Ratko Lasica

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.

Development and Validation of a Risk Scoring Model to Predict Net Adverse Cardiovascular Outcomes after Primary Percutaneous Coronary Intervention in Patients Pretreated with 600 mg Clopidogrel: Rationale and Design of the RISK‐PCI Study

BACKGROUND No comprehensive primary PCI (pPCI) risk model to predict net adverse cardiovascular events (NACE) has been reported with the use of clopidogrel 600 mg, which is now considered the standard loading dose. The primary hypothesis of the RISK-PCI trial is that an accurate risk prediction may be achieved by using clinical, angiographic, and procedural variables available at the time of intervention. METHODS The present single-center, longitudinal, cohort study will include 1,750 consecutive patients with ST-elevation myocardial infarction (STEMI), undergoing pPCI after pretreatment with 300 mg aspirin and 600 mg clopidogrel. The primary end-points of the trial (NACE) include major adverse cardiovascular events (MACE) and major bleeding. A logistic regression model will be developed to predict 30-day and 1-year NACE after pPCI. A risk score derived from study set data will be validated using validation set data. RESULTS Until June 1, 2008, 1,166 patients have been enrolled. Thirty-day follow-up is available in 1,007 patients. CONCLUSIONS The RISK-PCI study is designed to develop an accurate risk scoring system, using variables available at the time of intervention, to predict long-term adverse outcomes after pPCI.

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.

Impact of the Combined Left Ventricular Systolic and Renal Dysfunction on One-Year Outcomes after Primary Percutaneous Coronary Intervention

BACKGROUND The aim of this study was to assess the impact of combined left ventricular systolic dysfunction (LVSD) and renal dysfunction (RD) on 1-year overall mortality and major adverse cardiovascular events (MACEs) (comprising cardiovascular death, nonfatal renfarction, target vessel revascularization, and nonfatal stroke) in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). METHODS One thousand three hundred ninety eight patients with first myocardial infarction, undergoing pPCI were divided into four groups according to the presence of LVSD (ejection fraction [EF] <40%) and/or baseline RD (estimated glomerular filtration rate <60 mL/min per m(2)): Group I (no LVSD and no RD); Group II (LVSD, no RD); Group III (RD, no LVSD); Group IV (LVSD + RD). RESULTS One-year mortality rates in Groups I, II, III, and IV were 2.6%, 15.2%, 10.6%, and 34.2% and 1-year MACE rates were 5.7%, 19.5%, 17.1% and 35.7%, respectively. Patients in Groups II, III, and IV had an increased probability of 1-year overall mortality and MACE as compared to Group I. Overall mortality: Group II HR 2.1 (95% CI 1.1-4.2); Group III HR 2.1 (95% CI 1.1-4.1); Group IV HR 4.8 (95% CI 2.4-9.4); MACE: Group II HR 2.2 (95% CI 1.1-4.2); Group III HR 2.2 (95% CI 1.1-4.3); Group IV HR 5.1 (95% CI 2.6-10.1). The LVSD-RD combination was the strongest independent predictor for 1-year outcomes. CONCLUSIONS The LVSD-RD combination is associated with an approximately five-fold increase in 1-year overall mortality and MACE after pPCI. The evaluation of the renal function in patients with LVSD represents a simple method which enables a more precise stratification of the risks related to the occurrence of adverse events in long-term patient follow-up.

Stress hormones at rest and following exercise testing predict coronary artery disease severity and outcome

Abstract Objectives: Despite considerable knowledge regarding the importance of stress in coronary artery disease (CAD) pathogenesis, its underestimation persists in routine clinical practice, in part attributable to lack of a standardized, objective assessment. The current study examined the ability of stress hormones to predict CAD severity and prognosis at basal conditions as well as during and following an exertional stimulus. Materials and methods: Forty Caucasian subjects with significant coronary artery lesions (≥50%) were included. Within 2 months of coronary angiography, cardiopulmonary exercise testing (CPET) on a recumbent ergometer was performed in conjunction with stress echocardiography (SE). At rest, peak and after 3 min of recovery following CPET, plasma levels of cortisol, adrenocorticotropic hormone (ACTH) and NT-pro-brain natriuretic peptide (NT-pro-BNP) were measured by immunoassay sandwich technique, radioimmunoassay, and radioimmunometric technique, respectively. Subjects were subsequently followed a mean of 32 ± 10 months. Results and discussion: Mean ejection fraction was 56.7 ± 9.6%. Subjects with 1–2 stenotic coronary arteries (SCA) demonstrated a significantly lower plasma cortisol levels during CPET compared to those with 3-SCA (p < .05), whereas ACTH and NT-pro-BNP were not significantly different (p > .05). Among CPET, SE, and hormonal parameters, cortisol at rest and during CPET recovery demonstrated the best predictive value in distinguishing between 1-, 2-, and 3-SCA [area under ROC curve 0.75 and 0.77 (SE = 0.11, 0.10; p = .043, .04) for rest and recovery, respectively]. ΔCortisol peak/rest predicted cumulative cardiac events (area under ROC curve 0.75, SE = 0.10, p = .049). Conclusions: Cortisol at rest and following an exercise test holds predictive value for CAD severity and prognosis, further demonstrating a link between stress and unwanted cardiac events.

Coronary Microcirculation in Heart Failure with Preserved Systolic Function

BACKGROUND The Heart Failure with Preserved Ejection Fraction (HFpEF) is defined as the preserved left ventricular ejection fraction (LVEF) with the signs of heart failure, elevated natriuretic peptides, and either the evidence of the structural heart disease or diastolic dysfunction. The importance of this form of heart failure was increased after studies where the mortality rates and readmission to the hospital were founded similar as in patients with HF and reduced EF (HFrEF). Coronary microvascular ischemia, cardiomyocyte injury and stiffness could be important factors in the pathophysiology of HFpEF. METHODS The goal of this work is to analyse the relationship of HFpEF and coronary microcirculation in previous studies. RESULTS The useful diagnostic marker of coronary microcirculation in HFpEF may be the parameters measured by transthoracic echocardiography (TTE), the coronary flow reserve (CFR), as well as fractional flow reserve (FFR) and quantitative myocardial contrast echocardiography (MCE). Cardiac magnetic resonance (CMR) imaging represents the diagnostic gold standard in HFpEF. Coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD) is poorly understood and may be more prevalent amongst women than men. Troponin level may be important in risk stratification of HEpEF patients. CONCLUSION There are no precise answers with respect to the pathophysiological mechanism, nor are there any precise practical clinical assessment of and diagnostic method for coronary microvascular dysfunction and diastolic dysfunction. In accordance with that, there is no well-established treatment for HFpEF.

Sex and age differences and outcomes in acute coronary syndromes

BACKGROUND There is conflicting information about sex differences in presentation, treatment, and outcome after acute coronary syndromes (ACS) in the era of reperfusion therapy and percutaneous coronary intervention. The aim of this study was to examine presentation, acute therapy, and outcomes of men and women with ACS with special emphasis on their relationship with younger age (≤65years). METHODS From January 2010 to June 2015, we enrolled 5140 patients from 3 primary PCI capable hospitals. Patients were registered according to the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) registry protocol (ClinicalTrials.gov: NCT01218776). The primary outcome was the incidence of in-hospital mortality. RESULTS The study population was constituted by 2876 patients younger than 65years and 2294 patients older. Women were older than men in both the young (56.2±6.6 vs. 54.1±7.4) and old (74.9±6.4 vs. 73.6±6.0) age groups. There were 3421 (66.2%) patients with ST elevation ACS (STE-ACS) and 1719 (33.8%) patients without ST elevation ACS (NSTE-ACS). In STE-ACS, the percentage of patients who failed to receive reperfusion was higher in women than in men either in the young (21.7% vs. 15.8%) than in the elderly (35.2% vs. 29.6%). There was a significant higher mortality in women in the younger age group (age-adjusted OR 1.52, 95% CI: 1.01-2.29), but there was no sex difference in the older group (age-adjusted OR 1.10, 95% CI: 0.87-1.41). Significantly sex differences in mortality were not seen in NSTE-ACS patients. CONCLUSIONS In-hospital mortality from ACS is not different between older men and women. A higher short-term mortality can be seen only in women with STEMI and age of 65 or less.