Gordana Krljanac

Predicting 30-day major adverse cardiovascular events after primary percutaneous coronary intervention. The RISK-PCI score

BACKGROUND Identification of patients at risk for major adverse cardiovascular events (MACE) might help selecting candidates for aggressive treatment or early discharge after primary percutaneous coronary intervention (pPCI). METHODS The RISK-PCI is an observational trial of 2096 consecutive patients who underwent pPCI between 2006 and 2009, randomly allocated to derivation and validation sets with a set ratio of 80% to 20%. Thirty-day MACE comprising death, nonfatal reinfarction and stroke was the primary end point. Multivariable logistic regression was used to determine the independent predictors of outcome. A sum of weighted points for specific predictors was calculated to define the final score. RESULTS The RISK-PCI score comprised 12 independent predictors of 30-day MACE, with a graded 125-fold increase in the primary end point with increasing risk score from ≤ 1 to ≥ 15. The model showed good discrimination and calibration for the prediction of 30-day MACE (c-statistic 0.83, goodness-of-fit p = 0.72) and 30-day death (c-statistic 0.87, goodness-of-fit p = 0.56). Bootstrapping with 1000 resample confirmed the stability of the models performance. Patients were classified into risk classes, with the observed incidence of 30-day MACE of 1.9, 5.9, 13.3 and 39.4% in the low, intermediate, high and very high-risk classes, respectively. An 18-fold graded increase in the primary end point was observed between patients in a low risk class and those in a very high risk class. CONCLUSION We derived a novel risk model to predict 30-day MACE after pPCI, which might help clinician decide the most appropriate treatment in accordance with the patients risk profile.

Incidence, predictors, and 30-day outcomes of new-onset atrial fibrillation after primary percutaneous coronary intervention: insight into the RISK-PCI trial.

ObjectivesLimited data exist about the prognostic significance of new-onset atrial fibrillation (AF) after contemporary primary percutaneous coronary intervention (pPCI). The objective of this study was to identify the incidence and predictors of new-onset AF and associated adverse 30-day outcomes in AF patients who underwent pPCI. MethodsWe analyzed 2096 patients undergoing pPCI after pretreatment with 600 mg clopidogrel. Composite 30-day major adverse cardiovascular events were the primary end point. A logistic regression model was developed to identify risk factors for the occurrence of AF and prediction of its impact on 30-day outcomes. ResultsAF occurred in 6.2% of patients. Older age, Killip >1 heart failure at admission, systolic blood pressure of greater than 100 mmHg at admission, creatinine clearance greater than 60 ml/min, preprocedural infarction-related artery occlusion and postprocedural thrombolysis in myocardial infarction flow less than 3 were identified as independent predictors of the occurrence of AF. Rates of 30-day major adverse cardiovascular events [adjusted odds ratio (OR) 2.39, 95% confidence interval (CI): 1.47–3.87] and 30-day death (adjusted OR 2.67, 95% CI: 1.46–4.89) were higher in AF patients compared with patients without AF. A trend toward higher rate of ischemia-driven target vessel revascularization was observed in the AF group (adjusted OR 2.61, 95% CI: 0.82–8.39, P=0.10). ConclusionNew-onset AF after pPCI is associated with adverse 30-day outcomes. Accurate prediction of AF after pPCI might help deciding a more aggressive treatment approach aimed at preventing the adverse prognosis of these patients.

Usefulness of the RISK-PCI score to predict stent thrombosis in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a substudy of the RISK-PCI trial.

Stent thrombosis (ST) is an important cause of death after primary percutaneous coronary intervention (pPCI). This substudy aimed at evaluating the usefulness of the RISK-PCI score, originally developed for the prediction of 30-day major adverse cardiovascular events, to predict the occurrence of ST after pPCI. We analyzed 1972 consecutive patients who underwent pPCI with stent implantation between February 2007 and December 2009. Early ST (EST), late ST (LST), and cumulative 1-year ST (CST) were the predefined end points. Definite, probable, and possible ST were included. Models discrimination and calibration to predict ST was tested using receiver-operating characteristics curves and the goodness-of-fit (GoF) test. Sensitivity analyses and 1000-resample bootstrapping were used to evaluate the model’s performance. The rates of EST, LST, and CST were 4.6, 1.4, and 6.0 %, respectively. Compared with controls, the cumulative ST group was associated with much higher rates of adverse clinical outcomes at 30-day follow-up (adjusted odds ratio (OR) for death 6.45, adjusted OR for major bleeding 4.41) and at 12-month follow-up (adjusted OR for death 7.35, adjusted OR for major bleeding 4.56). Internal validation confirmed a reasonably good discrimination and calibration of the RISK-PCI score for the prediction of EST (area under the curve (AUC) 0.71, GoF 0.42), LST (AUC 0.69, GoF 0.36), and CST (AUC 0.70, GoF 0.22) after pPCI. ST after pPCI is associated with adverse 30-day and 1-year clinical outcomes. We conclude that the risk of ST could be accurately assessed using the RISK-PCI score, which might help in deciding upon measures aimed at preventing adverse prognosis.

Efficacy and safety of tirofiban-supported primary percutaneous coronary intervention in patients pretreated with 600 mg clopidogrel: results of propensity analysis using the Clinical Center of Serbia STEMI Register

Background: Studies with platelet glycoprotein IIb/IIIa receptor inhibitors (GPIs) showed conflicting results in primary percutaneous coronary intervention (PPCI) patients who were pretreated with 600 mg clopidogrel. We sought to investigate the short- and long-term efficacy and safety of the periprocedural administration of tirofiban in a largest Serbian PPCI centre. Methods: We analysed 2995 consecutive PPCI patients enrolled in the Clinical Center of Serbia STEMI Register, between February 2007 and March 2012. All patients were pretreated with 600 mg clopidogrel and 300 mg aspirin. Major adverse cardiovascular events, comprising all-cause death, nonfatal infarction, nonfatal stroke, and ischaemia-driven target vessel revascularization, was the primary efficacy end point. TIMI major bleeding was the key safety end point. Results: Analyses drawn from the propensity-matched sample showed improved primary efficacy end point in the tirofiban group at 30-day (OR 0.72, 95% CI 0.53–0.97) and at 1-year (OR 0.74, 95% CI 0.57–0.96) follow up. Moreover, tirofiban group had a significantly lower 30-day all-cause mortality (secondary end point; OR 0.63, 95% CI 0.40–0.90), compared with patients who were not administered tirofiban. At 1 year, a trend towards a lower all-cause mortality was observed in the tirofiban group (OR 0.74, 95% CI 0.53–1.04). No differences were found with respect to the TIMI major bleeding during the follow-up period. Conclusions: Tirofiban administered with PPCI, following 600 mg clopidogrel pretreatment, improved primary efficacy outcome at 30 days and at 1 year follow up without an increase in major bleeding.

Impact of high post-loading platelet aggregation on 30-day clinical outcomes after primary percutaneous coronary intervention. The antiplatelet regimen tailoring after primary PCI (ART-PCI) trial.

BACKGROUND Patients with high post-loading platelet aggregation (PPA) are at increased risk of stent thrombosis and death after primary percutaneous coronary intervention (pPCI). The objective of the present trial was to examine whether high PPA is associated with adverse clinical outcomes in pPCI patients whose therapy was modified in accordance with PPA. METHODS We analyzed 961 consecutive pPCI patients who underwent pPCI between February 2008 and June 2011. High PPA was defined as PPA >50%, 24h after the loading dose. Patients with high PPA were treated with aspirin 300 mg, clopidogrel 150 mg or ticlopidine 500 mg for 30 days. The co-primary efficacy and safety end points at 30 days were major adverse cardiovascular events (MACE) and major bleeding. RESULTS We detected high PPA to clopidogrel and aspirin in 44.4% and 16.5% of patients, respectively. The rates of 30-day MACE (adjusted OR 1.76, 95% CI 1.05-2.97), definite subacute stent thrombosis (DSST, adjusted OR 2.15, 95% CI 1.09-4.22) and nonfatal infarction (adjusted OR 3.99, 95% CI 1.57-10.13) were higher in patients with high PPA to clopidogrel compared with responders. High PPA to aspirin was not associated with an adverse 30-day clinical outcome. Compared with high PPA patients who were not tailored, a significantly better outcome with respect to the primary end point was observed in the tailored group (OR 0.42, 95% CI 0.19-0.93). CONCLUSION High PPA to clopidogrel was an independent predictor of 30-day adverse events after pPCI. Among high PPA patients, tailoring was associated with an improved primary outcome.

Sex Differences in Outcomes After STEMI: Effect Modification by Treatment Strategy and Age

Importance Previous works have shown that women hospitalized with ST-segment elevation myocardial infarction (STEMI) have higher short-term mortality rates than men. However, it is unclear if these differences persist among patients undergoing contemporary primary percutaneous coronary intervention (PCI). Objective To investigate whether the risk of 30-day mortality after STEMI is higher in women than men and, if so, to assess the role of age, medications, and primary PCI in this excess of risk. Design, Setting, and Participants From January 2010 to January 2016, a total of 8834 patients were hospitalized and received medical treatment for STEMI in 41 hospitals referring data to the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC) registry (NCT01218776). Exposures Demographics, baseline characteristics, clinical profile, and pharmacological treatment within 24 hours and primary PCI. Main Outcomes and Measures Adjusted 30-day mortality rates estimated using inverse probability of treatment weighted (IPTW) logistic regression models. Results There were 2657 women with a mean (SD) age of 66.1 (11.6) years and 6177 men with a mean (SD) age of 59.9 (11.7) years included in the study. Thirty-day mortality was significantly higher for women than for men (11.6% vs 6.0%, P < .001). The gap in sex-specific mortality narrowed if restricting the analysis to men and women undergoing primary PCI (7.1% vs 3.3%, P < .001). After multivariable adjustment for comorbidities and treatment covariates, women under 60 had higher early mortality risk than men of the same age category (OR, 1.88; 95% CI, 1.04-3.26; P = .02). The risk in the subgroups aged 60 to 74 years and over 75 years was not significantly different between sexes (OR, 1.28; 95% CI, 0.88-1.88; P = .19 and OR, 1.17; 95% CI, 0.80-1.73; P = .40; respectively). After IPTW adjustment for baseline clinical covariates, the relationship among sex, age category, and 30-day mortality was similar (OR, 1.56 [95% CI, 1.05-2.3]; OR, 1.49 [95% CI, 1.15-1.92]; and OR, 1.21 [95% CI, 0.93-1.57]; respectively). Conclusions and Relevance Younger age was associated with higher 30-day mortality rates in women with STEMI even after adjustment for medications, primary PCI, and other coexisting comorbidities. This difference declines after age 60 and is no longer observed in oldest women.

The Timing of Infarction Pain in Patients with Acute Myocardial Infarction after Previous Revascularization

Circadian variation of onset of acute myocardial infarction (AMI) has been noted in many studies, but there are no data about subgroups of patients with previous coronary artery bypass grafting (CABG). Because of abnormalities in the circadian rhythm of autonomic tone after surgery, it was very interesting to analyze the circadian patterns in the onset of symptoms of AMI in various subgroups of 1784 patients with previous CABG. As in the other studies, a peak occurred in the morning hours with 26.3% of the patients, but there was a second nearly equal, but higher, peak (26.4%) in the evening hours. The subgroups with specific clinical characteristics exhibited different patterns that determined these peaks in all populations. In patients older than 70 years of age, in both sexes, in smokers, diabetics, in patients with hypertension, in those undergoing beta-blocker therapy, and in patients without previous angina, two nearly equal peaks were observed, with higher evening peaks, except in those patients with hypertension and without angina. Only one peak in the evening hours was observed in a subgroup of patients with previous congestive heart failure (CHF) and non-STEMI. The subgroup of patients with previous angina and previous AMI exhibited no discernible peaks. The distribution of time of onset within the four intervals was not uniform, and the difference was statistically significant only for patients undergoing beta-blocker therapy at time of onset (p = 0.0013), nonsmokers (p = 0.0283), and patients with non-STEMI (p = 0.0412). It is well known that patients with AMI have a dominant morning peak of circadian variation of onset. However, analyzing a different subgroup of patients with AMI after previous CABG, it was found that some subgroups had two peaks of onset, but a higher evening peak (patients older than 70 years of age, smokers, diabetics, and a group of patients who were taking beta-blocker therapy). This subgroup of patients, together with the subgroups of patients with a dominant evening peak (patients with CHF and those with non-STEMI) and with patients with no peak (patients with previous angina and previous AMI), probably appear to modify characteristic circadian variation of infarction onset, expressing a higher evening peak, respectively to the previous CABG, with adverse consequences for central nervous system functioning.

Coronary care unit and primary percutaneous coronary intervention networks improve the standard of care: reperfusion therapy in ST elevation myocardial infarction in Serbia from 2002 to 2008.

To the Editor The importance of networks to successful treatment of patients with acute myocardial infarction with ST elevation (STEMI) depends on many factors. The main prognostic factor for this group of patients is time to reperfusion therapy. As a country in transition, in Serbia, the ability to administer reperfusion therapy is still low, even though it has been increasing in recent years [1–10]. We used the data of the Hospital National Registry for Acute Coronary Syndrome (ACS) of Serbia (HORACS) to analyze in-hospital mortality rate in STEMI patients with respect to treatment. Patients were grouped in three categories: first, those with thrombolytic therapy (TL); second, those with primary percutaneous coronary intervention (pPCI); and third, those without reperfusion therapy. We analyzed mortality rates in relation to patients’ clinical characteristics at presentation, age, sex, Killip class and time interval from symptom onset to hospital admission.

In-Hospital and Long-Term Prognosis after Myocardial Infarction in Patients with Prior Coronary Artery Bypass Surgery; 19-Year Experience

To present a 19-year experience of the prognosis of patients with acute myocardial infarction (AMI) and prior coronary artery bypass surgery (CABS), 748 patients with AMI after prior CABS (postbypass group) and a control group of 1080 patients with AMI, but without prior CABS, were analyzed. All indexes of infarct size were lower in the postbypass group. There was more ventricular fibrillation in the postbypass group. In-hospital mortality was similar (p = 0.3675). In the follow-up period, postbypass patients had more heart failure, recurrent CABS, reinfarction, and unstable angina than did control patients. Cumulative survival was better in the control group than in the postbypass group (p = 0.0403). Multiple logistic regression model showed that previous angina (p = 0.0005), diabetes (p = 0.0058), and age (p = 0.0102) were independent predictor factors for survival. Use of digitalis and diuretics, together with previous angina, also influenced survival (p = 0.0092), as well as male gender, older patients, and diabetes together (p = 0.0420). Patients with AMI after prior CABS had smaller infarct, but more reinfarction, reoperation, heart failure, and angina. Previous angina, diabetes, and age, independently, as well as use of digitalis and diuretics together with angina, and male gender, older patients, and diabetes together, influenced a worse survival rate in these patients.

Heart failure with improved ejection fraction: Is a newcomer in the family important?:

In the 2013 American College of Cardiology/American Heart Association guidelines, an emerging heart failure (HF) phenotype was introduced, named heart failure with preserved ejection fraction (HFpEF) improved. It is defined as improvement in left ventricular ejection fraction (LVEF) to> 40% in patients with previous heart failure with reduced ejection fraction (HFrEF). Later, similar entities with different names were described: heart failure with improved ejection fraction (HFIEF), heart failure with recovered ejection fraction (HFrecEF), and better HFEF. Although not consistent in cut-off LVEF values/degree of improvement, these groups of patients are clearly distinct from those with persistent HFrEF or HFpEF. In the current issue of the European Journal of Preventive Cardiology, Jorgensen and colleagues discuss the new HF entity, HFIEF. They should be acknowledged both for getting into the focus this important clinical topic and for using meta-analysis to get meaningful insights regarding a large number of the patients. They carried out a systematic review and meta-analysis on 24 observational studies in a group of 2663 patients with HFIEF (defined as 5% LVEF improvement) compared with 8355 patients with persistently reduced ejection fraction (HFpREF). LVEF was assessed at baseline and reassessed after 19 19 months, with follow-up of 39 12 months. The primary endpoints were all-cause mortality and appropriate implantable cardioverter defibrillator (ICD) discharge. Among HFIEF patients, LVEF improved by an average 16.3%. Meta-analysis covered studies with heterogeneous aetiology of HF, various therapeutic approaches and different baseline LVEF cut-off values. The results revealed a significantly lower risk of all-cause mortality in 25% of patients with HFIEF and a significantly lower risk of appropriate Implantable cardioverter defibrillator (ICD) activations, in comparison to HFpREF patients. The largest therapeutic benefit was demonstrated in patients who had cardiac resynchronization therapy-defibrillator (CRT-D) implantation. The variables associated with higher probability of HFIEF included: female sex, higher systolic blood pressure, absence of diabetes, nonischaemic origin for HF and lower left ventricular end-diastolic diameter LVEDD). Every meta-analysis has inherent methodological drawbacks, which may obscure the validity of the results and this study is not the exception to this rule. The meta-analysis of Jorgensen and colleagues was based on observational studies with some limitations such as: selection bias, different and unreported baseline variables, length of follow-up period and various definitions of LVEF improvement. The studies used in this meta-analysis came from a period with a long time span and, therefore, optimal HF medical therapy used was different or unreported. A major limitation was also a lead time bias, since HFIEF patients had to survive long enough for a second LVEF assessment. Furthermore, events occurring between the first and second LVEF measurements were not analysed, since patients later to be classified as HFpREF were more likely to die before reaching the second LVEF measurement. To make matters more complex, the precise time frame needed for ventricular remodelling to occur (spontaneously or under treatment) is unknown. The results obtained represent the patients who had both baseline and final data analysed (‘completers’), and it will be impossible to predict the effect of data from patients without full assessment (‘non-completers’) on the overall results. Furthermore, the methods for measurement of LVEF evolved significantly, from less precise to sophisticated methods, which may have altered the results. Finally, differentiation between long-term functional or structural improvement of LVEF, would need a ‘withdrawal’ study (LVEF reassessed after withdrawal of drug or device), which is obviously ethically challenging.