Aim. Analysis of the relevance of drug-induced bradycardia (DIB) as a medical and social problem, its main regularities and determination of the need for further study of this issue. Materials and Methods. The register study was performed on 01 Jan 2017-30 Jun 2018 (18 months) at the clinical base of the Ryazan Regional Clinical Cardiology Dispensary. Inclusion criteria were: 1) bradycardia/bradyarrhythmia syndrome with intake of at least one drug with a bradycardic effect (BCE), 2) signing Informed consent to the processing of personal and clinical data. No additional interventions were performed in the diagnosis or treatment of patients within the registry. Results. During 18 months, 191 patients (age 77.0 [69.0;82.0] years, 26.7% of men) were hospitalized with a verified diagnosis of DIB, which accounted for 52.6% of all cases of hospitalization for drug overdose. During the analyzed period, there was an increase in both the total number of drug overdoses (1.7 times, p0.001) and overdoses of drugs with BCE (1.8 times, p0.001). Main clinical manifestations of DIB: reduced heart rate (50 beats/min 80.0%, 40 beats/min 51.1%), sinoatrial (30.4%) and atrioventricular blocks (1st degree 8.2%, 2nd degree 10.4%, 3rd degree 14.1%), syncope (32.6%) and cardiac pauses 3 s (7.4%). Almost all (94.8%) the patients were hospitalized by ambulance, 40.7% to the intensive care unit; 17.8% required pacemaker implantation; hospital mortality was 5.2%. More than half (54.5%) of hospitalized patients took 2 drugs with BCE, 15.7% 3 and 3.14% 4 (both in monotherapy and as a part of a combination): beta-blockers 68.4%, antiarrhythmic preparations 38.9%, digoxin 25.8%, non-dihydropyridine calcium antagonists 10.5%, I1-imidazoline receptor agonist 9.5%, and other drugs with BCE 7.4%. To analyze the cause of DIB, we used clinical data of 135 patients (age 77.0 [69.0;82.0] years, 20.7% of men), who could indicate the exact dose of a taken drug with BCE. Among them, the absolute exceedance of the recommended dose of drugs with BCE was found in 14.1% of cases, while in 85.9% of cases summation/potentiation effect of several drugs with ВСЕ was observed, with intake of each in a therapeutic dose. Conclusion. The study confirmed high medical and social significance of the problem of DIB, which requires attention of practitioners, pharmacologists and clinical pharmacologists, health care providers, and also continuation of its study.
Aim. Analysis of drug-induced bradiarrhythmia (DIB) causes and predisposing factors, followed by the development of recommendations for practitioners on its prevention.Material and methods. The register included consistently all cases of hospitalization at the Regional Vascular Center (Ryazan) due to DIB in 2017 (n=114), 2018 (n=167), and retrospectively in 2014 (n=44). In total, 325 cases were reported: men - 26.1%, age 76.0 [68.0; 82.0] years; patients >65 years - 83.7%, and patients >75 years - 57.9%. The dose of medications with bradycardic action (BCA) taken the day before was known in 227 cases (69.8%), which allowed us to analyze the correctness of the intake regime in these cases.Results. The excess of a single and / or daily medication dose (absolute overdose, AOD) occurred only in 10.6% of cases and was associated with the patient's attempt to cope with the deterioration of the disease or an acute clinical situation on their own. In other cases, there was no formal violation of the Instructions, but there was an inhibition of the heart's conducting system activity, characteristic of an overdose of medication (the so-called "relative” overdose, ROD). It was due to the summation/potentiation of BCA of several medications or changes in the medication pharmacokinetics. There were no differences in the clinical and demographic characteristics of patients and the provision of medical care in the groups with AOD and ROD (p>0.05). The exception was a high frequency of bradycardia <40 beats / min in AOD group (75.0% vs 49.8%, p=0.019) and, as a result, - management in the conditions of the Intensive Care Unit (66.7% vs 39.9%, p=0.012). Frequency of pre-admission receiving medications in AOD and ROD groups also did not differ (p>0.05): beta-blockers - an average of 64.3%, antiarrhythmic drugs with BCA- 41.0%, cardiac glycosides 25.1% (frequency each of these medicationsin DIB cases over the 5-year period has not changed), an agonist of the 11-imidazoline receptors - moxonidine (12.3%, its frequency has increased 8.9 times in 5 years, p=0.004), non-dihydropyridine calcium antagonists - 7.9% (decrease frequency over 5 years 4.0 times, p=0.002), other - 16.7%. In 56.8% of cases, medications with BCA were used in combination. At admission, a decrease in glomerular filtration rate (GFR) <45 ml/min/1.73 m2 was registered in 56.8% of cases, <30 ml/min/1.73 m2 - in 31.8%, <15 ml/min/1.73 m2 -in 10.9% (differences between groups with p>0.05). Hospital lethality in the AOD group is 4.2%, in the ROD group- 5.4% (p>0.05).Conclusion. The main reasons of DIB are excess of the recommended dose, unrecorded summation/potentiation of BCA of several medications, and / or changes in the medication pharmacokinetics. Predisposing factors are self-medication of patients with worsening cardiovascular disease or acute clinical situations (e.g., hypertensive crisis), taking multiple medications with BCA, accession of heart disease, manifested by bradyarrhythmia, decrease in GFR, elderly and senile age.
Background Elderly and senile people are most likely to develop cardiovascular diseases, while they have a higher risk of adverse drug reactions. Systemic analysis of medically induced bradycardia (MIB) has not been performed. Aim To analyze the clinical features of MIB in patients ≥65 and ≥75 years according to the Hospital Register of Cardiac Drug Overdoses (storm) data. Materials and methods Analyzed 17,826 cases of hospitalization in the Regional Vascular Center from 01 Jan 2017 to 31 Dec 2019, of them with all types of cardiac drug overdoses – 363, of them with MIB – 52.6% (n=191). Results Average age of those hospitalized with MIB – 74.0 [65.0; 80.0] years: 76.0% were ≥65 years, 49.4% – ≥75 years. Among the cohort ≥65 years, there were more women – 74.3% (vs 52.3%, p=0.003), ≥75 years – 74.4% vs 65.5% (p=0.107). The ratio of absolute and relative overdoses did not depend on age and was 1:9. The frequency of pulse-reducing drug admission before hospitalization did not differ in age groups. In General, in the cohort with MIB: 68.4% – beta-blockers, 25.8% – digoxin, 38.9% – antiarrhythmic drugs with pulse-reducing action (PRA), 9.5% – imidazoline receptor agonists, 10.5% – calcium channel blockers with PRA, 7.4% – other drugs with PRA, while 54.5% of patients received a combination of ≥2 drugs with PRA, 15.7% – ≥3, and even 3.1% – ≥4. In older age groups, a Glomerular Filtration Rate (GFR) decrease in was more often: among ≥65 years GFR <60 ml/min × 1.73 m2 – 83.2% (vs 40.0% in younger patients, p<0.001), <45 ml/min × 1.73 m2 – 61.5% (vs 22.5%, p<0.001), <30 ml/min × 1.73 m2 – 34.5% (vs 15.0%, p<0.001), <15 ml/min × 1.73 m2 – 11.1% (vs 7.5%, p<0.264); among patients ≥75 years: GFR <60 ml/min × 1.73 m2 – 87.4% (vs 60.8%, p<0.001), <45 ml/min × 1.73 m2 – 66.0% (vs 40.2%, p<0.001), <30 ml/min × 1.73 m2 – 37.1% (vs 23.4%, p<0.018), <15 ml/min × 1.73 m2 – 12.0% (vs 8.4%, p<0.357). Patients ≥65 and ≥75 years were more likely to require: emergency hospitalization (97.0% vs 84.1% in younger patients, p<0.001 and 97.0% vs 91.1%, p=0.033), treatment in the intensive care unit (44.7% vs 20.5%, p=0.003 and 48.8% vs 29.2%, p=0.001), temporary pacemaker (58.3% vs 20.0%, p=0.107 and 57.1% vs 40.0%, p=0.284). Hospital mortality in persons ≥75 was 7.7% (vs 1.8% in younger patients, p=0.047), ≥65 – 3.8% (vs 4.6%, p=0.814). Conclusions Older age groups predominate among those hospitalized for MIB. They are characterized by a more pronounced lesion of glomerular filtration, a more severe condition, and a higher risk of death. Practical physicians underestimate the danger of prescribing drugs with PRA, especially in the form of combined therapy, in patients of older age groups, with impaired glomerular filtration, which requires drawing attention to this problem. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Ryazan State Medical University
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