The Portuguese Registry of Acute Coronary Syndromes (PRoACS) is a nationwide database that prospectively enrolled patients with acute coronary syndrome (ACS) from 44 Portuguese centers, beginning in October 2010. Patients were deemed eligible for inclusion if they were >18 years old, presented with angina at rest in the 48 hours prior to hospital admission and had an electrocardiogram (ECG) suggestive of ischemia (i.e. ST-segment deviation or T-wave inversion) and/or troponin or creatinine kinase myocardial band (CK-MB) elevation above the upper reference limit. Patients with atypical presentation (i.e. dyspnea or other) were also included if there was a troponin/CK-MB rise and fall consistent with MI. Patients with type 2, 4 or 5 MI according to the 2007 definition of MI were not included in the registry. Investigators from each center included data on previous medical history, clinical presentation, medication, ACS type, in-hospital treatment, and in-hospital and one-year outcomes in the overall dataset at an individual patient level.

In the present study, we included patients enrolled in the PRoACS between October 2010 and December 2019 who presented with CS and underwent PCI (Figure 1).

Figure 1.

Diagram of the patient population selection process. ACS: acute coronary syndrome; GPIs: glycoprotein IIb/IIIa inhibitors; MI: myocardial infarction; PCI: percutaneous coronary intervention; PRoACS: Portuguese Registry of Acute Coronary Syndromes.

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The final cohort was divided into two groups based on GPI therapy: patients who received adjunctive GPI therapy (GPI group) and those who did not (non-GPI group). The two groups were compared for baseline characteristics, treatment strategies and in-hospital outcomes. The primary endpoint was in-hospital mortality. Secondary endpoints were successful PCI, in-hospital reinfarction and major bleeding. Because clinical guidelines have evolved in the last decade, we analyzed time trends in the use of GPIs and other antithrombotic therapies.

Cardiogenic shock was defined as hypotension (systolic blood pressure <90 mmHg for more than 30 min or the need for supportive measures to maintain systolic blood pressure of >90 mmHg) plus evidence of end-organ hypoperfusion. STEMI was defined as a persistent (i.e. >30 min duration) ST-segment elevation of >0.1 mV in at least two contiguous leads or de novo left bundle branch block plus a clinical picture compatible with an ACS; non-ST-segment elevation ACS (NST-ACS) was considered to be present in all other patients fulfilling the PRoACS inclusion criteria. Anemia was defined as admission hemoglobin <12 g/dl regardless of gender. Chronic kidney disease was defined as serum creatinine >2.0 mg/dl prior to the index admission, previous need for dialysis, or previous renal transplantation. Valvular heart disease was defined as severe valvular stenosis or regurgitation or previous valve replacement. A history of heart failure (HF) was defined as previously symptomatic HF or HF under medical treatment. Mechanical complications included free wall or interventricular septum rupture or acute mitral regurgitation due to papillary muscle involvement. Successful PCI was defined as residual stenosis <30% and post-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow. Reinfarction was defined as recurrence of angina of >20 min duration, ischemic ECG changes, and re-elevation of cardiac biomarkers. Aborted cardiac arrest was defined as a reverted cardiac arrest during hospitalization, regardless of the cause. Major bleeding was defined according to the Global Use of Strategies to Open Occluded Arteries (GUSTO) definition.

This retrospective study complies with the Declaration of Helsinki. Only data available from existing medical records were accessed, and data were reported only in aggregate format.

The statistical analyses were performed using IBM SPSS Statistics version 20 (IBM, Armonk, NY). Categorical variables are expressed as frequencies and percentages. Continuous variables are expressed as mean±standard deviation or median and interquartile range for variables with and without a normal distribution, respectively. Comparisons between categorical variables were performed using the chi-square test and comparisons between continuous variables were performed using the Student's t test or the Wilcoxon test, according to normality of distribution. Tendencies for the use of drugs over the years was assessed using the chi-square test for trend. Logistic regression modeling was used to calculate adjusted odds ratios. Statistical significance was accepted for p-values <0.05.

Between October 2010 and December 2019, a total of 27 578 patients were included in the PRoACS and screened for enrollment. Of these, 566 patients had an MI complicated by CS, of whom 382 underwent PCI. Data regarding GPI therapy were missing for 25 patients, who were excluded from the analysis. Of the 357 patients enrolled, 107 received a GPI and 250 did not (Figure 1).

The main baseline characteristics are summarized in Table 1. Patients treated with GPIs were younger (64±13 vs. 69±13 years, p=0.001) than patients not receiving GPI but had a similar gender distribution. The groups were comparable regarding cardiovascular risk factors and comorbidities. Patients in the GPI group more often presented with STEMI (95% vs. 83%, p=0.002) and single-vessel disease (43% vs. 31%, p=0.044). They were also more likely to receive aspirin (97% vs. 89%, p=0.01) and clopidogrel (83% vs. 72%, p=0.028) than those in the non-GPI group. Patients receiving GPIs presented with an overall more severe clinical picture, indicated by a more frequent need for inotropic support (81% vs. 61%, p<0.001), levosimendan (8% vs. 2%, p=0.018), intra-aortic balloon pump (IABP) (20% vs. 8%, p=0.003) and temporary pacemaker (25% vs. 12%, p=0.002). Also, aborted sudden cardiac death was more frequent in the GPI group (37.4% vs. 24.0%, p=0.010). Table 2 shows in-hospital treatment details. In the GPI group, the most commonly used drug was eptifibatide (45%), followed by abciximab (41%) and tirofiban (14%). In 80% of cases, GPIs were used as an adjunctive during PCI and in 20% as a bailout strategy. Although the prevalence of GPI use decreased over the years in the PRoACS population (from 19.1% in 2011 to 7.9% in 2019, p<0.001), in acute ischemic CS this tendency was not noted (p=0.158) (Figure 2). There was a trend for increased use of ticagrelor (from 0% in 2011 to 91.7% in 2019, p<0.001) and decreased use of clopidogrel (from 94.6% in 2011 to 16.7% in 2019, p<0.001) over the years.

Figure 2.

Prevalence of use of glycoprotein IIb-IIIa inhibitors in acute ischemic cardiogenic shock, 2011–2019 (p=0.158).

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Overall in-hospital mortality was 34% (120 patients). Unadjusted in-hospital mortality was similar in the GPI and non-GPI groups (35.5% vs. 32.8%; odds ratio [OR] 1.13, 95% confidence interval [CI] 0.70–1.82, p=0.619) (Table 3). In the multivariate model, GPI use was still not associated with the outcome (OR 1.80, 95% CI 0.96–3.37, p=0.068). Only age, the use of inotropes and IABP were predictors of outcome (Table 3).

In-hospital outcomes are summarized in Table 4. More than 90% of patients in both groups had a successful PCI and GPI therapy had no impact on the angiographic result (OR 1.59; 95% CI 0.62–4.06, p=0.332 for successful PCI). Reinfarction (1.9% vs. 2.4%; OR 0.77, 95% CI 0.15–3.90, p=1.00) and major bleeding (OR 1.68, 95% CI 0.75–3.74, p=0.204) during hospitalization were also similar between groups.

One of the main limitations of our study is its observational nature, which inherently leads to selection bias. In the PRoACSs only 2% of the included patients had CS. We believe that selection bias may, to some extent, explain the lower-than-expected rate of CS. Patients who had a fatal outcome before admission to the coronary care unit would probably not have been included in the ProACS, while patients admitted to a general intensive care unit for other reasons (e.g. mechanical ventilation) would also probably be missing from the PRoACS. In fact, the GPI group had more need for hemodynamic support and higher rates of aborted cardiac death, which leads us to believe that GPIs were more likely to be administered in the setting of more severe illness. Mortality could therefore incorrectly appear to be higher in this group, preventing us from finding a potential benefit of GPI therapy. Also, to increase the sample size we had to include all PRoACS patients enrolled over the nine-year period of the registry, meaning that some of the patients were managed according to recommendation that are now outdated, in a clinical scenario that does not mirror current clinical practice. One consequence of this is that the use of novel P2Y12 inhibitors was low. Moreover, data on cardiac arrest prior to admission and other markers of shock such as serum lactate, urine output or kidney function were not available. We were also unable to collect data on physician-specified reasons for GPI use. Another important limitation is the small sample size, which may have hampered the detection of significant differences between groups.

Despite these limitations, our study provides valuable information about the use of GPI in a real-world population undergoing PCI for acute MI complicated by CS, for which very little data (and almost no randomized data) are available. In particular, it includes patients up until 2019, thus providing a clinical scenario that is closer to current practice than that of older studies.