Aims

Although routine invasive management is recommended in NSTEMI patients, the optimal timing of the procedure is not defined. The aim of this study was to assess outcomes in relation to timing of PCI in NSTEMI patients.

Methods and results

This was an observational, prospective, multicentre cohort study from the SWEDEHEART registry including all Swedish PCI centres. We included 40 494 consecutive PCI-treated patients who were admitted to any coronary care unit from 2006 to 2013. The primary outcome was all-cause death, and secondary outcomes were recurrent myocardial infarction (MI), stent thrombosis, and severe in-hospital bleeding. Outcomes were assessed within 1 year from admission in relation to pre-specified cut-offs to define early PCI: within 1, 2, or 3 days. Patients who received delayed PCI, compared with those who did not, were older, and had a higher prevalence of comorbidities (hypertension, hyperlipidaemia, diabetes, and prior stroke) but showed similar angiographic findings. Cox mixed-effects models showed a lower risk of all-cause death with early PCI across all three cut-offs: HR (95% CI) of 0.88 (0.80–0.98), 0.78 (0.71–0.86), and 0.75 (0.68–0.84), for the 1-, 2-, and 3-day cut-offs, respectively. Early PCI was associated with lower risk of recurrent MI for the 2- and 3-day cut-offs, but not for the 1-day cut-off. The reported rates of severe in-hospital bleeding were low, but tended to be higher in patients receiving delayed PCI.

Conclusion

In patients undergoing PCI for NSTEMI, early invasive treatment is associated with lower risk of ischaemic outcomes.

Introduction

Non-ST-elevation acute coronary syndrome (NSTE-ACS) is the most frequent manifestation of acute coronary syndromes (ACS). A routine invasive management (i.e. a diagnostic coronary angiogram followed by revascularization, if appropriate) compared with a selective invasive management not only improves symptoms, but also prognosis, as shown in several meta-analyses.14

While a routine invasive management now is established in high-risk NSTE-ACS patients,5 there is still uncertainty regarding the optimal timing of the procedure. Several relatively small studies611 and one larger trial12 have assessed early vs. late invasive treatment. As condensed in two meta-analyses, no difference could be seen with an early invasive vs. a delayed invasive management strategy in terms of all-cause mortality or myocardial infarction.13,14 However, in a pre-specified subgroup analysis of the Timing of Intervention in Acute Coronary Syndromes (TIMACS) study, high-risk patients (as defined by having a GRACE score >140) had substantial benefit of early revascularization within 24 h.12 This subgroup analysis forms the basis of the European Society of Cardiology recommendation of an early invasive management strategy in patients with GRACE score >140.5

Prior randomized studies are limited by their relatively small sample sizes with low number of events but also the heterogeneity in the timing of intervention. This has partly been overcome by also studying registry data from Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) and Global Registry of Acute Coronary Events (GRACE).15,16 In these studies, no apparent benefit of early vs. delayed revascularization was seen. Data were collected in the CRUSADE registry from 2001 until 2006 and results from both CRUSADE and GRACE were published about 10 years ago. Thus, these data are not necessarily representative of current clinical practice.

In the present study, we sought to investigate the impact of timing of PCI in patients with NSTEMI using a large, contemporary real-life ACS population from a nation-wide registry.

Methods

The Swedish Web-system for Enhancement and Development of Evidence- based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry covers most aspects of cardiac care in Sweden.

All cardiac care units (CCU) in Sweden (n = 72) are connected to RIKS-HIA (Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions; a part of SWEDEHEART), which includes information on all ACS patients treated at all CCUs in Sweden. Similarly, SCAAR (Swedish Coronary Angiography and Angioplasty Registry; also a part of SWEDEHEART) includes information on all coronary angiograms and percutaneous coronary intervention (PCI) procedures performed at all PCI centres in Sweden. Data are entered through a web-based interface, and the reliability of the information is monitored by random checks of source data, with a reported agreement of 96%.17 The SWEDEHEART database was combined with the Swedish National Patient Register (NPR), and the Swedish population register, to detect recurrent myocardial infarction, and mortality, respectively. The study was approved by the ethics committee in Uppsala.

Study population

In this study, we included patients who were admitted to any Swedish CCU between 1 January 2006 and 31 December 2013 and treated with in-hospital PCI due to NSTEMI (only first entry in database was used, see

for a selection flowchart).

Outcomes

The pre-specified primary outcome was death from all causes (obtained from the cause of death register), and secondary outcomes were myocardial infarction (MI, obtained from the NPR), stent thrombosis (from SCAAR), and in-hospital severe bleeding (from RIKS-HIA) up to 1 year after hospital admission. Myocardial infarction was assessed from Day 30 after admission to 1 year, as to avoid ‘contamination’ from the index event. In-hospital severe bleeding (as registered in RIKS-HIA) includes fatal or cerebral bleeding, or bleeding requiring surgery or transfusion.

Statistical analysis

Patient characteristics are reported as medians and 25th–75th percentiles for continuous variables and percentages and frequencies for categorical variables. Unadjusted Kaplan–Meier event rates of the primary and secondary outcomes are plotted in relation to delay of PCI according to three pre-specified cut-offs: within 1 day, within 2 days, within 3 days. The exact times of admission and start of procedure was not registered, only date. Therefore, for example, ‘within 2 days’ could span from 24 h 1 min delay to 47 h 59 min delay.

In the adjusted analyses, mixed effects Cox models were created for each of the above cut-offs, with the following covariates: age (entered as a restricted cubic spline), gender, hypertension, treating hospital (entered as a random effect variable), diabetes, hyperlipidaemia, smoking, prior coronary artery bypass surgery (CABG), prior PCI, previous stroke, peripheral arterial disease, previous cancer, PCI access (i.e. right radial, left radial, femoral from radial, femoral or other), estimated glomerular filtration rate (GFR), angiography findings, stent treatment, number of placed stents, acuteness of the procedure, cardiogenic shock, serious comorbidities that limit treatment (i.e. cancer, dementia, or other serious disease), glycoprotein IIb/IIIa inhibitor use. Event rates and hazard ratios (HR) with 95% confidence intervals (CI) are presented for the primary and secondary outcomes. For bleeding, no time-to-event data were available. Thus, for each component of severe in-hospital bleeding, percentages and frequencies are presented.

Multiple imputation of missing values was performed by chained equations, with 15 imputations. The covariates with most missing values were smoking status and estimated GFR (∼4% missing in each, see

for full information on missing values).

The baseline covariate profile was sufficiently balanced over the two delay groups (for all three splits of time) for using the mixed effects Cox model directly on the full population. In addition, as a sensitivity analysis, we estimated the effect of early PCI via 1-1 propensity score matching, where the above covariates were used also to estimate the propensity scores.

The statistical software R version 3.2.2 (R Core Team, 2015) was used for all analyses, employing the coxme package.18

Results

Patients

A total of 40 494 patients were included in the study. The baseline characteristics are shown in Table 1. Patients who received delayed PCI were older, and had a slightly higher prevalence of comorbidities, e.g. hypertension, hyperlipidaemia, diabetes, and prior stroke. The proportion of patients with male gender was marginally higher in those who received early PCI.

Table 1

Baseline characteristics overall and in relation to delay of percutaneous coronary intervention using three different cut-offs

Characteristic n 0–1 day >1 day 0–2 days >2 days 0–3 days >3 days 
n = 20 676 n = 19 818 n = 28 502 n = 11 992 n = 33 087 n = 7407 
Age 40 493 67.0 (59.0–75.0) 70.0 (62.0–78.0) 67.0 (59.0–75.0) 71.0 (63.0–78.0) 67.0 (60.0–76.0) 72.0 (63.0–79.0) 
Male gender 40 494 15154 (73.3%) 13813 (69.7%) 20768 (72.9%) 8199 (68.4%) 23982 (72.5%) 4985 (67.3%) 
Hypertension 40 088 9754 (47.6%) 10 142 (51.7%) 13 654 (48.4%) 6242 (52.6%) 15 995 (48.8%) 3901 (53.3%) 
Hyperlipidaemia 40 324 6432 (31.3%) 7200 (36.5%) 9132 (32.2%) 4500 (37.7%) 10 815 (32.8%) 2817 (38.2%) 
Diabetes mellitus 40 494 3868 (18.7%) 4531 (22.9%) 5552 (19.5%) 2847 (23.7%) 6579 (19.9%) 1820 (24.6%) 
Smoking: 38 782       
 No  7672 (38.5%) 7535 (39.9%) 10 632 (38.8%) 4575 (40.1%) 12 339 (38.9%) 2868 (40.8%) 
 Yes  4960 (24.9%) 3974 (21.1%) 6602 (24.1%) 2332 (20.4%) 7556 (23.8%) 1378 (19.6%) 
 Former  7275 (36.5%) 7366 (39.0%) 10 141 (37.0%) 4500 (39.4%) 11 853 (37.3%) 2788 (39.6%) 
CABG 40 378 1668 (8.1%) 2168 (11.0%) 2440 (8.6%) 1396 (11.7%) 2957 (9.0%) 879 (11.9%) 
PCI 40 249 3407 (16.6%) 3448 (17.5%) 4773 (16.8%) 2082 (17.5%) 5607 (17.0%) 1248 (17.0%) 
Stroke 39 346 1161 (5.8%) 1518 (7.9%) 1694 (6.1%) 985 (8.4%) 2023 (6.3%) 656 (9.1%) 
Peripheral arterial disease 40 494 834 (4.0%) 1132 (5.7%) 1162 (4.1%) 804 (6.7%) 1433 (4.3%) 533 (7.2%) 
Prior cancer 40 494 407 (2.0%) 522 (2.6%) 596 (2.1%) 333 (2.8%) 722 (2.2%) 207 (2.8%) 
Access: 40 494       
 Femoral  7055 (34.1%) 8855 (44.7%) 10265 (36.0%) 5645 (47.1%) 12296 (37.2%) 3614 (48.8%) 
 Right radial  12002 (58.0%) 9417 (47.5%) 15990 (56.1%) 5429 (45.3%) 18172 (54.9%) 3247 (43.8%) 
 Left radial  842 (4.1%) 793 (4.0%) 1161 (4.1%) 474 (4.0%) 1370 (4.1%) 265 (3.6%) 
 Femoral from radial  548 (2.7%) 544 (2.7%) 770 (2.7%) 322 (2.7%) 891 (2.7%) 201 (2.7%) 
 Other  229 (1.1%) 209 (1.1%) 316 (1.1%) 122 (1.0%) 358 (1.1%) 80 (1.1%) 
Angiography findings: 40 459       
 No significant stenoses  448 (2.2%) 522 (2.6%) 659 (2.3%) 311 (2.6%) 772 (2.3%) 198 (2.7%) 
 1-vessel disease  9652 (46.7%) 8620 (43.5%) 13160 (46.2%) 5112 (42.7%) 15231 (46.1%) 3041 (41.1%) 
 2-vessel disease  6113 (29.6%) 6033 (30.5%) 8518 (29.9%) 3628 (30.3%) 9883 (29.9%) 2263 (30.6%) 
 3-vessel disease  3538 (17.1%) 3613 (18.2%) 4886 (17.2%) 2265 (18.9%) 5686 (17.2%) 1465 (19.8%) 
 Left main disease  909 (4.4%) 1011 (5.1%) 1254 (4.4%) 666 (5.6%) 1488 (4.5%) 432 (5.8%) 
Stent procedure 40 221 18188 (88.5%) 17208 (87.4%) 25025 (88.4%) 10371 (87.2%) 29014 (88.3%) 6382 (86.8%) 
Number of stents placed 40 221 1.0 (1.0–2.0) 1.0 (1.0–2.0) 1.0 (1.0–2.0) 1.0 (1.0–2.0) 1.0 (1.0–2.0) 1.0 (1.0–2.0) 
Delay to PCI, days 40 494 1.0 (0.0–1.0) 3.0 (2.0–4.0) 1.0 (0.0–2.0) 4.0 (3.0–5.0) 1.0 (0.0–2.0) 5.0 (4.0–6.0) 
P2Y12 inhibitor 40 447       
 Clopidogrel  16 249 (78.7%) 16 585 (83.8%) 22 756 (79.9%) 10 078 (84.1%) 26 582 (80.4%) 6252 (84.5%) 
 Prasugrel  273 (1.3%) 130 (0.7%) 333 (1.2%) 70 (0.6%) 364 (1.1%) 39 (0.5%) 
 Ticagrelor  3120 (15.1%) 2107 (10.6%) 4024 (14.1%) 1203 (10.0%) 4538 (13.7%) 689 (9.3%) 
 Ticlopidine  45 (0.2%) 32 (0.2%) 52 (0.2%) 25 (0.2%) 64 (0.2%) 13 (0.2%) 
Characteristic n 0–1 day >1 day 0–2 days >2 days 0–3 days >3 days 
n = 20 676 n = 19 818 n = 28 502 n = 11 992 n = 33 087 n = 7407 
Age 40 493 67.0 (59.0–75.0) 70.0 (62.0–78.0) 67.0 (59.0–75.0) 71.0 (63.0–78.0) 67.0 (60.0–76.0) 72.0 (63.0–79.0) 
Male gender 40 494 15154 (73.3%) 13813 (69.7%) 20768 (72.9%) 8199 (68.4%) 23982 (72.5%) 4985 (67.3%) 
Hypertension 40 088 9754 (47.6%) 10 142 (51.7%) 13 654 (48.4%) 6242 (52.6%) 15 995 (48.8%) 3901 (53.3%) 
Hyperlipidaemia 40 324 6432 (31.3%) 7200 (36.5%) 9132 (32.2%) 4500 (37.7%) 10 815 (32.8%) 2817 (38.2%) 
Diabetes mellitus 40 494 3868 (18.7%) 4531 (22.9%) 5552 (19.5%) 2847 (23.7%) 6579 (19.9%) 1820 (24.6%) 
Smoking: 38 782       
 No  7672 (38.5%) 7535 (39.9%) 10 632 (38.8%) 4575 (40.1%) 12 339 (38.9%) 2868 (40.8%) 
 Yes  4960 (24.9%) 3974 (21.1%) 6602 (24.1%) 2332 (20.4%) 7556 (23.8%) 1378 (19.6%) 
 Former  7275 (36.5%) 7366 (39.0%) 10 141 (37.0%) 4500 (39.4%) 11 853 (37.3%) 2788 (39.6%) 
CABG 40 378 1668 (8.1%) 2168 (11.0%) 2440 (8.6%) 1396 (11.7%) 2957 (9.0%) 879 (11.9%) 
PCI 40 249 3407 (16.6%) 3448 (17.5%) 4773 (16.8%) 2082 (17.5%) 5607 (17.0%) 1248 (17.0%) 
Stroke 39 346 1161 (5.8%) 1518 (7.9%) 1694 (6.1%) 985 (8.4%) 2023 (6.3%) 656 (9.1%) 
Peripheral arterial disease 40 494 834 (4.0%) 1132 (5.7%) 1162 (4.1%) 804 (6.7%) 1433 (4.3%) 533 (7.2%) 
Prior cancer 40 494 407 (2.0%) 522 (2.6%) 596 (2.1%) 333 (2.8%) 722 (2.2%) 207 (2.8%) 
Access: 40 494       
 Femoral  7055 (34.1%) 8855 (44.7%) 10265 (36.0%) 5645 (47.1%) 12296 (37.2%) 3614 (48.8%) 
 Right radial  12002 (58.0%) 9417 (47.5%) 15990 (56.1%) 5429 (45.3%) 18172 (54.9%) 3247 (43.8%) 
 Left radial  842 (4.1%) 793 (4.0%) 1161 (4.1%) 474 (4.0%) 1370 (4.1%) 265 (3.6%) 
 Femoral from radial  548 (2.7%) 544 (2.7%) 770 (2.7%) 322 (2.7%) 891 (2.7%) 201 (2.7%) 
 Other  229 (1.1%) 209 (1.1%) 316 (1.1%) 122 (1.0%) 358 (1.1%) 80 (1.1%) 
Angiography findings: 40 459       
 No significant stenoses  448 (2.2%) 522 (2.6%) 659 (2.3%) 311 (2.6%) 772 (2.3%) 198 (2.7%) 
 1-vessel disease  9652 (46.7%) 8620 (43.5%) 13160 (46.2%) 5112 (42.7%) 15231 (46.1%) 3041 (41.1%) 
 2-vessel disease  6113 (29.6%) 6033 (30.5%) 8518 (29.9%) 3628 (30.3%) 9883 (29.9%) 2263 (30.6%) 
 3-vessel disease  3538 (17.1%) 3613 (18.2%) 4886 (17.2%) 2265 (18.9%) 5686 (17.2%) 1465 (19.8%) 
 Left main disease  909 (4.4%) 1011 (5.1%) 1254 (4.4%) 666 (5.6%) 1488 (4.5%) 432 (5.8%) 
Stent procedure 40 221 18188 (88.5%) 17208 (87.4%) 25025 (88.4%) 10371 (87.2%) 29014 (88.3%) 6382 (86.8%) 
Number of stents placed 40 221 1.0 (1.0–2.0) 1.0 (1.0–2.0) 1.0 (1.0–2.0) 1.0 (1.0–2.0) 1.0 (1.0–2.0) 1.0 (1.0–2.0) 
Delay to PCI, days 40 494 1.0 (0.0–1.0) 3.0 (2.0–4.0) 1.0 (0.0–2.0) 4.0 (3.0–5.0) 1.0 (0.0–2.0) 5.0 (4.0–6.0) 
P2Y12 inhibitor 40 447       
 Clopidogrel  16 249 (78.7%) 16 585 (83.8%) 22 756 (79.9%) 10 078 (84.1%) 26 582 (80.4%) 6252 (84.5%) 
 Prasugrel  273 (1.3%) 130 (0.7%) 333 (1.2%) 70 (0.6%) 364 (1.1%) 39 (0.5%) 
 Ticagrelor  3120 (15.1%) 2107 (10.6%) 4024 (14.1%) 1203 (10.0%) 4538 (13.7%) 689 (9.3%) 
 Ticlopidine  45 (0.2%) 32 (0.2%) 52 (0.2%) 25 (0.2%) 64 (0.2%) 13 (0.2%) 

Angiographic findings were similar in patients who received early vs. delayed PCI, and the number of stents used was similar. However, femoral access was used more commonly in those who received delayed PCI.

Primary outcome: death from all causes

The primary outcome of death from all causes occurred less frequently in patients who underwent early PCI as compared with patients receiving delayed PCI, across all three cut-offs to define ‘early’ (Figures 13).

Figure 1

One-day cut-off—Outcomes (A: All-cause death, B: myocardial infarction, C: stent thrombosis) in relation to delay of percutaneous coronary intervention (unadjusted), cut-off 1 day.

Figure 1

One-day cut-off—Outcomes (A: All-cause death, B: myocardial infarction, C: stent thrombosis) in relation to delay of percutaneous coronary intervention (unadjusted), cut-off 1 day.

Figure 2

Two-day cut-off—Outcomes (A: All-cause death, B: myocardial infarction, C: stent thrombosis) in relation to delay of percutaneous coronary intervention (unadjusted), cut-off 2 days.

Figure 2

Two-day cut-off—Outcomes (A: All-cause death, B: myocardial infarction, C: stent thrombosis) in relation to delay of percutaneous coronary intervention (unadjusted), cut-off 2 days.

Figure 3

Three-day cut-off—Outcomes (A: All-cause death, B: myocardial infarction, C: stent thrombosis) in relation to delay of percutaneous coronary intervention (unadjusted), cut-off 3 days.

Figure 3

Three-day cut-off—Outcomes (A: All-cause death, B: myocardial infarction, C: stent thrombosis) in relation to delay of percutaneous coronary intervention (unadjusted), cut-off 3 days.

In the multivariable analyses, early PCI was associated with a reduction in the primary outcome using all three cut-offs to define early; within 1 day: HR 0.89 (95% CI 0.80–0.98, P = 0.018), 2 days: HR 0.78 (95% CI 0.71–0.86, P < 0.001), and within 3 days: HR 0.75 (95% CI 0.68–0.84, P < 0.001) (Table 2). Results of the sensitivity analyses were similar to the main analyses in direction and magnitude (

).
Table 2

Outcomes at 1 year in relation to delay of percutaneous coronary intervention procedure

Endpoint Early PCI
 
Delayed PCI
 
Unadj HR (95% CI) Adjusted HR (95% CI) P-value 
All-cause death, 1-day cut-off 801/20 676 (3.9%) 1004/19 818 (5.1%) 0.75 (0.71–0.79) 0.89 (0.80–0.98) 0.018 
All-cause death, 2-day cut-off 1083/28 502 (3.8%) 722/11 992 (6.0%) 0.67 (0.64–0.71) 0.78 (0.71–0.86) <0.001 
All-cause death, 3-day cut-off 12993/33 087 (3.9%) 506/7407 (6.8%) 0.62 (0.59–0.66) 0.75 (0.68–0.84) <0.001 
MI, 1-day cut-off 984/20 676 (5%) 1239/19 818 (6.5%) 0.83 (0.79–0.88) 0.95 (0.87–1.03) 0.23 
MI, 2-day cut-off 1399/28 502 (5.2%) 824/11 992 (7.1%) 0.78 (0.74–0.83) 0.88 (0.81–0.96) 0.0055 
MI, 3-day cut-off 1662/33 087 (5.3%) 561/7407 (7.8%) 0.75 (0.70–0.80) 0.86 (0.78–0.95) 0.0030 
Stent thrombosis, 1-day cut-off 129/20 541 (0.6%) 139/19 680 (0.7%) 1.00 (0.83–1.21) 0.89 (0.70–1.14) 0.37 
Stent thrombosis, 2-day cut-off 182/28 323 (0.7%) 86/11 898 (0.7%) 1.02 (0.83–1.25) 0.90 (0.69–1.16) 0.41 
Stent thrombosis, 3-day cut-off 208/32 872 (0.6%) 60/7349 (0.8%) 0.94 (0.75–1.19) 0.79 (0.59–1.06) 0.11 
Endpoint Early PCI
 
Delayed PCI
 
Unadj HR (95% CI) Adjusted HR (95% CI) P-value 
All-cause death, 1-day cut-off 801/20 676 (3.9%) 1004/19 818 (5.1%) 0.75 (0.71–0.79) 0.89 (0.80–0.98) 0.018 
All-cause death, 2-day cut-off 1083/28 502 (3.8%) 722/11 992 (6.0%) 0.67 (0.64–0.71) 0.78 (0.71–0.86) <0.001 
All-cause death, 3-day cut-off 12993/33 087 (3.9%) 506/7407 (6.8%) 0.62 (0.59–0.66) 0.75 (0.68–0.84) <0.001 
MI, 1-day cut-off 984/20 676 (5%) 1239/19 818 (6.5%) 0.83 (0.79–0.88) 0.95 (0.87–1.03) 0.23 
MI, 2-day cut-off 1399/28 502 (5.2%) 824/11 992 (7.1%) 0.78 (0.74–0.83) 0.88 (0.81–0.96) 0.0055 
MI, 3-day cut-off 1662/33 087 (5.3%) 561/7407 (7.8%) 0.75 (0.70–0.80) 0.86 (0.78–0.95) 0.0030 
Stent thrombosis, 1-day cut-off 129/20 541 (0.6%) 139/19 680 (0.7%) 1.00 (0.83–1.21) 0.89 (0.70–1.14) 0.37 
Stent thrombosis, 2-day cut-off 182/28 323 (0.7%) 86/11 898 (0.7%) 1.02 (0.83–1.25) 0.90 (0.69–1.16) 0.41 
Stent thrombosis, 3-day cut-off 208/32 872 (0.6%) 60/7349 (0.8%) 0.94 (0.75–1.19) 0.79 (0.59–1.06) 0.11 

Secondary outcomes

For recurrent MI, there was a similarly lower incidence in patients receiving early vs. delayed PCI (Figures 13). The benefit of early PCI was seen in the multivariable analyses when using the cut-offs of 2 or 3 days, but not using the 1-day cut-off.

The rates of stent thrombosis did not differ between groups, regardless of delay time from admission to PCI (Table 2).

Overall, reported severe in-hospital bleeding was uncommon. Deadly bleeding was only captured in 5 out of 40 407 patients. Bleeding requiring surgery or transfusion occurred in 1% of patients. In patients receiving delayed PCI, bleeding requiring surgery or transfusion tended to be higher than in those treated with early PCI (Table 3).

Table 3

Severe in-hospital bleeding in relation to delay of percutaneous coronary intervention procedure

Severe in-hospital bleeding Total
N = 40 407 
Delay 0–1 day
n = 20 676 
Delay >1 day
n = 19 818 
Delay 0–2 days
n = 28 502 
Delay >2 days
n = 11 992 
Delay 0–3 days
n = 33 087 
Delay >3 days
n = 7407 
Deadly 0.0% (5) 0.0% (2) 0.0% (3) 0.0% (2) 0.0% (3) 0.0% (3) 0.0% (2) 
Requiring surgery or transfusion 0.8% (344) 0.6% (123) 1.1% (221) 0.6% (181) 1.4% (163) 0.7% (228) 1.6% (116) 
Cerebral 0.1% (23) 0.1% (14) 0.0% (9) 0.1% (16) 0.1% (7) 0.1% (19) 0.1% (4) 
Severe in-hospital bleeding Total
N = 40 407 
Delay 0–1 day
n = 20 676 
Delay >1 day
n = 19 818 
Delay 0–2 days
n = 28 502 
Delay >2 days
n = 11 992 
Delay 0–3 days
n = 33 087 
Delay >3 days
n = 7407 
Deadly 0.0% (5) 0.0% (2) 0.0% (3) 0.0% (2) 0.0% (3) 0.0% (3) 0.0% (2) 
Requiring surgery or transfusion 0.8% (344) 0.6% (123) 1.1% (221) 0.6% (181) 1.4% (163) 0.7% (228) 1.6% (116) 
Cerebral 0.1% (23) 0.1% (14) 0.0% (9) 0.1% (16) 0.1% (7) 0.1% (19) 0.1% (4) 

Discussion

In this large, contemporary real-world study of outcomes in relation to timing of PCI in NSTE-ACS patients, early PCI was associated with lower risk of both death from all causes and recurrent MI. For the 1-day cut-off, the Kaplan–Meier curves for mortality (Figure 1) were overlapping for approximately the first 60 days. This may be due to an accumulation of patients who are at very high risk (e.g. those with severe heart failure, hemodynamic instability, refractory angina or patients with life-threatening ventricular arrhythmia) where an urgent invasive management strategy is recommended.5 This is a group of patients who are at a very high ischaemic risk and generally not included in clinical trials.

Although it is widely accepted that coronary angiography followed by revascularization in NSTE-ACS prevents recurrent ischaemia and improves outcomes, there is inconsistency in the results from previous studies on the benefit of an early invasive strategy. In several of the smaller clinical trials (of between 142 and 815 patients), no benefit in terms of ischaemic outcomes was seen with an early invasive management,69,11 whereas reduced ischaemic events were seen in studies by Zhang et al.,10 Milosevic et al.19 and in patients with a GRACE score >140 included in TIMACS.12 In the older registry data from CRUSADE and GRACE, no apparent benefit with early invasive management was seen.15,16 In other observational data [post hoc analyses from the RCTs SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy)], early invasive management was associated with reductions in ischaemic events.20,21 In SYNERGY, invasive management within 6 h was associated with lower rates of the composite of death/MI20 and in ACUITY, a delay of invasive management >24 h was an independent predictor of adverse outcome, including mortality.21

The present study adds additional information from a large, contemporary, nation-wide cohort, where the results correspond with the more recent of the above-mentioned studies. Furthermore, our study reflects routine clinical practice and is by that not limited by the usually very narrow risk spectrum of patients in randomized clinical trials. During the last decade, several advancements in the management of ACS patients have been made; improved stent technology,22 an increasing tendency towards using primarily a radial approach rather than femoral for PCI, improving safety of the procedure23,24, and more effective, rapid-acting anti-thrombotic therapy.25,26

We show that early PCI for NSTEMI is safe (the reported bleeding rates were very low) and associated with better outcomes in a broad NSTEMI population.

Limitations

This was a study from a registry, with its inherent limitations (e.g. selection bias, and differences in groups with regard to baseline characteristics, also unmeasured bias). One specific limitation is that the reason for delayed arrival in the catheter lab was not registered in the database. While every effort was made to adjust for possible confounding variables, the risk of residual confounding is acknowledged. As such, the results should be considered hypothesis generating. In addition, the resolution regarding delay times is in days, not in hours or minutes, which leads to additional uncertainty regarding the delay time. Furthermore, the bleeding information registered in SWEDEHEART is limited. Therefore, a potential for under-reporting of bleeding events is acknowledged. And, finally, MI events were assessed from 30 days onward, as to avoid ‘contamination’ from the index event. Thus, potential differences in early MIs could not be assessed.

Conclusion

In patients undergoing PCI for NSTEMI, early invasive treatment is associated with lower rates of ischaemic events at 1 year.

Supplementary material

Funding

This research was funded by AstraZeneca within the Externally Sponsored Research Programme ESR-14-10720.

Conflict of interest: D.L.: Institutional research grants and lecture fees from AstraZeneca. J.A.: Reports no conflicts of interest. O.A.: Consulting fee, advisory board and speaker fee Astra Zeneca, research Grant St Jude Medical, speaker fee Bristol-Meyers Squibb. F.B.: Lecture fees from Bristol-Myers Squibb and AstraZeneca. F.C.: Lecture fees from AstraZeneca. S.K.: Reports no conflicts of interest. B.L.: institutional research grant from AstraZeneca. H.R.: Reports no conflicts of interest. G.S.: institutional research grants from Boston Scientific. C.V.: institutional research grants from AstraZeneca and The Medicines Company, lecture and advisory board fees from AstraZeneca, The Medicines Company and Boeringer Ingelheim, lecture fees from Bristol Myers Squibb, Pfizer and CSL Behring, and is on the Clinical Endpoint Committee for Pfizer, Bristol Myers Squibb, Philips and AstraZeneca.

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Author notes

See page 6 for the editorial comment on this article (doi:10.1093/ehjqcco/qcw059)

Supplementary data