Revascularization in non-ST-segment elevation myocardial infarction (NSTEMI) relieves symptoms, reduces hospital stay and improves prognosis.1–3 However, the indications for and timing of revascularization depend on various factors, some inherent to the patient (such as age, gender and comorbidities) and others external, including the availability of resources. Consequently, although an invasive approach combined with optimal medical therapy is associated with improved survival at all ages,4 a non-invasive approach is more often adopted in older patients, in whom the presence of comorbidities is seen as a limitation to coronary angiography.1,5 With regard to gender differences, various studies have shown that women undergo coronary angiography less often than men,6 although the benefits are similar for both sexes.7 Data from the Global Registry of Acute Coronary Events (GRACE), the largest multinational registry of patients with acute coronary syndrome (ACS), show an inverse relation between the likelihood of a patient undergoing percutaneous coronary intervention (PCI) and the patient's risk.8 This demonstrates the complexity surrounding the factors that determine the best therapeutic approach to adopt; the decision whether to perform coronary angiography depends on available resources and the hospital protocols and, most importantly, individual clinical judgment.

The aim of this study was to assess the impact of a conservative strategy in NSTEMI during hospitalization and in the medium term.

A population of 3799 patients with NSTEMI was selected from the databases of the Portuguese Registry on Acute Coronary Syndromes (ProACS) and the Portuguese Society of Cardiology between 1 October 2010 and 1 October 2013. NSTEMI was defined as elevated cardiac biomarkers (troponin or the MB isoenzyme of creatine kinase [CK-MB]) with symptoms compatible with myocardial ischemia but without persistent ST-segment elevation (<30 min) on the admission 12-lead ECG. Patients for whom information was available on coronary angiography and/or PCI were included (n=3780). A conservative strategy was defined as absence of coronary angiography and an invasive strategy as coronary angiography during hospitalization, irrespective of whether this was followed by PCI. Coronary lesions were defined as non-significant with <50% stenosis, significant with ≥50% and <100% stenosis, and occluded with 100% stenosis. Treated vessels were defined using the ProACS criteria (residual stenosis <30% and TIMI 3 flow following angioplasty). The patients were divided into three groups: group 1, patients treated by a conservative strategy during hospitalization (n=623); group 2, patients who underwent coronary angiography without PCI (n=1229); and group 3, patients who underwent PCI (n=1928). The groups were compared in terms of clinical and procedural data and the following in-hospital complications: (1) reinfarction, defined in the ProACS as recurrence of chest pain suggestive of ischemia after resolution of the initial episode of pain, lasting >20 min and accompanied by electrocardiographic alterations and new elevation of cardiac biomarkers above previous levels (CK-MB twice the reference value or >50% higher than the previous value, or troponin I or T >20% above the previous value); (2) heart failure (HF); (3) mechanical complications, defined as rupture of the free wall or the ventricular septum or severe acute mitral regurgitation due to papillary muscle involvement; (4) new-onset paroxysmal or persistent atrial fibrillation (AF); (5) second-degree atrioventricular block (Mobitz 2) or higher; (6) sustained ventricular tachycardia (VT), defined as the presence during hospitalization of monomorphic or polymorphic VT lasting >30 s or associated with hemodynamic instability; (7) resuscitated cardiac arrest from any cause during hospitalization; (8) ischemic or hemorrhagic stroke; and (9) major bleeding, defined according to the GUSTO classification9 as intracerebral bleeding or bleeding with hemodynamic compromise requiring treatment or need for transfusion of red cell concentrates. Patients’ destination after discharge was recorded and they were followed for up to a year.

The primary endpoint was defined as in-hospital or one-year mortality from any cause. The secondary endpoint was defined as the presence of at least one of the following in-hospital complications: major bleeding or need for transfusion of red cell concentrates, need for invasive ventilation (specifying whether an endotracheal tube, laryngeal mask or tracheostomy was used), HF or reinfarction.

The decision-making process for revascularization in NSTEMI is complex, due to the heterogeneity of such patients in terms of risk and prognosis.2 Risk stratification is therefore recommended to identify patients at high short- and long-term risk of death or cardiovascular events, in order to opt for an early invasive strategy and optimal medical therapy.2,3 Immediate (<2 hours) invasive evaluation should be performed in patients with refractory angina, cardiogenic shock, or hemodynamic or electrical instability, and an early invasive strategy (<24 hours) should be adopted in patients with at least one high-risk criterion (Table 10). In patients with a GRACE risk score of <140 but with at least one secondary high-risk criterion (Table 10) an invasive evaluation should be performed preferably within 72 hours of admission. In other low-risk patients without recurrent symptoms, a non-invasive assessment of inducible ischemia should be performed before hospital discharge. However, meta-analyses of clinical trials10,11 have shown that an invasive strategy can be adopted as routine. The meta-analysis by Hoenig et al.10 of five trials – TACTICS-TIMI 18, ICTUS, RITA-3, FRISC-II and VINO – showed that an invasive strategy in unstable angina/NSTEMI results in a reduction of 33% in relative risk for the endpoints of refractory angina and rehospitalization at six to 12 months. While an invasive strategy is associated with a two-fold increase in the risk of periprocedural myocardial infarction (MI), there are significant 27% and 22% relative risk reductions in the rate of MI assessed at six to 12 months and three to five years, respectively. Fox et al.,11 in a meta-analysis of the FRISC-II, ICTUS and RITA-3 trials, showed that a routine versus selective invasive strategy in patients with NSTEMI reduces long-term rates of cardiovascular death or MI over a five-year period, and the largest effect is seen in high-risk patients. Age, diabetes, prior MI, ST-segment depression, hypertension, BMI <25 kg/m2 or ≥35 kg/m2, and treatment strategy were independent predictors of cardiovascular death or nonfatal MI over the follow-up period.11 Registry data1 show that a routine invasive strategy is associated with a reduction in the combined endpoint of death and MI, the difference being mainly due to higher mortality with a conservative approach.

Despite all this evidence, there is an inverse relation between patient risk and adoption of an invasive strategy,5,8 as also demonstrated in the study by Puymirat et al. based on the FAST-MI registry,1 in which patients treated by an invasive strategy were younger and had lower GRACE scores than those treated by a conservative approach.

The present study, covering several Portuguese centers, set out to analyze the extent of use and impact of a conservative strategy for NSTEMI in a real-world population based on a multicenter registry with uniform inclusion criteria.

The findings highlight the differences seen in other registries, notably older age, higher prevalence of females and of high-risk criteria (also seen in GRACE score categories) in patients treated by a conservative strategy, who are also less likely to be prescribed medication known to reduce mortality and morbidity in ACS patients,2 another example of the paradoxical relation between patient risk and treatment strategy.

A conservative strategy is an independent predictor of in-hospital and one-year mortality (the primary endpoint) and of in-hospital complications (the secondary endpoint), as in other studies.1,10,11 However, stratification by GRACE score category revealed no difference in in-hospital mortality between strategies in the low and intermediate risk categories, in contrast to published data.2,8 One possible explanation is the small number of deaths in these categories, making it difficult to detect real differences in the population from which the study sample was taken. One-year mortality was significantly higher in the intermediate and high risk categories, as were in-hospital complications.

These findings raise questions concerning the factors determining the decision not to adopt an invasive strategy, particularly the presence of non-cardiac comorbidities and the possible failure to make use of cardiovascular risk scores.

Of in-hospital complications, it should be noted that reinfarction was more common in the invasive strategy group (in contrast to the findings of Bauer et al.12), particularly in those undergoing PCI. The definitions used in our study of reinfarction – which does not specify the vessel in which the new event occurred – and of the PCI-treated vessel – which only considers immediate angiographic success, not procedural or clinical success13 – mean that the cause of reinfarction cannot be definitively established, and could have been related, for example, to incomplete revascularization.

Among the other predictors of in-hospital and one-year mortality and in-hospital complications, age14,15 is associated with a lower probability of an invasive strategy,16,17 which is important in view of the increasing prevalence of cardiovascular disease in aging populations.4,18

It is also worth noting the heterogeneity of patients who underwent coronary angiography without PCI, in 21.6% of whom no angiographically significant CAD was detected and 36.8% of whom were referred for CABG, meaning that 41.6% had significant CAD but did not undergo revascularization. Despite this heterogeneity, patients in this group had better outcomes than those treated conservatively, which highlights the importance of assessment of coronary anatomy when deciding on the therapeutic strategy to adopt.

In contrast to reports in the literature,2 a conservative strategy was not associated with longer hospital stay. Although the data do not indicate the reason for this, it may be because patients who underwent coronary angiography without PCI were less likely to be discharged home and had a higher rate of interhospital transfer, which may be due to a greater number of patients with indication for surgery. However, the study design does not allow a causal relation to be established.

The study has the limitations of all registries, since not all centers in Portugal are represented in the ProACS and those that are do not include all their patients. The limitations of the registry format also mean that the reasons for not adopting an invasive strategy are not specified, including patient preferences and contraindications. It also has the limitations inherent to observational studies, including the impossibility of proving causality in cases of correlation between parameters and the fact that treatment strategies were not randomized. The results should therefore be treated as merely indicative.

The present study, based on real-life clinical practice, shows that a conservative strategy in patients with NSTEMI is associated with higher in-hospital mortality, in-hospital complications and one-year and one-year mortality.

The authors have no conflicts of interest to declare.