Jarkovský, Jiří

Abstract Background Cardiovascular disease (CVD) is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular (CV) benefits and are recommended for T2DM patients with atherosclerotic CVD (ASCVD). However, real-world data on their adoption in high-risk populations, particularly myocardial infarction (MI) and stroke survivors, remain limited. Purpose To assess real-world utilization of GLP-1RAs and SGLT2i among T2DM patients with ASCVD focusing on trends, disparities by age, sex, and region from 2015 to 2023. Methods A nationwide cohort study using data from the National Registry of Reimbursed Health Services (2015–2023), covering all reimbursed health services in the Czech Republic. Patients with nonfatal MI (ICD-10: I21, I22) or stroke (I63, I64) and confirmed T2DM were included. Prescriptions were identified at the event or within 12 months post-event. Utilization trends were analyzed, and logistic regression was used to determine predictors of medication use. Results Among 116,218 MI patients (median age:68 years, 33.5% women), 53,128 (46%) had T2DM (median age:71 years, 37% women). Within 12 months post-MI, 2.1% received GLP-1RAs and 10.6% received SGLT2i, with increasing trends from 0.3% (2015) to 4.8% (2023) (GLP-1RAs) and 0.4% (2015) to 34.8% (2023) (SGLT2i). Women were less likely to receive SGLT2i (aOR: 0.70 [95%CI:0.65–0.74]), while no significant difference was observed for GLP-1RAs (aOR:0.98 [95%CI:0.86–1.12]). Older patients (>70 years) had lower odds of receiving GLP-1RAs (aOR:0.31 [95%CI:0.27–0.36]) and SGLT2i (aOR:0.53 [95%CI:0.50–0.56]). Prescription rates were highest in Prague (3.1% GLP-1RAs; 13.5% SGLT2i) and lowest in the Moravian-Silesian Region (1.4% GLP-1RAs; 8.8% SGLT2i). Among 164,729 stroke patients (median age:73 years, 49% women), 78,562 (48%) had T2DM (median age:75 years, 50% women). Within 12 months post-stroke, 1.2% received GLP-1RAs and 3.7% received SGLT2i, with increasing trends from 0.2% (2015) to 2.8% (2023) (GLP-1RAs) and 0.1% (2015) to 10.4% (2023) (SGLT2i). Women were less likely to receive GLP-1RAs (aOR:0.82 [95%CI:0.72–0.95]) and SGLT2i (aOR:0.57 [95%CI:0.52–0.62]). Older patients (>70 years) had lower odds of receiving GLP-1RAs (aOR:0.31 [95%CI:0.27–0.36]) and SGLT2i (aOR:0.40 [95%CI:0.37–0.44]). Regional disparities were notable, with prescription rates varying from 0.8–2.1% (GLP-1RAs) and 2.4–5.2% (SGLT2i). Conclusions Prescribing rates for GLP-1RAs and SGLT2i have increased over the past eight years but remain low, even among MI and stroke survivors. Women, older patients, and those in lower-income regions are significantly less likely to receive these therapies. Targeted interventions are needed to improve secondary prevention in high-risk diabetic populations and to address these disparities.Myocardial infarction patients Stroke patients

Abstract Aims Glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular risk in patients with Type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease and are recommended in guidelines. We evaluated the real-world effectiveness of GLP-1RA therapy on cardiovascular outcomes in patients with T2D after myocardial infarction (MI) or ischaemic stroke and examined trends and disparities. Methods and results Using nationwide Czech registry data (2015–24), we identified patients with incident nonfatal MI or ischaemic stroke and confirmed T2D. GLP-1RA users—initiating therapy within 12 months post-event—were propensity score matched to non-users. The primary outcome was major adverse cardiovascular events (MACE: nonfatal MI, nonfatal stroke, cardiovascular death); secondary outcomes included individual components and all-cause mortality. GLP-1RA therapy was initiated in only ∼2% of MI and stroke survivors with T2D. Among 126 845 MI survivors, 28 206 had T2D; the matched cohort comprised 2271 patients (401 GLP-1RA; median follow-up 35 months). GLP-1RA use was associated with lower risk of MACE (HR 0.7; 95% CI, 0.52–0.93), all-cause (HR 0.61; 95% CI, 0.47–0.80), and cardiovascular death (HR 0.54; 95% CI, 0.36–0.80). Among 177 115 stroke survivors, 73 750 had T2D; the matched cohort comprised 2235 patients (385 GLP-1RA; median follow-up 27 months). GLP-1RA use was associated with lower risk of MACE (HR 0.71; 95% CI, 0.54–0.94), all-cause (HR 0.59; 95% CI, 0.46–0.76), and cardiovascular death (HR 0.55; 95% CI, 0.37–0.81). Conclusion GLP-1RA therapy after MI or stroke in T2D was associated with substantially lower risks of MACE, cardiovascular, and all-cause death in real-world practice. Utilization remained low, particularly among women and older adults, underscoring the need for broader and more equitable implementation in secondary prevention.

Abstract Background Throughout the COVID-19 pandemic many countries reported a decline in myocardial infarction (MI) and stroke admissions. Factors leading to the decline remain uncertain. Purpose In this nationwide study spanning the first two years of the COVID-19 pandemic we evaluated the changes in MI and stroke admissions as the effect of pandemic intensity and nationwide lockdown. We also investigated sex and age differences. We benefited from the fact that the Czech Republic had both, the lowest and one of the highest COVID-19 incidence. Methods We compared the first (March 1, 2020, to February 28, 2021) and the second (March 1, 2021, to February 28, 2022) pandemic years overall and during the COVID-19 waves with the preceding year (March 1, 2019, to February 28, 2020). The occurrence of MI and stroke, patient characteristics, and mortality data were obtained from two nationwide registers covering every hospitalization and every death in the Czech Republic. Results During the first and second pandemic year as compared to the preceding year there were 13,856 and 14,123 vs 15,499 MI admissions, representing a -10,6% (p<0.001) and -8,9% (p<0.001) decline; and 23,194 and 23,231 vs 25,046 stroke admissions, representing a -7.4% (p<0.001) and -7.2% (p<0.001) decline respectively. The significant decline appeared in both MI and stroke in all COVID-19 waves (spring 2020, spring 2021, autumn 2020/winter 2021, -autumn 2021/winter 2022). The greatest MI hospitalization decline (-16%) occurred during the first strict national lock down, during the first COVID-19 wave (spring 2020), the pandemic wave with the lowest COVID-19 incidence. Both, MI and stroke admissions reversed to pre-pandemic numbers during the summer (2020, 2021) when most lockdown restrictions were lifted. The decline in MI was greater in women than in men during both the first (-11.8%, -10%; p<0.001) and second (-10.8%, -7.9%; p<0.001) pandemic years, also for stroke in women greater than in men during the first (-9%, -5.9%; p<0.001) and second (-9.7%, -4.8%; p<0.001) pandemic years. The 30-day all-cause mortality in patients with MI was higher during the first (10.6%; p<0.001) but not the second (9.6%; p=0.34) pandemic year as compared to the preceding year (9.3%), whereas the 30-day mortality in patients with stroke remained unchanged. Conclusions There was a decline in both MI and stroke admissions during the first two years of the pandemic, but such decline was not related to COVID-19 incidence. The greatest reduction in both, MI and stroke admissions, appeared during the first lockdown in the first COVID-19 wave (spring 2020), the period of the lowest COVID-19 incidence. Moreover, the decline in MI and stroke admissions was greater in women. This highlights potential sex differences in health effect. Health authorities should be aware of these findings, in order to adapt their message and restriction measures in case of future major epidemics.Myocardial infarction casesStroke cases

AbstractBackground and PurposeDuring the coronavirus disease 2019 (COVID‐19) pandemic many countries reported a decline in stroke volumes. The aim of this study was to analyze if the decline was related to the intensity of the COVID‐19 pandemic.MethodsThe first pandemic year (1 March 2020 to 28 February 2021) overall and during the three COVID‐19 waves were compared with the preceding year. Volumes of acute ischaemic stroke (AIS), subarachnoid hemorrhage, intracerebral hemorrhage and recanalization treatments (intravenous thrombolysis [IVT] and mechanical thrombectomy [MT]) were obtained from the National Register of Reimbursed Health Services. Door‐to‐needle time, onset‐to‐door time and National Institutes of Health Stroke Scale at admission were obtained from the Registry of Stroke Care Quality.ResultsDuring the pandemic year compared to the preceding year there were 26,453 versus 28,771 stroke admissions, representing an 8.8% decline (p < 0.001). The declines (−10%, −11%, −19%) appeared in COVID‐19 waves (spring 2020, autumn 2020, winter 2021) except for an increase (2%) during summer 2020. Admissions for AIS declined by 10.2% (p < 0.001), whilst hemorrhagic stroke volumes were minimally decreased. The absolute volumes of IVT and MT decreased by 9.4% (p < 0.001) and 5.7% (p = 0.16), respectively. However, the proportions of ischaemic stroke patients receiving IVT (18% vs. 18%; p = 0.72) and MT (6% vs. 6%; p = 0.28) remained unchanged.ConclusionsThere was a decline in stroke admissions, but such decline was not related to COVID‐19 incidence. The frequency of use of recanalization procedures (IVT, MT) and times (onset‐to‐door time, door‐to‐needle time) in AIS were preserved in the Czech Republic during the first year of the pandemic.

Abstract Introduction: IgM-secreting myeloma is rare, encompassing about 1% of all the myeloma cases. Given its rarity, the characteristics and survival of these patients have not been extensively studied. Therefore, we carried out a multicenter retrospective study in patients with IgM myeloma. Methods: The study protocol was reviewed and approved by the Institutional Review Board of each participating institution. Clinical data were gathered and included age, sex, hemoglobin, calcium, LDH, estimated glomerular filtration rate (GFR), presence of lytic bone lesions, International Staging System score, cytogenetic abnormalities, final outcome and overall survival (OS) time. OS was defined as the time in months from diagnosis to last follow-up or death. The Chi-square and the rank-sum tests were used to compare categorical and continuous variables, respectively. The Kaplan-Meier method was used to estimate OS and the log-rank waas used to compare groups. The Cox proportional-hazard regression method was used to fit univariate and multivariate survival models, reported as hazard ratio (HR) with 95% confidence intervals (CI). All reported p-values are two-sided, and were considered significant if less than 0.05. Results: A total of 159 patients with IgM myeloma from 20 centers from Europe, USA and Latin America were included in this analysis. Patients were diagnosed between 1996 and 2015. The median age at diagnosis was 65 years (range 37-86 years) with a male predominance (68%). The median serum IgM level was 2510 mg/dl (range 27-12,100 mg/dl) with 25% of patients having a serum IgM within normal limits but an IgM monoclonal spike detectable in serum electrophoresis. Hemoglobin levels <10 g/dl were seen in 49 patients (32%), serum calcium was elevated in 24 (16%), estimated GFR of 60 ml/min or less in 56 (37%), lytic lesions were detected in 86 (58%), and serum LDH was elevated in 28 (24%). ISS scores of 1, 2 and 3 were seen in 53 (36%), 63 (43%) and 31 (21%) of patients, respectively. Although immunohistochemistry and/or flow cytometry data were limited, CD20 expression was seen in 15/26 (58%) and cyclin D1 in 10/15 (67%) patients. The most common cytogenetic abnormalities were t(11;14) in 26/67 (39%), del13q in 25/76 (33%) and del17p in 6/76 (8%) patients. 149 patients (94%) received at least one line of systemic therapy for myeloma of which 13 (9%) received rituximab as part of initial therapy. After a median follow-up of 47 months, 74 patients (47%) have died. The median OS was 62 months (95% CI 51-79 months). Cause of death was known in 38 patients, and the most common was myeloma progression (74%). IN the univariate analysis, prognostic factors associated with a worse OS were age (HR 1.03, 95% CI 1.01-1.06; p=0.01) and ISS score (ISS 2: HR 1.43, 95% CI 0.83-2.48; p=0.2, and ISS 3: HR 3.03, 95% CI 1.54-5.98; p=0.001, using ISS 1 as reference group), while male sex was associated with a better OS (HR 0.56, 95% CI 0.34-0.90; p=0.02). Hemoglobin, calcium, estimated GFR and lytic lesions were not associated with OS. In the multivariate analysis, male sex was associated with a better OS (HR 0.57, 95% CI 0.35-0.95; p=0.03) and ISS with worse OS (ISS 2: HR 1.57, 95% CI 0.89-2.74; p=0.12, and ISS 3: HR 2.76, 95% CI 1.38-5.55; p=0.004, using ISS 1 as reference group). Conclusion: Patients with IgM myeloma apparently present with similar clinical characteristics as patients with non-IgM myeloma. Pathologically, CD20 and cyclin D1 expression is common. The most common cytogenetic abnormalities identified were t(11;14) and del13q. Survival does not appear shorter than non-IgM myeloma patients, and the ISS appears to have similar prognostic value. Disclosures Castillo: Millennium: Research Funding; Janssen: Honoraria; Otsuka: Consultancy; Biogen: Consultancy; Abbvie: Research Funding; Pharmacyclics: Honoraria. Ghobrial:Celgene: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Novartis: Honoraria; Takeda: Honoraria; Noxxon: Honoraria; Amgen: Honoraria. Hájek:Celgene: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; BMS: Honoraria; Takeda: Consultancy. Hungria:International Myeloma Foundation Latin America: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Amgen: Consultancy; Roche: Consultancy; Bristol: Consultancy; Janssen: Consultancy, Speakers Bureau. Niesvizky:Celgene: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Onyx: Consultancy, Research Funding, Speakers Bureau. Reagan:Alexion: Honoraria; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Richardson:Celgene: Membership on an entity's Board of Directors or advisory committees. Spicka:Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Millenium: Honoraria. Gertz:Celgene: Honoraria; Med Learning Group: Honoraria, Speakers Bureau; Research to Practice: Honoraria, Speakers Bureau; Alnylam Pharmaceuticals: Research Funding; Novartis: Research Funding; Prothena Therapeutics: Research Funding; Ionis: Research Funding; NCI Frederick: Honoraria; Sandoz Inc: Honoraria; GSK: Honoraria; Annexon Biosciences: Research Funding.

AbstractIgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37, 43, 19, and 70%, respectively. The median serum IgM level was 2,895 mg dL−1 with 19% of patients presenting with levels >6,000 mg dL−1. International Staging System (ISS) stages 1, 2, and 3 were seen in 40 (33%), 54 (44%), and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t(11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (P = 0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes.