Clinical and pharmacogenetic features of patients with upper gastrointestinal lesions at a multidisciplinary hospital: the role of nonsteroidal anti-inflammatory drugs.

OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed medications, but their use can be associated with a number of adverse reactions, including upper gastrointestinal lesions. The aim of the study was to identify clinical and pharmacogenetic factors associated with upper gastrointestinal lesions, including those linked to NSAIDs, in patients at a multidisciplinary hospital. METHODS: The study included 92 patients (mean age 59.4±16.5 years; 47 women), who underwent esophagogastroduodenoscopy during inpatient treatment. Patients' intake of NSAIDs and gastroprotectors during the year before hospitalization was considered. Demographic, clinical, laboratory data of patients were compared between groups, including genotyping for CYP2C9*2 rs179985, CYP2C9*3 rs1057910, CYP2C8*3 rs11572080, CYP2C8*3 rs10509681, PTGS-1 rs10306135, PTGS-1 rs12353214, and PTGS-2 rs20417 using real-time PCR. RESULTS: In NSAIDs+ patients, PTGS1 rs10306135 AT+TT genotypes increased the chance of developing gastrointestinal complications by 5.4 times (95 % CI=1.30-22.27). In total sample, smoking (OR=3.12, 95 % CI=1.15-8.46), and alcohol intake (OR=4.09, 95 % CI=1.05-15.87) increased odds of gastrointestinal damage. In NSAIDs+ patients omeprazole, famotidine and both famotidine and omeprazole during the last year were as ineffective as not taking gastroprotectors; in total sample famotidine (OR=0.19, 95 % CI=0.04-0.93) and two gastroprotectors (OR=0.13, 95 % CI=0.02-0.75) reduced the chance of upper gastrointestinal lesions. CONCLUSIONS: Pharmacogenetic features of patients may significantly contribute to the development NSAIDs-induced upper gastrointestinal injuries.

STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) guidelines recommend pharmaco-invasive treatment if timely primary percutaneous coronary intervention (PCI) is unavailable. Full-dose tenecteplase is associated with an increased risk of intracranial hemorrhage in older patients. Whether pharmaco-invasive treatment with half-dose tenecteplase is effective and safe in older patients with STEMI is unknown. METHODS: STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) was an investigator-initiated, open-label, randomized, multicenter study. Patients ≥60 years of age with ≥2 mm ST-segment elevation in 2 contiguous leads, unable to undergo primary PCI within 1 hour, were randomly assigned (2:1) to half-dose tenecteplase followed by coronary angiography and PCI (if indicated) 6 to 24 hours after randomization, or to primary PCI. Efficacy end points of primary interest were ST resolution and the 30-day composite of death, shock, heart failure, or reinfarction. Safety assessments included stroke and nonintracranial bleeding. RESULTS: Patients were assigned to pharmaco-invasive treatment (n=401) or primary PCI (n=203). Median times from randomization to tenecteplase or sheath insertion were 10 and 81 minutes, respectively. After last angiography, 85.2% of patients undergoing pharmaco-invasive treatment and 78.4% of patients undergoing primary PCI had ≥50% resolution of ST-segment elevation; their residual median sums of ST deviations were 4.5 versus 5.5 mm, respectively. Thrombolysis In Myocardial Infarction flow grade 3 at last angiography was ≈87% in both groups. The composite clinical end point occurred in 12.8% (51/400) of patients undergoing pharmaco-invasive treatment and 13.3% (27/203) of patients undergoing primary PCI (relative risk, 0.96 [95% CI, 0.62-1.48]). Six intracranial hemorrhages occurred in the pharmaco-invasive arm (1.5%): 3 were protocol violations (excess anticoagulation in 2 and uncontrolled hypertension in 1). No intracranial bleeding occurred in the primary PCI arm. The incidence of major nonintracranial bleeding was low in both groups (<1.5%). CONCLUSIONS: Halving the dose of tenecteplase in a pharmaco-invasive strategy in this early-presenting, older STEMI population was associated with electrocardiographic changes that were at least comparable to those after primary PCI. Similar clinical efficacy and angiographic end points occurred in both treatment groups. The risk of intracranial hemorrhage was higher with half-dose tenecteplase than with primary PCI. If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02777580.

Randomized Comparison of Two Approaches to Initial Warfarin Dosing: Time in Therapeutic Range of International Normalized Ratio During Hospitalization.

AIM: To perform a randomized, open-label comparison of average time in therapeutic range (TTR) of international normalized ratio (INR) using two approaches to initial warfarin dosing during hospitalization: the standard method and the one using individual patient characteristics (clinical algorithm - the studied approach). MATERIALS AND METHODS: We randomly assigned 60 patients with different indications for vitamin K antagonist therapy to the studied approach (n=31, intervention group) or to the standard method (n=29, control group). А target INR range for all patients was 2.0 to 3.0. RESULTS: The average TTR and portions of INR values within target range during the whole time of drug dosing turned out to be small. TTR was 22.4% with standard method and 21.4% with clinical algorithm, which was well below desired 60%. CONCLUSION: The opportunities for achieving target INR in inpatient settings, regardless of warfarin dosing regimen, are limited.

Long-term follow-up of antithrombotic management patterns in patients with acute coronary syndrome in Russia: an observational study (EPICOR-RUS study).

OBJECTIVE: This study sought to describe the short- and long-term (up to 2 years) antithrombotic management patterns in a real-life setting for patients hospitalized for an acute coronary syndrome (ACS) event, and to document clinical outcomes. RESEARCH DESIGN AND METHODS: EPICOR-RUS was a multicenter (34 centers), prospective, observational, longitudinal cohort study conducted across Russia on antithrombotic management in hospitalized (within 24 hours of symptom onset) ACS patients with 2 year follow-up. CLINICAL TRIAL REGISTRATION: NCT01373957. RESULTS: A total of 600 ACS patients (71.1% male, mean age 60 years) were enrolled; 599 were included for analysis. Diagnosis comprised STEMI (n = 375, 62.6%), NSTEMI (n = 147, 24.5%), and unstable angina (UA) (n = 77, 12.9%). Percutaneous coronary intervention (PCI) was conducted in 64.3% of patients with STEMI (with or without thrombolysis), 36.7% with NSTEMI, and 58.4% with UA. There was undertreatment with dual antiplatelet therapy (DAPT) for STEMI, NSTEMI, and UA: 14.7%, 25.9% and 16.9% of patients, respectively, were not receiving DAPT during hospitalization, and 10.1%, 21.8% and 16.9% at discharge. Post-discharge, of the STEMI group, only 72.4% of patients who were managed by PCI and 39.8% of conservatively treated patients received DAPT at 12 months. The respective figures in the NSTEMI group were 77.3% and 26.4%. In the STEMI cohort the cumulative incidence of all-cause mortality was 3.2% at 1 year and 5.1% at 2 years of follow-up; in the NSTEMI cohort this was 2.7% and 4.8%, respectively. There were no deaths by 12 months and one death by 24 months (1.3%) in the UA population. CONCLUSION: Despite evidence-based guidelines for the management of ACS, the real-world setting in Russia shows discrepancies in clinical practice, highlighting the need for improvements for the optimal management of high-risk patients with ACS.