Rate Of Adverse Cardiovascular Events Research Articles

Modified Balloon Use After Rotational Atherectomy Reduces Major Adverse Cardiovascular Event Rates in Severely Calcified Coronary Lesions: A Systematic Review and Meta-Analysis

Modified Balloon Use After Rotational Atherectomy Reduces Major Adverse Cardiovascular Event Rates in Severely Calcified Coronary Lesions: A Systematic Review and Meta-Analysis

Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis refractory to biologic therapy: 2-year clinical and radiographic results from the open-label extension of the SELECT-AXIS 2 study.

The efficacy and safety of upadacitinib in patients with ankylosing spondylitis (AS) and inadequate response/intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR) were evaluated through 1 year in the SELECT-AXIS 2 study. Here, we assess 2-year efficacy, safety, and imaging outcomes in SELECT-AXIS 2. Patients who received continuous upadacitinib, and those who switched from placebo to upadacitinib at week 14, could enter the open-label extension (OLE). Efficacy endpoints included Assessment of SpondyloArthritis international Society (ASAS) and Axial Spondyloarthritis Disease Activity Score (ASDAS) responses, and changes from baseline in measures of disease activity, back pain, function, and quality of life. Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). As observed (AO) and AO with non-responder imputation (AO-NRI) analyses were used for binary endpoints; AO with mixed-effects model for repeated measures (AO-MMRM) for continuous endpoints; and AO-analysis of covariance for mSASSS. Treatment-emergent adverse events (TEAEs) in patients receiving ≥ 1 upadacitinib dose through week 104 are presented as events (E)/100 patient-years (PY). Subgroup analyses were performed by prior tumor necrosis factor/interleukin-17 inhibitor exposure and bDMARD lack of efficacy/intolerance. Of 420 patients who entered the bDMARD-IR AS study, 409 entered the OLE, and 331 (continuous upadacitinib, n = 163; placebo to upadacitinib, n = 168) completed week 104. Improvements in efficacy measures were sustained through the OLE, with similar response rates between the continuous upadacitinib and placebo to upadacitinib groups at week 104. At week 104, 64.9% and 61.7% of patients, respectively, had achieved ASAS 40% response (AO-NRI). Mean changes from baseline were similar between the two groups at week 104 across measures (ASDAS: -2.1 and -2.0; total back pain: -4.9 and -4.6, respectively; AO-MMRM). Over 93.0% of patients showed no radiographic progression (mSASSS mean change from baseline < 2) at week 104. The overall TEAE rate was 165.2 E/100 PY, with low rates of major adverse cardiovascular and venous thromboembolic events (0.3 E/100 PY each). Upadacitinib efficacy, including very low rates of radiographic progression, was demonstrated through 104 weeks in treatment-refractory patients with active AS. Treatment was well tolerated, with no newly identified safety signals. NCT04169373.

Dapagliflozin versus empagliflozin and major adverse cardiovascular events in type 2 diabetes: a nationwide cohort study

Abstract Background Large randomized clinical trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure, chronic kidney disease, or type 2 diabetes mellitus (T2DM) at high risk of atherosclerotic cardiovascular disease. Whether these effects might differ between individual SGLT2-inhbitors remain unclear given the lack of head-to-head comparisons. Purpose To examine the association between treatment with dapagliflozin versus empagliflozin and the long-term rate of major adverse cardiovascular events (MACE) in patients with T2DM. Methods Using nationwide registries, all Danish residents with T2DM, who initiated treatment with dapagliflozin or empagliflozin from 2015 to 2020, were identified. Only treatment with dapagliflozin or empagliflozin was considered in the present analysis, since approximately 3% initiated treatment with other SGLT2-inhibitors (i.e., canagliflozin and ertugliflozin). Patients were followed from date of the first claimed prescription of dapagliflozin or empagliflozin until the outcome of interest, emigration, death, or end of study (December 31, 2021). The primary outcome was a composite endpoint of major adverse cardiovascular events (i.e., time to first heart failure hospitalisation, acute myocardial infarction (AMI), stroke, or all-cause mortality). The primary outcome was compared between the dapagliflozin and empagliflozin group, overall and in prespecified subgroups of interest, with multivariable Cox proportional hazards regression models. Results In total, 61,031 patients with T2DM initiated treatment with dapagliflozin (N=21,028; 34.5%) or empagliflozin (N=40,003; 65.5%). The median age of study population was 62.6 years (25th-75th percentile, 54.2-70.8 years), and 62.6% were men. There were no clinically significant differences between the dapagliflozin and empagliflozin group with respect to age, sex, and clinical characteristics. The median follow-up was 3.1 years (25th-75th percentile, 1.9-4.5 years). The adjusted long-term hazard ratios of the primary outcome, overall and in prespecified subgroups of interest, are displayed in the Figure. Compared with empagliflozin, treatment with dapagliflozin was not associated with a significantly different rate of the primary outcome (HR 1.02 [95% CI, 0.97-1.07]). The observed association was consistent across clinically relevant subgroups, including in patients with and without heart failure, chronic kidney disease, and atherosclerotic cardiovascular disease. Conclusion In a large, nationwide cohort of patients with T2DM, treatment with dapagliflozin was associated with a similar rate of major adverse cardiovascular outcomes compared with empagliflozin, and this association was consistent across clinically relevant subgroups. These findings suggest that the benefits of SGLT2-inhibitors can be characterized as a class-effect.

Exploring the long-term effects of dapagliflozin in patients with stable acute myocardial infarction and preserved ejection fraction through a propensity score matching study

Abstract Background and Aims The recent Emmy trial underscored notable improvements in cardiac structure and function among post-acute myocardial infarction (AMI) patients treated with Empagliflozin, compared to those receiving a placebo. However, limitations such as a small sample size and a short follow-up period hindered the assessment of potential differences in actual clinical events between the groups. Consequently, our study aimed to evaluate the long-term outcomes, survival rates, rates of major adverse cardiovascular events (MACE), and heart failure (HF) incidence in patients with preserved ejection fraction (EF) who experienced AMI and underwent successful percutaneous coronary intervention (PCI), comparing those who received early initiation of Dapagliflozin with those who did not. Methods Data from the Taipei Medical University Research Database in Taiwan identified 7,081 inpatients who met the criteria of AMI status post successful PCI, with a left ventricular ejection fraction (LVEF) greater than 50% and absence of clinical symptoms indicative of heart failure. Exclusion criteria included individuals with a pre-existing diagnosis of heart failure before the index AMI episode and those with an LVEF below 50%, resulting in the exclusion of 357 patients from our study. The study subjects were then divided into two groups: those treated with Dapagliflozin and those not treated with Dapagliflozin, with matching for age, diabetes mellitus, and chronic kidney disease in a 1:2 ratio. Results The cohort study included of 756 patients who met the criteria of this study, among whom 252 were Dapagliflozin users and 504 were not. Over a 7-year follow-up period, Kaplan-Meier survival analyses revealed a significant reduction in cardiovascular mortality and all-cause mortality among Dapagliflozin users compared to non-users (p &amp;lt; 0.01). However, no significant differences were observed in heart failure, recurrent AMI, or stroke during the follow-up. Multivariate Cox analysis indicated the use of Dapagliflozin (hazard ratio = 0.310, 95% confidence interval = 0.188-0.510, p &amp;lt; 0.001) and age of diagnosis (hazard ratio = 1.063, 95% confidence interval =1.045-1.081, p &amp;lt; 0.001) were both independent predictors of all cause death. Conclusions In patients with stabilized AMI, the use of Dapagliflozin was associated with a decreased risk of all-cause death, especially cardiovascular mortality. However, there were no significant differences observed in the rates of heart failure, recurrent AMI, or stroke over the seven-year follow-up period.Baseline characteristicsKaplan–Meier curves of all cause death

Prognostic implication of computational angiography-derived fractional flow reserve in patients with non-obstructive coronary artery disease

Abstract Background Non-obstructive coronary artery disease (NOCAD) is proved to have high association with rate of major adverse cardiovascular events (MACE) in recent studies, yet risk stratification of symptomatic Non-Obstructive Coronary Artery Disease (NOCAD) patients remains uncertain. Objectives Our study assessed clinical value of single-vessel, multi-vessel, and three-vessel computational angiography-derived fractional flow reserve (caFFR) measurement in NOCAD patients. Methods We enrolled patients with ≤ 50% stenosis with a caFFR value ≥ 0.8 in all three coronary arteries on coronary angiography. The sum of caFFR values in the three vessels was computed for each patient. Patient stratification was based on median value of the following criteria: single vessel analysis, multi-vessel analysis, 3-vessel (3V) analysis. The primary endpoint of this study was major adverse cardiac events (MACE) at 5 years, defined as a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. Results A total of 490 patients were included (mean age 64.39 ± 11.16, 55.5% male). The 5-year MACE rates in single-vessel analysis were statistically insignificant between low and high caFFR groups (Left anterior descending artery (P=0.163); Left circumflex artery (P=0.797); Right coronary artery (P=0.127)). In multi-vessel analysis, patients in multiple-vessel low-caFFR group (with 2-3 vessels lower than median value of all coronary arteries) show an increased risk of 5-year MACE than patients in single-vessel low-caFFR group (0-1 vessel) (hazard ratio [HR] 2.648, 95% confidence interval [CI] 1.141 - 6.145, P = 0.023). In 3-vessel analysis, patients in the low 3V-caFFR group demonstrated a greater 5-year MACE risk than the high 3V-caFFR group ([HR] 2.43, 95% 95%[CI] 1.087 - 5.433, P = 0.031). Conclusion In patients with NOCAD, the higher count of vessels exhibiting with low caFFR values and the low 3V-caFFR values have been found to be associated with increased rate of MACE over a 5-year period. We demonstrated that both multiple-vessel and 3V-caFFR measurements serve as valuable prognostic indicators for risk assessment in NOCAD patients.

Comparative characteristics and invasive management in patients with non-ST elevation acute coronary syndromes in two high-volume hospitals from Romania and Germany

Abstract Introduction Cardiovascular disease (CVD) carries the highest mortality burden across Europe, acute coronary syndromes (ACS) being responsible for most CVD-related deaths. However, significant regional differences in ACS management have been reported. Purpose To describe the characteristics and management of patients with higher-risk non-ST elevation ACS (NSTE-ACS) in 2 high-volume hospitals from 2 European countries with different prevalence of CVD and different income (Germany – GER and Romania – RO). Methods All consecutive invasively managed high and very-high risk NSTE-ACS patients admitted in 2022 in two high-volume hospitals from GER and RO were identified. Patient clinical profiles, coronary anatomy, revascularization strategies, and in-hospital outcomes were compared. Results were adjusted for age and gender. Results 707 patients (345 GER, 66.7% male; 362 RO, 71.5% male; p&amp;gt;0.05) were included. RO patients were younger (65.5 vs. 70.1 years), with higher rates of hypertension (88.7% vs. 82.0%), dyslipidemia (95.6% vs. 81.7%), diabetes (46.1% vs. 34.5%), and active smoking (37.3% vs. 23.5%) (all p&amp;lt;0.05); whereas GER patients had higher rates of atrial fibrillation (36.2% vs. 23.2%), chronic respiratory disease (24.6% vs. 10.5%), sleep apnoea (9.0% vs. 1.4%), thyroid disorders (24.1% vs. 6.4%), and prior revascularization by percutaneous coronary interventions (PCI) (36.5% vs. 20.2%) or coronary artery bypass grafting (CABG) (15.7% vs. 3.0%) (all p&amp;lt;0.05). Mean left ventricular ejection fraction (LVEF) was lower in the RO cohort (43.4% vs. 48%, p&amp;lt;0.001). Rates of myocardial infarction diagnosed by high-sensitivity troponin I assays (88.7% GER, 87.6% RO), and median diagnosis-to-cathlab intervals (12.8 hours GER, 15.5 hours RO) were similar (all p&amp;gt;0.05). In the obstructive coronary artery disease (CAD) group (80.3% GER, 84.3% RO), no differences were found in multivessel disease rates (67.1% GER, 69.8% RO) or mean SYNTAX score (18.6 GER, 16.9 RO) (all p&amp;gt;0.05). For type 1 NSTE-ACS (67% GER vs. 79% RO, p&amp;lt;0.001), PCI represented the main revascularization method (88.3% GER vs. 78.3% RO, p&amp;lt;0.05). Excluding patients with prior CABG undergoing PCI, complete revascularization (residual SYNTAX score ≤8), was reported in 77.1% GER and 84.4% RO of the PCI cases (p&amp;gt;0.05). Intravascular imaging was used in 28.4% of PCIs in GER, and in none in RO. In-hospital mortality (7.0% GER, 6.8% RO), and rates of major adverse cardiovascular events, defined as a composite of death, myocardial infarction, and stroke (8.1% GER, 9.1% RO), were similar (all p&amp;gt;0.05). Conclusions Higher-risk NSTE-ACS patient profiles mirror overall country CVD risk patterns. Compared to Germany, patients in Romania are younger, with a higher CVD risk factor burden, lower LVEF, underdiagnosis of major non-CVD comorbidities, and delayed CAD diagnosis. Despite similar guideline-directed management and in-hospital outcomes in both centres, these aspects may influence the long-term prognosis.

Contemporary LDL-cholesterol management in male and female patients at high-cardiovascular risk: results from the European observational SANTORINI study

Abstract Background Middle aged women have a faster increase in atherosclerotic cardiovascular disease (ASCVD) events than men over time. Undertreatment with guideline-recommended therapy in women may be one of the drivers for this burden. Purpose To compare high- or very high-risk male and female patients regarding contemporary 1-year low-density lipoprotein cholesterol (LDL-C) goal attainment, lipid-lowering therapy (LLT) intensity, and major adverse cardiovascular event (MACE) rate. Methods SANTORINI is an observational, prospective study that enrolled high- and very high-cardiovascular risk patients between March 2020 and Feb 2021, across 623 sites and 14 countries in Europe from primary &amp; secondary care settings, with a further 1-year prospective follow-up. We included all patients with an LDL-C measurement at baseline and 1-year follow up (1yFU) for the current analysis. LDL-C goal attainment was defined separately for high and very-high risk categories according to 2019 ESC/EAS guidelines. Results Overall, 5197 males with a mean age of 65 years, and 2013 females with a mean age 66 years were included. At baseline, male patients had higher prevalence of pre-existing ASCVD (81.6% vs. 63.5%), and a lower prevalence of familial hypercholesterolaemia (8.7% vs. 17.2%) than female patients (Table 1). The proportion of patients reaching LDL-C goal improved from baseline to 1yFU, but was greater in males (22.9% and 33.3%, respectively) than females (16.9% and 24.6%, respectively). Similarly, the proportion of patients receiving no LLT decreased from baseline to 1yFU for both sexes, however, more females than males received no LLT at 1yFU (male: 20.7% to 2.7%; female: 23.9% to 3.9%). High intensity statin use increased for both sexes but was higher for males (22.2% to 27.3%) than for females (15.5% to 19.5%) at 1yFU. By contrast, PCSK9i use at baseline and 1yFU was lower for males (6.6% to 9.3%) than for females (9.8% to 13.4%). Nevertheless, the use of combination LLT at 1yFU was lower among females than males (male: 27.8% to 42.2%; female: 26.7% to 40.2%). During follow-up, MACE-4 was higher in males (5.31/100 patient years [PY]; 95% confidence interval [CI]: 4.68–5.95) than in females (3.63/100PY; 95% CI: 2.79–4.47). Similar results were observed for MACE-3 (Table 2). Conclusions Despite similar guideline recommendations, use of combination LLT and high intensity statin therapy was lower in female patients at high or very high cardiovascular risk than in male patients over one year of follow-up. Accordingly, female patients had lower LDL-C goal attainment both at baseline and at one-year. Nevertheless, due to intrinsic risk factors, female patients had lower rates of MACE-4 and MACE-3 than male patients.

Rationale and design of the SHASTA-3 and SHASTA-4 studies: randomized, double-blind, placebo-controlled, phase 3 studies of plozasiran in patients with severe hypertriglyceridemia

Abstract Severe hypertriglyceridemia (sHTG) confers an increased risk of atherosclerotic cardiovascular disease (ASCVD) and acute pancreatitis (AP). sHTG-associated AP is a substantial source of morbidity, mortality, reduced quality of life and financial burden to health care systems. Currently available therapeutic approaches for sHTG are often insufficient to reduce triglyceride (TG) levels and prevent AP. Plozasiran, an investigational siRNA therapeutic, inhibits hepatic production of apolipoprotein C3 (APOC3), a key regulator of lipoprotein lipase-mediated TG metabolism and clearance. In a phase 2 study of sHTG patients [TG ≥500 mg/dL (≥5.65 mmol/L)], plozasiran demonstrated durable reductions in TG levels of up to -80%, 12 weeks after the last dose, and decreased TG below 500 mg/dL (5.65 mmol/L), a threshold of increased risk for AP in most participants. The SHASTA-3 and SHASTA-4 trials will evaluate safety and efficacy of plozasiran, including AP rates, in patients with sHTG. SHASTA-3 and SHASTA-4 are phase 3, randomized, double-blind, placebo-controlled, multi-center trials. Key inclusion criteria are prior sHTG and fasting TG ≥500 mg/dL (≥5.65 mmol/L), at screening. Key exclusion criteria include use of any hepatocyte targeted siRNA treatments that target lipids and/or TGs within 1 year (except inclisiran at least 4 weeks prior to enrollment), siRNA or ASO within 60 days, known FCS diagnosis, and AP within 4 weeks of screening. 700 adults with sHTG will be enrolled in these two trials in several sites across multiple countries. Patients will be randomized 2:1 to receive 4 quarterly subcutaneous injections of plozasiran 25 mg or matching placebo over a 1-year double-blinded period, followed by post-treatment evaluation or entry into the open-label extension study. The randomization will be stratified based on TG levels (≥880 mg/dL vs &amp;lt;880 mg/dL [≥ vs &amp;lt;10 mmol/L]) and prior history of AP, within 5 years of screening. The primary efficacy endpoint of the studies is placebo-adjusted percent change in fasting TG from baseline to month 12 with plozasiran. Secondary endpoints include percent change in fasting TG from baseline to month 10 compared to placebo, percent of patients achieving fasting TGs of &amp;lt;500 mg/dL (&amp;lt;5.65 mmol/L) and TGs of &amp;lt;150 mg/dL (&amp;lt;1.69 mmol/L) at month 10 and 12 compared to placebo, and event rate of adjudicated abdominal clinical events including ER visits and hospitalization for abdominal pain attributed to HTG and events of documented pancreatitis. The effect of plozasiran on other lipids and lipoproteins, inflammatory biomarkers, and liver fat content using magnetic resonance imaging-proton density fat fraction will be assessed. Adjudicated major adverse cardiovascular event rates, safety and tolerability will be assessed. SHASTA-3 and SHASTA-4 are designed to determine whether the quarterly-dosed APOC3 siRNA plozasiran, added to standard of care, safely reduces TG levels and the rate of AP in patients with sHTG.

Primary Percutaneous Coronary Intervention in Multivessel Disease: Complete versus Culprit-only Revascularization

Objective: To compare the clinical outcomes of complete revascularization and culprit-only revascularization in patients with multivessel coronary artery disease (CAD) who presented with ST-segment elevation myocardial infarction (STEMI) at Hayatabad Medical Complex, Peshawar. Methodology: A prospective, randomized controlled trial was conducted, enrolling 400 patients with multivessel CAD. Patients were randomly assigned to either the complete revascularization group (n=200) or the culprit-only revascularization group (n=200). The primary outcomes assessed included cardiovascular death, reinfarction, and the need for repeat revascularization over a six-month follow-up period. Statistical analysis was performed using chi-square tests and Kaplan-Meier survival analysis. Results: Complete revascularization significantly reduced the rates of major adverse cardiovascular events compared to culprit-only revascularization. Cardiovascular death was lower in the complete revascularization group (4% vs 9%, p = 0.02), as was reinfarction (5% vs 11%, p = 0.01), and repeat revascularization (7% vs 15%, p = 0.004). Kaplan-Meier analysis showed a significant improvement in event-free survival in the complete revascularization group. Conclusion: Complete revascularization significantly improves clinical outcomes in patients with multivessel CAD presenting with STEMI, reducing cardiovascular death, reinfarction, and repeat revascularization. This study supports complete revascularization as a preferred treatment strategy in such patients to improve long-term outcomes. Keywords: coronary artery disease, STEMI, complete revascularization, culprit-only PCI, cardiovascular outcomes

Sarcopenia Influences Clinical Outcome in Hospitalized Patients with Peripheral Artery Disease Aged 75 Years and Older

ObjectivesSarcopenia represents a relevant comorbidity in patients with peripheral artery disease (PAD). However, only few studies exist assessing the clinical burden of sarcopenia in PAD. MethodsAll hospitalizations of patients aged ≥75 years who were admitted due to PAD within 2005-2020 in Germany were included in the study and stratified for sarcopenia. Temporal trends and the impact of sarcopenia on treatment procedures as well as adverse in-hospital events were investigated. ResultsOverall, 1,166,848 hospitalization-cases of patients admitted due to PAD (median age 81.0 [78.0-85.0] years; 49.5% female sex) were included, of which 2109 (0.2%) were coded with sarcopenia. Prevalence of sarcopenia in these patients increased during the observational period from 0.05% in 2005 to 0.34% in 2020 (β 2.61 [95%CI 2.42 to 2.80], P<0.001). Sarcopenic PAD patients were more often female (52.1% vs. 49.5%, P=0.015), obese (6.6% vs. 5.5%, P=0.021) and revealed higher prevalences of comorbidities (Charlson comorbidity index, 7.00 [6.00-9.00] vs. 6.00 [5.00-7.00], P<0.001). Sarcopenia was associated with reduced usage of reperfusion treatments (endovascular intervention: OR 0.409 [95%CI 0.358-0.466], P<0.001; surgical revascularization: OR 0.705 [95%CI 0.617-0.805],P<0.001), but higher conduction of amputation (OR 1.365 [95%CI 1.231-1.514], P<0.001) and higher rates of major adverse cardiovascular and cerebrovascular events (OR 1.313 [95%CI 1.141-1.512], P<0.001) and in-hospital death (OR 1.229 [95%CI 1.052-1.436], P=0.009). ConclusionsSarcopenia is an under-recognized condition in PAD patients of high clinical relevance causing a crucial disease burden. Awareness of the ailment needs to be increased in daily clinical practice to identify sarcopenia and improve clinical outcome of this vulnerable patient group.

Geographical Differences in the Safety and Efficacy of Tofacitinib Versus TNFi: APost Hoc Analysis of ORAL Surveillance.

In ORAL Surveillance, incidence rates (IRs) of major adverse cardiovascular events (MACE) and malignancies (excluding non-melanoma skin cancer [NMSC]) in cardiovascular (CV)-risk-enriched patients with rheumatoid arthritis (RA) were numerically greater with tofacitinib in North America versus the rest of the world, due to underlying risk factors. Here, we evaluated the safety and efficacy of tofacitinib versus tumor necrosis factor inhibitors (TNFi) among patients with RA across geographical regions. Patients with RA in ORAL Surveillance (NCT02092467), who were aged ≥ 50years with ≥ 1additional CV risk factor, received tofacitinib 5 or 10mg twice daily or TNFi; 45.9% were from either Poland or North America. This post hoc analysis stratified patients by region (Poland, North America, Other countries). Efficacy endpoints included Clinical Disease Activity Index, Disease Activity Score in 28 joints, with C-reactive protein (DAS28-4[CRP]), and Health Assessment Questionnaire-Disability Index (HAQ-DI). IRs and hazard ratios for adverse events were reported. Of 4362 patients (Poland, N = 759; North America, N = 1243; Other countries, N = 2360), more patients from North America versus Poland/Other countries had CV risk factors such as body mass index ≥ 30kg/m2 and history of diabetes/hypertension; however, more patients from Poland versus other regions were ever smokers and more patients from Poland/North America versus Other countries had history of coronary artery disease. MACE IRs were similar in North America and Poland, and numerically higher versus Other countries. IRs for malignancies (excluding NMSC) were numerically higher in NorthAmerica versus Poland/Other countries with tofacitinib. Serious infections IRs werenumerically higher in North America versus Poland across treatments. Venousthromboembolism/all-cause mortality IRs were generally comparable across regions. DAS28-4(CRP)/HAQ-DI improvements were generally lowest in North America. Differences in safety outcomes were driven by the presence of baseline risk factors; North America and Poland demonstrated a higher proportion of patients with some baseline CV risk factors/comorbidities versus Other countries. NCT02092467 (ClinicalTrials.gov).

Relationship of Subendocardial Perfusion to Myocardial Injury, Cardiac Structure, and Clinical Outcomes Among Patients With Hypertension.

Coronary microvascular dysfunction has been implicated in the development of hypertensive heart disease and heart failure, with subendocardial ischemia identified as a driver of sustained myocardial injury and fibrosis. We aimed to evaluate the relationships of subendocardial perfusion with cardiac injury, structure, and a composite of major adverse cardiac and cerebrovascular events consisting of death, heart failure hospitalization, myocardial infarction, and stroke. Layer-specific blood flow and myocardial flow reserve (MFR; stress/rest myocardial blood flow) were assessed by 13N-ammonia perfusion positron emission tomography in consecutive patients with hypertension without flow-limiting coronary artery disease (summed stress score <3) imaged at Brigham and Women's Hospital (Boston, MA) from 2015 to 2021. In this post hoc observational study, biomarkers, echocardiographic parameters, and longitudinal clinical outcomes were compared by tertiles of subendocardial MFR (MFRsubendo). Among 358 patients, the mean age was 70.6±12.0 years, and 53.4% were male. The median MFRsubendo was 2.57 (interquartile range, 2.08-3.10), and lower MFRsubendo was associated with older age, diabetes, lower renal function, greater coronary calcium burden, and higher systolic blood pressure (P<0.05 for all). In cross-sectional multivariable regression analyses, the lowest tertile of MFRsubendo was associated with myocardial injury and with greater left ventricular wall thickness and volumes compared with the highest tertile. Relative to the highest tertile, low MFRsubendo was independently associated with an increased rate of major adverse cardiac and cerebrovascular events (adjusted hazard ratio, 2.99 [95% CI, 1.39-6.44]; P=0.005) and heart failure hospitalization (adjusted hazard ratio, 2.76 [95% CI, 1.04-7.32; P=0.042) over 1.1 (interquartile range, 0.6-2.8) years median follow-up. Among patients with hypertension without flow-limiting coronary artery disease, impaired MFRsubendo was associated with cardiovascular risk factors, elevated cardiac biomarkers, cardiac structure, and clinical events.

Temporal trends in the treatment and outcome of nonagenarians with acute coronary syndrome.

Nonagenarians are a fast-growing age group among acute coronary syndrome (ACS) patients. While new therapeutic options have improved outcomes of ACS patients, data regarding very elderly ACS patients are limited. We aimed to evaluate temporal trends in the treatment and outcomes of nonagenarian ACS patients. Included were ACS patients aged below 90 years enrolled in ACS Israeli Survey. Patients were divided into two groups according to enrolment period: early (2000-2010) and recent (2012-2021). The primary endpoints were 30-day major adverse cardiovascular events and all-cause mortality. Secondary outcomes included in-hospital and 1-year all-cause mortality. Included were 316 elderly ACS patients. Of them, 184 were enrolled in the early and 132 in recent surveys. Patients enrolled in the recent period were more commonly referred for an invasive strategy and more commonly received guideline-based medical therapy. All-cause mortality at 30 days was significantly lower in the recent group compared with the early group (12.5 and 26.1%, respectively, P = 0.005). Rates of 30-day major adverse cardiovascular events were also significantly lower in the recent group (21.9 and 35.9%, respectively, P = 0.012). Patients in the recent group received more aggressive medical therapy in discharge but at 30-day follow-up, no difference in medical treatment was observed in the two groups. There were no significant differences in 1-year mortality rates. Treatment of nonagenarians with ACS has improved over the past decade. Treatment improvement was associated with a significant improvement in 30-day outcomes without any effect in 1 year. Nevertheless, even with contemporary treatment, nonagenarians with ACS remain a high-risk group with high mortality rates.

Three-Year Safety and Efficacy of Endovascular Treatment of Common Femoral Artery in 150 PAD Patients.

Background: The gold standard treatment for peripheral arterial disease (PAD) of the common femoral artery (CFA) is open common femoral endarterectomy (CFAE). Interest in the less invasive endovascular treatment (EVT) is growing due to PAD patients' frequent co-morbidities. Aims: We aimed to evaluate three-year EVT outcomes in multimorbid PAD patients with severe calcified CFA lesions. Methods: Using the prospectively maintained "all-comers" Duesseldorf PTA Registry, we analysed the three-year outcomes of 150 patients with EVT of the CFA. Between January 2017 and October 2023, 66 patients received a rotational excisional atherectomy (REA) followed by a drug-coated balloon angioplasty (DCB), and 84 patients received a DCB alone. Results: All procedures involved the CFA, 49% additionally involved the proximal superficial femoral artery (SFA), and 10% of the lesions involved the profunda femoris artery (PFA). The procedural success rate was 97% and independent of PAD stage, with a higher level of stent implantation in the DCB group (58% vs. 39%, p < 0.05). The primary patency rate at one year was 83% for REA + DCB and 87% for DCB (p = 0.576), while secondary patency after three years was 97%. The MALE rate at three years was mainly driven by cdTLR (REA + DCB: (20%) vs. DCB: (14%), p = 0.377), while major amputations were low in both groups (REA + DCB: 3% vs. DCB: 1%). Overall, the major adverse cardiovascular events (MACEs) rate at three years was low (REA + DCB: (5%) vs. DCB: (11%), p = 0.170). Conclusions: The EVT of severely calcified CFA lesions is safe and effective, with high three-year patency rates and low rates of major adverse limb events (MALEs) and MACEs. This registry demonstrates that vessel preparation with REA minimizes the need for stenting.

Treatment of Patients With De Novo Small-Vessel Coronary Lesions: Analysis of Six Randomised Controlled Trials Comparing Paclitaxel-Coated Balloons With Drug-Eluting Stents.

Both paclitaxel-coated balloons (PCB) and drug-eluting stents (DES) are indicated for the treatment of de novo small-vessel coronary lesions. Since the evidence comparing these two types of devices is limited, we undertook a meta-analysis on this issue. Our meta-analysis compared the efficacy of PCBvs. DESin the treatment of patients with de novo coronary lesions of size ≤ 2.75 mm. Only randomized controlled trials (RCTs) were included. The two treatments under comparison were PCBvs DES; the endpoint was the rate of major adverse cardiovascular events (MACE). Our statistical methods were based on the reconstruction of individual patient data from Kaplan-Meier curves using the IPDfromKM algorithm. After this reconstruction, our statistical calculations included hazard ratio (HR) estimation with a 95% confidence interval (CI), assessment of between-trial heterogeneity, and risk of bias for each RCT. Our literature search identified six RCTs that met our inclusion criteria (PICCOLETO, BELLO, RESTORE SVD, BASKET-SMALL2, PICCOLETO-II, and DISSOLVE). In our main analysis, the six treatment groups using PCB were compared with the six control groups using DES. The results showed an HR of1.029 (95%CI, 0.7446to 1.422; P=0.86) over a follow-up of 36months. Heterogeneity analysis across the six control groups showed worse outcomes in the BELLO trial and better outcomes in the three trials employing a limus-eluting stent. To evaluate trial heterogeneity through the comparison of the six PCB arms, fivetrials showed similar outcomes while the BELLO trial fared significantly worse. Risk of bias for each RCT was appropriate. Our results indicate that in de novo small-vessel coronary lesions, PCBand DESshowed similar outcomes, despite some cross-study variability. Our results provided meta-analytic confirmation that no recommendations can be made in favor of PCB or DES in the treatment of de novo small-vessel coronary lesions based on current data.

Pulsatile Left Ventricular Assistance in High-Risk Percutaneous Coronary Interventions: Short-Term Outcomes.

To document the real-world experience with the use of pneumatic pulsatile mechanical circulatory support (MCS) with the PulseCath iVAC2L during high-risk percutaneous coronary interventions (HR-PCIs). Background: The use of MCS in HR-PCIs may reduce the rate of major adverse cardiovascular events (MACEs) at 90 days. The PulseCath iVAC2L is a short-term pulsatile transaortic left ventricular (LV) assist device that has been in use since 2014. The iVAC2L Registry tracks its safety and efficacy in a variety of hospitals worldwide. Methods: The iVAC2L Registry is a multicenter, observational registry that aggregates clinical data from patients treated with the iVAC2L worldwide. A total of 293 consecutive cases were retrospectively collected and analyzed. Estimated rates of in-hospital clinical endpoints were described. All-cause mortality was used as the primary endpoint and other outcomes of interest were used as secondary endpoints. The rates obtained were reported and contextualized. Results: The in-hospital rate of all-cause mortality was 1.0%, MACE was 3.1%. Severe hypotension occurred in 8.9% of patients. Major bleeding and major vascular complications occurred in 1.0% and 2.1%, respectively. Acute myocardial infarction occurred in 0.7% of patients. Cerebrovascular events occurred in 1.4% of patients. Cardiac arrest occurred in 1.7% of patients. A statistically significant improvement in blood pressure was observed with iVAC2L activation. Conclusions: The results of the present study suggest that the iVAC2L is capable of improving hemodynamics with a low rate of adverse events. However, confirmatory studies are needed to validate these findings.

Long-Term Outcomes Following Sirolimus-Coated Balloon or Drug-Eluting Stents for Treatment of In-Stent Restenosis.

Evidence suggests that drug-coated balloons may benefit in-stent restenosis (ISR) treatment. However, the efficacy of new-generation sirolimus-coated balloon (SCB) compared with the latest generation drug-eluting stents (DESs) has not been studied in this setting. All patients in the EASTBORNE (The All-Comers Sirolimus-Coated Balloon European Registry) and DEB-DRAGON (DEB vs Thin-DES in DES-ISR: Long Term Outcomes) registries undergoing percutaneous coronary intervention for DES-ISR were included in the study. The primary study end point was target lesion revascularization at 24 months. Secondary end points were major adverse cardiovascular events, all-cause death, myocardial infarction, and target vessel revascularization at 24 months. Our goal was to evaluate the efficacy and safety of SCB versus thin-struts DES in ISR at long-term follow-up. A total of 1545 patients with 1679 ISR lesions were included in the pooled analysis, of whom 621 (40.2%) patients with 621 lesions were treated with thin-strut DES and 924 (59.8%) patients with 1045 lesions were treated with SCB. The unmatched cohort showed no differences in the incidence of target lesion revascularization (10.8% versus 11.8%; P=0.568); however, there was a trend toward lower rates of myocardial infarction (7.4% versus 5.0%; P=0.062) and major adverse cardiovascular events (20.8% versus 17.1%; P=0.072) in the SCB group. After propensity score matching (n=335 patients per group), there were no significant differences in the rates of target lesion revascularization (11.6% versus 11.8%; P=0.329), target vessel revascularization (14.0% versus 13.1%; P=0.822), myocardial infarction (7.2% versus 4.5%; P=0.186), all-cause death (5.7% versus 4.2%; P=0.476), and major adverse cardiovascular event (21.5% versus 17.6%; P=0.242) between DES and SCB treatment. In patients with ISR, angioplasty with SCB compared with thin-struts DES is associated with comparable rates of target lesion revascularization, target vessel revascularization, myocardial infarction, all-cause death, and major adverse cardiovascular events at 2 years.

Systemic inflammation and health outcomes in patients receiving treatment for atherosclerotic cardiovascular disease.

The burden and outcomes of inflammation in patients with atherosclerotic cardiovascular disease (ASCVD) are not well defined beyond the controlled settings of trials and research cohorts. This was an observational study of ASCVD adults undergoing C-reactive protein testing in Stockholm's healthcare (2007-21). After excluding C-reactive protein tests associated with acute illness or medications/conditions that bias C-reactive protein interpretation, systemic inflammation was evaluated over a 3-month ascertainment window. Determinants of C-reactive protein ≥ 2 mg/L were explored with logistic regression. C-reactive protein categories were compared via negative-binomial/Cox regression for subsequent healthcare resource utilization and occurrence of major adverse cardiovascular events, heart failure hospitalization, and death. A total of 84 399 ASCVD adults were included (46% female, mean age 71 years, 59% with C-reactive protein ≥ 2 mg/L). Female sex, older age, lower kidney function, albuminuria, diabetes, hypertension, and recent anaemia were associated with higher odds of C-reactive protein ≥ 2 mg/L. The use of renin-angiotensin system inhibitors, antiplatelets, and lipid-lowering therapy was associated with lower odds. Over a median of 6.4 years, compared with C-reactive protein < 2 mg/L, patients with C-reactive protein ≥ 2 mg/L had higher rates of hospitalizations, days spent in hospital, outpatient consultations, and dispensed medications (P < .05 for all). They also had a higher rate of major adverse cardiovascular events [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.27-1.33], heart failure (HR 1.24; 95% CI 1.20-1.30), and death (HR 1.35; 95% CI 1.31-1.39). Results were consistent across subgroups and granular C-reactive protein categories and robust to the exclusion of extreme C-reactive protein values or early events. Three in five adults with ASCVD have systemic inflammation, which is associated with excess healthcare resource utilization and increased rates of cardiovascular events and death.

Frailty and Clinical Outcomes of Ticagrelor Versus Clopidogrel in Older Adults With Acute Myocardial Infarction.

Ticagrelor is recommended over clopidogrel in acute coronary syndrome based on the results of the PLATO (Study of Platelet Inhibition and Patient Outcomes) trial. We aimed to emulate PLATO in older adults with and without frailty and with acute coronary syndrome treated with percutaneous coronary intervention. We created a new-user cohort of Medicare fee-for-service beneficiaries aged ≥65 years hospitalized for acute coronary syndrome from 2014 to 2018 and initiated ticagrelor or clopidogrel following percutaneous coronary intervention. Frailty was defined using a validated claims-based frailty index ≥0.25. Coprimary outcomes were major adverse cardiovascular events and major bleeding. Follow-up began on the date of first outpatient prescription for ticagrelor or clopidogrel and ended on the earliest date for an outcome event, death, discontinuation of the index drug, or disenrollment from Medicare. The study included 42 843 older adults; 23% were frail. After propensity score matching, the rates of major adverse cardiovascular events per 100 person-years comparing ticagrelor versus clopidogrel groups were 7.8 and 7.3 in the frail cohort (hazard ratio [HR], 1.07 [95% CI, 0.84-1.36]) and 3.7 and 4.2 in the nonfrail cohort (HR, 0.87 [95% CI, 0.75-1.02]). The corresponding rates of major bleeding were 4.3 and 3.8 in the frail cohort (HR, 1.12 95% CI, [0.80-1.56]) and 2.2 and 1.8 in the nonfrail cohort (HR, 1.22 [95% CI, 0.98-1.51]). There was a trend toward a modest reduction in risk of major adverse cardiovascular events and a trend toward a modest increase in risk of major bleeding with ticagrelor compared with clopidogrel in the nonfrail cohort. There was insufficient evidence for the benefit of ticagrelor in frail older adults.

Navigating Cardiovascular Risk and Lipid Management in Indian Patients: Key Messages from the Lipid Association of India 2024 Consensus Statement IV.

Effective lipid management is crucial for preventing atherosclerotic cardiovascular disease (ASCVD). The Western lipid guidelines may not apply to Indian subjects because of the vast differences in cardiovascular (CV) disease epidemiology. To overcome this challenge, the Lipid Association of India (LAI) in 2016 proposed an ASCVD risk stratification algorithm. The appropriate low-density lipoprotein cholesterol (LDL-C) goals for various risk groups were proposed, with an LDL-C target of <50 mg/dL recommended for the first time globally for patients in the very high-risk group. Subsequently, in 2020, an extreme risk group was added because of observations that patients with more severe or extensive ASCVD, along with multiple risk factors and comorbidities, had increased rates of adverse CV events and could benefit from more intensive LDL-C lowering. The extreme risk group was subdivided into categories A and B, with LDL-C targets as low as 30 mg/dL or lower. The availability of further evidence regarding the significance of novel risk factors and the availability of new LDL-C lowering therapies necessitated refining the ASCVD risk assessment algorithm, defining LDL-C targets for subjects with these risk factors, and incorporating recommendations for attaining very low LDL-C levels in a defined, select group of patients. Accordingly, the LAI expert group recently published the Consensus Statement IV, which is a comprehensive document addressing several key issues about risk stratification and dyslipidemia management in Indian subjects. LDL-C and nonhigh-density lipoprotein cholesterol (non-HDL-C) are not only primary and co-primary targets for lipid-lowering therapy but also risk factors for ASCVD risk stratification. Apolipoprotein B is a secondary target. The risk assessment algorithm has been updated to incorporate several nonconventional yet relevant CV risk factors. Additionally, the role of subclinical atherosclerosis has been highlighted. The CV risk due to subclinical atherosclerosis has been considered equivalent to that of established ASCVD, and hence, similar LDL-C targets have been recommended. Furthermore, a new risk category-extreme risk group category C has been added for the small subgroup of patients who continue to experience ASCVD sequelae despite achieving LDL-C levels of 30 mg/dL or lower. An ultralow LDL-C target (10-15 mg/dL) has been recommended along with optimal control of risk factors and guideline-directed management of comorbidities. Dyslipidemia management should be effective with sustained LDL-C lowering. In high-risk situations (e.g., acute coronary syndrome), the LDL-C target should be achieved as early as possible, preferably within the first 2 weeks. The present document summarizes the key messages from the LAI Consensus Statement IV.