms or there was evidence of ischemia.
Risk factors, clinical antecedents, treatments, complementary tests, and main diagnosis at discharge were collected from all patients by trained medical staff. The diagnostic and therapeutic NSTEMI protocols were made according to ESC clinical practical guidelines [2]. The antecedent of previous coronary heart disease patients and previous HF were codified according to the protocols used in previous papers of our group [16].
To estimate mortality risk we determined the GRACE score [17] and to estimate the bleeding risk we determined the the CRUSADE risk [18].
After discharge, the follow-up of patients has been made according to our previous studies [16]. Primary endpoints assessed through follow- up were cardiovascular mortality, all-cause mortality and first major adverse cardiovascular event (MACE) that included hospital readmission for ACS, HF, stroke or bleeding as well as deaths attributable to cardiac causes.
Quantitative variables are presented as mean (Interquartile Range (IQR)) and differences were assessed by Student’s t-test and Chi-square test. Qualitative variables are presented as percentages and differences were analyzed by analysis of variance (ANOVA) test. Survival analyses were performed after verifying the proportional risk assumption by the Schoenfeld residuals test.
We used propensity score matching to minimize the possibility that CCR was not assigned after a randomization phase [19, 20]. We applied a greedy 1 : 1 matching algorithm without replacement and defined optimal matching as a standard deviation of 0.2. First of all, a binary logistic regression where the dependent variable was CCR, and explanatory variables were age, gender, hypertension, diabetes, dyslipidemia, previous coronary heart disease, HF or stroke, GRACE score, revascularization, and medical treatments recommended at discharge was performed. Secondly two groups of 500 of patients with the same probability of receiving CCR were created. The predictive capacity of the model used to generate the propensity score was 0.79 (95% confidence interval (CI) 0.73–0.845; p = 0.01) with a good fit (Hosmer-Lemeshow p = 0.13).
All-cause mortality predictors were assessed by Cox regression models using all
variables that obtained p values
A total of 1722 patients
In a total of 524 patients (30.4%) CCR was performed and in 1198 (69.6%) CV revascularization was performed. When we compared both groups (Table 1) we observed that patients in the CCR group were younger, male, with lower rates of anemia, previous coronary artery disease, previous revascularization, and heart failure. Also, they had lower Killip class and lower GRACE and CRUSADE scores compared with those with CV revascularization. Indeed, at discharge, they were more frequently prescribed on aspirin, beta-blockers, diuretics, and statins and less on diuretics. We have not found differences between both groups in terms of the access of the angiography; in the CCR the radial access was used in 94.2% of the patients in the CV group the radial access was used in 93.1% of the patients.
Baseline characteristics | CCR (n = 524) | Culprit vessel only (n = 1198) | p | |
Age (years), mean |
80.7 |
81.7 |
||
Female, n (%) | 193 (36.8) | 499 (41.7) | 0.060 | |
BMI (kg/m |
30 ± 21 | 28 ± 7 | 0.016 | |
Previous CAD, n (%) | 151 (28.8) | 442 (36.9) | 0.001 | |
Previous AMI, n (%) | 30 (10.5) | 188 (19.4) | 0.001 | |
Previous PCI, n (%) | 63 (12.0) | 115 (9.6) | 0.129 | |
Previous CABG, n (%) | 14 (2.7) | 111 (9.3) | ||
Previous STROKE, n (%) | 50 (9.5) | 151 (12.6) | 0.069 | |
Previous HF, n (%) | 32 (6.1) | 132 (11.0) | 0.001 | |
CKD, n (%) | 46 (8.8) | 140 (11.7) | 0.3074 | |
COPD, n (%) | 85 (16.2) | 194 (16.2) | 0.989 | |
PAD, n (%) | 38 (7.3) | 143 (11.9) | 0.004 | |
Previous neoplasia, n (%) | 43 (8.2) | 105 (8.7) | 0.050 | |
Smoker, n (%) | 40 (7.6) | 64 (5.3) | 0.066 | |
Hypertension, n (%) | 412 (78.6) | 910 (76.0) | 0.228 | |
Diabetes, n (%) | 190 (36.3) | 451 (37.6) | 0.584 | |
Dislypidemia, n (%) | 256 (48.9) | 600 (50.1) | 0.639 | |
AF, n (%) | 89 (17.0) | 245 (20.5) | 0.094 | |
IN hospital management | ||||
SBP (mmHg), mean |
141 |
139 |
0.183 | |
DBP (mmHg), mean |
75 |
73 |
0.020 | |
HR (bpm), mean |
78 |
80 |
0.036 | |
Troponin peak (ng/mL), mean |
17 |
9 |
0.015 | |
Hemoglobin (g/dL), mean |
13.0 |
12.8 |
0.005 | |
Creatinine (mg/dL), mean |
1.1 |
1.2 |
0.038 | |
eGRF (mL/min/1.72 m |
74 |
71 |
0.143 | |
Glycemia (mg/dL), mean |
135 |
153 |
||
Total cholesterol (mg/dL), mean |
164 |
162 |
0.489 | |
LDL cholesterol (mg/dL), mean |
97 |
96 |
0.636 | |
LVEF, mean |
55 |
53 |
||
GRACE, mean |
154 |
163 |
||
CRUSADE, mean |
27 |
32 |
||
KILLIP n (%) | ||||
I | 424 (80.9) | 810 (67.6) | ||
II | 72 (13.8) | 262 (22.0) | ||
III | 22 (4.2) | 102 (8.6) | ||
IV | 6 (1. 2) | 24 (2.0) | ||
Charlson index, mean |
2.7 |
2.9 |
0.393 | |
Medical therapy at discharge | ||||
ASA, n (%) | 490 (93.5) | 867 (72.4) | ||
CLOPIDOGREL, n (%) | 436 (83.2) | 568 (47.4) | ||
TICAGRELOR, n (%) | 29 (5.5) | 9 (0.8) | ||
OAC, n (%) | 167 (13.9) | 56 (10.7) | 0.064 | |
Beta-blockers, n (%) | 356 (67.9) | 638 (53.3) | ||
ACEI/ARB, n (%) | 360 (54.5) | 653 (54.5) | ||
STATIN, n (%) | 456 (87.0) | 835 (69.7) | ||
MRA, n (%) | 15 (5.3) | 60 (6.2) | 0.564 | |
Diuretics, n (%) | 127 (24.2) | 423 (35.3) | ||
BMI, body mass index; CAD, coronary artery disease; AMI, acute myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; HF, heart failure; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; PAD, peripheral artery disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; eGRF, estimated glomerular filtration rate; LDL, low density lipoprotein; LVEF, left ventricular ejection fraction; ASA, aspirin; OAC, oral anticoagulant; ACEI, angiotensin-converting-enzyme inhibitor, ARBs, angiotensin II receptor blockers; MRA, mineralorcorticoid recepctor antagonists; SD, standar desviation. |
We have not found differences between groups in terms of intrahospitalary complications: In the CCR group we observed 13.7% bleeding, 10.2% acute kidney injury and, 2.1% recurrent MI. In the CV group we observed 12.0% bleeding, 9.6% acute kidney injury and, 1.7% recurrent MI.
Five hundred pairs of patients with the same possibility of receiving CCR were obtained after the propensity score matching (Fig. 1). We did not observe statistical differences between groups (Table 2).
Baseline characteristics | CCR (n = 500) | Culprit vessel only (n = 500) | p | |
AGE (years), mean |
81.1 |
81.2 |
0.692 | |
FEMALE, n (%) | 109 (21.8) | 119 (238) | 0.962 | |
BMI (kg/m |
30 ± 30 | 28 ± 10 | 0.365 | |
Previous CAD, n (%) | 97 (19.4) | 95 (19.0) | 0.340 | |
Previous AMI, n (%) | 17 (3.4) | 28 (5.6) | 0.525 | |
Previous PCI, n (%) | 38 (7.6) | 29 (5.8) | 0.116 | |
Previous CABG, n (%) | 8 (1.6) | 22 (4.4) | 0.018 | |
Previous STROKE, n (%) | 27 (5.4) | 42 (8.4) | 0.131 | |
Previous HF, n (%) | 17 (3.4) | 20 (4.0) | 0.827 | |
CKD, n (%) | 23 (4.6) | 30 (6.0) | 0.513 | |
COPD, n (%) | 48 (9.6) | 47 (9.4) | 0.545 | |
PAD, n (%) | 24 (4.8) | 27 (5.4) | 0.926 | |
Previous neoplasia, n (%) | 16 (3.2) | 13 (2.6) | 0.136 | |
Smoker, n (%) | 22 (4.4) | 25 (5.0) | 0.901 | |
Hypertension, n (%) | 232 (46.4) | 263 (52.6) | 0.394 | |
Diabetes, n (%) | 115 (23.0) | 119 (23.8) | 0.567 | |
Dislypidemia, n (%) | 148 (29.6) | 167 (33.4) | 0.720 | |
AF, n (%) | 49 (9.8) | 43 (8.6) | 0.245 | |
In hospital management | ||||
SBP (mmHg), mean |
139 |
142 |
0.208 | |
DBP (mmHg), mean |
74 |
74 |
0.987 | |
HR (bpm), mean |
80 |
79 |
0.827 | |
Troponin peak (ng/mL), mean |
27 |
13 |
0.121 | |
Hemoglobin (g/dL), mean |
12.9 |
12.8 |
0.644 | |
Creatinine (mg/dL), mean |
1.2 |
1.1 |
0.747 | |
Glycemia (mg/dL), mean |
135 |
143 |
0.243 | |
eGRF (mL/min/1.72 m |
67 |
63 |
0.800 | |
Total cholesterol (mg/dL), mean |
165 |
161 |
0.290 | |
LDL cholesterol (mg/dL), mean |
97 |
95 |
0.600 | |
LVEF, mean |
54 |
54 |
0.577 | |
GRACE, mean |
157 |
156 |
0.704 | |
CRUSADE, mean |
29 |
28 |
0.520 | |
KILLIP n (%) | 0.753 | |||
I | 400 (80.0) | 379 (75.9) | ||
II | 79 (15.7) | 80 (16.0) | ||
III | 15 (3.9) | 35 (6. 9) | ||
IV | 6 (1.2) | 6 (1.2) | ||
Charlson index, mean |
2.9 |
2.6 |
0.189 | |
Medical therapy at discharge | ||||
ASA, n (%) | 464 (92.8) | 440 (88.0) | 0.071 | |
CLOPIDOGREL, n (%) | 391 (78.1) | 389 (77.8) | 0.887 | |
OAC, n (%) | 52 (10.5) | 45 (9.3) | 0.176 | |
Beta-blockers, n (%) | 349 (69.8) | 321 (64.3) | 0.608 | |
ACEI/ARB, n (%) | 341 (68.2) | 345 (69.1) | 0.773 | |
STATIN, n (%) | 426 (85.3) | 432 (86.5) | 0.748 | |
ARM, n (%) | 10 (2.1) | 11 (2.2) | 0.633 | |
Diuretics, n (%) | 144 (28.8) | 180 (36.0) | 0.059 | |
BMI, body mass index; CAD, coronary artery disease; AMI, acute myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass grafting; HF, heart failure; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; PAD, peripheral artery disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; eGRF, estimated glomerular filtration rate; LDL, low density lipoprotein; LVEF, left ventricular ejection fraction; ASA, aspirin; OAC, oral anticoagulant; ACEI, angiotensin-converting-enzyme inhibitor; ARBs, angiotensin II receptor blockers; MRA, mineralorcorticoid recepctor antagonists; SD, standar desviation. |
The in- hospital mortality was 5.8% (56 patients) with higher rates in CV revascularization (7.3%) vs CCR (2.5%), p = 0.005.
The median follow-up was 45.7 months (IQR 17.4–70.0) and only 6.6% of the
patients in each group were lost during the follow-up. Cardiovascular mortality
was 28.1%, all-cause mortality 40.4% and, 56.1% of the patients experienced at
least one MACE. As shown in Fig. 2A, cardiovascular mortality (32.6% vs 17.4%,
p
Kaplan-Meyer curves for cardiovascular mortality (A) and all- cause mortality (B) through follow-up.
Kaplan-Meyer curves for MACE (A) and recurrent ACS (B) through follow-up.
The results of the multivariate analysis are presented in Tables 3 and 4. Age, previous coronary artery disease, previous heart failure, diabetes mellitus, and the GRACE score were predictors of higher cardiovascular and all-cause mortality. Complete revascularization was independently associated with 33% lower cardiovascular mortality and 26% all-cause mortality. It was not associated with lower MACE or recurrent ACS during the follow-up.
CV mortality | All-cause mortality | MACE | |
HR (95% CI) | HR (95% CI) | HR (95% CI) | |
Age | 1.07 (1.02–1.11); p |
1.06 (1.02–1.09); p = 0.001 | 1.04 (1.01–1.06); p = 0.004 |
Sex | 0.88 (0.63–1.25); p = 0.495 | 0.81 (0.61–1.08); p = 0.148 | 0.83 (0.67–1.03); p = 0.108 |
Previous CAD | 1.72 (1.21–2.43); p = 0.002 | 1.47 (1.10–1.96); p = 0.008 | 1.24 (0.99–1.56); p = 0.0057 |
Previous HF | 2.54 (1.51–4.28); p |
1.97 (1.24–3.12); p = 0.004 | 1.44 (0.95–2.17); p = 0.079 |
DM | 1.82 (1.29–2.56); p |
1.50 (1.14–1.99); p = 0.004 | 1.54 (1.24–1.91); p |
PAD | 1.70 (0.88–2.63); p = 0.127 | 1.84 (1.22–2.74); p = 0.004 | 1.61 (1.12–2.31); p = 0.009 |
Atrial fibrillation | 1.19 (0.79–1.80); p = 0.389 | 1.36 (0.98–1.88); p = 0.062 | 1.37 (1.06–1.78); p = 0.014 |
GRACE score | 1.00 (1.00–1.01); p = 0.042 | 1.00 (0.99–1.01); p = 0.050 | 0.99 (0.99–1.00); p = 0.308 |
CCR | 0.67 (0.47–0.94); p = 0.021 | 0.74 (0.57–0.97); p = 0.035 | 0.88 (0.71–1.08); p = 0.226 |
Beta-blockers | 0.85 (0.60–1.20); p = 0.371 | 0.74 (0.56–0.97); p = 0.031 | 1.21 (0.97–1.51); p = 0.089 |
Recurrent ACS | |
sHR (95% CI) | |
Age | 0.97 (0.89–1.06); p = 0.562 |
Sex | 0.98 (0.52–1.86); p = 0.967 |
Previous CAD | 0.95 (0.50–1.78); p = 0.877 |
Previous HF | 0.55 (0.11–2.60); p = 0.454 |
DM | 1.59 (0.86–2.93); p = 0.135 |
Stroke | 2.23 (1.06–4.71); p = 0.034 |
Atrial fibrillation | 1.92 (0.87–4.23); p = 0.101 |
Beta-blockers | 0.67 (0.34–1.33); p = 0.262 |
ACEIs | 1.01 (0.41–2.46); p = 0.971 |
LVEF | 1.00 (0.97–1.02); p = 0.823 |
CCR | 0.80 (0.16–1.63); p = 0.500 |
Antiagregants | 0.39 (0.05–2.99); p = 0.371 |
CV, cardiovascular mortality; MACE, major adverse cardiovascular event; HR, hazard ratio; CI, confidence interval; CAD, coronary artery disease; HF, heart failure; DM, diabetes mellitus; PAD, peripheral artery disease; CCR, complete revascularization; LVEF, left ventricular. |
In our study, we described the long-term prognostic benefit of CCR in a cohort of elderly patients with NSTEMI and MVD. To the best of our knowledge, this is the first work suggesting that CCR is associated with lower mortality during a long-term follow-up in this high-risk population. Our data suggest that elderly patients should also be managed according to current guidelines to improve their long-term prognosis. Our results support the need for further randomized studies to confirm these findings.
Currently, the proportion of elderly patients is growing worldwide. In 2030, it
is expected that the proportion of patients older than 80 years could be more
than 5% in Europe and Northern America [22].
However, they have been underrepresented in most clinical trials. Elderly
patients are less likely to undergo an invasive strategy compared with younger
patients [12, 13] and many facts
[23] could influence this decision like that
elderly patients are considered more likely than younger patients to suffer
complications following revascularization procedures or the presence of
comorbidity that could heavily influence the patient selection for an invasive
strategy [24, 25]. It happens even though a randomized
controlled trial has previously reported that in patients
A large body of evidence exists in STEMI patients in supporting the role of CCR in patients with MVD undergoing primary PCI [27, 28, 29, 30, 31, 32] and recently the benefit of CCR in NSTEMI patients with MVD has been suggested [6, 32]. However, the long-term prognosis benefit of CCR is not well known in elderly people. In our study, we observed that only 30.4% of patients were completely revascularized; this rate is lower than the 51.2% reported by Harada et al. [23], but it has been published that the rates of CCR could vary from 30% to 61% regardless of age [33, 34] as we observed.
For the first time, in our study, we demonstrated that in a real cohort of elderly NSTEMI patients CCR reduces long-term cardiovascular and all-cause mortality. It is associated with a 51% reduction of cardiovascular mortality and 49% reduction of all-cause mortality being the most important independent prognostic factor. Our results contrast with the recent study of Rumiz et al. [35] that did not find a prognostic benefit of complete revascularization in elderly people with STEMI. However, this study is performed in a different population and probably the results could not be extrapolated to our population. To our knowledge, these findings were not previously reported and we think they may have relevant implications for the management of this prevalent group of patients.
Our study has some strengths and limitations. First of all, it was a retrospective study and it therefore is subject to the classical limitations and bias that are inherent to those studies. Although propensity score analyses are more robust than traditional regression techniques, they have certain weaknesses compared to randomized clinical trials, such as and adjustments to reduce biases effectively reduced the number of subjects. The important issue of the timing (during the index hospital admission, or during a separate hospital admission) of CCR was not addressed in this study. We do not have data about anatomical (chronic total occlusion, severe tortuosity of coronary vessels…), technical factors, or aspects of the angiography like procedure time, fluoroscopic time, and contrast volume. Also, we do not have data about the repeat revascularization during the follow-up. Finally, long-term outcomes could be modified by many circumstances that might not be available with the follow-up protocol of our center [36]. Nonetheless, since clinical features and event rates were similar to previous reports [37, 38], we believe that these limitations might not have had a major influence on the validity of our results.
However, the study includes patients with several comorbidities and is thus representative of the broad range of patients encountered in day-to-day clinical practice and it has a long term follow up comparing with most of the studies performed in elderly people who were restricted to short-term follow-up (six months).
Our study highlighted the long- term prognostic benefit of complete
revascularization in elderly people (
RAB and AC conceived and designed the study and wrote the paper; PRV, DIÁ, BÁÁ, BD, LAR, CAJ, BCÁ collected the data; JRGJ and JMGA reviewed the paper. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.
All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Galicia (Approval Number2015/221).
We would like to thank patients participation and thank to all the peer reviewers for their opinions and suggestion.
This research received no external funding.
The authors declare no conflict of interest.