Ratko Lasica

University of Belgrade, Belgrade, SE, Serbia

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Publications (19)36.54 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: 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. 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. 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. 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.
    European heart journal. Acute cardiovascular care. 03/2014; 3(1):56-66.
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    ABSTRACT: Background: Bleeding is a potentially catastrophic complication after primary percutaneous coronary intervention (PPCI). It occurs most frequently within the first 30 days following the intervention. The aim of this study was to generate a simple and accurate risk model for the prediction of bleeding after PPCI. Methods and Results: The training set included 2,096 patients enrolled in the RISK-PCI trial. The model was validated using a database of 961 patients enrolled in the ART-PCI trial. Bleeding was defined as type ≥3a bleeding according to the Bleeding Academic Research Consortium definition. Multivariate logistic regression was used to evaluate the predictors of outcome. A sum of weighted points for specific predictors was calculated to determine the final score. The model included 5 independent predictors of 30-day bleeding: gender (female); history of peptic ulcer; creatinine clearance at admission (<60ml/min); hemoglobin at presentation (<125g/dl); and Killip class >1 heart failure at admission. The model showed good discrimination and calibration for the prediction of bleeding in the derivation set (C-statistic, 0.79; goodness of fit, P=0.12) and in the validation set (C-statistic, 0.76; goodness of fit, P=0.37). Patients were classified into 3 risk classes and the observed incidence of 30-day bleeding of 1.0%, 3.5% and 10.7% corresponded to the low-, intermediate- and high-risk classes, respectively. Conclusions: A simple risk model was developed that has a reasonably good capacity for the prediction of 30-day bleeding after PPCI.
    Circulation Journal 04/2013; · 3.58 Impact Factor
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    ABSTRACT: 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.
    Heart and Vessels 09/2012; · 2.13 Impact Factor
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    ABSTRACT: 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 300mg, clopidogrel 150mg or ticlopidine 500mg for 30days. The co-primary efficacy and safety end points at 30days 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.
    International journal of cardiology 05/2012; · 7.08 Impact Factor
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    ABSTRACT: 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). 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). 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. 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.
    Journal of Interventional Cardiology 11/2011; 25(2):132-9. · 1.50 Impact Factor
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    ABSTRACT: Limited 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. We 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. AF 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). New-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.
    Coronary artery disease 11/2011; 23(1):1-8. · 1.56 Impact Factor
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    ABSTRACT: 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 model's 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 patient's risk profile.
    International journal of cardiology 06/2011; · 7.08 Impact Factor
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    ABSTRACT: Acute heart failure (AHF) has an adverse impact on short- and long-term outcomes in patients with acute ST-elevation myocardial infarction (STEMI). The aims of the present study were to determine independent predictors for the occurrence of AHF during hospitalization and to assess the impact of AHF on 30-day and 1-year outcomes in patients with STEMI who were successfully treated with primary percutaneous coronary intervention (pPCI). The study included 1,074 consecutive patients with STEMI who had no signs of heart failure (HF) at admission (Killip class I) and were treated with successful pPCI. Successful PPCI was defined as postprocedural TIMI 3 grade flow. Acute HF developed in 11.1% patients during hospitalization, which was predominantly mild to moderate (Killip classes II and III). Independent predictors for the occurrence of AHF were: anterior infarction, peak creatinine-kinase (CK) > 2,000 U/L and 3-vessel coronary disease. 30-day and 1-year mortality rates were significantly higher in patients with AHF compared to patients without AHF. AHF during hospitalization was an independent predictor of 30-day mortality (hazard ratio [HR] 10.5) and 1-year mortality (HR 4.4). Even after successful pPCI, the occurrence of AHF during hospitalization remains an independent predictor of 30-day and 1-year mortality.
    The Journal of invasive cardiology 07/2010; 22(7):307-11. · 1.57 Impact Factor
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    ABSTRACT: 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. 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. Until June 1, 2008, 1,166 patients have been enrolled. Thirty-day follow-up is available in 1,007 patients. 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.
    Journal of Interventional Cardiology 07/2009; 22(4):320-8. · 1.50 Impact Factor
  • Basic &amp Clinical Pharmacology &amp Toxicology 06/2009; 105(s1):53. · 2.12 Impact Factor
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    ABSTRACT: Balanced and coordinated antioxidant defence enzyme activities are of utmost importance for correct physiological function and for shielding against unwelcome pathological conditions. We determined the activities of copper-zinc superoxide dismutase (CuZnSOD), catalase, glutathione peroxidase and glutathione reductase in erythrocytes isolated from patients receiving different therapy (streptokinase alone or in combination with metoprolol or with carvedilol) for up to 168 hr after starting treatment for acute myocardial infarction. We observed increased CuZnSOD activity in erythrocytes isolated from patients treated with streptokinase-carvedilol (after 6, 24 and 168 hr) and in erythrocytes isolated from patients treated with streptokinase-metoprolol (after 24 hr). In addition, positive correlation between CuZnSOD and catalase activities was found in erythrocytes isolated from patients that received streptokinase-carvedilol after 168 hr. As metoprolol does not react directly with hydrogen peroxide, it would appear that combined streptokinase-metoprolol therapy exerted its effects primarily via by beta-blockade whereas combined streptokinase-carvedilol therapy appeared to function via both beta-blockade and direct antioxidant mechanisms.
    Basic &amp Clinical Pharmacology &amp Toxicology 09/2007; 101(2):138-42. · 2.12 Impact Factor
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    ABSTRACT: Carvedilol has previously been demonstrated to be beneficial in patients with acute myocardial infarction (AMI) and left ventricular (LV) dysfunction. However, metoprolol has not to date been randomly evaluated in the same patient population. The objective of this study was to compare the effects of treatment with carvedilol versus metoprolol in patients with LV dysfunction after AMI. The study enrolled 313 high-risk patients with anterior AMI and LV ejection fraction of <45%, randomly assigned to treatment with carvedilol or metoprolol. Patients were followed-up for a mean period of 13.4 months. The primary end point was time to composite adverse events (t-CAE). The secondary end points were time to composite hard events (t-CHE) and health-related quality of life. No differences were found either in the primary end point of t-CAE or in the secondary end point of t-CHE. A significant benefit was observed in 4 of 8 health-related quality of life domains in the carvedilol group, with fewer carvedilol group patients being withdrawn from therapy in the hospital. Treatment with carvedilol, in comparison to that with metoprolol in patients with AMI and LV dysfunction, did not differ significantly in regard to the primary end point of t-CAE or to the secondary end point of t-CHE but resulted in better long-term quality of life and favorable early safety profile.
    American heart journal 08/2007; 154(1):116-22. · 4.65 Impact Factor
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    ABSTRACT: There have only been a few studies of the chronobiological occurrence of acute aortic dissection (AAD), and most were international and multicentered. The aim of the present study, conducted at only one center, was to determine the most frequent daily, monthly, and seasonal occurrences of AAD. The study population included 204 patients (66.5% male) treated at our institute between January 1, 1998 and January 1, 2004. A significantly higher frequency of AAD occurred from 6:00 AM to 12:00 noon, compared with other time periods (P < 0.001). The results showed a significant circadian variation in AAD (P < 0.001) with a peak between 9:00 AM and 10:00 AM. No significant variation was found for the day of the week; however, AAD occurred most frequently on Wednesday and Monday. The frequency of AAD was found to be significantly higher during winter versus other seasons (P < 0.001). The analysis of monthly variations of the onset of AAD confirmed a peak in February (12.9%) and in January (12.3%). Similar to other cardiovascular diseases, AAD exhibits significant circadian and seasonal/monthly variations. Our findings indicate that the prevention of AAD, especially during the aforementioned vulnerable periods, is possible by adequate tailoring of the treatment of hypertension, which is the main AAD predisposing factor.
    International Heart Journal 08/2006; 47(4):585-95. · 1.23 Impact Factor
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    ABSTRACT: We have previously shown the protective effects of both Larginine and phystigmine in an experimental model of severe hemorrhagic shock, when these substances were used as monotherapy. It was of interest to investigate whether the combination of L-arginine (300 mg/kg, i.v. bolus) and physostigmine (0.07 mg/kg, i.v. bolus) could produce further beneficial cardiovascular and/or metabolic effects in anaesthetized hemorrhaged rabbits (intermittent bleeding; 40% of the estimated blood volume for 15 min). Selected cardiovascular and biochemical parameters were assessed before bleeding and at several points up to 60 min after the end of bleeding. Drugs were injected 1-2 min after the end of bleeding (Phy-group) or 10 min later (L-Arg+Phy-group). Control rabbits received the corresponding volumes of saline only (0.6-2.0 ml; S-group). Physostigmine (0.07 mg/kg) produced a rapid and sustained increase in mean arterial pressure, the effect being attenuated in L-argininepretreated rabbits (Phy- and L-Arg+Phy-group respectively). The beneficial effecs of L-arginine on heart rate and hemoglobin oxygen saturation in venous blood were not completely lost in rabbits of the LArg+ Phy group, and such a combination partially improved acid-base status (decrease in PaCO2 in arterial blood) and produced further hemodilution (decresase in hematocrit) 15-60 min after the end of bleeding. However, the combination of L-arginine and physostigmine does not offer any significant advantage over the monotherapy with these drugs in hemorrhagic shock.
    Acta Veterinaria. 01/2006;
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    Vojnosanitetski pregled. Military-medical and pharmaceutical review 10/2005; 62(9):661-70. · 0.21 Impact Factor
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    ABSTRACT: Intramural haematoma is the precursor or the variant of a classical aortic dissection where hemorrhage occurs within the aortic wall (aortic media) and in absence of initial intimal tear. This entity looks like a classical aortic dissection, but it differs from it by its pathological characteristics. Although the intimal tear is absent, the prognosis of patients with intramural haematoma is similar to that of patients with classical aortic dissection; it is therefore very important for these patients to be early diagnosed. With a development of modern non-invasive diagnostical techniques the intramural haematoma is more often diagnosed and actually amounts at 10 to 30% of all acute aortic syndrome cases. Clinical characteristics and death rate of patients with intramural hematoma are similar to those of patients with classical aortic dissection, especially when it is obvious that there is a considerable risk for intramural haematoma to complicate into aortic ulcer, aortic aneurysm or rupture. Since intramural haematoma comprehensive diagnostic technique does not exist, safe therapy has not been yet established. Future randomized studies and serial observation of patients with intramural hemorrhage are indispensable not only to clarify these patients' survival predictors but also to define a model of optimal therapy.
    Medical Archives 02/2005; 59(2):121-3.
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    ABSTRACT: L-NAME (1-10 mM, 30 min of incubation) potentiates the tension developed (Td) in the isolated rat hemidiaphragm stimulated by direct subtetanic electrical stimulation (OSES) (F = 14 Hz). The aim of our study was to investigate the possible modulatory effect of local anaesthetic (lidocaine) and beta adrenergic blockers, propranolol and atenolol, on the L-NAME- induced potentiation of isometric contractility (1C). Lidocaine (0.1 mM, 5 min incubation) did not change Td by itself. Also, in the presence of lidocaine (0.1 mM, 5 min incubation), the stimulatory effect of L-NAME (3 mM, 30 min incubation) was preserved. In contrast, lidocaine itself (0.1 mM, 30 min incubation) produced an increase of Td up to 50%. The incubation of the muscle with both lidocaine (0.1 mM, 30 min incubation) and L-NAME (3 mM, 30 min incubation) produced an almost additive stimulatory effects, up to 90% on Td. Propranolol itself (1 µM, 5 min incubation) did not change Td. In the presence of propranolol, L-NAME maintained the stimulatory effect on Td. Propranolol (1 µM, 30 min incubation) did not change Td itself, but abolished the stimulatory effect of L-NAME. Atenolol (1 µM, 30 min incubation) neither significantly changed Td nor L-NAME-induced potentiation of Td.
    Acta Veterinaria. 01/2005;
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    ABSTRACT: It has been suggested that superoxide dismutase (SOD) plays an important role in endothelial dysfunction in essential hypertension (EH), by competing with nitric oxide for superoxide, thus influencing nitric oxide bioavailability. To answer the question of whether endothelial dysfunction is consequence of altered SOD expression we determined SOD activity in patients with different stages of EH. In this study 45 EH patients and 25 normotensive subjects were included. EH patients were divided into the three groups according to the guidelines of European Society of Hypertension. SOD activity was determined spectrophotometrically in RBC and plasma of EH patients and controls. The results obtained have shown that all groups of EH patients exhibit lower SOD activity than control normotensive subjects. Significant correlation between SOD activity and both diastolic (p<0.05, r=-0.394) and systolic blood pressure (p<0.05, r=-0.356) was found. Lowering of SOD activity in patients with different stages of EH leads to inefficient detoxification of superoxide in EH. An excess of superoxide of both cellular and extracellular origin takes part in enhanced degradation of nitric oxide and altered vasodilation, and consequent endothelial dysfunction.
    Medical Archives 01/2005; 59(3):156-9.
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    ABSTRACT: Despite advances in prophylaxis, diagnostic modalities, and therapeutic options, pulmonary embolism remains a commonly undiagnosed entity with lethal outcome. Clinically, pulmonary embolism ranges from massive thromboembolism with cardiogenic shock to asymptomatic, microebolism with anatomically small emboli without hemodynamic, respiratory or other disturbances. A patient with massive pulmonary embolism complicated with ventricular fibrillation, respiratory arrest and cardiogenic shock was treated with a total dose of 3 750 000 IU of intravenous streptokinase in the 8-hour time period. After successful cardiopulmonary resuscitation, and thrombolytic therapy, the patient regained hemodynamic stability six hours after admission; all clinical and electrocardiographic signs of the right ventricle insufficiency disappeared. This case report suggested that treatment with the high-dose of streptokinase could be beneficial in the patients with massive pulmonary embolism complicated with cardiogenic shock, which must be confirmed by further randomized trials.
    Vojnosanitetski pregled. Military-medical and pharmaceutical review 62(7-8):581-5. · 0.21 Impact Factor