Trilaciclib Prior to Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer: Final Efficacy and Subgroup Analysis from a Randomized Phase II Study.

PURPOSE: We report final antitumor efficacy results from a phase II study of trilaciclib, an intravenous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, administered prior to gemcitabine plus carboplatin (GCb) in patients with metastatic triple-negative breast cancer (NCT02978716). PATIENTS AND METHODS: Patients were randomized (1:1:1) to group 1 [GCb (days 1, 8); n = 34], group 2 [trilaciclib prior to GCb (days 1, 8); n = 33], or group 3 [trilaciclib (days 1, 8) and trilaciclib prior to GCb (days 2, 9); n = 35]. Subgroup analyses were performed according to CDK4/6 dependence, level of programmed death-ligand 1 (PD-L1) expression, and RNA-based immune signatures using proportional hazards regression. T-cell receptor (TCR) ß CDR3 regions were amplified and sequenced to identify, quantify, and compare the abundance of each unique TCRß CDR3 at baseline and on treatment. RESULTS: Median overall survival (OS) was 12.6 months in group 1, not reached in group 2 (HR = 0.31; P = 0.0016), 17.8 months in group 3 (HR = 0.40; P = 0.0004), and 19.8 months in groups 2 and 3 combined (HR = 0.37; P < 0.0001). Efficacy outcomes were comparable regardless of cancer CDK4/6 dependence status and immune signatures. Administering trilaciclib prior to GCb prolonged OS irrespective of PD-L1 status but had greater benefit in the PD-L1-positive population. T-cell activation was enhanced in patients receiving trilaciclib. CONCLUSIONS: Administering trilaciclib prior to GCb enhanced antitumor efficacy, with significant improvements in OS. Efficacy outcomes in immunologic subgroups and enhancements in T-cell activation suggest these improvements may be mediated via immunologic mechanisms.

A Systematic Review of Network Meta-Analyses and Real-World Evidence Comparing Apixaban and Rivaroxaban in Nonvalvular Atrial Fibrillation.

There is no direct evidence comparing the 2 most commonly prescribed direct oral anticoagulants, apixaban and rivaroxaban, used for stroke prevention in nonvalvular atrial fibrillation (NVAF). A number of network meta-analyses (NMAs) of randomized control trials and real-world evidence (RWE) studies comparing the efficacy, effectiveness, and safety of apixaban and rivaroxaban have been published; however, a comprehensive evidence review across the available body of evidence is lacking. In this study, we aimed to systematically review and evaluate the clinical outcomes of apixaban and rivaroxaban using a combination of data gleaned from both NMAs and RWE studies. The review identified 21 NMAs and 5 RWE studies. The data demonstrated that apixaban was associated with fewer major bleeding events compared to rivaroxaban. There was no difference in the efficacy/effectiveness profiles between these treatments. Bleeding is a serious complication of anticoagulation therapy for the management of NVAF, and is associated with increased rates of hospitalization, morbidity, mortality, and health-care expenditure. The majority of studies in this comprehensive evidence review suggests that apixaban has a lower risk of major bleeding events compared to rivaroxaban in patients with NVAF.

Systematic Literature Review of the Burden of Disease and Treatment for Transfusion-dependent ß-Thalassemia.

PURPOSE: ß-Thalassemia is an inherited blood disorder characterized by reduced or no production of adult hemoglobin. Systematic identification of the burden of ß-thalassemia with contemporary treatments is lacking in published literature. Thus, a gap exists in understanding the baseline burden on which to assess future treatments. Therefore, a systematic literature review (SLR) was performed to assess management and outcomes in patients with transfusion-dependent ß-thalassemia (TDT) who received long-term transfusion regimens. METHODS: Searches of MEDLINE, EMBASE, and 5 conference websites were conducted to identify clinical-practice studies in Italy, France, Germany, Greece, the United States, and the United Kingdom, published since January 2007. The review found 135 articles meeting the SLR criteria. FINDINGS: Among patients carrying 2 ß-thalassemia mutations, 64%-89% underwent regular transfusions at intervals of between 2 and 4 weeks. Transfusion-associated complications that were reported included iron overload, transfusion reactions, alloimmunization, and infections. Analyses of 42, 25, and 73 studies reporting liver iron concentration (median, 8.5 mg/g of dry weight [dw]; interquartile range [IQR], 4.5-11.0 mg/g dw), cardiac T2* magnetic resonance imaging (median, 27.4 ms; IQR, 26.0-30.2 ms), and serum ferritin (median, 1465.0 ng/mL; IQR, 1238.2-1797.0 ng/mL), respectively, showed wide ranges in iron levels and a general trend toward improved iron control in recent years. Adverse transfusion reactions and alloimmunization were reported in ~50% and 10%-20% in patients, respectively. Rates of transfusion-transmitted infections were highly variable by study but were lower in more recent cohorts. Complications stemming from iron overload and underlying disease captured in this SLR included cardiac disease, liver disease, and endocrine and musculoskeletal disorders. Approximately 10% of patients were diagnosed with heart failure, with rates ranging from 2.9% to 20.9% across 6 studies. Other significant complications reported with ß-thalassemia included pain (25%-69%), psychiatric disorders (25%-30%), and reduced health-related quality of life. Despite substantial improvements in survival, patients with TDT remained at an increased risk for early mortality. IMPLICATIONS: Consistent with improvements in transfusion practices and iron monitoring and management, outcomes in patients with TDT have improved. However, iron overload and disease-associated complications remain a challenge in this population. This review supports the burden of disease affecting patients with ß-thalassemia and provides a baseline health status against which to assess future improvements in care.

Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial.

BACKGROUND: Trilaciclib is an intravenous cell-cycle inhibitor that transiently maintains immune cells and haemopoietic stem and progenitor cells in G1 arrest. By protecting the immune cells and bone marrow from chemotherapy-induced damage, trilaciclib has the potential to optimise antitumour activity while minimising myelotoxicity. We report safety and activity data for trilaciclib plus gemcitabine and carboplatin chemotherapy in patients with metastatic triple-negative breast cancer. METHODS: In this randomised, open-label, multicentre, phase 2 study, adult patients (aged ≥18 years) with evaluable, biopsy-confirmed, locally recurrent or metastatic triple-negative breast cancer who had no more than two previous lines of chemotherapy were recruited from 26 sites in the USA, three in Serbia, two in North Macedonia, one in Croatia, and one in Bulgaria; sites were academic and community hospitals. Availability of diagnostic samples of tumour tissue confirming triple-negative breast cancer was a prerequisite for enrolment. Eligible patients were randomly assigned (1:1:1) by an interactive web-response system, stratified by number of previous lines of systemic therapy and the presence of liver metastases, to receive intravenous gemcitabine 1000 mg/m2 and intravenous carboplatin (area under the concentration-time curve 2 µg × h/mL) on days 1 and 8 (group 1), gemcitabine and carboplatin plus intravenous trilaciclib 240 mg/m2 on days 1 and 8 (group 2), or gemcitabine and carboplatin on days 2 and 9 plus trilaciclib on days 1, 2, 8, and 9 (group 3) of 21-day cycles. Patients continued treatment until disease progression, unacceptable toxicity, withdrawal of consent, or discontinuation by the investigator. The primary objective was to assess the safety and tolerability of combining trilaciclib with gemcitabine and carboplatin chemotherapy. The primary endpoints were duration of severe neutropenia during cycle 1 and the occurrence of severe neutropenia during the treatment period. Overall survival was included as a key secondary endpoint. Analyses were in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with EudraCT, 2016-004466-26, and ClinicalTrials.gov, NCT02978716, and is ongoing but closed to accrual. FINDINGS: Between Feb 7, 2017, and May 15, 2018, 142 patients were assessed for eligibility and 102 were randomly assigned to group 1 (n=34), group 2 (n=33), or group 3 (n=35). Of all patients, 38 (37%) had received one or two lines of previous chemotherapy in the metastatic setting. Median follow-up was 8·4 months (IQR 3·8-13·6) for group 1, 12·7 months (5·5-17·4) for group 2, and 12·9 months (6·7-16·8) for group 3. Data cutoff for myelosuppression endpoints was July 30, 2018, and for antitumour activity endpoints was May 17, 2019. During cycle 1, mean duration of severe neutropenia was 0·8 day (SD 2·4) in group 1, 1·5 days (3·5) in group 2, and 1·0 day (2·6) in group 3 (group 3 vs group 1 one-sided adjusted p=0·70). Severe neutropenia occurred in nine (26%) of 34 patients in group 1, 12 (36%) of 33 patients in group 2, and eight (23%) of 35 patients in group 3 (p=0·70). Overall survival was 12·6 months (IQR 5·8-15·6) in group 1, 20·1 months (9·4-not reached) in group 2, and 17·8 months (8·8-not reached) in group 3 (group 3 vs group 1 two-sided p=0·0023). The most common treatment-emergent adverse events were anaemia (22 [73%] of 34), neutropenia (21 [70%]), and thrombocytopenia (18 [60%]) in group 1; neutropenia (27 [82%] of 33), thrombocytopenia (18 [55%]) and anaemia (17 [52%]) in group 2; and neutropenia (23 [66%] of 35), thrombocytopenia (22 [63%]), and nausea (17 [49%]) in group 3. There were no treatment-related deaths. INTERPRETATION: No significant differences were observed in myelosuppression endpoints with trilaciclib plus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer; however, the regimen was generally well tolerated and overall survival results were encouraging. Further studies of trilaciclib in this setting are warranted. FUNDING: G1 Therapeutics.

Anticoagulant selection for patients with VTE-Evidence from a systematic literature review of network meta-analyses.

The aim of this study was to systematically review published network meta-analyses (NMAs) that compare venous thromboembolism (VTE) treatments. A systematic literature search (in MEDLINE, Embase, and Cochrane Database of Systematic Reviews through September 2017) was conducted to identify NMAs that compared the safety and efficacy of direct oral anticoagulants (DOACs) for the treatment of VTE in the acute and extended treatment settings. The NMAs included randomized controlled trials comparing multiple DOACs, low-molecular weight heparin, unfractionated heparin, and vitamin K antagonists (VKAs). The quality of the NMA results were evaluated using the Grading of Recommendations and Evaluation (GRADE) assessment. The SLR identified 294 records and nine NMAs (68 trials). Among the NMAs, three evaluated the acute treatment setting, five the extended, and one in both treatment settings. The NMAs showed a significant reduction in major bleeding and clinically relevant bleeding (CRB) with apixaban compared to other DOACs. Major bleeding with apixaban was reduced compared to dabigatran, edoxaban, and fondaparinux-VKA combination in all comparisons in the acute setting (range of effect estimates: 0.30-0.43). CRB was reduced with apixaban compared to dabigatran, edoxaban, and rivaroxaban in the acute and extended settings (range of effect estimates: 0.23-0.72). No significant differences were seen in efficacy outcomes between the DOACs. This SLR of NMAs systematically collected all indirect evidence of the impact of apixaban compared to other anticoagulants in patients with VTE. In the absence of head-to-head trials, well-conducted NMAs provide the best evidence.

Comparison of Recommendations and Use of Cardiovascular Risk Equations by Health Technology Assessment Agencies and Clinical Guidelines.

OBJECTIVES: To identify risk equations for cardiovascular diseases (CVDs) in primary and secondary prevention settings that are used or recommended by health technology assessment (HTA) organizations and in clinical guidelines (CGs). METHODS: A targeted literature review was conducted using a two-stage search strategy. First, HTA reviews of manufacturers' drug submissions, reports from established HTA organizations (Europe, Canada, and Australia), and CGs from countries with and without HTA organizations, including the United States, were identified. Documents published between September 30, 2006 and September 30, 2016, were examined for cardiovascular risk equations, recommendations, and commentaries. Next, publications associated with risk equations and cited by HTA and CG documents were retrieved. This literature was examined to extract commentaries and risk equation study characteristics. RESULTS: The review identified 47 risk equations, 25 in the primary CVD prevention setting (i.e., patients with no CVD history), including 5 for CVD prevention in diabetes and 22 solely in secondary prevention settings; 11 were identified for heart failure, 3 for stroke or transient ischemic attack, 2 for stable angina, and 11 for acute coronary syndrome or related conditions. A small set of primary prevention equations was found to be commonly used by HTAs, whereas secondary prevention equations were less common in HTA documents. CGs provided more risk equations as options than HTA documents. CONCLUSIONS: Although there is an abundance of risk equations developed for primary and secondary prevention, there remains a need for additional research to provide sufficient clinical and HTA guidance for risk estimation, particularly in high-risk or secondary prevention settings.

Low cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies in 55 study reports.

OBJECTIVE: To use the relation between cigarette consumption and cardiovascular disease to quantify the risk of coronary heart disease and stroke for light smoking (one to five cigarettes/day). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline 1946 to May 2015, with manual searches of references. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective cohort studies with at least 50 events, reporting hazard ratios or relative risks (both hereafter referred to as relative risk) compared with never smokers or age specific incidence in relation to risk of coronary heart disease or stroke. DATA EXTRACTION/SYNTHESIS: MOOSE guidelines were followed. For each study, the relative risk was estimated for smoking one, five, or 20 cigarettes per day by using regression modelling between risk and cigarette consumption. Relative risks were adjusted for at least age and often additional confounders. The main measure was the excess relative risk for smoking one cigarette per day (RR1_per_day-1) expressed as a proportion of that for smoking 20 cigarettes per day (RR20_per_day-1), expected to be about 5% assuming a linear relation between risk and consumption (as seen with lung cancer). The relative risks for one, five, and 20 cigarettes per day were also pooled across all studies in a random effects meta-analysis. Separate analyses were done for each combination of sex and disorder. RESULTS: The meta-analysis included 55 publications containing 141 cohort studies. Among men, the pooled relative risk for coronary heart disease was 1.48 for smoking one cigarette per day and 2.04 for 20 cigarettes per day, using all studies, but 1.74 and 2.27 among studies in which the relative risk had been adjusted for multiple confounders. Among women, the pooled relative risks were 1.57 and 2.84 for one and 20 cigarettes per day (or 2.19 and 3.95 using relative risks adjusted for multiple factors). Men who smoked one cigarette per day had 46% of the excess relative risk for smoking 20 cigarettes per day (53% using relative risks adjusted for multiple factors), and women had 31% of the excess risk (38% using relative risks adjusted for multiple factors). For stroke, the pooled relative risks for men were 1.25 and 1.64 for smoking one or 20 cigarettes per day (1.30 and 1.56 using relative risks adjusted for multiple factors). In women, the pooled relative risks were 1.31 and 2.16 for smoking one or 20 cigarettes per day (1.46 and 2.42 using relative risks adjusted for multiple factors). The excess risk for stroke associated with one cigarette per day (in relation to 20 cigarettes per day) was 41% for men and 34% for women (or 64% and 36% using relative risks adjusted for multiple factors). Relative risks were generally higher among women than men. CONCLUSIONS: Smoking only about one cigarette per day carries a risk of developing coronary heart disease and stroke much greater than expected: around half that for people who smoke 20 per day. No safe level of smoking exists for cardiovascular disease. Smokers should aim to quit instead of cutting down to significantly reduce their risk of these two common major disorders.

Organised cervical cancer screening programme in the Belgrade municipality of Cukarica - Evaluation of process indicators.

PURPOSE: To evaluate the process indicators for monitoring the Organized Cervical Cancer Screening Programme (OCCSP) conducted in the Belgrade municipality of Cukarica within the first three-year interval, and to compare Pap test coverage for women aged 25 to 64 before and after implementing the organised programme. METHODS: We analyzed the coverage by invitation, compliance with invitation and coverage by Pap test for the first three-year interval of the OCCSP (20th Dec 2012 - 19th Dec 2015) as well as the results of opportunistic screening for the same period and coverage by Pap test for women aged 25 to 64 for the last three years prior to the implementation of the OCCSP. RESULTS: After the first three years of the OCCSP implementation, coverage by invitation was 42.9%, compliance to invitation 66.7% and coverage by Pap test was 28.6%. During the same period, outside of the program (opportunistic screening) coverage by Pap test was 9.4%. In the last three years prior to the implementation of the OCCSP coverage by Pap test for women aged 25 to 64 was 21.4%. CONCLUSION: After the first three-year interval of the OCCSP implementation, the overall (organised + opportunistic) Pap test coverage for women aged 25-64 has almost doubled compared to the period when we conducted exclusively opportunistic screening (38.4 vs 21.4%). However, incentive payment for the smear takers and better coordination and planning of capacity-building is needed in order to achieve the 75% Pap tests coverage recommended by the National Programme for Early Detection of Cervical Cancer.

Leptin and adiponectin levels in discordant dichorionic twins at 72 hours of age-associations with anthropometric parameters and insulin resistance.

BACKGROUND: Insulin resistance (IR) in adults has been associated with intrauterine growth restriction (IUGR). Leptin and adiponectin correlations with anthropometric parameters and IR at 72 h in discordant twins were tested. METHODS: We included 24 discordant (birth weight discordance ≥20% in relation to the heavier cotwin) and 30 concordant (birth weight discordance ≤10%) twins. RESULTS: A correlation between leptin (but not adiponectin) level and birth weight (BW), birth length and head circumference in IUGR twins was recorded (p<0.05). Insulin sensitivity (IS) and homeostatic model assessment (HOMA)-IR in IUGR twins were similar to appropriate-for-gestational-age cotwins and unrelated to adipokines. In IUGR twins, adiponectin and insulin associated positively. In larger concordant twins' leptin level correlated with HOMA-IR and insulin. CONCLUSIONS: Leptin, but not adiponectin, levels correlate positively with anthropometric parameters in IUGR twins. IR in IUGR twins is unrelated to adipokines in the first few days of life.

Lipids and Adipokines in Cord Blood and at 72 h in Discordant Dichorionic Twins.

BACKGROUND: Intrauterine growth restriction (IUGR) is a risk factor for developing metabolic syndrome later in life. We explored whether adipokine concentrations in cord blood (CB) and on day 3 (D3) were related to impaired fetal growth and lipids in IUGR twins. PATIENTS AND METHODS: Thirty-six discordant (birth weight [BW] discordance ≥20% calculated in relation to the heavier co-twins) and 42 concordant (BW discordance ≤ 10%) twin pairs were included. RESULTS: In IUGR twins, both adiponectin/BW and triglyceride (TG) levels were significantly higher, while total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were lower in CB. On D3, both leptin and HDL-C levels were significantly lower and TG levels were significantly higher in IUGR twins. In the discordant group, the alterations in lipids were not related to any adipokine. CONCLUSIONS: IUGR is related to lower leptin level and proatherogenic lipid profile (higher TG and lower HDL-C), which are not influenced by adipokine at birth.

Stressful life events and breast cancer risk: a hospital-based case-control study.

PURPOSE: Elucidation of the factors contributing to the incidence of breast cancer is of crucial importance for the development of preventive or therapeutic strategies targeting the disease. Research on stress and breast cancer has been documented by various studies published over the years. In view of breast cancer importance as the most commonly occurring malignancy in females in Serbia, this study was undertaken to examine the association between stressful life events and breast cancer risk. METHODS: The present hospital-based case-control study comprised 120 new breast cancer cases and 120 hospital controls matched with respect to age (± 2 years). This study used the Paykel Life Events Scale to obtain information about stressful life events in the years before diagnosis. The SPSS statistical package was used and odds ratios (OR) and 95% confidence intervals (95% CI) were calculated from multivariate conditional logistic regression model. RESULTS: Multiple conditional logistic regression analysis revealed six independent predictors of breast cancer risk: experience of severe and moderate threats (first 25 life events from the scale) (OR=3.15, 95% CI=2.01-4.93), son's military service (OR=6.09, 95% CI=4.17-12.37), death of close family member (OR=7.98, 95% CI=2.18-9.14), moderate financial difficulties (OR=3.26, 95%CI=1.24-8.56), maternal death in childhood (OR=3.46, 95% CI=1.21-9.92) and serious financial difficulties (OR=3.55, 95% CI=1.20-10.52). CONCLUSION: Stress exposure has been proposed to contribute to the etiology of breast cancer. There is a need for understanding the differing physiological effects of types or times of stress exposure.

Clinical benefit of cetuximab and prognostic value of cetuximab-related skin toxicity in metastatic colorectal cancer: a single institution analysis.

PURPOSE: To evaluate the clinical benefits of cetuximab (CTX) and the prognostic value of CTX-related skin toxicity in metastatic colorectal cancer (mCRC) patients. METHODS: Sixty patients were tested for KRAS mutation at the Department of Oncology, Clinical Centre Nis. We assessed 34 wild-type KRAS mCRC patients treated with CTX. All of them were refractory to prior fluoropyrimidine, oxaliplatin and irinotecan-based regimens. The maximum grade skin toxicity according to treatment cycle was analyzed. Skin toxicity was grouped into clinically non-relevant skin toxicity (grade 0-1: Group 1) and clinically relevant skin toxicity (grade 2-4: Group 2). RESULTS: Ten out of 33 patients (30.30%) achieved partial response (PR). Eight additional patients (24.24%) showed stable disease (SD), whereas 15 (45.45%) had disease progression (PD). No patient achieved complete response (CR). Overall response rate (ORR) was 30.30%, whereas the disease control rate (DCR) was 54.54%.The median progression free survival (PFS) was 14 weeks. Some degree of skin toxicity was observed in 79.41% (27/34) of the patients. Clinically non-relevant skin toxicity was observed in 50% (17/34), and clinically relevant in 50 % (17/34) of the patients. Grade 4 skin toxicity was documented in 1 patient. The mean PFS in Group 1 was 12.65±5.59 weeks and in Group 2 22.82±12.16 (p<0.05). The results showed that grade 2-4 skin toxicity was associated with significantly better response to treatment than skin toxicity grade 0-1, with regard to ORR (80.00 vs 20.00%; p<0.05) and DCR ( 66.66 vs 33.33%; p<0.05). CONCLUSION: Cetuximab has clinical benefit when given alone or in combination with irinotecan in patients with irinotecan-refractory CRC. Skin toxicity was one of the predictors of response and it was in line with what was expected.

Short-term exposure to UV-A, UV-B, and UV-C irradiation induces alteration in cytoskeleton and autophagy in human keratinocytes.

Ultraviolet radiation (UV) induces a series of morphological and ultrastructural alterations in human epidermis. Alterations observed in irradiated keratinocytes in morphological studies done before were cell retraction with loss of intercellular interactions, surface blebbing, and eventually cell death by apoptosis. The aim of this study was to investigate effect of UV-A, UV-B, and UV-C irradiation on the cytoskeleton of human keratinocytes. Keratinocytes were obtained by exfoliative scrubbing procedure from buccal mucosa of healthy individuals, and treated with UV-A, UV-B, and UV-C radiation. Afterward, treated cell were labeled with anti-alfa-tubulin and anti-human-cytokeratin and analyzed by light and confocal microscopy. The intensity of the cytokeratin labeling was found to be much higher in all irradiated cells than in control cells as observed by light microscope and measured with the Image J program. This measurement showed that with the decrease in the wavelengths of UV irradiation the intensity of the labeling of cells increases. Although the authors expected to find the collapse of microtubules toward the cell nucleus or their rearrangement in UV-treated cells, these alterations were not verified on cell smears labeled with anti-alfa tubulin observed by confocal microscope. When they used electron microscopy to examine in more detail the morphology of irradiated cells, they did not find apoptotic cells, but found features of autophagy in UV-treated keratinocytes. The authors assume that autophagy found as a result of UV radiation of human keratinocytes acts as a cytoprotective mechanism against UV-induced apoptosis.

[Influence of the double antiplatelet therapy on patency of the occluded artery after acute myocardial infarction with ST-segment elevation].

BACKGROUND/AIM: Most patients with acute myocardial infarction with ST-segment elevation (STEMI) are still treated with pharmacological reperfusion, which is not always successful. That is the reason for searching possibilities for a better success of reperfusion with adding new antiplatelet drugs. The aim of this study was to investigate weather addition of clopidogrel as a second antiplatelet drug, improves the patency of the infarct-related artery after STEMI. METHODS: We prospectively enrolled 65 patients, 29-72 years old, hospitalized due to the first STEMI within 6 hours after the on-set of a chest pain. They were treated with a fibrinolytic agent (streptokinase or tissue plasminogen activator--tPA), aspirin, and low molecular heparin (enoxaparin). A group of 50 patients, beside this therapy, received clopidogrel. Coronary angiography was performed between 5th and 10th day of hospitalization to assess for late patency of the infarct-related artery. Infarct-related artery was considered as patent if thrombolysis in myocardial infarction (TIMI) flow grade was 2 or 3, and as occluded if TIMI flow grade was 0 or 1. RESULTS: In the group of patients who received double antiplatelet therapy (aspirin and clopidogrel), infarct-related artery was occluded in 3 cases (6%); in the group of patients without clopidogrel, infarct-related artery was occluded in 4 patients (26.7%),p < 0.05. There were less frequency of postinfarction angina (6% vs 13.3%), and rarer necessity for rescue percutaneous coronary intervention (4% vs. 13.3%) in the first group, but without statistical significance. CONCLUSION: Adding of clopidogrel to the standard reperfusion pharmacotherapy, as a second antiplatelet drug, increases the number of patients with patent infarct-related artery and the success of reperfusion.