Introduction
Chronic coronary syndromes (CCS) [previously stable angina (SA)] are a prevalent manifestation of coronary artery disease (CAD) [1]. It is a consequence of prolonged life expectancy, the growing incidence of CAD risk factors, and the improved survival of patients with acute coronary syndrome (ACS) [2]. Due to significant advances in both the diagnosis and treatment of CAD, the guidelines for CCS management have been modified by the European Society of Cardiology (ESC) three times [3–5].
Changes in the recommendations for the management of patients with CCS require continuous monitoring of the results of treatment in daily clinical practice. Despite that, the number of studies regarding the early and long-term outcomes in this group of patients is limited [6–12]. Randomized trials and international registries often recruit carefully selected patients, which are often not representative of populations in daily practice in aspects of clinical characteristics, management, and treatment. [7–10, 13, 14].
Therefore, the aim herein was to compare the clinical characteristics, management, and in-hospital and five-year outcomes of patients with CCS enrolled in the Prospective REgistry of Stable AnGina management and treatment (PRESAGE; ClinicalTrials.gov identifier, NCT03781492), treated in the years 2006–2007 and 2015–2016.
Methods
Registry design
The study was based on the data from the PRESAGE Registry. In brief, the PRESAGE Registry is an ongoing, single-center, prospective observational study recruiting consecutive patients who underwent coronary angiography and were discharged from the 3rd Department of Cardiology, Silesian Center for Heart Diseases in Zabrze, Poland, with the diagnosis of CCS [12]. The hospital is a tertiary referral cardiology center with advanced diagnostic and treatment facilities.
All admitted patients with suspected CCS were screened for eligibility to enter the registry, and they were not enrolled until CCS was confirmed. The diagnosis of CCS was based on clinical symptoms, electrocardiography, and coronary angiography, following contemporary guidelines of the European Society of Cardiology (ESC) [3–5, 15]. Patients with microvascular or vasospastic angina were also enrolled on the registry. Pharmacological treatment and interventional strategies were used following the current recommendations of the ESC [3–5, 15].
Data collection
Complete patient baseline characteristics, treatments, and in-hospital data were obtained by reviewing the hospital records. A subsequent analysis included only data from the first hospitalization due to CCS. Five-year follow-up data after index hospitalization were acquired from the National Health Fund, including diagnosis (ICD-10 codes) and procedures (ICD-9 codes) of the following hospitalization. To obtain complete follow-up data, only inhabitants of the Silesia Province, inhabited by 4.5 million residents, were selected for analysis.
Endpoints and definitions
The composite endpoints involved death, non-fatal myocardial infarction (MI), and acute coronary syndrome (ACS)-driven unplanned revascularization within a five-year observation period. Death was considered as an all-cause death. Non-fatal MI was defined as an ischemic event that met the ESC/American College of Cardiology criteria for MI [16]. ACS-driven repeated revascularization was defined as additional, unplanned percutaneous coronary angioplasty (PCI) or coronary artery bypass grafting (CABG), performed as an urgent procedure because of acute ischemic symptoms [17].
Major bleeding was defined as clinically overt bleeding: i) with an ensuing decrease in hemoglobin to below 5 g/dL (3.1 mmol/L) or an absolute decrease of hematocrit by more than 15%; or ii) resulting in hemodynamic disorders; or iii) requiring blood transfusion. Hypertension was defined as repeated systemic blood pressure measurements exceeding 140/90 mm Hg or treatment with antihypertensive drugs for a known diagnosis of hypertension. Diabetes mellitus was diagnosed by the fasting plasma glucose level > 125 mg/dL (7.0 mmol/L), a random plasma glucose level > 200 mg/dL (11.1 mmol/L), or a history of diabetes mellitus, including patients treated with diet, oral medications, or insulin. Hypercholesterolemia was defined as a baseline cholesterol level greater than 200 mg/dL (5.2 mmol/L) and/or a low-density lipoprotein level greater than 130 mg/dL (3.4 mmol/L), or previously diagnosed and treated hypercholesterolemia. Obesity was diagnosed as a body mass index ≥ 30 kg/m2. Positive family history (PFH) of premature CAD was recognized if CAD was revealed in a first-degree relative < 50 years of age in men and < 60 years in women. Contrast-induced nephropathy (CIN) was defined as impaired renal function based on relative (≥ 25%) or absolute (≥ 44 umol/L) increase of creatinine concentration in the blood serum up to 3 days after the first or subsequent coronary angiography and the absence of an alternative explanation of renal dysfunction [18]. Significant CAD was defined as hemodynamically significant stenosis in coronary arteries with a diameter ≥ 2.0 mm as determined by visual assessment. A ≥ 50% stenosis of the left main (LM) artery or the proximal segment of the left anterior descending (LAD) artery and a ≥ 70% stenosis in other segments were considered hemodynamically significant.
Non-significant CAD was defined as < 50% lesions in LM or proximal LAD and < 70% lesions in other segments of coronary arteries with a diameter ≥ 2.0 mm as determined by visual assessment. Smooth coronary arteries were defined as the lack of any atherosclerotic lesions in the coronary arteries.
Patients enrolled on the PRESAGE Registry were divided into two groups: those treated in the years 2006–2007 and those treated in the years 2015–2016. Differences were assessed in clinical presentation and treatment, and both in-hospital and five-year outcomes, including the occurrence of the composite endpoint.
Statistical analysis
Continuous variables were expressed as median with 1st and 3rd quartile (Q1-Q3) due to non-normal distribution. The normality assumption was checked with the use of the Kolmogorov-Smirnov test. Differences between the groups were calculated with the use of the Student t-test or Mann-Whitney U test for normally or non-normally distributed data, respectively. Categorical variables were summarized using frequency tables and compared with the chi-square test or the Fisher exact test.
To evaluate the independent predictors of composite endpoints and all-cause mortality, Cox proportional hazard regression analysis was used. Variables with P values less than 0.20 in the univariable Cox regression analysis were entered into the multivariable Cox regression model with backward elimination. Schoenfeld residuals were used to check the proportional hazards assumption. Results from the Cox regression analysis were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). For all analyses, a 2-tailed p-value < 0.05 was considered as significant. Between groups differences in survival time were assessed by means of the Kaplan-Meier method and compared using log-rank test. Moreover confounder-adjusted survival curves were also plotted using a direct standardization method.
The SAS software, version 9.4 (SAS Institute Inc., Cary, NC, USA) and R version 4.4 (R Foundation for Statistical Computing, Vienna, Austria.) were used for all calculations [19].
Results
From January 2006 to December 2016, a total of 11,000 consecutive patients were enrolled in the PRESAGE Registry. Patients who died during hospitalization, numbered 59 (0.54%), and those treated between 2008–2014, totaling 7466 (67.9%), were excluded from the analysis. Consequently, the analysis ultimately included a total of 3475 patients. The entire cohort consisted of Caucasian patients.
Patients were divided into two groups: those treated in the years 2006–2007 [1300 (37.4%)] and those treated in the years 2015–2016 [2175 (62.6%)]. Patients treated in the years 2006–2007, compared to those treated in 2015–2016, were younger, with a greater prevalence of previous CAD, MI, and PCI, but with a lower incidence of comorbidities (Table 1).
|
Years 2006–2007 |
Years 2015–2016 |
P-value |
|
|
Age, years, median IQR |
61.8 (54.9–68.5) |
66.1 (59.7–72.7) |
< 0.001 |
|
Female sex, % (n/n) |
27.3 (355/1300) |
37.9 (824/2175) |
< 0.001 |
|
Previous CAD, % (n/n) |
62.2 (809/1300) |
41.2 (876/2128) |
< 0.001 |
|
Previous MI, % (n/n) |
49.6 (645/1300) |
28.1 (597/2128) |
< 0.001 |
|
Previous PCI, % (n/n) |
39 (507/1300) |
28.9 (614/2128) |
< 0.001 |
|
Previous CABG, % (n/n) |
9.6 (125/1300) |
10.1 (215/2133) |
0.68 |
|
Previous stroke, % (n/n) |
5.2 (67/1300) |
6.3 (134/2143) |
0.2 |
|
Arterial hypertension, % (n/n) |
73.8 (960/1300) |
83.5 (1801/2157) |
< 0.001 |
|
Diabetes, % (n/n) |
30.3 (392/1294) |
35.3 (756/2140) |
0.002 |
|
Hypercholesterolemia, % (n/n) |
75.9 (985/1297) |
71.4 (1526/2136) |
0.004 |
|
Obesity, % (n/n) |
28.2 (366/1300) |
36.1 (746/2065) |
< 0.001 |
|
History of smoking, % (n/n) |
62.7 (815/1300) |
46.2 (987/2136) |
< 0.001 |
|
Active smoking, % (n/n) |
23 (299/1300) |
25.2 (538/2136) |
0.15 |
|
COPD, % (n/n) |
5.9 (76/1292) |
6.6 (142/2136) |
0.37 |
|
Atrial fibrillation, % (n/n) |
8.7 (113/1292) |
20.3 (434/2142) |
< 0.001 |
|
Peripheral arterial disease, % (n/n) |
11.6 (151/1300) |
16.5 (353/2136) |
< 0.001 |
|
LVEF < 35%, % (n/n) |
15.1 (165/1091) |
14.5 (216/1493) |
0.64 |
|
GFR < 60 ml/min/1.73 m2, % (n/n) |
12.4 (161/1296) |
19.4 (421/2168) |
< 0.001 |
|
Family history of premature MI, % (n/n) |
29.1 (378/1300) |
26.1 (533/2044) |
0.06 |
|
NYHA class III or more, % (n/n) |
9.1 (118/1300) |
11.7 (241/2065) |
0.018 |
Patients treated in the years 2015–2016 had angiographically less extensive CAD with a lower frequency of surgical revascularization procedures (Table 2).
|
Variable |
Years 2006–2007 |
Years 2015–2016 |
P-value |
|
CAD |
|||
|
Smooth arteries, n [%] |
2 (0.2) |
95 (4.4) |
< 0.001 |
|
Significant CAD, n [%] |
1061 (81.6) |
1317 (60.6) |
< 0.001 |
|
Single-vessel CAD, n [%] |
462 (35.5) |
594 (27.3) |
< 0.001 |
|
Multivessel CAD, n [%] |
599 (46.1) |
723 (33.2) |
< 0.001 |
|
Chronic total occlusion, n [%] |
527 (40.5) |
492 (22.6) |
< 0.001 |
|
Interventional treatment |
|||
|
PCI, n [%] |
543 (41.8) |
871 (40) |
0.32 |
|
Bare-metal stent, n [%] |
347 (26.7) |
32 (1.5) |
< 0.001 |
|
Drug-eluting stent, n [%] |
99 (7.6) |
772 (35.5) |
< 0.001 |
|
Drug-eluting balloon, n [%] |
0 (0) |
49 (2.3) |
< 0.001 |
|
CABG, n [%] |
201 (15.5) |
205 (9.4) |
< 0.001 |
The in-hospital, six-month, one-, three- and five-year outcomes are presented in Table 3 and Figure 1. Patients treated in the years 2006–2007 had a lower frequency of non-fatal MI and major bleeding during the index hospitalization. The incidence of composite endpoints did not vary significantly between the two groups during the entire period after the index hospitalization. Patients treated in the years 2006–2007 had a lower mortality rate both within three and five years after discharge.
|
Years 2006–2007 |
Years 2015–2016 |
P-value |
|
|
In-hospital complications |
|||
|
Non-fatal MI, n [%] |
0 (0) |
12 (0.6) |
0.005a |
|
Target vessel revascularization, n [%] |
0 (0) |
6 (0.3) |
0.09a |
|
Stroke, n [%] |
1 (0.1) |
1 (0.05) |
1.00a |
|
Major bleeding, n [%] |
17 (1.3) |
8 (0.4) |
0.003a |
|
6-month composite endpoint |
|||
|
Death, n [%] |
25 (1.9) |
50 (2.3) |
0.46 |
|
Non-fatal MI, n [%] |
26 (2) |
17 (0.8) |
0.002 |
|
ACS driven revascularization, n [%] |
22 (1.7) |
32 (1.5) |
0.61 |
|
Any, n [%] |
59 (4.5) |
80 (3.7) |
0.21 |
|
12-month composite endpoint |
|||
|
Death, n [%] |
47 (3.6) |
80 (3.7) |
0.92 |
|
Non-fatal MI, n [%] |
31 (2.4) |
28 (1.3) |
0.015 |
|
ACS driven revascularization, n [%] |
29 (2.2) |
52 (2.4) |
0.76 |
|
Any, n [%] |
90 (6.9) |
135 (6.2) |
0.41 |
|
36-month composite endpoint |
|||
|
Death, n [%] |
110 (8.5) |
233 (10.7) |
0.03 |
|
Non-fatal MI, n [%] |
53 (4.1) |
76 (3.5) |
0.38 |
|
ACS driven revascularization, n [%] |
63 (4.8) |
108 (5) |
0.87 |
|
Any, n [%] |
186 (14.3) |
338 (15.5) |
0.33 |
|
60-month composite endpoint |
|||
|
Death, n [%] |
171 (13.2) |
390 (17.9) |
< 0.001 |
|
Non-fatal MI, n [%] |
87 (6.7) |
116 (5.3) |
0.1 |
|
ACS driven revascularization, n [%] |
106 (8.2) |
146 (6.7) |
0.11 |
|
Any, n [%] |
290 (22.3) |
522 (24) |
0.25 |
In the multivariable analysis of the entire study population, left main disease was the strongest factor associated with both mortality and the composite endpoint incidence during the five-year follow-up period (adjusted hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.36 to 3.96, p = 0.002, HR, 2.18, 95% CI, 1.42 to 3.34, p < 0.001, respectively, Figures 2 and 3). Results of the univariable Cox regression analysis for the mortality (Table 4) and for the composite endpoint as well as its components (Table 5) are also provided. The time of treatment was taken into account in the multivariable analysis, but was not an independent predictor of five-year outcomes (Fig. 2 and 3).
|
Variable |
HR (95% CI) |
P-value |
|
Left main CAD |
3.319 (2.255–4.886) |
< 0.001 |
|
Peripheral artery disease |
2.738 (2.279–3.289) |
< 0.001 |
|
Chronic total occlusion |
2.057 (1.741–2.430) |
< 0.001 |
|
NYHA class III or more |
2.810 (2.295–3.441) |
< 0.001 |
|
COPD |
2.717 (2.135–3.457) |
< 0.001 |
|
Diabetes |
1.876 (1.587–2.217) |
< 0.001 |
|
History of smoking |
1.356 (1.144–1.607) |
< 0.001 |
|
LDL cholesterol (per 1 mmol/l increase) |
0.925 (0.850–1.007) |
0.073 |
|
Age (per 1 year increase) |
1.043 (1.034–1.053) |
< 0.001 |
|
Creatinine level (per 10 μmol/l increase) |
1.004 (1.003–1.005) |
< 0.001 |
|
LVEF (per 5% increase) |
0.735 (0.709–0.763) |
< 0.001 |
|
Hematocrit (per 10% increase) |
0.559 (0.451–0.692) |
< 0.001 |
|
Admission years 2015–2016 vs. 2006–2007 |
1.393 (1.163–1.667) |
< 0.001 |
|
Composite endpoint |
Myocardial infarction |
|||
|
Variable |
HR (95% CI) |
P-value |
HR (95% CI) |
P-value |
|
Left main CAD |
2.752 (1.932–3.919) |
< 0.001 |
1.309 (0.487–3.522) |
0.5934 |
|
Significant CAD |
2.379 (1.986–2.849) |
< 0.001 |
3.096 (2.077–4.613) |
< 0.001 |
|
Peripheral artery disease |
2.277 (1.942–2.671) |
< 0.001 |
1.614 (1.142–2.282) |
0.0067 |
|
COPD |
2.284 (1.844–2.830) |
< 0.001 |
1.932 (1.230–3.036) |
0.0043 |
|
NYHA class III or more |
2.145 (1.788–2.572) |
< 0.001 |
1.047 (0.660–1.661) |
0.8452 |
|
Diabetes |
1.701 (1.479–1.955) |
< 0.001 |
1.332 (1.004–1.766) |
0.0466 |
|
Age (per 1 year increase) |
1.030 (1.023–1.038) |
< 0.001 |
1.015 (1.000–1.030) |
0.0505 |
|
Creatinine level (per 10 μmol/l increase) |
1.003 (1.003–1.004) |
< 0.001 |
1.003 (1.002–1.005) |
< 0.001 |
|
LVEF (per 5% increase) |
0.805 (0.780–0.831) |
< 0.001 |
0.929 (0.865–0.998) |
0.0443 |
|
Hematocrit (per 10% increase) |
0.679 (0.566–0.814) |
< 0.001 |
0.892 (0.615–1.294) |
0.5465 |
|
Admission years 2015–2016 vs. 2006–2007 |
1.084 (0.939–1.251) |
0.2725 |
0.804 (0.609–1.061) |
0.1237 |
|
PCI |
CABG |
|||
|
Variable |
HR (95% CI) |
P-value |
HR (95% CI) |
P-value |
|
Left main CAD |
2.023 (0.954–4.290) |
0.0663 |
– |
0.9910 |
|
Significant CAD |
3.603 (2.443–5.312) |
< 0.001 |
4.590 (1.069–19.706) |
0.0404 |
|
Peripheral artery disease |
1.355 (0.964–1.905) |
0.0803 |
3.984 (1.650–9.619) |
0.0021 |
|
COPD |
1.470 (0.920–2.351) |
0.1075 |
– |
0.9889 |
|
NYHA class III or more |
1.223 (0.813–1.840) |
0.3332 |
1.580 (0.465–5.367) |
0.4636 |
|
Diabetes |
1.410 (1.087–1.830) |
0.0097 |
2.286 (0.971–5.384) |
0.0585 |
|
Age (per 1 year increase) |
1.012 (0.998–1.025) |
0.0968 |
0.984 (0.941–1.028) |
0.4688 |
|
Creatinine level (per 10 μmol/l increase) |
1.001 (0.999–1.004) |
0.3094 |
1.000 (0.988–1.011) |
0.9582 |
|
LVEF (per 5% increase) |
0.976 (0.912–1.046) |
0.4968 |
1.212 (0.894–1.643) |
0.2149 |
|
Hematocrit (per 10% increase) |
1.073 (0.761–1.513) |
0.6887 |
2.735 (0.841–8.895) |
0.0946 |
|
Admission years 2015–2016 vs. 2006–2007 |
0.853 (0.659–1.103) |
0.2255 |
0.987 (0.409–2.382) |
0.9769 |
Discussion
Despite the changes in the ESC guidelines [3, 4], an improvement in the long-term outcomes measured by the occurrence of death, non-fatal MI, and the ACS-driven revascularization was not observed. Moreover, patients treated in the years 2006–2007 had a lower mortality rate both at three and five years after discharge. Although this earlier group had more extensive CAD as evidenced by angiography, they were younger and had a lower incidence of comorbidities compared to patients treated in 2015–2016. The distant results of treatment appear to depend not only on the therapeutic tools utilized but also on factors like age and the presence of coexisting comorbidities.
The current data about treatment and outcomes of patients with stable angina derive mainly from randomized studies [20–24] with specific inclusion or exclusion criteria. By contrast, there are only a few registries assessing characteristics and long-term outcomes of patients with CCS over a timespan similar to the present analysis [7–9, 25]. They differ in enrollment criteria. In the Euro Heart Survey (EHS) Registry, consecutive outpatients with de novo CCS were enrolled in 2002 [9]. In the CLARIFY (Prospective Observational Longitudinal Registry of Patients with Stable Coronary Artery Disease), patients with previous MI, evidence of coronary stenosis > 50%, confirmed symptomatic myocardial ischemia, or a prior revascularization procedure were recruited in the years 2009 and 2010 [7, 8]. In the START (STable coronary Artery diseases RegisTry), patients with stable CAD discharged from cardiology wards were enrolled into the registry in the years 2016–2017 if they had at least one of the following clinical conditions: typical or atypical stable angina, documented ischemia at stress test, previous coronary revascularization, or prior episode of ACS [25].
Similar to our analysis, both demographic and clinical characteristics of patients enrolled on the mentioned registries have changed over the years. The mean age of the study population increased from 61 years in the EHS study to 64.2 years in the CLARIFY registry and to 67.6 years in the START registry [7, 8, 25].
The available registries of patients with stable CAD, similar to the current analysis, demonstrate that women constitute a minority. Women included in these reports were older and had a higher incidence of arterial hypertension, type 2 diabetes. Despite that, they had less extensive CAD and were less frequently qualified for revascularization treatment [26–28]. In another paper based on the PRESAGE registry, it was demonstrated that women had a lower incidence of death and the composite endpoint during 12-month follow-up [28].
The incidence of some CAD risk factors and comorbidities increased during this time. Hypertension was noted in 62% of patients in the EHS [9], 71% in the CLARIFY [7, 8], and 79.4% in the START registry [25]. The incidence of diabetes mellitus increased from 18% in the EHS [9], to 29%, and in the CLARIFY [7, 8], to 35.3% amongst patients treated in the years 2015–2016 in the PRESAGE registry.
Despite the greater prevalence of previous MI, PCI, and significant CAD in angiography, patients included in the present analysis, who were treated in the years 2006–2007, surprisingly, had a lower mortality rate both three and five years after index hospitalization compared to those treated in 2015–2016. It is worth mentioning that patients treated in the years 2015–2016 were nearly five years older. Unfortunately, it was not possible to indicate the causes of their deaths, but it should be assumed that many of them were of non-cardiac origin.
Spoon et al. noted a marked modification in causes of death after PCI from predominantly cardiac in 1991 to non-cardiac in 2008 [29]. The predominance of non-cardiac deaths was reported by Wang et al. in patients with stable CAD included in the Heart and Soul study [30].
The COROnariens stables en régionNORd-pas-de-Calais (CORONOR) registry included patients with an average age of 67 ± 12 years with stable CAD and a history of MI or coronary revascularization, or at least 50% obstruction in at least one coronary vessel [31]. During a five-year follow-up period, most deaths were non-cardiovascular (52%) and one of the strongest factors associated with cardiovascular death was age.
Moreover, at discharge, patients from the current registry treated in the years 2015–2016 were prescribed an angiotensin-converting enzyme inhibitor (ACEI), an angiotensin receptor blocker (ARB), statins, and — less frequently — beta blockers. It was probably related to the lower percentage of significant CAD, previous MI, and revascularization procedures. The outcomes only confirm the role of optimal medical therapy (OMT) in patients with less evident atherosclerosis, especially with coexisting risk factors and comorbidities. They correspond to the outcomes of COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) and ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), both of which confirmed the role of the aggressive use of OMT [23, 24].
Long-term mortality rates in patients with CCS vary in several studies, depending on clinical characteristics and enrolment criteria. In the REACH registry, in the subgroup of patients with established cerebrovascular disease, the mortality rate was 2.8% per year [32]. The five-year all-cause death rate in the CLARIFY and CORONOR registries was 8.5% and 16.5%, respectively [8, 31].
Some factors related to poor prognosis in the CORONOR and PRESAGE registries were similar. The strongest factor related to both mortality and composite endpoint incidence in the present analysis was the left main disease. Its role in prognosis in patients with CCS is well documented [33, 34]. Variables associated with cardiovascular death in the CORONOR registry during a five-year follow-up included age, prior aortic or peripheral intervention, low left ventricular ejection fraction, and low estimated glomerular filtration rate. In the CICD (Chronic Ischemic Cardiovascular Disease) Pilot registry, independent predictors of all-cause mortality/hospitalization included age, history of previous peripheral revascularization, chronic kidney disease, or chronic obstructive pulmonary disease (COPD) during a six-month follow-up [10]. Both the current study and other ones confirmed the role of non-cardiological factors. The analysis involved consecutive patients treated in a highly specialized cardiovascular center featuring complete diagnostic workup and therapeutic management. Despite a relatively high rate of ACE-I/ARBs, statins, and beta blockers prescribed at discharge, the five-year mortality in the two following periods was 13.2% and 17.9%. It only confirms the role of proper treatment of comorbidities like PAD, diabetes mellitus, renal failure, or COPD, which might increase both cardiovascular and non-cardiovascular risk of death. Finally, insufficient specialized outpatient care might play a role in a relatively higher distant mortality rate.
Identifying patients with a high risk of not only cardiovascular but also non-cardiovascular death should be an integral part of medical management. It has special importance due to the ageing CCS population and the increasing problem of coexisting diseases in recent years.
Conclusions
Patients with CCS treated in the years 2006–2007 compared to those treated in 2015–2016 were younger, with a greater prevalence of previous MI, PCI, and more extensive CAD in angiography, but with lower incidence of comorbidities and death three and five years after index hospitalization. The strongest factor related to the risk of death and composite endpoint during the five-year follow-up was left main disease. The time of treatment was not an independent predictor of five-year outcomes.
Limitations
In addition to the typical limitations associated with the retrospective design, several other limitations need to be considered in the present study. First, the present analysis was based on the data of patients treated in a single, high-volume, tertiary referral hospital with advanced diagnostic and treatment facilities. Second, fractional flow reserve measurement, Syntax score values, and the completeness of revascularization were available only for a very limited number of patients and therefore were not included in the analysis. Third, there was no data regarding the Canadian Cardiovascular Society Angina score at admission and causes of death during the follow-up period.
Conflict of interests: The authors report no competing interests.
