Clinical profile of patients with no-reperfusion therapy in Bosnia and Herzegovina and Serbia

Abstract

Introduction

Reperfusion strategies with primary percutaneous coronary intervention (PCI) and fibrinolytic drugs are the most effective therapies in patients with ST-elevation myocardial infarction (STEMI) who present within 12 h from symptoms onset.^1–3 The preferred strategy is primary PCI, which produces greater benefits than fibrinolysis.³ Unfortunately, many patients present to hospitals that do not have PCI capability both in Europe and USA.^4,5 Furthermore, the guidelines do not state precisely the preferred reperfusion strategy in STEMI patients presenting after 2 h of symptom onset.^1,2 Fibrinolysis remains, therefore, the main reperfusion strategy for STEMI patients worldwide and especially in many countries with economy in transition, where a network of tertiary hospitals with catheterization facilities has yet to be fully developed.^6–10

The International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC; ClinicalTrials.gov, NCT01218776) is a registry representing all types of hospitals and all geographical regions in many areas of the Western Balkans.¹¹ We assessed the clinical profile of patients with STEMI who failed to receive reperfusion therapies by fibrinolysis or primary PCI. These data may play a role for future organization of national strategies of reperfusion in STEMI patients in Bosnia and Herzegovina and Serbia.

Methods

Study population

This is a cohort study of 633 patients who were discharged with a diagnosis of STEMI in 14 hospitals in Bosnia and Herzegovina (both Republic Sprska and Bosnia and Herzegovina Federation) and Serbia reporting data to the ISACS-TC registry from October 2012 to September 2013. There are seven academic tertiary cardiovascular centres [two from Bosnia and Herzegovina (one from Federation of Bosnia and Herzegovina and one from Republic Srpska) and five from Serbia] and seven secondary centres (five from Bosnia and Herzegovina–Republic Srpska and two from Serbia), all providing coronary care units. Patients were potentially eligible if they were admitted to hospital with a diagnosis of suspected STEMI. Patients were included in the study if they fulfilled a revised European Society of Cardiology/American College of Cardiology/American Heart Association (ESC/ACC/AHA) definition of MI (raised cardiac troponin concentration above the 10% coefficient of variation taken 12–24 h after the onset of symptoms or raised creatine kinase concentration above twice the upper limit of normal) accompanied by at least one of the following: (i) ischaemic symptoms; (ii) development of pathological Q-wave on the electrocardiogram (ECG); (iii) ECG changes indicative of ischaemia; (iv) delivery of primary coronary angioplasty; and (v) compatible post-mortem findings.¹²

Demographic and medical data were collected for all patients during hospitalization.

Data collection and primary endpoints

Collected data included patient demographics, medical history, clinical presentation, in-hospital therapy, therapeutic interventional procedures, and in-hospital mortality (Tables 1 and 2). Patients were categorized into three groups based on the treatment strategy: Group A: reperfusion by fibrinolysis, Group B: primary PCI, and Group C: patients who failed to receive any reperfusion therapy.

We evaluated four acute process-of-care measures at admission: (i) antiplatelet therapy (aspirin and/or clopidogrel), (ii) fibrinolytic therapy, (iii) primary PCI, and (iv) evidence-based secondary prevention therapies [beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins]. The primary endpoint was in-hospital mortality.

Statistical analyses

Descriptive statistics were used to illustrate the data. For categorical variables, frequencies and percentages were reported. Differences between groups were analysed using Pearson's χ² test (or Fisher's exact test for cells <5). For continuous variables, means and standard deviations (SDs) were used to present the data while analysis was performed using the two sample t-test. Medians were reported for exposition purposes, when necessary. For all analysis, statistical significance was defined as a value of P < 0.05. Statistical evaluation was performed using the STATA Version 11 statistical software system.

Results

Among 633 STEMI patients, 61 (9.6%) received fibrinolytic therapy (Group A), almost exclusively with streptokinase (79.3%), 402 (63.5%) underwent primary PCI (Group B), and 170 (26.9%) received no-reperfusion therapy (Group C). Mean age of the enrolled patients was comparable among Groups A and B (from 60.3 to 60.5 years). Conversely, patients in Group C were older (mean age 69.1 years) and nearly 45% were female. Differences in clinical characteristics are outlined in Table 1. There were significant differences in risk factors and clinical presentation among the three groups. Patients in Group C were more likely to had diabetes (46 vs. 20.7% in Group A and 25.1% in Group B, P < 0.001), and a significant cardiovascular history, with higher rates of prior stroke, prior angina, prior MI, prior coronary artery bypass graft, and peripheral artery disease. Accordingly, patients in Group C presented more often with Killip Class ≥2 (33.3 vs. 24.5% in Group A and 15.3% in Group B, P < 0.001) and were more likely to present after 12 h from symptoms onset (61.3 vs. 13.6% in Group A and 13.4% in Group B). Nevertheless, the proportion of patients with STEMI eligible for, but not receiving any form of, reperfusion therapy was remarkably high (38.7%). Table 2 illustrates medications administrated at admission and prescribed at discharge. More than 96% of patients in Groups A and B received recommended antiplatelet therapy. Patients in Group C received less medical therapy than those in Groups A and B. At discharge, the most commonly prescribed medication in Group C was aspirin (90.6%), followed by statins (86.2%), and clopidogrel (85.5%). Beta-blockers and ACE inhibitors were prescribed just in 78.6 and 76.7% of the patients, respectively.

In multivariable analyses (Table 3), factors significantly associated with no-reperfusion therapy were age >65 years ([odds ratio (OR): 6.54, 95% confidence interval (CI): 2.85–15.02, P < 0.001], diabetes, and prior MI; factors significantly associated with reperfusion were prior PCI and time from symptoms onset to admission within 12 h (OR: 0.13, 95% CI: 0.07–0.26, P < 0.001).

There was significantly reduced in-hospital mortality in patients who received reperfusion therapy with fibrinolysis or primary PCI (OR: 0.27, 95% CI: 0.09–0.76, P = 0.01).

Figure 1 shows the outcomes of the 159 latecomers. Five per cent of these patients received fibrinolysis, whereas 33.3% received PCI. Unadjusted in-hospital mortality was lower in the PCI group (7.6 vs. 12.5%).

Figure 1

In-hospital mortality in patients presenting after 12 h from symptoms onset according to treatment group. Among 633 STEMI patients, 159 (25.1%) were admitted after 12 h from symptoms onset. Of these, 8 (5%) were treated by fibrinolysis (Group A), 53 (33.3%) received primary PCI (Group B), and 98 (61.6%) failed to receive any reperfusion therapy. Unadjusted in-hospital mortality rates were lower in Group B (7.6 vs. 12.5% in Group A and 9.2% in Group C).

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Discussion

The current study compares the clinical profiles of STEMI patients admitted to hospitals in Bosnia and Herzegovina and Serbia with different patterns of therapies. We found that patients with no-reperfusion therapy (Group C) were prevalently older, had more frequently diabetes, prior MI, and presented more often after 12 h from symptoms onset.

Latecomers

Unfortunately, only two-third of patients presenting to hospitals were treated with mechanical reperfusion or received fibrinolytic drugs. These data are in keeping with previous observations.^13,14 Among 8305 patients with STEMI in the Acute Coronary Syndrome registry, 28.3% did not receive any form of reperfusion.¹⁵ Current guidelines do not recommend reperfusion treatment in patients with STEMI presenting >12 h after symptom onset.^1,2 Nevertheless, it is observed from recent studies a significant reduction in 12-month mortality in patients with STEMI presenting 12–72 h after symptom onset.^16,17 In our study, PCI was associated with significantly lower rates of in-hospital mortality in patients presenting after 12 h from symptom onset (median range 48 h) The trend observed towards a better clinical outcome in the invasive group should be interpreted with caution due to the limited number of patients and insufficient power for the assessment of clinical events.

One possible explanation for delay to hospital admission is underutilization of Emergency Medical Services (EMSs).^10,18 In fact, only 25.6.% of non-reperfused patients used EMSs. The inability to routinely align hospital capacity with patient demand for EMS results in widespread waste and inefficiency. Delay in activating EMSs by patients who are experiencing symptoms has been found to be the most important factor in failure to provide procedures and poor outcomes of patients.¹⁸ Another factor, that needs an urgent improvement, is the lack of a well-organized regional network of EMSs that inevitably leads to barriers in transport to the nearest hospital center and limited primary PCI access for STEMI patients.¹⁰

Elderly

In the setting of acute coronary syndromes, the ESC/ACC/AHA guidelines recommend that the elderly patient's candidacy for intervention is evaluated with similar standards to those used for younger patients.^1,2 Although some studies emphasize the risks of PCI as a function of age, PCI seems to be preferred to fibrinolysis as a reperfusion option for elderly patients who experienced STEMI.^19–22 Our study highlights the importance of primary PCI in elderly STEMI patients since advanced age was a predictor of no-reperfusion therapy (OR: 6.54, 95% CI: 2.85–15.0, P < 0.001), and no-reperfusion therapy was associated with in-hospital mortality (OR: 3.62, 95% CI: 1.88–7.02, P < 0.001).

Diabetes and prior MI

Previous observations suggest that both diabetes and prior MI are associated with higher risk for mortality and cardiovascular events.^23,24 Accordingly, diabetes and prior MI are independent predictors of death in the Thrombolysis In Myocardial Infarction risk score.²⁵ Despite this evidence, our findings demonstrate that physicians still disregard patients presenting with diabetes or prior MI, and especially those presenting with both.

The adjusted odds ratio of not receiving reperfusion therapy was significant for diabetes (OR: 1.93, 95% CI: 1.01–3.70, P = 0.047) and prior MI (OR: 2.79, 95% CI: 1.17–6.67, P = 0.021). People with both diabetes and prior MI were five times more likely not to receive reperfusion therapy than the remaining population (OR: 4.61, 95% CI: 1.91–10.9, P < 0.001). Mortality rates were 11.8% in diabetic patients, 8.1% with prior MI, and 17.7% in those with both these baseline characteristics. Improvement of myocardial perfusion is obviously a key issue to improve outcomes in these patients. Our data highlight the importance of aggressive strategies in this high-risk population.^1,2,22,26

Bosnia and Herzegovina vs. Serbia

Bosnia and Herzegovina and Serbia belong to the group of countries with economy in transition and have an increased incidence and mortality from ACS.²⁷ Time to reperfusion is of particular concern, because it influences short- and long-term outcomes.^3,13,14,28 These countries have often been viewed as especially vulnerable with respect to health-care access.²⁹ Most people live in rural areas, which may explain delayed access to health services, and low rates of reperfusion therapies within 6 h after symptom onset. Only 64.3% of patients from Bosnia and Herzegovina and 76.6% of patients from Serbia arrived on time for reperfusion therapy (either with fibrinolysis or mechanical reperfusion). The clinical approach to the occluded infarct-related artery late after MI remains variable and controversial, but current practice shows a strong trend in favour of PCI, which is based on the late open-artery hypothesis. Unfortunately, the number of patients treated with PCI after 12 h of the onset of symptoms was still disappointing, since just 33% of them received such procedure. These findings were most striking for Bosnia and Herzegovina, where a well-developed primary PCI network has yet to extend.^8,9

Limitations

This analyses is limited only to STEMI patients from Bosnia and Herzegovina and Serbia and reflects only a small proportion of STEMI patients in the ISACS-TC registry. Thus, confounding or unknown factors could have influenced the outcomes. Yet, observational studies provide complementary approaches and are more likely to reflect everyday practice in order to suggest intervention specifically directed to improve patient outcomes.³⁰

Conclusions

We found that although the majority of STEMI patients from Bosnia and Herzegovina and Serbia underwent primary PCI, the care of older patients and diabetics was characterized by limited use of reperfusion therapy ad worse outcomes. Differences in time delay from symptoms onset to hospital admission have strongly influenced the rates of primary PCI. Elderly and diabetics are socio-demographic groups that are more likely to underuse EMS. Our findings indicate that better EMS activation in these high-risk patients may potentially improve the treatment of STEMI in Bosnia and Herzegovina and Serbia.

Acknowledgements

We are grateful to Drs Marisa De Rosa and Rita Rielli (Dipartimento Sanità, CINECA, Bologna, Italy) for their precious collaboration and frequent assistance into the ISACS-TC registry data-house.

Conflict of interest: none declared.

References

Author notes