Lipid-lowering therapy with inclisiran in the real-world setting: Initial data from a national health care service.

BACKGROUND: Inclisiran, a small-interfering RNA enabling long-term inhibition of PCSK9 synthesis, demonstrates good safety and efficacy profile in clinical trials. Real-world data on the potential to attain lipid-goals and reduce treatment gaps is lacking. OBJECTIVES: To investigate the implementation of inclisiran in real-world clinical setting. METHODS: Data from a nationwide healthcare organization on patients initiating inclisiran between 3/2022-11/2023. Patients' characteristics, lipid-lowering therapies, post-treatment reduction in low-density lipoprotein cholesterol (LDL-C), and attainment of treatment goals, were evaluated. RESULTS: Inclisiran was initiated by 503 patients (57 % women; mean age 66±11 years). Cardiovascular disease was present in 54 %, and peak LDL-C levels >190 mg/dL documented in 64 %. Prior exposure to PCSK9 monoclonal antibodies was evident in 28 %. Lipid profile >2 months after filling first prescription, was available in 397 patients (347 with ≥2 injections). In patients treated by inclisiran only (n = 254), median LDL-C reduction from peak levels was 57 % (IQR, 48 %-67 %), and from pre-injection levels 40 % (19 %-54 %). In those with concomitant lipid-lowering therapies (n = 143), median LDL-C reduction from peak levels was 66 % (IQR, 55 %-73 %), and from pre-injection levels 46 % (23 %-59 %). LDL-C < 70 mg/dL was attained by 39 % and LDL-C < 55 mg/dL by 21.9 %. Of those treated with concomitant statin therapy, 38 % attained LDL-C < 55 mg/dL. Overall, 6.5 % discontinued inclisiran therapy after initial injection. CONCLUSIONS: In real-world practice, inclisiran showed good efficacy in reducing LDL-C with high interindividual variability. However, attainment rates of lipid-goals were suboptimal due to limited use of combination lipid-lowering therapy and high-rates of severe hypercholesterolemia in our patient population cohort.

CHA2DS2-VASc Score as a Predictor of Adverse Outcomes after Ischemic Stroke in Patients without Atrial Fibrillation.

BACKGROUND: Ischemic stroke is associated with increased risk of morbidity and mortality in future vascular events. OBJECTIVES: To investigate whether CHA2DS2-VASc scores aid in risk stratification of middle-aged patients without atrial fibrillation (AF) experiencing ischemic stroke. METHODS: We analyzed data of 2628 patients, aged 40-65 years with no known AF who presented with acute ischemic stroke between January 2020 and February 2022. We explored the association between CHA2DS2-VASc scores categorized by subgroups (score 2-3, 4-5, or 6-7) with major adverse cardiac and cerebrovascular events (MACCE) including recurrent stroke, myocardial infarction, coronary revascularization, or all-cause death during a median follow-up of 19.9 months. RESULTS: Mean age was 57 years (30% women); half were defined as low socioeconomic status. Co-morbidities included hypertension, diabetes, obesity, and smoking in 40-60% of the patients. The incidence rate of MACCE per 100 person-years was 6.7, 12.2, and 21.2 in those with score 2-3, 4-5, and 6-7, respectively. In a multivariate cox regression model, compared to patients with score 2-3 (reference group), those with score 4-5 and 6-7 had an adjusted hazard ratio (95% confidence interval [95%CI]) for MACCE of 1.74 (95%CI 1.41-2.14) and 2.87 (95%CI 2.10-3.93), respectively. The discriminative capacity of CHA2DS2-VASc score for overall MACCE was modest (area under curve 0.63; 95%CI 0.60-0.66), although better for myocardial infarction 0.69 (95% CI 0.61-0.77). CONCLUSIONS: CHA2DS2-VASc score may predict future MACCE in middle-aged patients with ischemic stroke and no history of AF.

Cardiorespiratory Fitness and Risk of Cardiovascular Events and Mortality in Middle Age Patients without Known Cardiovascular Disease.

BACKGROUND: Low cardiorespiratory fitness is an established risk predictor for chronic non-communicable diseases. We aimed to investigate the prognostic significance of fitness level on the risk of major adverse cardiac events (MACE, the composite of myocardial infarction, stroke, or all-cause death), in a contemporary cohort of middle-aged subjects without cardiovascular disease. METHODS: Retrospective analysis of patients aged 40-60 years without a history of cardiovascular disease. Degree of fitness was determined according to a graded, maximal treadmill exercise stress testing (EST) time achieved, classified into age- and sex-specific quintiles (Q), and categorized as low (Q1), moderate (Q2-Q4) or high (Q5) fitness groups. A multivariable Cox proportional hazard regression model was used to assess the association of fitness level with the risk of MACE. RESULTS: A total of 6836 patients were included, of which 44.5% were women, and the mean age was 52 years. Overall, 289 MACE events occurred during a median follow-up of 7 years. Level of fitness was inversely associated with the presence of cardiovascular risk factors. The multivariable adjusted hazard ratio (95% confidence interval) for MACE was 1.65 (1.12-2.44) and 2.17 (1.40-3.38) in those at moderate and low fitness levels, compared to the high-fitness group (reference), respectively. For each decrease of one metabolic equivalent (MET) unit achieved at peak exercise, the relative risk for MACE increased by 18%. The association between low fitness and MACE was not modified by other risk factors (P-for-interaction non-significant). CONCLUSIONS: Low fitness level, as captured by a maximal treadmill EST, is an independent risk predictor for MACE among middle-age individuals without known cardiovascular disease. The association of low fitness with high burden of cardiometabolic risk factors highlight the importance of lifestyle intervention in this patient population.

Strategy for Totally Percutaneous Management of Vascular Injury in Combined Transfemoral Transcatheter Aortic Valve Replacement and Endovascular Aortic Aneurysm Repair Procedures.

Minimally invasive treatment of severe aortic stenosis by transcatheter aortic valve replacement (TAVR) and infrarenal abdominal aortic aneurysm by endovascular aortic aneurysm repair (EVAR) requires large-bore vascular access. These percutaneous transfemoral interventions may be performed as a combined procedure, however, vascular injury may necessitate surgical vascular repair. We implemented a strategy designed to enable percutaneous vascular repair, with stent-graft implantation, if necessary, after these combined procedures. We identified all combined percutaneous TAVR and EVAR procedures which were performed at our institution. Patient and procedural characteristics and clinical outcomes were analyzed. Six consecutive patients underwent total percutaneous combined TAVR and EVAR procedures. In all cases, TAVR was performed first and was followed by EVAR. Both common femoral arteries served as primary access sites for delivery of the implanted devices and hemostasis was achieved by deployment of vascular closure devices. Secondary access sites included the right brachial artery in all patients and superficial femoral arteries in 50% of the patients. In all cases an "0.014" 300-cm length "safety" wire was delivered to the common femoral artery or descending aorta by way of a secondary access site to facilitate stent graft delivery. Successful device implantation was achieved in all cases. Vascular closure device failure occurred in 2 patients and was treated by stent graft implantation by way of the brachial and superficial femoral arteries, without need for surgical vascular repair. A strategy designed to facilitate percutaneous vascular repair after combined EVAR and TAVR procedures may enable a truly minimally invasive procedure.

A Patient With Single Coronary Artery and Pectus Excavatum Presenting With Non-ST Elevation Myocardial Infarction.

We report the case of a 51-year-old male with pectus excavatum (PEX) who presented with stress-related chest pain as a symptom of acute non-ST elevation myocardial infarction. Coronary angiography (CAG) revealed a suspected single coronary artery (SCA) anatomy with diffuse atherosclerotic narrowing, without evidence of other coronary ostia in the aortic root. The diagnosis was confirmed on cardiac computed tomography (CCTA) as the SCA of the R-I type by Lipton classification. The percutaneous coronary intervention was performed with good angiographic results and resolution of symptoms.

Trends in occurrence of takotsubo syndrome and association with SARS-CoV-2 infection and COVID-19 vaccination.

AIMS: Takotsubo syndrome (TTS) is a serious heart disease associated with significant morbidity and mortality. TTS has been related to SARS-CoV-2 infection and COVID-19 vaccine; however, the current data are scarce. We aimed to examine the associations between SARS-CoV-2 infection and its vaccine with TTS. METHODS: We conducted a nested case-control study in a cohort of 3 237 909 adults from the largest healthcare provider in Israel. Patients were followed from 1 March 2020 until 31 December 2021 for the occurrence of TTS. Ten randomly selected controls were matched to each case of TTS on age, sex, and duration of follow-up. Exposure to SARS-CoV-2 infection and COVID-19 vaccine in the prior 30 days was assessed in cases and controls. RESULTS: During the follow-up 144 patients developed TTS and were matched to 1440 controls. The mean age of cases and their matched controls was 71.4 ±â€Š12 years, and 136 (94.4%) of them were women. Conditional logistic regression analysis showed that SARS-CoV-2 infection and COVID-19 vaccine were not associated with an increased risk of TTS; odds ratio (OR) = 2.04 [95% confidence interval (CI), 0.50-8.2] and 0.87 (0.49-1.54), respectively. The absolute number of TTS cases in the prepandemic period (March-December 2018-2019) was 82 in 2018 and 80 in 2019. The number of TTS cases decreased to 56 during the corresponding period of 2020 (first pandemic year) and increased back to 81 in 2022. CONCLUSION: No significant association was found between SARS-CoV-2 infection or COVID-19 vaccination and TTS occurrence.

Association between SARS-CoV-2 infection and new-onset atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with substantial morbidity and mortality. New-onset AF (NOAF) has been related recently to SARS-CoV-2 infection; however, the evidence supporting this link is still scarce. We aimed to examine the association between SARS-CoV-2 infection and NOAF. METHODS: We conducted a nested-case control study in a cohort of 2,931,046 adults from the largest healthcare provider in Israel. Subjects were followed from March 1st, 2020, until June 30th, 2022, for the occurrence of NOAF. Ten randomly selected controls were matched to each case of NOAF on age, sex, and duration of follow-up. Exposure to SARS-CoV-2 infection in the prior 30 days was assessed in cases and controls. To account for surveillance bias we performed a lag-time analysis and assessed the association with a negative control exposure (low back pain). Data was analyzed using conditional logistic regression. RESULTS: During the follow-up 18,981 patients developed NOAF and were matched to 189,810 controls. The mean age of cases and matched controls was 73.8 ± 13 years, and 51.1% of them were women. Multivariable analysis showed that SARS-CoV-2 infection was associated with an increased risk of NOAF; adjusted-OR, 4.24 (95% CI, 3.89-4.62). The association remained significant on lag-time analysis; however, the strength of the association was gradually attenuated with increasing lag-time but stabilized around a lag-time of 20 days. The negative control exposure (low back pain) was associated only with small increased risk of NOAF; adjusted-OR of 1.13 (95% CI, 1.02-1.26). CONCLUSION: SARS-CoV-2 infection appears to be associated with increased risk of NOAF.

Guideline-Directed Low-Density Lipoprotein Cholesterol Management After Acute Ischemic Stroke: Findings from a National Health Care Service.

Patients with ischemic stroke are at high risk for future cardiovascular events and should be treated intensively with lipid-modifying agents. Combination lipid-lowering therapies are often needed to achieve updated guideline-directed treatment goals. However, real-world data on intensification of lipid-lowering therapies and attainment of low-density lipoprotein cholesterol (LDL-C) targets early after ischemic stroke are limited. We extracted data from the largest healthcare provider in Israel on patients hospitalized with acute ischemic stroke between January 2020 and February 2022. Included were 3,027 patients surviving ≥1 year after stroke, with documented LDL-C levels and lipid-lowering medications at 2 time periods (0 to 3 months and 6 to 12 months after discharge). Participants were classified according to preexisting stroke and/or coronary artery disease. The use of combination lipid-lowering therapy (ezetimibe and/or proprotein convertase subtilisin/kexin type 9 [monoclonal antibodies] inhibitor plus statin) in the study population increased between the 2 timepoints from 3.6% to 5.1%, reaching 10.5% in those with previous coronary artery disease and stroke. LDL-C levels <70 and <55 mg/100 ml were attained by 42.3% and 22.9% of patients early after hospitalization, and in 49.5% and 27.1% during 6 to 12 months after hospitalization, respectively. Attainment of guideline-recommended LDL-C goals was higher in patients treated with combination lipid-lowering therapies and in those with preexisting cardiovascular disease. In conclusion, despite the advances in drug development and the availability of several mechanisms to lower cholesterol levels, the attainment of guideline-recommended LDL-C targets after acute ischemic stroke is suboptimal. Intensification of treatment with combination lipid-lowering therapies after hospitalization is uncommonly performed in clinical practice, even in those with preexisting cardiovascular disease.

[DOES INCIDENTAL CALCIUM DEPOSITION IN NON-CARDIAC CT SCANS PREDICT CARDIOVASCULAR MORBIDITY AND MORTALITY IN YOUNG ADULTS - A RETROSPECTIVE STUDY].

INTRODUCTION: Calcium score (CS) in cardiac CT scans represents an effective tool in the early diagnosis of cardiovascular disease. Few studies evaluated the value of incidental arterial calcification (AC) in non-cardiac CT scans, especially in young adults with no prior cardiovascular disease. AIMS: To examine the relationship between arterial calcifications and the incidence of cardiovascular events. METHODS: A retrospective study in patients aged 40-51 years old with no history of cardiovascular disease who underwent chest CT scans between 1.9.2012-31.8.2013 for reasons not related to cardiovascular disease. We assessed the presence of AC in the aorta and coronary arteries and its association with the rates of coronary catheterization for acute coronary syndrome (ACS), cardiac mortality and emergency room (ER) visits or hospitalizations for cardiovascular disease. Furthermore, we examined the association between AC and atherosclerotic risk factors. RESULTS: A total of 407 patients underwent CT scans for non-cardiovascular reasons within the timeframe specified; 308 were included in the study, 150 men and 158 women with average follow-up period of 7.2+0.29 years. There was an increased frequency in ACS and coronary catheterizations in patients with a positive AC compared to those with null AC (11.6% vs. 0.5% respectively, P= 0.0001, OR = 29.1). A positive AC was found more in men than women (35% vs. 20.9% respectively, P=0.006, OR=2.18). Patients with a positive AC had more ER and hospital admissions (33.7 % vs. 14.4% respectively, P<0.0001, OR=3). Patients with diabetes, hypertension and hyperlipidemia exhibited higher rates of positive AC. CONCLUSIONS: Although multivariate analysis is still to be conducted, it seems that AC is associated with cardiovascular morbidity and increased incidence of coronary catheterizations. Primary preventive strategies in patients with positive AC may reduce cardiovascular morbidity and mortality.

[AMIODARONE-INDUCED THYROTOXICOSIS - RISK FACTORS AND PREDICTORS OF OUTCOME: A RETROSPECTIVE STUDY].

BACKGROUND: Amiodarone induced thyrotoxicosis (AIT) occurs with considerable incidence and is associated with significant morbidity and mortality. Factors that predict poor prognosis in this disease have not yet been sufficiently investigated. OBJECTIVES: We examined the characteristics and short-term clinical outcomes of patients with AIT (up to six months from diagnosis). We evaluated the relationship between T3 and T4 levels at time of presentation and complications associated with AIT. METHODS: A retrospective epidemiological study was conducted reviewing all cases diagnosed with thyrotoxicosis and amiodarone consumption of patients treated in the Carmel Medical Center between the years 2004-2008. We examined the characteristics of patients who tend to develop AIT. In addition, we examined whether T3 and T4 levels at the time of presentation were a predictor of a poor prognosis. Three major complications associated with AIT were defined as primary outcomes within six months of diagnosis: 1. mortality; 2. development of AIT-related complications that required hospitalization; 3. the need for thyroidectomy. RESULTS: A total of 400 patients were diagnosed with thyrotoxicosis and consumed amiodarone. However, only 39 patients met the definition of AIT. The composite outcome of mortality, AIT-related complications and thyroidectomy were found in the vast majority of patients (94.8%, 37 out of 39 participants); 3 (7.6%) died and 35 (89.7%) were hospitalized with AIT-related complications and 8 (20.5%) required thyroidectomy. We found a statistically significant relationship between high T4 levels (above 64.3 mcg/dL or above 3 times the upper limit of the norm) and the composite of two main endpoints: mortality and the need for thyroidectomy in the first half year of diagnosis (P=0.009). CONCLUSIONS: AIT is associated with significant morbidity and mortality. An elevated level of free T4 reflects the severity of AIT. In patients with significantly increased T4 values, an early surgical intervention should be considered.