European Heart Journal – Quality of Care and Clinical Outcomes (2016) 2, 45–51 doi:10.1093/ehjqcco/qcv025
ORIGINAL ARTICLE
Reperfusion therapy for ST-elevation acute myocardial infarction in Eastern Europe: the ISACS-TC registry Edina Cenko 1, Beatrice Ricci 1, Sasko Kedev 2, Zorana Vasiljevic 3, Maria Dorobantu 4,5, Olivija Gustiene 6, Bozˇidarka Knezˇevic´ 7, Davor Milicˇic´8, Mirza Dilic 9, Dijana Trninic 10, Fraser Smith 11, Olivia Manfrini 1, Lina Badimon 12, and Raffaele Bugiardini 1* 1 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Massarenti 9, Bologna 40138, Italy; 2University Clinic of Cardiology, Medical Faculty, University of St Cyril & Methodius, Skopje, Macedonia; 3Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia; 4University of Medicine and Pharmacy ‘Carol Davila’, Bucharest, Romania; 5Department of Cardiology and Internal Medicine, Floreasca Emergency Hospital, Bucharest, Romania; 6Department of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania; 7Clinical Center of Montenegro, Center of Cardiology, Podgorica, Montenegro; 8Department for Cardiovascular Diseases, University Hospital Center Zagreb, University of Zagreb, Zagreb, Croatia; 9Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina; 10Clinical Center of Banja Luka, Republika Srpska, Bosnia and Herzegovina; 11University of Leeds, Leeds, UK; and 12Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, CiberObn-Institute Carlos III, Autonomous University of Barcelona, Barcelona, Spain
Received 9 September 2015; revised 20 October 2015; accepted 24 October 2015; online publish-ahead-of-print 27 October 2015
See page 4 for the editorial comment on this article (doi:10.1093/ehjqcco/qcv031)
Aims
Widespread availability of tertiary hospitals with catheterization facilities, although vigorously promoted, has yet to become a reality in many countries with economy in transition. We sought to evaluate the clinical profile and mortality of patients who were hospitalized with a diagnosis of ST-segment elevation myocardial infarction (STEMI) and either received reperfusion therapy or remained without reperfusion in Eastern Europe. ..................................................................................................................................................................................... Methods Data were obtained from the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC; and results NCT01218776) on STEMI patients admitted to 57 hospitals in Eastern European countries from January 2010 to February 2015. The primary endpoint was 30-day mortality. Of 7982 patients, 65 (0.8%) had a documented contraindication to reperfusion, 5973 (75.5%) received fibrinolysis (n ¼ 1032) or underwent primary percutaneous coronary intervention (p-PCI; n ¼ 4941), and 1944 patients (24.6%) did not receive any reperfusion therapy. The overall unadjusted 30-day mortality rate was 7.9%. Thirty-day mortality rates were higher in non-reperfusion patients (16.0 vs. 5.0% in the p-PCI group and 7.4% in fibrinolysis group). The strongest factors associated with not attempting reperfusion therapy among these patients were female sex (OR 1.29 CI 1.07 – 1.56), age (OR 1.02; CI 1.01 – 1.03), prior MI (OR 1.79; CI 1.38 – 2.32), prior cerebrovascular events (OR 1.87; CI 1.30 – 2.68), chronic kidney disease (OR 1.76; CI 1.22–2.53), Killip class .1 (OR 1.31; CI 1.06–1.62), and time to admission .12 h (OR 15.9; CI 13.1–19.3). ..................................................................................................................................................................................... Conclusions A substantial number of patients are still not offered any reperfusion therapy in many Eastern European countries with economy in transition, and this was associated with increased 30-day mortality. Time from symptoms onset to admission .12 h was the highest ranking among factors related to lack of reperfusion therapy. Quality improvement efforts should focus on minimizing delay to hospital admission among STEMI patients.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Eastern European countries † ST-segment elevation myocardial infarction † Reperfusion therapies
Introduction A substantial number of patients, in particular in Eastern and Southern Europe, did not receive any reperfusion therapy after ST-segment elevation myocardial infarction (STEMI), in a survey of
37 countries by the European Society of Cardiology (ESC).1 The International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC) was launched in 2010 to drive equal access to life-saving therapies and procedures in STEMI patients across European countries with economy in transition.2,3
* Corresponding author. Tel/fax: +39 051 347290, Email:
[email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email:
[email protected].
46 Previous work was based on aggregated country-level data on patients admitted with STEMI during 2010 or 2011. Data were collected on the use of reperfusion treatment and mortality, the numbers of cardiologists, and the availability of primary percutaneous coronary intervention (p-PCI) facilities. Information came from national or regional registries or from expert estimates when registries did not exist.1 However, population-level or aggregate relationships do not necessarily represent individual-level data. For example, Kristensen et al. examined the number of p-PCI per million inhabitants and the number of catheterization laboratories providing p-PCI services 24 h a day. In such a model, the aggregated p-PCI variable represents many material factors that were simultaneously changing over time with no evidence of a causal relationship between the percentage of patients not receiving any reperfusion therapy and mortality. We sought to evaluate the individual-level relationship between clinical profile and mortality of patients who were hospitalized with a diagnosis of STEMI and either received reperfusion therapy or remained without reperfusion in Eastern European countries participating to the ISACS-TC registry.
Methods Study population The details of the ISACS-TC registry (ClinicalTrials.gov: NCT01218776) have been previously published.2 Briefly, the ISACS-TC network is constituted of 29 tertiary and 28 secondary hospitals. All hospitals had intensive coronary care units and medical reperfusion therapy. The tertiary hospitals had cardiac catheterization facilities. Hospitals are located in urban areas of at least 10 000 inhabitants. Data from the ISACS-TC hospitals were collected from January 2010 to February 2015. The study was approved by the local research ethics committee from each hospital. Patients provided written consent for evaluation of their medical notes and monitoring of their health status.
Data collection and inclusion criteria Diagnosis of STEMI was performed according to universal standardized criteria.4 STEMI patients were categorized into three groups: patients eligible for reperfusion who received reperfusion by p-PCI (n ¼ 4941); patients eligible for reperfusion who received fibrinolysis (n ¼ 1032); and patients eligible for reperfusion but for whom reperfusion was not attempted (n ¼ 1944). Patients transferred to a tertiary hospital for p-PCI after fibrinolysis (n ¼ 66) were included among patients receiving p-PCI. Additionally, patients who underwent angiography but had anatomy unsuitable for PCI were included among the patients receiving p-PCI. There were 65 patients ineligible for reperfusion based on a documented contraindication. They were excluded from the analysis. Reasons of contraindications to reperfusion therapy in our STEMI population were recent surgery and/or trauma, active bleeding at admission, and comorbid disease (Figure 1).
Measures of outcome The primary endpoint was 30-day mortality after admission.
Statistical analysis Patient groups were compared by one-way analysis of variance (ANOVA) or Kruskal – Wallis rank test for continuous variables and Pearson’s x 2 test for categorical variables. Kaplan– Meier curve was calculated for
E. Cenko et al.
Figure 1 Study flow chart.
30-day mortality rates. Log-rank test was used to compare event rates among the three treatment groups. Multivariable logistic regression analysis was performed to evaluate the factors associated with no reperfusion therapy among eligible patients. Results are presented as odds ratios (OR) and 95% confidence intervals (CIs). Constant relevant covariates included in the analyses were: sex; age; cardiovascular risk factors such as history of hypercholesterolaemia, history of diabetes, history of hypertension, and smoking status; clinical history of ischaemic heart disease (prior angina pectoris, prior myocardial infarction, prior PCI, and prior coronary artery bypass graft) clinical history of cardiovascular disorders (prior peripheral artery disease, prior heart failure, and prior stroke and/or prior transient ischaemic attack), severity of clinical presentation (anterior myocardial infarction or left bundle branch block, Killip Class .1, systolic blood pressure, heart rate, and serum creatinine levels ≥175 mmol/L), and time from symptoms onset to admission .12 h. Another multivariable logistic regression analysis was performed to evaluate the adjusted mortality rates among the treatment groups. A C-index (area under the receiver-operator characteristic curve) was generated for the regression models to measure the concordance. For all analyses, statistical significance was defined as a value of P , 0.05. Statistical evaluation was performed using STATA 11 (StataCorp., College Station, TX, USA).
Results The ISACS-TC database enrolled 7982 patients who were admitted with a diagnosis of STEMI. After excluding 65 patients with contraindication to fibrinolysis the final study population was 7917 patients. Of such patients, 1944 (24.6%) did not receive any timely (within 24 h) reperfusion therapy (p-PCI or fibrinolysis). Of patients with reperfusion therapy, 1032 (13.0%) received fibrinolytic therapy and 4941 underwent p-PCI (62.4%) (Figure 2).
Use of reperfusion Patients who had reperfusion therapy were younger, more often male, presented to the hospital earlier after symptom onset, and less often had diabetes mellitus, prior myocardial infarction (MI), prior heart failure, renal insufficiency, and signs of heart failure on
47
Reperfusion therapy for STEMI
presentation compared with patients without reperfusion therapy (Table 1). Eligible patients who were reperfused by p-PCI shared similar characteristics to patients who had reperfusion by fibrinolysis (Table 1).
Variables associated with lack of reperfusion therapy Among patients who did not undergo reperfusion therapy, the variables most strongly associated with lack of therapy include increased age, signs of heart failure on presentation, prior MI, prior stroke and/ or transient ischaemic attacks, renal insufficiency, increased heart rate at admission, and female sex. Time from symptoms onset to admission .12 h was the highest ranking among the covariates studied (Table 2).
Acute medications Patients who had reperfusion by p-PCI were more likely to receive acute (≤12 h from admission) medications compared with the other two groups (Table 3). Late elective PCI (.48 h from admission) was performed more often in patients who received fibrinolysis than in those with no reperfusion therapy (21.9 vs. 6.9%, P , 0.001), suggesting that a substantial proportion of physicians considered patients who received fibrinolysis as eligible candidates for a more complete revascularization.
Figure 2 Treatment strategies in the overall ST-segment elevation myocardial infarction population (n ¼ 7917).
Table 1
Baseline characteristics by treatment group (n 5 7917)
Characteristics
p-PCI (n 5 4941)
Fibrinolysis (n 5 1032)
No reperfusion (n 5 1944)
P-valuea
............................................................................................................................................................................... Female sex
1386 (28.1)
273 (26.5)
740 (37.1)
,0.001
Age (years) Diabetes
60.6 + 11.5 1078 (22.4)
58.9 + 11.6 216 (22.2)
65.9 + 12.5 556 (30.8)
,0.001 ,0.001
Hypertension
3157 (65.2)
557 (56.0)
1228 (65.4)
,0.001
Hypercholesterolaemia Current smoking
1781 (40.7) 2144 (44.5)
263 (34.0) 469 (46.6)
538 (35.0) 526 (28.1)
,0.001 ,0.001
Family history of CAD
1554 (33.6)
209 (22.4)
650 (38.0)
,0.001
Prior angina pectoris Prior MI
694 (14.1) 593 (12.0)
95 (9.2) 102 (9.9)
350 (18.0) 325 (16.7)
,0.001 ,0.001
Prior PCI
711 (14.4)
54 (5.2)
224 (11.5)
,0.001
Prior CABG History of heart failure
37 (0.8) 168 (3.4)
10 (1.0) 26 (2.5)
56 (2.9) 122 (6.3)
,0.001 ,0.001
Prior cerebrovascular eventsb
187 (3.8)
30 (2.9)
144 (7.4)
,0.001
Prior peripheral artery disease
70 (1.4)
33 (3.2)
84 (4.3)
,0.001
Time to admission .12 h Time to admission (min, IQR)
411 (8.7) 220 (120– 360)
79 (7.7) 180 (116–315)
1081 (59.6) 505 (180–1200)
,0.001 ,0.001
EMS
889 (18.0)
380 (36.8)
499 (25.7)
,0.001
Transferred to a tertiary centre Killip class .1
736 (29.4) 564 (20.6)
128 (29.6) 215 (25.7)
318 (27.1) 564 (36.1)
0.31 ,0.001
Anterior STEMI and/or LBBB
1388 (28.1)
197 (19.1)
547 (28.2)
,0.001
Systolic blood pressure (mmHg) Heart rate (b.p.m.)
142.1 + 22.3 80.4 + 15.8
137.3 + 27.5 78.1 + 19.0
136.6 + 23.7 82.1 + 18.1
,0.001 ,0.001
Serum creatinine ≥175 mmol/L
153 (3.1)
24 (2.3)
198 (10.2)
,0.001
30-day mortality
248 (5.0)
76 (7.4)
303 (16.0)
,0.001
............................................................................................................................................................................... Clinical presentation
Data are numbers (percentages) or mean + SD, unless otherwise stated. CAD, coronary artery disease; BMI, body mass index; MI, myocardial infarction; p-PCI, primary percutaneous coronary intervention; CABG, coronary artery bypass graft; EMS, emergency medical services; LBBB, left bundle branch block; IQR, interquartile range. a Patient groups were compared by one-way analysis of variance (ANOVA) or Kruskal –Wallis rank test for continuous variables and Pearson’s x 2 test for categorical variables. b Prior stroke and/or prior transient ischaemic attack.
48
E. Cenko et al.
Outcomes The overall unadjusted 30-day mortality rate was 7.9%. The incidence of 30-day mortality was higher in patients who did not have reperfusion therapy in comparison with those who did. Among patients with reperfusion therapy 30-day mortality was higher in the fibrinolysis group than in the p-PCI group (Figure 3 and Table 1). After adjustment for baseline characteristics, the incidence of
Table 2 therapy
Independent predictors of no reperfusion
OR
95% CI
P-value
................................................................................ Female sex
1.29
1.07– 1.56
0.008
Age (years)
1.02
1.01– 1.03
,0.001
Diabetes Hypertension
1.12 0.80
0.91– 1.38 0.65– 0.98
0.26 0.03
Hypercholesterolaemia
0.79
0.65– 0.96
0.01
Current smoking Prior angina pectoris
0.58 0.90
0.47– 0.72 0.70– 1.16
0.001 0.45
Prior MI
1.79
1.38– 2.32
,0.001
Prior PCI Prior CABG
0.67 1.65
0.52– 0.85 0.87– 3.11
0.001 0.11
History of heart failure
0.83
0.53– 1.31
0.44
Prior cerebrovascular eventsa Prior peripheral artery disease
1.87 1.63
1.30– 2.68 0.99– 2.68
0.001 0.05
13.1– 19.3
,0.001
Killip class .1 Anterior STEMI and/or LBBB
Time to admission .12 h
1.31 0.56
1.06– 1.62 0.46– 0.69
0.01 ,0.001
Systolic blood pressure (1SD incrementb)
1.06
0.95– 1.17
0.25
15.9
Heart rate (1SD incrementb)
1.26
1.10– 1.44
0.001
Serum creatinine ≥175 mmol/L
1.76
1.22– 2.53
0.002
Model C-index ¼ 0.845. Of the 7917 STEMI patients included in the model, 1944 were non-reperfused with either p-PCI or fibrinolysis. STEMI, ST-segment elevation myocardial infarction; MI, myocardial infarction; p-PCI, primary percutaneous coronary intervention; CABG, coronary artery bypass graft; LBBB, left bundle branch block; SD, standard deviation. a Prior stroke and/or prior transient ischemic attack. b SDs for heart rate and systolic blood pressure in the overall population are 17 b.p.m. and 25 mmHg.
Table 3
30-day mortality was still higher for patients with no reperfusion (adjusted OR 1.84, 95% CI 1.30–2.62, P ¼ 0.001; referent, reperfusion by p-PCI), but not for patients with reperfusion by fibrinolysis (adjusted OR 1.48, 95% CI 0.96 –2.28, P ¼ 0.07; referent, reperfusion by p-PCI) (Table 4).
Discussion The ISACS-TC registry offered an opportunity to evaluate the individual-level relationship between the use of reperfusion therapy, clinical profile, and mortality in a contemporary population of STEMI patients in Eastern Europe. We demonstrated that a substantial number of patients are still not offered any reperfusion therapy in these countries with economy in transition. Our key insight was that the individual-level factors, such as time from symptoms onset to admission .12 h, age, and congestive heart failure at presentation, were significantly associated with lack of reperfusion therapy among the eligible population. Lack of reperfusion was associated with higher adjusted 30-day mortality. We also observed that hospital-level factors, such as the presence of catheterization services at the first hospital admission, were not different among treatment groups (P ¼ 0.31).
Secondary and tertiary hospitals in Eastern Europe The East of Europe is the most diverse, heterogeneous, and complex transnational cooperation area in Europe, comprising a broad mixture of countries. The emergence of new countries and with it the establishment of new frontiers has changed the patterns of political, economic, social, and cultural relationships. The area has been undergoing a fundamental change in healthcare system patterns following the 1990s. While some regions, especially the capital cities, are adapting well to the new healthcare challenges implementing p-PCI as first-choice treatment for STEMI, others regions are still widely using fibrinolysis. Nevertheless, a substantial number of patients are still not offered any reperfusion therapy.5 Our analysis of STEMI patients presenting to hospitals in Eastern Europe revealed that the number of patients transferred from secondary to tertiary hospitals failed to have a negative impact on the timely delivery of reperfusion therapy (within 12 h from symptom onset). Despite many patients arriving at p-PCI centres within the allocated time
Medication use at admission by treatment group (n 5 7917) p-PCI (n 5 4941)
Fibrinolysis (n 5 1032)
No reperfusion (n 5 1944)
P-valuea
Aspirin
4872 (99.4)
999 (97.3)
1756 (91.6)
,0.001
Clopidogrel Unfractioned heparin
4782 (97.9) 3211 (66.2)
871 (84.6) 580 (57.9)
1449 (75.8) 702 (37.7)
,0.001 ,0.001
...............................................................................................................................................................................
LMWH
1880 (39.0)
488 (49.4)
1005 (53.6)
,0.001
Beta blockers ACE inhibitors
3661 (74.9) 3913 (80.0)
873 (84.9) 847 (82.2)
1370 (71.6) 1379 (71.9)
,0.001 ,0.001
Data are numbers (percentages). p-PCI, primary percutaneous coronary intervention; LMWH, low-molecular-weight heparins; ACE, angiotensin-converting enzyme. a Patient groups were compared by Pearson’s x 2 test.
49
Reperfusion therapy for STEMI
period, often other factors delay hospital admission and subsequently result in no reperfusion therapy being given.
Age and lack of reperfusion therapy use Among patients who were timely admitted to hospital, increasing age was the strongest factor independently associated with lack
of reperfusion use. Similar to prior studies, we found that female sex, signs of heart failure on presentation, prior revascularization with CABG, and presence of atherosclerotic comorbidities, such as prior cerebrovascular events and prior MI, were highly associated with lack of reperfusion.6,7 Patient age is associated with an increased risk of complications and poor prognosis.8,9 Additionally, the presence of comorbidities on admission with STEMI may adversely affect prognosis. 10,11 Comorbidity increases by 50% in ages up to 64 years, and by 80% in people of ages 80 and older.12 Although the elderly might benefit from reperfusion therapy during STEMI, the eldest and most frail patients are excluded from reperfusion strategies, even when they are eligible.13 Decision-making in clinical practice among patients with advanced age deserves more thought and clarification.
Prior revascularization and lack of reperfusion therapy use
Figure 3 Kaplan – Meier estimates of 30-day mortality among the three treatment groups.
Table 4
Interestingly, prior revascularization with CABG was a factor associated with lack of reperfusion therapy. Patients’ and interventional cardiologists’ safety concerns regarding performing p-PCI without surgical back-up may explain these data. The guidelines would require that the nearest possible cardiac surgical centre that enters
Independent predictors of 30-day mortality OR
95% CI
P-value
............................................................................................................................................................................... Treatment strategy p-PCI
1 (Reference)
Fibrinolysis
1.48
0.96–2.28
0.07
No reperfusion
1.84
1.30–2.62
0.001
............................................................................................................................................................................... Female sex
1.18
0.88–1.56
0.25
Age (years) Diabetes
1.03 1.18
1.02–1.05 0.87–1.59
,0.001 0.28
Hypertension
0.70
0.53–0.94
0.02
Hypercholesterolaemia Current smoking
0.36 0.76
0.26–0.51 0.54–1.06
,0.001 0.11
Prior angina pectoris
0.63
0.42–0.95
0.03
Prior MI Prior PCI
1.10 1.51
0.75–1.61 1.03–2.21
0.59 0.03
Prior CABG
0.96
0.36–2.57
0.94
History of heart failure Prior cerebrovascular eventsa
0.59 1.70
0.33–1.06 1.09–2.65
0.08 0.01
Prior peripheral artery disease
1.84
0.97–3.51
0.06
Time to admission .12 h Killip class .1
1.15 6.11
0.83–1.61 4.59–8.12
0.38 ,0.001
Anterior STEMI and/or LBBB
1.40
1.04–1.87
0.02
Systolic blood pressure (1SD incrementb) Heart rate (1SD incrementb)
0.67 1.29
0.58–0.78 1.08–1.53
,0.001 0.004
Serum creatinine ≥175 mmol/L
1.98
1.30–3.01
0.001
Model C-index ¼ 0.857. Of the 7917 STEMI patients included in the model, 627 died. STEMI, ST-segment elevation myocardial infarction; MI, myocardial infarction; p-PCI, primary percutaneous coronary intervention; CABG, coronary artery bypass graft; LBBB, left bundle branch block; SD, standard deviation. a Prior stroke and/or prior transient ischaemic attack. b SDs for heart rate and systolic blood pressure in the overall population are 17 b.p.m. and 25 mmHg.
50 into a transfer agreement is to be utilized, preferably within 30 min ambulance time.14 Careful consideration should therefore be given to any transfer agreement by the institutions, since these patients may represent a significant challenge to transport within the required time frame.
Other factors associated with lack of reperfusion therapy use Finally, we found that even after adjustment for differences in baseline characteristics, female sex, and signs of heart failure on presentation correlated with no reperfusion therapy. Recent data indicate that women are more likely to exceed in-hospital and pre-hospital time guidelines for p-PCI with consequent higher chance of missing the opportunity for reperfusion.15,16 One of the most concerning findings was that patients with the congestive heart failure and the highest risk of death from STEMI were the least likely to receive reperfusion therapy. These data parallel early observations published in 1998.17 Withholding reperfusion therapy from these patients is inappropriate.
Comparison with previous work Recent reports using population-level data showed that contemporary reperfusion strategies do not correlate with improvements in mortality. In-hospital mortality for STEMI patients in Poland varied between 4.4% for patients treated with p-PCI and 25.0% for patients treated with fibrinolysis. Paradoxically, 11.5% mortality was reported for patients receiving no reperfusion therapy.1 Yet Poland reports a remarkable number of patients treated with p-PCI (735 per 1 000 000 inhabitants) and a highly significant number of patients treated with fibrinolysis (132 per 1 000 000 inhabitants).1 These findings suggest that reperfusion therapy in the form of fibrinolysis may not improve outcomes for individual patients. If true, this would have large implications as many health systems are devoting enormous resources to increase rates of fibrinolysis. However, this conflicts with prior literature18 – 20 and is inconsistent with data presented within the current study, which noted consistent relationships between timely access to reperfusion therapy and mortality, whether p-PCI or fibrinolysis was performed. The key to understanding this apparent discrepancy is the misleading notion that population-level or aggregate relationships may represent individual-level relationships.
Take home message STEMI care in Eastern Europe is still hindered by the lack of available quality data.21 Our best estimates suggest that the proportion of STEMI patients who are now being treated with p-PCI rather than fibrinolytic therapy has approximately doubled. In addition, the growth of STEMI systems of care have increased the number of STEMI patients arriving at hospitals, patients who will likely have died in prior years.22 Nevertheless, a substantial number of patients are still not offered any reperfusion therapy, and this is associated with increased 30-day mortality. Time from symptoms onset to admission .12 h is the highest ranking among factors related to lack of reperfusion therapy.
E. Cenko et al.
Limitations Our results should be interpreted in light of some considerations. Hospital participation in ISACS-TC registry is voluntary, which may lead to only those with favourable statistics engaging. Participating hospitals were instructed to submit consecutive STEMI patient records. However, there were no specific measures to verify whether consecutive patients were actually submitted. Due to the non-homogeneity of centres enrolled (secondary versus tertiary hospitals), data may not be generalizable to hospital practices nationwide and therefore may not allow a direct comparison between countries.
Conclusions Quality improvement efforts in Eastern Europe should focus on minimizing delay to hospital admission among STEMI patients. This could be achieved by targeting a reduced time from symptom onset to seeking reperfusion treatment and by developing improved treatment options for late presenters who are at high risk of early mortality. Conflict of interest: none declared.
References 1. Kristensen SD, Laut KG, Fajadet J, Kaifoszova Z, Kala P, Di Mario C, Wijns W, Clemmensen P, Agladze V, Antoniades L, Alhabib KF, De Boer MJ, Claeys MJ, Deleanu D, Dudek D, Erglis A, Gilard M, Goktekin O, Guagliumi G, Gudnason T, Hansen KW, Huber K, James S, Janota T, Jennings S, Kajander O, Kanakakis J, Karamfiloff KK, Kedev S, Kornowski R, Ludman PF, Merkely B, Milicic D, Najafov R, Nicolini FA, Nocˇ M, Ostojic M, Pereira H, Radovanovic D, Sabate´ M, Sobhy M, Sokolov M, Studencan M, Terzic I, Wahler S, Widimsky P, European Association for Percutaneous Cardiovascular Interventions. Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries. Eur Heart J 2014;35:1957 –1970. 2. Bugiardini R, Badimon L, Manfrini O, on the behalf of the ISACS-TC Investigators. Rationale and design of the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) Project. Eur Heart J Suppl 2014;16:A1 –A6. 3. Bugiardini R, Dorobantu M, Vasiljevic Z, Kedev S, Knezˇevic´ B, Milicˇic´ D, Calmac L, Trninic D, Daullxhiu I, Cenko E, Ricci B, Puddu PE, Manfrini O, Koller A, Badimon L, ISACS-TC Investigators. Unfractionated heparin-clopidogrel combination in ST-elevation myocardial infarction not receiving reperfusion therapy. Atherosclerosis 2015;241:151–156. 4. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, Thygesen K, Alpert JS, White HD, Jaffe AS, Katus HA, Apple FS, Lindahl B, Morrow DA, Chaitman BA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche´ P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, LopezSendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S, ESC Committee for Practice Guidelines (CPG). Third universal definition of myocardial infarction. Eur Heart J 2012;33:2551 –2567. 5. Bugiardini R, Manfrini O, Stakic MM, Cenko E, Boytsov S, Merkely B, Becker D, Dilic M, Vasiljevic Z, Koller A, Badimon L. Exploring in-hospital death from myocardial infarction in Eastern Europe: from the International Registry of Acute Coronary Syndromes in Transitional Countries (ISACS-TC); on the Behalf of the Working Group on Coronary Pathophysiology & Microcirculation of the European Society of Cardiology. Curr Vasc Pharmacol 2014;12:903 –909. 6. Eagle KA, Goodman SG, Avezum A, Budaj A, Sullivan CM, Lopez-Sendon J. Practice variation and missed opportunities for reperfusion in ST-segment-elevation myocardial infarction: findings from the Global Registry of Acute Coronary Events (GRACE). Lancet 2002;359:373 –377. 7. Eagle KA, Nallamothu BK, Mehta RH, Granger CB, Steg PG, Van de Werf F, Lo´pez-Sendo´n J, Goodman SG, Quill A, Fox KA, Global Registry of Acute Coronary Events (GRACE) Investigators. Trends in acute reperfusion therapy for
51
Reperfusion therapy for STEMI
8.
9.
10.
11.
12. 13.
14.
ST-segment elevation myocardial infarction from 1999 to 2006: we are getting better but we have got a long way to go. Eur Heart J 2008;29:609 –617. Eagle KA, Lim MJ, Dabbous OH, Pieper KS, Goldberg RJ, Van de Werf F, Goodman SG, Granger CB, Steg PG, Gore JM, Budaj A, Avezum A, Flather MD, Fox KA, GRACE Investigators. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA 2004;291:2727 –2733. Manfrini O, Dorobantu M, Vasiljevic Z, Kedev S, Knezevic B, Milicic D, Dilic M, Trninic D, Daullxhiu I, Gustiene O, Ricci B, Martelli I, Cenko E, Koller A, Badimon L, Bugiardini R, on the behalf of the Working Group on Coronary Pathophysiology & Microcirculation of the European Society of Cardiology. Acute coronary syndrome in octogenarian patients: results from the international registry of acute coronary syndromes in transitional countries (ISACS-TC) registry. Eur Heart J Suppl 2014;16:A87 –A94. McManus DD, Nguyen HL, Saczynski JS, Tisminetzky M, Bourell P, Goldberg RJ. Multiple cardiovascular comorbidities and acute myocardial infarction: temporal trends (1990– 2007) and impact on death rates at 30 days and 1 year. Clin Epidemiol 2012;4:115 –123. Schmidt M, Jacobsen JB, Lash TL, Bøtker HE, Sørensen HT. 25 year trends in first time hospitalisation for acute myocardial infarction, subsequent short and long term mortality, and the prognostic impact of sex and comorbidity: a Danish nationwide cohort study. BMJ 2012;344:e356. Fortin M, Bravo G, Hudon C, Vanasse A, Lapointe L. Prevalence of multimorbidity among adults seen in family practice. Ann Fam Med 2005;3:223 –228. Bugiardini R, Eskola M, Huhtala H, Niemela¨ K, Karhunen P, Miglio R, Manfrini O, Pizzi C, Nikus K. Coronary revascularisation in stable patients after an acute coronary syndrome: a propensity analysis of early invasive versus conservative management in a register-based cohort study. BMJ Open 2013;3. doi:10.1136/ bmjopen-2013-002559. Steg PG, James SK, Atar D, Badano LP, Blo¨mstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van‘t Hof A, Widimsky P, Zahger D. Task Force on the management of ST-segment elevation acute myocardial infarction of the
15.
16.
17.
18.
19.
20.
21.
22.
European Society of Cardiology (ESC). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569 –2619. Vasiljevic Z, Krljanac G, Davidovic G, Panic G, Radovanovic S, Mickovski N, Srbljak N, Markovic-Nikolic N, Curic-Petkovic S, Panic M, Cenko E, Manfrini O, Martelli I, Koller A, Badimon L, Bugiardini R. Gender differences in case fatality rates of acute myocardial infarction in Serbia. Eur Heart J Suppl 2014;16:A48 –A55. D’Onofrio G, Safdar B, Lichtman JH, Strait KM, Dreyer RP, Geda M, Spertus JA, Krumholz HM. differences in reperfusion in young patients with ST-segmentelevation myocardial infarction: results from the VIRGO study. Circulation 2015; 131:1324 –1332. Barron HV, Bowlby LJ, Breen T, Rogers WJ, Canto JG, Zhang Y, Tiefenbrunn AJ, Weaver WD. Use of reperfusion therapy for acute myocardial infarction in the United States: data from the National Registry of Myocardial Infarction 2. Circulation 1998;97:1150 –1156. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994;343:311 – 322. Morrison LJ, Verbeek PR, McDonald AC, Sawadsky BV, Cook DJ. Mortality and prehospital thrombolysis for acute myocardial infarction: a meta-analysis. JAMA 2000; 283:2686 –2692. Gale CP, Allan V, Cattle BA, Hall AS, West RM, Timmis A, Gray HH, Deanfield J, Fox KA, Feltbower R. Trends in hospital treatments, including revascularisation, following acute myocardial infarction, 2003 – 2010: a multilevel and relative survival analysis for the National Institute for Cardiovascular Outcomes Research (NICOR). Heart 2014;100:582 – 589. Smith FG, Brogan RA, Alabas O, Laut KG, Quinn T, Bugiardini R, Gale CP. Comparative care and outcomes for acute coronary syndromes in Central and Eastern European Transitional countries: a review of the literature. Eur Heart J Acute Cardiovasc Care 2014; doi:10.1177/2048872614551545. Tatu-Chitoiu G, Cinteza M, Dorobantu M, Udeanu M, Manfrini O, Pizzi C, Vintila M, Ionescu DD, Craiu E, Burghina D, Bugiardini R. In-hospital case fatality rates for acute myocardial infarction in Romania. CMAJ 2009;180:1207 –1213.
