Abstract
Background
Although delays in treatment are known to worsen outcomes in ST-elevation myocardial infarction, their effect in non-ST-elevation myocardial infarction (NSTEMI) is less clear. Care quality and timely revascularization should be comparable across presentation sites to optimize patient outcomes.
Methods
Using the Manitoba Centre for Health Policy data, we retrospectively analyzed adult NSTEMI patients who underwent cardiac catheterization and revascularization from January 2001 to March 2021. Patients were grouped by initial presentation site—rural hospital, urban noncardiac hospital, or specialized cardiac centre. We assessed in-hospital, 1-year, and long-term outcomes.
Results
Of 30,817 NSTEMI patients, 19,482 underwent catheterization, and 12,567 received revascularization. Distribution by site was as follows: 44% at cardiac centres, 28.5% at urban noncardiac hospitals, and 27.5% at rural hospitals. Urban noncardiac hospital patients experienced significantly higher cardiovascular mortality in-hospital (hazard ratio [HR] 1.64; 95% confidence interval [CI] 1.09-2.47), at 1 year (HR 1.30; 95% CI 1.11-1.53), and over an average 6.65-year follow-up period (HR 1.15; 95% CI 1.07-1.24). Rural hospital patients showed a lower mortality incidence, potentially due to selection bias if critically ill patients did not survive the transfer. Both rural and urban noncardiac cohorts had elevated rates of major adverse cardiovascular events at all follow-up intervals. Time to catheterization was notably delayed for nonspecialized sites (cardiac centre, 0.83 ± 1.90 vs urban noncardiac 3.20 ± 3.05 vs rural, 3.09 ± 2.56 days; P < 0.001).
Conclusions
NSTEMI patients presenting to rural and urban nonspecialized hospitals experience worse short- and long-term outcomes, including increased incidence of major adverse cardiovascular events and mortality. These findings highlight the need for strategies to reduce disparities in access to specialized cardiac care.
Keywords: NSTEMI, revascularization, site of presentation, outcomes
Résumé
Contexte
Tandis que les retards dans le traitement aggravent les conséquences cliniques dans les cas d'infarctus du myocarde avec élévation du segment ST (STEMI), leur effet dans les cas d'infarctus du myocarde sans élévation du segment ST (NSTEMI) demeure moins clair. La qualité des soins et une revascularisation en temps opportun devraient être équivalentes quel que soit le lieu de prise en charge initiale afin d'optimiser les bénéfices cliniques pour les patients.
Méthodes
À partir des données du Centre manitobain des politiques en matière de santé, nous avons analysé rétrospectivement les cas de patients adultes atteints d'un NSTEMI qui ont subi un cathétérisme cardiaque et une revascularisation entre janvier 2001 et mars 2021. Les patients ont été regroupés selon le lieu de prise en charge initiale : hôpital rural, hôpital urbain non spécialisé en cardiologie ou centre cardiaque spécialisé. Nous avons évalué les résultats lors de l'hospitalisation, à un an et à long terme.
Résultats
Sur les 30 817 patients atteints d'un NSTEMI, 19 482 ont subi un cathétérisme et 12 567 ont bénéficié d'une revascularisation. La répartition par site était la suivante : 44 % dans des centres cardiaques, 28,5 % dans des hôpitaux urbains non spécialisés et 27,5 % dans des hôpitaux ruraux. Les patients des hôpitaux urbains non spécialisés en cardiologie ont présenté une mortalité cardiovasculaire significativement plus élevée à l'hôpital (rapport de risque [RR] 1,64; intervalle de confiance [IC] à 95 % 1,09-2,47), à un an (RR 1,30; IC à 95 % 1,11-1,53) et au cours d'un suivi moyen de 6,65 ans (RR 1,15; IC à 95 % 1,07-1,24). Les patients des hôpitaux ruraux présentaient une mortalité plus faible, potentiellement en raison d’un biais de sélection si les patients gravement malades ne survivaient pas au transfert. Les cohortes rurales et urbaines non spécialisées en cardiologie ont présenté des taux élevés d'événements cardiovasculaires indésirables majeurs (ECIM) à tous les temps de suivi. Le délai avant le cathétérisme était nettement plus long dans les sites non spécialisés (centre cardiaque 0,83 ± 1,90 vs urbain non spécialisé 3,20 ± 3,05 vs rural 3,09 ± 2,56 jours ; p < 0,001).
Conclusion
Les patients atteints d'un NSTEMI se présentant dans des hôpitaux ruraux ou urbains non spécialisés en cardiologie ont des résultats cliniques moins favorables à court et à long terme, avec notamment une augmentation des ECIM et de la mortalité. Ces résultats soulignent la nécessité de mettre en place des stratégies visant à réduire les disparités dans l'accès aux soins cardiaques spécialisés.
Expedited access to specialized cardiac care is critical in the treatment of patients with acute coronary syndrome (ACS). Previous work has shown that ACS patients who live in rural settings have delayed access to emergency medical care1, 2, 3 and are less likely to undergo coronary angiography.4, 5, 6 For patients with ST-elevation myocardial infarction (STEMI) in particular, delayed access to care has been associated with an increased risk of mortality7; accordingly, emergent revascularization, including thrombolytic therapy in centres without rapid access to percutaneous coronary intervention (PCI), is recommended by major society guidelines.8,9
In contrast to STEMI, routine emergent revascularization including thrombolysis is not indicated in the management of non-ST-elevation myocardial infarction (NSTEMI), and therefore, these patients often are not transferred rapidly to PCI-capable centres, and rather are treated in rural or community hospitals. Among patients with NSTEMI, previous work has shown that patients who live in rural areas have delayed emergency medical response times1 and time to first medical contact.2 They are also less likely to be adherent to dual-antiplatelet therapy,10 and toundergo coronary angiography4,11 However, whether these disparities result in differences in the incidence of hard outcomes such as major adverse cardiovascular events (MACE) or mortality is unknown. We therefore conducted a study with the goal of defining outcomes in patients with NSTEMI based on initial presentation to a rural hospital, an urban community hospital, or a specialized cardiac referral hospital.
Methods
Data sources
Manitoba, a central Canadian province, has a government-administered, single-payer, universal healthcare system and a population of about 1.3 million people. The Manitoba Centre for Health Policy (MCHP) is a population health data centre repository that holds population-wide de-identified health information for Manitoba residents.12,13 All databases are de-identified but contain a scrambled personal health identification number (PHIN) that allows linking of unique individuals across databases. This study was approved by the University of Manitoba Health Research Ethics Board (HS22575 (H2019:062)).
Study population
Adult patients with a diagnosis of NSTEMI who underwent cardiac catheterization between the study dates of January 1, 2001 and March 31, 2021 were identified. NSTEMI was defined as a patient having hospitalization with International Classification of Diseases (ICD) version 9 (ICD-9) codes 410.7x or 410.7, or ICD, version 10 (ICD-10) code I21.4 among the first 3 diagnostic codes. The index date was the date of hospitalization with the NSTEMI diagnosis. Patients were excluded if they had a diagnosis of cardiogenic shock at the time of index admission or were undergoing chronic hemodialysis treatment (Fig. 1).
Figure 1.
Study flow. CABG, coronary artery bypass grafting; Cath, catheterization; Jan, January; NSTEMI, non-ST-elevation myocardial infarction; PCI, percutaneous coronary intervention.
Patients who presented to St. Boniface Hospital, Winnipeg, Manitoba were classified as the group of patients presenting to a specialized cardiac referral hospital. Patients who presented to another hospital in the city of Winnipeg, Manitoba were classified as the group of patients presenting to urban noncardiac hospitals. All other patients presenting to hospitals outside of Winnipeg, Manitoba were classified as the group of patients presenting to rural hospitals.
Variables
Collected data included demographics (age, gender), location of initial healthcare contact, and comorbidities, including history of myocardial infarction, diabetes mellitus, hypertension, heart failure, stroke, chronic kidney disease, and atrial fibrillation. We also collected medication use, including renin-angiotensin inhibitors (RASis), beta-blockers, loop diuretics, sodium-glucose cotransporter-2 (SGLT2) inhibitors, nitrates, and warfarin. A code definition for the list of comorbidities and medications adjusted for can be found in Supplemental Table S1.
Outcomes
The primary outcome was all-cause mortality. Death was identified by date through a linkage to the Vital Statistics Database. Secondary outcomes included cardiovascular (CV) mortality (identified using vital statistics with a main cause of death with ICD-10 code I00-I99); MACE, defined as CV death, nonfatal myocardial infarction (MI), and unplanned revascularization within 12 months following index admission; and stroke (ischemic or hemorrhagic). The occurrence of MACE+, which comprised CV mortality, nonfatal MI, stroke, and HF hospitalization, also was ascertained. Individuals were followed from the date of their index hospital admission until either their death, being lost to follow-up, or the end-of-study date (March 31, 2021).
Statistical analysis
Descriptive statistics were calculated using medians with interquartile ranges for continuous variables and proportions for categorical variables. Group comparisons were conducted using the Kruskal-Wallis test for continuous variables, the χ2 test for categorical variables, and Fisher's exact test when categorical outcomes included < 5 patients.
We used Cox proportional hazards regression to analyze the effect of hospital presentation on mortality and CV events. We used logistic regression for the analysis of short-term mortality and other short-term outcomes. A full list of comorbidities and medications adjusted for can be found in Table 1. The proportional hazards assumption was tested for by plotting Schoenfeld residuals against time, and visual inspection for uniformity. Outcomes from our models were expressed in hazard ratios (HRs) and odds ratios (ORs), as appropriate, with 95% confidence intervals (CIs).
Table 1.
Study cohort baseline characteristics
| Characteristic | All study participants = 19,475 |
|||
|---|---|---|---|---|
| Initial presentation in cardiac centre∗ |
Initial presentation in urban, noncardiac centre |
Initial presentation in rural, noncardiac centre |
P | |
| N = 8579 (44.05%) | N = 5545 (28.47%) | N = 5351 (27.48%) | ||
| Weekend presentation | 1506 (17.55%) | 1470 (26.51%) | 1463 (27.34%) | < 0.001 |
| Age, y, mean +/- SD | 65.10 ± 12.31† | 65.49 ± 12.42† | 66.24 ± 12.26 | < 0.001 |
| Gender, female | 2691 (31.37) | 1868 (33.69) | 1713 (32.01) | 0.01 |
| Days from admission to catheterization (median) | 0 (0–1) | 2 (1–4) | 2 (1–4) | < 0.001 |
| Days from admission to catheterization, mean +/- SD, median (range) | 0.83 ± 1.90 27 (0–27) |
3.20 ± 3.05 30 (0–30) |
3.09 ± 2.56 28 (0–28) |
< 0.001 |
| Comorbidities | ||||
| Myocardial infarction | 2516 (29.33) | 964 (17.39) | 802 (14.90) | < 0.001 |
| Diabetes mellitus | 3321 (38.71) | 2074 (37.40) | 2078 (38.83) | 0.21 |
| Hypertension | 7133 (83.14) | 4553 (82.11) | 4421 (82.62) | 0.28 |
| Heart failure | 1285 (14.98) | 701 (12.64) | 640 (11.96) | < 0.001 |
| Stroke | 1209 (14.09) | 825 (14.88) | 711 (13.29) | 0.06 |
| CABG | 563 (6.56) | 337 (6.08) | 295 (5.51) | 0.04 |
| CKD | 1043 (12.16) | 595 (10.73) | 610 (11.40) | 0.03 |
| Atrial fibrillation | 1546 (18.02) | 894 (16.12) | 906 (16.93) | 0.01 |
| CCI score, SD | ||||
| 0 | 219 (2.55) | 221 (3.99) | 187 (3.49) | |
| 1 | 1016 (11.84) | 748 (13.49) | 740 (13.83) | |
| 2 | 1613 (18.80) | 1045 (18.85) | 1063 (19.87) | |
| 3 | 1724 (20.10) | 1104 (19.91) | 1055 (19.72) | |
| 4 | 1392 (16.23) | 875 (15.78) | 844 (15.77) | |
| 5 | 966 (11.26) | 632 (11.40) | 530 (9.90) | |
| 6 | 731 (8.52) | 429 (7.74) | 421 (7.87) | |
| 7 | 471 (5.49) | 240 (4.33) | 232 (4.34) | |
| 8 | 232 (2.70) | 148 (2.67) | 159 (2.97) | |
| 9 | 135 (1.57) | 60 (1.08) | 65 (1.21) | |
| 10 | 56 (0.65) | 29 (0.52) | 34 (0.64) | |
| 11 | 18 (0.21) | 9 (0.16) | 17 (0.32) | |
| 12 | † | † | † | |
| Total CCI score, mean (SD) | 3.66 (2.11) | 3.47 (2.09) | 3.48 (2.13) | < 0.001 |
| Medications | ||||
| RAAS inhibitors | 3937 (45.89) | 2424 (43.72) | 2642 (49.37) | < 0.001 |
| ACEi | 2522 (64.06) | 1521 (62.75) | 1652 (62.53) | |
| ARB | 1415 (35.94) | 903 (37.25) | 990 (37.47) | |
| Beta-blocker | 2657 (30.97) | 1636 (29.50) | 1502 (28.07) | 0.001 |
| Loop diuretics | 1047 (12.20) | 695 (12.53) | 662 (12.37) | 0.84 |
| SGLT-2i | 129 (1.50) | 46 (0.83) | 61 (1.14) | 0.001 |
| Nitrates | 1535 (17.89) | 968 (17.46) | 735 (13.74) | < 0.001 |
| Warfarin | 371 (4.32) | 234 (4.22) | 231 (4.32) | 0.95 |
| Distance from home to SBH, km, mean (SD) | 55.47 (124.0) | 16.94 (59.49) | 162.89 (168.64) | < 0.001 |
| Distance from home to SBH, km, median (IQR) | 7.80 (4.81–26.6) | 7.24 (4.90–10.13) | 98.37 (50.42–204.88) | |
Values are n (%), unless otherwise indicated.
ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CABG, coronary artery bypass grafting; CCI, Charlson Comorbidity Index; CKD, chronic kidney disease; IQR, interquartile range; RAAS, renin-angiotensin-aldosterone system; SBH, St Boniface Hospital; SD, standard deviation; SGLT2i, sodium glucose cotransporter 2 inhibitor.
Presentation to St Boniface Hospital anytime.
Not statistically different between those 2 groups.
Significance was set a priori at P < 0.05. All statistical analyses were performed using SAS software (version 9.4; SAS Institute, Cary, NC).
Results
Baseline data
From a total of 30,817 patients diagnosed with NSTEMI during the study period, 19,482 patients underwent cardiac catheterization, of whom 12,567 were treated with either PCI or coronary artery bypass grafting (CABG) surgery and were included in the analysis (Fig. 1). Of these, 44% presented directly to the cardiac referral hospital, 28.5% presented to an urban hospital, and 27.5% presented to a rural hospital (Table 1). Rates of comorbidities were generally similar in all 3 groups, although patients who presented to the cardiac referral hospital were more likely to have a history of cardiac comorbidities, such as MI, atrial fibrillation, heart failure, or previous CABG. Patients who presented primarily to the cardiac referral centre underwent coronary angiography significantly earlier (0.83 ± 1.90 days) than did patients at an urban (3.20 ± 3.05 days) or rural (3.09 ± 2.56 days) hospital.
In-hospital outcomes
Compared to patients who presented directly to a specialized cardiac hospital, patients who presented to an urban noncardiac hospital were observed to have a significantly higher risk of in-hospital CV mortality (HR 1.64; 95% CI 1.09-2.47; Table 2). Conversely, patients whose initial presentation was to a rural hospital had a lower risk of in-hospital all-cause and CV mortality (HR 0.51; 95% CI 0.29-0.91).
Table 2.
Outcomes during hospitalization
| Study outcomes | Initial presentation setting | Events, # | Odds ratio (95%CI), unadjusted | Odds ratio (95% CI), adjusted1 |
|---|---|---|---|---|
| All-cause mortality | Urban NCC | 52 | 1.47 (1.00–2.15) | 1.41 (0.96–2.08) |
| Rural NCC | 19 | 0.55 (0.33–0.93) | 0.51 (0.30–0.86) | |
| CV mortality | Urban NCC | 41 | 1.76 (1.18–2.63) | 1.64 (1.09–2.47) |
| Rural NCC | 14 | 0.57 (0.32–1.01) | 0.51 (0.29–0.91) |
CI, confidence interval; CV, cardiovascular; NCC, noncardiac centre.
Characteristics of patients who died during the index hospital admission
Patients who died during the index hospitalization were generally older, had more comorbidities, were more likely to be present on weekends, and experienced delays in catheterization (Table 3). Supplemental Table S2 details the trends in time from presentation to catheterization for NSTEMI patients over the past 20 years, stratified by initial presentation site (rural hospital, urban noncardiac centre, or specialized cardiac referral centre).
Table 3.
Characteristics of the patients who died during their index hospital admission, irrespective of the site of presentation
| Characteristic | Died during index hospitalization |
Survived index hospitalization |
P |
|---|---|---|---|
| N = 126 (0.65) | N = 19,349 (99.35) | ||
| Age, all patients, y | 74.89 ± 10.46 | 65.46 ± 12.32 | < 0.001 |
| Age, female patients, y | 75.85 ± 10.78 | 68.29 ± 12.31 | < 0.001 |
| Age, male patients, y | 74.19 ± 10.24 | 64.12 ± 12.10 | < 0.001 |
| Gender, female | 53 (42.06) | 6219 (32.14) | 0.02 |
| Weekend presentation | 39 (30.95) | 4400 (22.74) | 0.03 |
| Days from admission to catheterization, mean (SD) | 3.06 (3.49) | 2.12 (2.71) | < 0.001 |
| Days from admission to catheterization, median (IQR) | 2 (1–4) | 1 (0–3) | < 0.001 |
| Revascularization (PCI + CABG) | 55 (43.65) | 12,352 (63.84) | < 0.001 |
| Only angiogram—no revascularization | 71 (56.35) | 6997 (36.16) | < 0.001 |
| PCI | 44/55 (80) | 10,713/12,352 (86.76) | < 0.001 |
| CABG | 11/55 (20) | 1715/12,352 (13.88) | 0.96 |
| Comorbidities | |||
| Myocardial infarction | 39 (30.95) | 4243 (21.93) | 0.01 |
| Diabetes mellitus | 67 (53.17) | 7406 (38.28) | < 0.001 |
| Hypertension | 118 (93.75) | 15,989 (82.63) | < 0.001 |
| Heart failure | 45 (35.71) | 2581 (13.34) | < 0.001 |
| Stroke | 48 (38.10) | 2697 (13.94) | < 0.001 |
| CABG | 12 (9.52) | 1183 (6.11) | 0.11 |
| CKD | 34 (26.98) | 2214 (11.44) | < 0.001 |
| Atrial fibrillation | 40 (31.75) | 3306 (17.09) | < 0.001 |
| Medications | |||
| RAAS inhibitors | 75 (59.52) | 8928 (46.14) | 0.003 |
| Beta-blocker | 59 (46.83) | 5736 (29.64) | < 0.001 |
| Loop diuretics | 39 (31.95) | 2365 (12.22) | < 0.001 |
| SGLT-2i | † | 233 (1.20) | 0.20∗ |
| Nitrates | 29 (23.02) | 3209 (16.58) | 0.05 |
| Warfarin | 12 (9.52) | 824 (4.26) | 0.001 |
Values are n (%) or mean ± standard deviation, unless otherwise indicated.
CABG, coronary artery bypass grafting; CKD, chronic kidney disease; IQR, interquartile range; PCI, percutaneous coronary intervention; RAAS, renin-angiotensin-aldosterone system; SD, standard deviation; SGLT-2i, sodium glucose cotransporter 2 inhibitor.
Fisher exact test.
Censored because of database privacy policy (less than 7 persons or events).
30-day outcomes
Compared to patients who presented directly to a specialized cardiac hospital, no differences were observed in risk of all-cause or CV mortality at 30 days for patients who presented to urban noncardiac or rural hospitals (Table 4). However, both of these groups had significantly higher risks of MACE.
Table 4.
Outcomes at 30-d follow-up
| Study outcomes | Initial presentation setting | Events, # | Odds ratio (95% CI), unadjusted | Odds ratio (95% CI), adjusted1 |
|---|---|---|---|---|
| All-cause mortality | Urban NCC | 99 | 0.96 (0.75–1.24) | 0.96 (0.74–1.24) |
| Rural NCC | 87 | 0.88 (0.67–1.14) | 0.84 (0.64–1.11) | |
| CV mortality | Urban NCC | 81 | 1.06 (0.82–1.38) | 1.05 (0.80–1.37) |
| Rural NCC | 64 | 0.90 (0.68–1.19) | 0.87 (0.65–1.15) | |
| MACE | Urban NCC | 3115 | 1.63 (1.53–1.75) | 1.77 (1.63–1.92) |
| Rural NCC | 3529 | 2.47 (2.30–2.65) | 2.05 (1.88–2.23) | |
| MACE + | Urban NCC | 3157 | 1.63 (1.52–1.74) | 1.60 (1.49–1.71) |
| Rural NCC | 3567 | 2.46 (2.29–2.64) | 2.37 (2.20–2.55) |
CI, confidence interval; CV, cardiovascular; MACE, major adverse cardiovascular events; MACE +, MACE, including CV mortality, nonfatal myocardial infarction, stroke, and heart failure hospitalization; NCC, noncardiac centre.
1-year outcomes
Compared to patients who presented directly to a specialized cardiac hospital, patients who presented to noncardiac urban hospitals had a higher risk of all-cause (HR 1.23; 95% CI 1.06-1.43) and CV mortality, as well as a higher risk of MACE (Table 5). By contrast, patients whose initial presentation was to a rural hospital were not observed to have an increased risk of all-cause or CV mortality at 1 year, but they did have a higher risk of MACE (HR 1.65; 95% CI 1.54-1.77). These differences persisted when hospitalization for heart failure was added to the MACE outcome.
Table 5.
Outcomes at 1-y follow-up
| Study outcomes | Initial presentation setting | Events, # | Odds ratio (95% CI), unadjusted | Odds ratio (95% CI), adjusted |
|---|---|---|---|---|
| All-cause mortality | Urban NCC | 354 | 1.16 (1.01–1.34) | 1.23 (1.06–1.43) |
| Rural NCC | 288 | 0.97 (0.83–1.12) | 0.99 (0.84–1.16) | |
| CV mortality | Urban NCC | 217 | 1.24 (1.06–1.45) | 1.30 (1.11–1.53) |
| Rural NCC | 160 | 1.03 (0.87–1.21) | 1.04 (0.88–1.24) | |
| MACE | Urban NCC | 3537 | 1.65 (1.54–1.77) | 1.65 (1.54–1.77) |
| Rural NCC | 3849 | 2.40 (2.23–2.58) | 2.37 (2.20–2.56) | |
| MACE + | Urban NCC | 3641 | 1.65 (1.54–1.77) | 1.67 (1.55–1.79) |
| Rural NCC | 3923 | 2.36 (2.20–2.55) | 2.37 (2.20–2.26) |
CV, cardiovascular; MACE, major adverse cardiovascular events; MACE +, MACE, including CV mortality, nonfatal myocardial infarction, stroke, and heart failure hospitalization; NCC, noncardiac centre.
Long-term outcomes
At an average of 6.65 years of follow-up from the time of index ACS hospitalization, patients who initially presented to urban noncardiac centres had an increased risk of all-cause (HR 1.17; 95% CI 1.10-1.24) and CV (HR 1.15; 95% CI 1.07-1.24) mortality (Table 6). Patients whose initial presentation was to a rural hospital also had an increased long-term risk of CV mortality (HR 1.09; 95% CI 1.01-1.17) and trended toward having an increased all-cause mortality risk (HR 1.05; 95% CI 0.98-1.12). Both groups had higher long-term risk of MACE, MI, and heart failure.
Table 6.
Outcomes at the longest-term (average 6.65 y) follow-up
| Study outcomes | Initial presentation setting | Events, # | Hazard ratio (95% CI), unadjusted | Hazard ratio (95% CI), adjusted∗ |
|---|---|---|---|---|
| All-cause mortality | Urban NCC | 2122 | 1.11 (1.05–1.18) | 1.17 (1.10–1.24) |
| Rural NCC | 1428 | 1.03 (0.96–1.09) | 1.05 (0.98–1.12) | |
| CV mortality | Urban NCC | 850 | 1.09 (1.02–1.17) | 1.15 (1.07–1.24) |
| Rural NCC | 565 | 1.06 (0.98–1.15) | 1.09 (1.01–1.17) | |
| MACE | Urban NCC | 4354 | 1.25 (1.20–1.30) | 1.24 (1.20–1.30) |
| Rural NCC | 4329 | 1.61 (1.55–1.67) | 1.59 (1.53–1.66) | |
| MACE + | Urban NCC | 4449 | 1.24 (1.19–1.29) | 1.24 (1.19–1.29) |
| Rural NCC | 4381 | 1.59 (1.53–1.65) | 1.57 (1.51–1.63) | |
| Stroke | Urban NCC | 1118 | 1.19 (1.10–1.29) | 1.22 (1.12–1.32) |
| Rural NCC | 770 | 1.02 (0.94–1.12) | 1.03 (0.94–1.13) | |
| MI | Urban NCC | 3740 | 1.28 (1.22–1.33) | 1.27 (1.21–1.32) |
| Rural NCC | 4029 | 1.72 (1.65–1.80) | 1.69 (1.62–1.77) | |
| HF hospitalization | Urban NCC | 1350 | 1.19 (1.11–1.28) | 1.26 (1.17–1.36) |
| Rural NCC | 1028 | 1.12 (1.03–1.21) | 1.16 (1.07–1.26) |
Reference = initial presentation in cardiac centre.
CI, confidence interval; CV, cardiovascular; MACE, major adverse cardiovascular events; MACE +, MACE, including CV mortality, nonfatal myocardial infarction, stroke, and heart failure (HF) hospitalization; MI, myocardial infarction; NCC, noncardiac centre.
Adjusted by age, sex, cardiac revascularization, renin-angiotensin-aldosterone system inhibitors, weekend, beta-blockers, loop diuretics, mineralocorticoid receptor antagonists, sodium glucose cotransporter 2 inhibitors, nitrates, warfarin, chronic kidney disease, heart failure, hypertension, stroke, atrial fibrillation, myocardial infarction, coronary artery bypass grafting.
Discussion
Among patients with NSTEMI managed with an invasive strategy, patients whose initial hospital presentation was to a rural or noncardiac urban hospital were observed to have an increased risk of in-hospital, short- and long-term adverse outcomes, including MACE and mortality.
Such findings are somewhat unexpected in an NSTEMI population, for whom time to prompt reperfusion is generally not an emergent therapeutic concern.1,14 By contrast, these findings are expected for STEMI patients, in whom prompt reperfusion is required and in whom clear disadvantages for rural patients have been documented.1,14 Research shows that rural patients with NSTEMI are less likely to undergo angiography4, 5, 6,11; however, our cohort included only patients who underwent coronary angiography. Of note, the time to coronary angiography was significantly lower in the group of patients who presented directly to the cardiac referral centre.
These outcome differences appear to be multifactorial and may be influenced by province-specific circumstances. A proportion of NSTEMI patients have an occluded culprit coronary artery, and delays in revascularization can exacerbate myocardial damage, leading to an increased risk of heart failure and all-cause mortality.15, 16, 17 A systematic review of 7 studies, encompassing 40,777 patients, found that approximately 25.5% had an occluded coronary artery, supplying predominantly the inferolateral and posterior myocardial territories.18 Other studies have reported that the incidence of occluded coronary arteries in the context of NSTEMI ranges between 19.9% and 29%.15, 16, 17,19
Some patients presenting to nonspecialized centres may have experienced recurrent chest pain after admission, although such incidences were not captured in the provincial repository. Due to factors such as distance from a tertiary cardiac centre, bed availability, and other unknown considerations, clinicians may have opted for supportive management, including analgesics, rather than contacting the on-call interventional cardiologist for expedited catheterization. These delays likely contributed to the observed adverse outcomes in NSTEMI patients treated at noncardiac centres. Access to patient-level data is essential for a deeper understanding of the factors contributing to these outcome disparities.
Another possibility is that differences in follow-up and long-term management played a role in the observed inferior outcomes among patients whose initial presentation was not to a specialized cardiac centre. Current major society guidelines recommend the use of high-potency P2Y12 inhibitors, such as ticagrelor in preference to clopidogrel, and previously work has shown that ACS patients admitted to rural hospitals in the US were less than half as likely to be prescribed ticagrelor vs clopidogrel.20 Residence in a rural location also has been associated with a decreased likelihood of long-term compliance to dual-antiplatelet therapy in both chronic and acute coronary syndrome patients,10,21 and it is associated with decreased compliance with secondary prevention medication use in general in ACS patients.22
Although previous studies in Canadian NSTEMI populations have shown decreased rates of cardiac catheterization4,23,24 and an increased risk of rehospitalization6 for rural patients, ours is the first to our knowledge to show an increased risk of outcomes such as MACE and mortality. A previous study of rural NSTEMI patients in New Zealand showed an increased risk of mortality (OR 1.16) at 2 years, but in contrast to our findings, not at 30 days or 1 year. Our study is additionally unique on the basis of the long average follow-up time of > 6 years, suggesting that persistent health advantages occur for NSTEMI patients who present initially to specialized cardiac centres, compared to rural or urban nonspecialized centres; this finding lends further support to the hypothesis that long-term follow-up by a CV specialist is important for such patients.
We observed a discrepancy in in-hospital outcomes between patients who presented to an urban noncardiac hospital—who had a higher risk of in-hospital mortality—compared to those who presented directly to the cardiac centre, and patients who presented to rural hospitals—who both did not. Although the reason for this difference is unclear, one possibility is that a lower threshold for transfer existed for rural hospitals, which are generally less well-resourced than urban hospitals, resulting in more prompt transfer to the cardiac centre. By contrast, higher-risk patients at urban centres may have (at least initially) been managed at those urban centres. Another possibility is that high-risk rural patients identified by emergency medical services bypassed the rural hospital altogether and were directed preferentially to the cardiac referral centre. Another possible explanation is that high-risk patients presenting to rural centres may have died before being transferred to a regional centre for cardiac catheterization. As a result, those who underwent coronary angiography represented a relatively lower-risk cohort due to a natural selection process. Understanding the factors contributing to these outcome differences is particularly important in Manitoba, where the sole tertiary cardiac centre is located in the southern region, requiring patients from the north to travel more than 1000 km for specialized care.
Urgency in patient transfers to a regional cardiac centre often is influenced more by geographic proximity than by standardized clinical metrics, a situation that represents a critical gap in equitable care delivery. An essential point to highlight is the need for triage and transport systems that prioritize objective, evidence-based indicators of clinical urgency rather than logistic convenience.
Limitations of this study include the retrospective nature of its design, and the inherent limitations of same. Although we corrected for multiple potential confounding factors in our analysis, unmeasured confounders could exist and could have affected the results. In addition, we are unable to determine the frequency with which patients in each cohort were followed up by a CV specialist, the medications they were prescribed following their index admission, and their compliance to medical therapy. Therefore, we are unable to conclude whether these factors played significant roles in the outcome disparities we observed.
Conclusion
NSTEMI patients presenting to rural and nonspecialized urban hospitals had worse short- and long-term outcomes, including higher MACE and mortality rates, compared to those treated at specialized cardiac centres. These findings highlight the need for targeted strategies to improve access to specialized CV care and reduce healthcare disparities.
Acknowledgments
Data Statement
Data used in this study are from the Population Health Research Data Repository housed at the Manitoba Centre for Health Policy, University of Manitoba, and are derived from data provided by Manitoba Health, Seniors, and Active Living, Vital Statistics, and Shared Health Diagnostic Services. The results and conclusions are those of the authors, and no official endorsement by Manitoba Health is intended or should be inferred.
Ethics Statement
This study was approved by the University of Manitoba Health Research Ethics Board (HS22575 (H2019:062)).
Patient Consent
The authors confirm that patient consent is not applicable to this article. This is a retrospective data analysis using de-identified data; therefore, the institutional review board did not require consent from the patients.
Funding Sources
This work was funded by an Establishment Grant, Department of Internal Medicine, University of Manitoba.
Disclosures
The authors have no conflicts of interest to disclose.
Footnotes
See page 1473 for disclosure information.
To access the supplementary material accompanying this article, visit CJC Open at https://www.cjcopen.ca/ and at https://doi.org/10.1016/j.cjco.2025.07.005.
Supplementary Material
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