Overall Incidence Of Cardiovascular Events Research Articles

Methylphenidate and Short-Term Cardiovascular Risk

There are concerns about the safety of medications for treatment of attention-deficit/hyperactivity disorder (ADHD), with mixed evidence on possible cardiovascular risk. To assess whether short-term methylphenidate use is associated with risk of cardiovascular events. This retrospective, population-based cohort study was based on national Swedish registry data. Participants were individuals with ADHD aged 12 to 60 years with dispensed prescriptions of methylphenidate between January 1, 2007, and June 30, 2012. Each person receiving methylphenidate (n = 26 710) was matched on birth date, sex, and county to up to 10 nonusers without ADHD (n = 225 672). Statistical analyses were performed from September 13, 2022, to May 16, 2023. Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias, 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a bayesian within-individual design. Analyses were stratified by history of cardiovascular events. The cohort included 252 382 individuals (15 442 [57.8% men]; median age, 20 (IQR, 15-31) years). The overall incidence of cardiovascular events was 1.51 per 10 000 person-weeks (95% highest density interval [HDI], 1.35-1.69) for individuals receiving methylphenidate and 0.77 (95% HDI, 0.73-0.82) for the matched controls. Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41; 95% HDI, 1.09-1.88) compared with matched controls (IRR, 1.18; 95% HDI, 1.02-1.37). The posterior probabilities were 70% for at least a 10% increased risk of cardiovascular events in individuals receiving methylphenidate vs 49% in matched controls. No difference was found in this risk between individuals with and without a history of cardiovascular disease (IRR, 1.11; 95% HDI, 0.58-2.13). In this cohort study, individuals receiving methylphenidate had a small increased cardiovascular risk vs matched controls in the 6 months after treatment initiation. However, there was little evidence for an increased risk of 20% or higher and for differences in risk increase between people with and without a history of cardiovascular disease. Therefore, before treatment initiation, careful consideration of the risk-benefit trade-off of methylphenidate would be useful, regardless of cardiovascular history.

Transposition of internal carotid artery over hypoglossal nerve in eversion carotid endarterectomy

To analyze in-hospital and long-term results of eversion carotid endarterectomy (CEE) with transposition of internal carotid artery (ICA) over hypoglossal nerve. A cohort prospective open-label study included 919 patients with severe ICA stenosis for the period from January 2017 to April 2020. The 1st group (n=172) included patients who underwent eversion CEE with ICA transposition over hypoglossal nerve; the 2nd group (n=747) - who underwent conventional eversion CEE. ICA transposition technique included standard mobilization of the carotid arteries, cross-clamping, arterial wall incision, removal of atherosclerotic plaque and ICA translocation above the hypoglossal nerve for subsequent anastomosis. All patients were examined every 6 months. Mean follow-up period was 17.5±6.9 months. There were no significant between-group differences in cardiovascular morbidity. However, all complications occurred in the 2nd group (traditional eversion CEE). Nevertheless, incidence of adverse events was minimal and combined endpoint did not exceed 0.6% (n=5). Both groups were also comparable by overall incidence of cardiovascular events in long-term period. All ICA restenoses (over 70%) were symptomatic with similar incidence (4 (2.3%) vs. 18 (2.4%), respectively, p=0.83; OR 0.96; 95% CI 0.32-2.88). Mean restenosis-free period was 7.2±2.6 months. In case of significant restenosis, redo CEE with patch repair was performed. There were no cardiovascular complications. All cases of hypoglossal nerve injury occurred in the 2nd group (0 vs. 18 (100%), respectively; p=0.0001; OR 0.003; 95% CI=5.21-0.17) without ICA transposition over the hypoglossal nerve. Eversion CEE with ICA transposition over the hypoglossal nerve ensures optimal conditions for successful redo CEE in case of restenosis. This technique facilitates ICA mobilization without hypoglossal nerve injury. This aspect is valuable for successful postoperative outcome and adequate quality of life. ICA transposition is not difficult and does not require additional experience. Transposition per se is not a risk factor of ICA restenosis. Thus, ICA transposition may be routinely recommended in patients eligible for eversion CEE.

Meta-analysis and systematic review of the cardiotoxicity of TAS-102.

e16053 Background: Fluoropyrimidines such as 5-FU and capecitabine are known to be cardiotoxic drugs. TAS-102 (trifluridine-tipiracil) is a novel oral fluoropyrimidine that was recently FDA approved to treat gastric and colon cancer. However, the incidence of cardiac related events of TAS-102 is not fully ascertained. We performed a meta-analysis and systematic review to determine the incidence of cardiotoxic events associated with TAS-102. Methods: We performed a literature search through PubMed, Embase, and Web of Science to identify any publications in any language up to December 31st, 2019 where TAS-102 (and equivalent terms such as “trifluridine-tipiracil” and “Lonsurf”) was used. These were then manually reviewed to identify any publications reporting cardiac events. Randomized controlled trials (RCTs) were included for meta-analysis to determine the incidence of cardiotoxic events, which were summarized as pooled odds ratios (OR) when compared to placebo. Non-randomized, non-controlled clinical trials (phase I and phase II studies) were included in the systematic review but excluded from the pooled OR calculation. Results: 869 publications were identified in the initial literature search, of which 17 trials (3 Phase III studies, 6 Phase II studies, and 8 phase I studies) met inclusion criteria. A total of 1,877 patients among 4 RCTs were included in the meta-analysis. Compared with placebo, TAS-102 did not increase the risk of myocardial infarction (OR 1.97 95% CI [0.22-17.89]), hypertension (OR 0.73 95% CI [0.37, 1.44]), palpitations (OR 1.51 95% CI [0.30, 7.56]), cardio-pulmonary arrest (OR 0.83 95% CI [0.11-6.32]), or syncope (OR 1.50 95% CI [0.06-37.14]). Among the 1,252 patients receiving TAS-102, the overall incidence of cardiovascular events was low, with hypertension being the most common side effect (21 events), followed by palpitations (6 events), cardiopulmonary arrest (2 events), and myocardial infarction (3 events), though there was no statistically significant increased risk compared to placebo. No deaths were reported. Conclusions: Unlike other fluoropyrimidines, TAS-102 appears to be a cardiogentle drug, with no increased risk of cardiac events compared to placebo. Since fluoropyrimidines remain the backbone of treatment for gastrointestinal malignancies, TAS-102 can offer an alternative to patients who developed cardiotoxicities from other agents. Prospective studies with consideration of cardiac risk factors are required.

Contrast Induced Acute Kidney Injury and its Impact on Mid-Term Kidney Function, Cardiovascular Events and Mortality

The existence and clinical relevance of contrast induced acute kidney injury (CI-AKI) is still heavily debated and angiographic procedures are often withheld in fear of CI-AKI, especially in CKD-patients. We investigated the incidence of CI-AKI in cardiovascular high risk patients undergoing intra-arterial angiography and its impact on mid-term kidney function, cardiovascular events and mortality. We conducted a prospective observational trial on patients undergoing planned intra-arterial angiographic procedures. All subjects received standardized intravenous hydration prior to contrast application. CI-AKI was defined according to a ≥25% increase of creatinine from baseline to either 24hrs or 48hrs after angiography. Plasma creatinine and eGFR were recorded from the institutional medical record system one and three months after hospital discharge. Patients were followed up for two years to investigate the long term effects of CI-AKI on cardiovascular events and mortality. We studied 706 (317 female) patients with a mean eGFR of 52.0 ± 15 ml·min−1·1.73 m−2. The incidence of CI-AKI was 10.2% (72 patients). In 94 (13.3%) patients serum creatinine decreased ≥25% either 24 or 48 hours after angiography. Patients with CI-AKI had a lower creatinine and a higher eGFR at baseline, but no other independent predictors of CI-AKI could be identified. Kidney function was not different between both groups one and three months after discharge. After a two year follow up the overall incidence of cardiovascular events was 56.5% in the CI-AKI group and 58.8% in the Non CI-AKI group (p = 0.8), the incidence of myocardial infarctions, however, was higher in CI-AKI-patients. Overall survival was also not different between patients with CI-AKI (88.6%) and without CI-AKI (84.7%, p = 0.48). The occurrence of CI-AKI did not have any negative impact on mid-term kidney function, the incidence of cardiovascular events and mortality. Considerable fluctuations of serum creatinine interfere with the presumed diagnosis of CI-AKI. Necessary angiographic procedures should not be withheld in fear of CI-AKI.

Effects of patient age on outcomes after carotid endarterectomy: A retrospective, single-center study in Korea.

In this single-center, retrospective study, we aimed to compare early and late outcomes after carotid endarterectomy (CEA) between younger and elderly patients and to investigate the impact of patient age on the overall incidence of cardiovascular events after CEA.A total of 613 patients with 675 CEAs between January 2007 and December 2014 were stratified by patient age into 2 groups: younger (≤60 years, n = 103 CEAs, 15.3%) and elderly (>60 years, n = 572 CEAs, 84.7%) groups. The study outcomes were defined as the occurrence of major adverse events (MAEs), including fatal or nonfatal stroke or myocardial infarction (MI), or any-cause mortality, and overall cardiovascular events (meaning the composite incidence of stroke or MI) during the perioperative period and within 4 years after CEA.Although there were no significant differences in the incidence of 30-day MAEs and any of the individual MAE manifestations between the 2 groups, the differences in the MAE incidence (P = .006) and any-cause mortality (P = .023) within 4 years after CEA were significantly greater in patients in the elderly group. For overall incidence of cardiovascular events, no significant difference was noted between the 2 groups (P = .096). On multivariate analysis, older age (>60 years) did not affect the incidence of perioperative MAEs and individual MAE manifestations; however, older age was significantly associated with an increased risk of 4-year MAEs (hazard ratio [HR], 3.68, 95% confidence interval [CI], 1.35-10.0; P = .011) and any-cause mortality (HR, 3.26, 95% CI, 1.02-10.5; P = .047). With regard to the 4-year overall incidence of cardiovascular events, older age was not an independent predictor of increased risk of these cardiovascular events.Our study indicates that the risks of perioperative MAEs and the 4-year overall incidence of cardiovascular events do not significantly differ between younger and elderly Korean patients undergoing CEA, although there was a higher risk of 4-year any-cause mortality in the elderly patients. Older age does not appear to be an independent risk factor for perioperative MAEs and overall cardiovascular events within 4 years after CEA.

Comparison of outcomes after carotid endarterectomy between type 2 diabetic and non-diabetic patients with significant carotid stenosis

BackgroundWe aimed to compare early and late outcomes after carotid endarterectomy (CEA) between Korean type 2 diabetic and non-diabetic patients and to investigate the impact of diabetes on the overall incidence of cardiovascular events after CEA.MethodsWe retrospectively analyzed 675 CEAs, which were performed on 613 patients with significant carotid stenosis between January 2007 and December 2014. The CEAs were divided into a type 2 diabetes mellitus (DM) group (n = 265, 39.3%) and a non-DM group (n = 410, 60.7%). The study outcomes included the incidence of major adverse events (MAEs), defined as fatal or nonfatal stroke or myocardial infarction or all-cause mortality, during the perioperative period and within 4 years after CEA.ResultsPatients in the DM and non-DM groups did not differ significantly in the incidence of MAEs or any of the individual MAE manifestations during the perioperative period. However, within 4 years after CEA, the difference in the MAE incidence was significantly greater in the DM group (P = 0.040). Analysis of the individual MAE manifestations indicated a significantly higher risk of stroke in the DM group (P = 0.006). Multivariate analysis indicated that diabetes was not associated with MAEs or individual MAE manifestations during the perioperative period, whereas within 4 years after CEA, diabetes was an independent risk factor for MAEs overall (hazard ratio [HR], 1.62; 95% confidence interval [CI] 1.06–2.48; P = 0.026) and stroke (HR, 2.55; 95% CI 1.20–5.41; P = 0.015) in particular.ConclusionsDiabetic patients were not at greater risk of perioperative MAEs after CEA; however, the risk of late MAE occurrence was significantly greater in these patients. Within 4 years after CEA, DM was an independent risk factor for the occurrence of MAEs overall and stroke in particular.

Efficacy and safety of a novel, nebulized glycopyrrolate for the treatment of COPD: effect of baseline disease severity and age; pooled analysis of GOLDEN 3 and GOLDEN 4.

BackgroundThe efficacy and safety of nebulized glycopyrrolate inhalation solution (GLY), administered twice daily (BID) via the innovative eFlow® Closed System nebulizer (PARI Pharma GmbH, Starnberg, Germany), were demonstrated in two replicate, placebo-controlled, 12-week Phase III studies (GOLDEN 3 and GOLDEN 4). This report evaluates the efficacy and safety of GLY by baseline disease severity and age in the pooled GOLDEN 3 and GOLDEN 4 patient population (N=1,294).MethodsPatients were grouped by baseline predicted post-bronchodilator FEV1 (<50%, ≥50%) and age (<65, ≥65, ≥75 years).ResultsGLY (25 and 50 μg BID) produced significant improvements in trough FEV1 in FEV1% predicted <50% (0.070 L, 0.079 L) and ≥50% (0.112 L, 0.126 L) subgroups (P<0.01 vs placebo), and in patients aged <65 (0.056 L, 0.086 L), ≥65 (0.140 L, 0.124 L), and ≥75 (0.144 L, 0.120 L) years (P<0.05 vs placebo). St George’s Respiratory Questionnaire (SGRQ) total score was significantly improved with GLY 25 and 50 μg BID (P<0.05 vs placebo) in FEV1% predicted <50% (−3.237, −3.061) and ≥50% (−3.392, −2.322) and in <65 years (−3.447, −2.318) and ≥65 years (−3.053, −3.098) subgroups. In patients aged ≥75 years, GLY 25 μg reduced SGRQ total score by −6.278 units (P<0.01 vs placebo). The incidence of treatment-emergent adverse events was similar between GLY and placebo across all subgroups, and the overall incidence of cardiovascular events was low.ConclusionsNebulized GLY improved lung function and health status and was well tolerated over 12 weeks in patients with moderate-to-very-severe COPD, irrespective of baseline disease severity and age.Clinical trial registrationNCT02347761, NCT02347774.

Efficacy and safety of etomidate-based sedation compared with propofol-based sedation during ERCP in low-risk patients: a double-blind, randomized, noninferiority trial

Etomidate is a short-acting intravenous hypnotic with a safety profile that is superior to alternative drugs such as propofol. However, there is a lack of evidence on the safety of etomidate in ERCP. The objective of this study was to compare efficacy and safety profiles of etomidate and propofol for endoscopic sedation. This single-center, randomized, double-blind, noninferiority trial included patients with American Society of Anesthesiologists (ASA) physical status I to II who had been scheduled for ERCP. All patients received .05 mg/kg midazolam intravenously as pretreatment before receiving etomidate or propofol. Either etomidate or propofol was then administered according to group allocation. The primary endpoint was an overall respiratory event. A noninferiority margin of 10% was assumed. Sixty-three and 64 patients were enrolled in the etomidate and propofol groups, respectively. Respiratory events were identified in 10 patients (15.6%) in the etomidate group and 16 patients (25.4%) on the propofol group, with a rate difference of -9.8% (1-sided 97.5% confidence interval, -∞ to 4.2%). The overall incidence of cardiovascular events tended to be higher in the etomidate group (67.2% vs 50.8%, P= .060). In particular, tachycardia (heart rate > 100 beats/min) was more common in the etomidate group than in the propofol group (64.1% vs 34.9%, P= .001). Transient hypotension tended to be less common in the etomidate group (6.3 vs 15.9%, P= .084). Etomidate-based sedation during ERCP was noninferior to propofol-based sedation in terms of the overall incidence of respiratory events in patients with ASA physical status I to II. (International Clinical Trials Registry Platform number: KCT0001926.).

Baseline Characterization of Japanese Peripheral Arterial Disease Patients - Analysis of Surveillance of Cardiovascular Events in Antiplatelet-Treated Arteriosclerosis Obliterans Patients in Japan (SEASON).

Despite mounting evidence of increased cardiovascular events in patients with peripheral arterial disease (PAD), the overall incidence of cardiovascular events in PAD patients has not been fully clarified in Japan. The prospective Surveillance of cardiovascular Events in Antiplatelet-treated arterioSclerosis Obliterans patients in JapaN (SEASON) is a prospective observational multicenter study and here we report the baseline clinical characteristics, including atherosclerosis risk factor prevalence, in PAD patients treated with antiplatelet agents. The SEASON registry enrolled 11,375 patients in 1,745 institutions and the data for 10,322 patients were analyzed. At baseline, the average age was 73.8±9.9 years, 60.0% were male and 83.9% were in Fontaine stage I or II. They had arteriosclerosis risk factors, such as current smoking (16.2%), hypertension (61.5%), diabetes mellitus (38.3%) and dyslipidemia (38.8%). There were complications including heart disease (29.7%), cerebrovascular disease (17.1%) and chronic kidney disease (14.3%). A subpopulation analysis revealed that the proportions of patients with risk factors were high in patients with lower ankle-brachial pressure index value. The baseline characteristics of the SEASON population demonstrate that real-world PAD patients have cardiovascular risk factors and comorbidities next to definite PAD patients. Further analysis of this database will contribute to understanding the real-world situation of PAD patients receiving antiplatelet therapy in Japan. (Circ J 2016; 80: 712-721).

Analysis on Outcome of 3537 Patients with Coronary Artery Disease: Integrative Medicine for Cardiovascular Events

Aims. To investigate the treatment of hospitalized patients with coronary artery disease (CAD) and the prognostic factors in Beijing, China. Materials and Methods. A multicenter prospective study was conducted through an integrative platform of clinical and research at 12 hospitals in Beijing, China. The clinical information of 3537 hospitalized patients with CAD was collected from September 2009 to May 2011, and the efficacy of secondary prevention during one-year followup was evaluated. In addition, a logistic regression analysis was performed to identify some factors which will have independent impact on the prognosis. Results. The average age of all patients was 64.88 ± 11.97. Of them, 65.42% are males. The medicines for patients were as follows: antiplatelet drugs accounting for 91.97%, statins accounting for 83.66%, β-receptor blockers accounting for 72.55%, ACEI/ARB accounting for 58.92%, and revascularization (including PCI and CABG) accounting for 40.29%. The overall incidence of cardiovascular events was 13.26% (469/3537). The logistic stepwise regression analysis showed that heart failure (OR, 3.707, 95% CI = 2.756–4.986), age ≥ 65 years old (OR, 2.007, 95% CI = 1.587–2.53), and myocardial infarction (OR, 1.649, 95% CI = 1.322–2.057) were the independent risk factors of others factors for cardiovascular events that occurred during followup of one-year period. Integrative medicine (IM) therapy showed the beneficial tendency for decreasing incidence of cardiovascular events, although no statistical significance was found (OR, 0.797, 95% CI = 0.613~1.036). Conclusions. Heart failure, age ≥ 65 years old, and myocardial infarction were associated with an increase in incidence of cardiovascular events, and treatment with IM showed a tendency for decreasing incidence of cardiovascular events.

Intrauterine growth restriction is associated with persistent aortic wall thickening and glomerular proteinuria during infancy

Low birth weight, caused either by preterm birth or by intrauterine growth restriction, has recently been associated with increased rates of adult renal and cardiovascular disease. Since aortic intima–media thickening is a noninvasive marker of preclinical vascular disease, we compared abdominal aortic intima–media thickness among intrauterine growth restricted and equivalent gestational age fetuses in utero and at 18 months of age. The relationship between intrauterine growth restriction, fetal aortic thickening, and glomerular function during infancy was measured by enrolling 44 mothers with single-fetus pregnancies at 32 weeks gestation: 23 growth restricted and 21 of appropriate gestational age as controls. Abdominal aortic intima–media thickness was measured by ultrasound at enrollment and again at 18 months of age. Fetuses with intrauterine growth restriction had significantly higher abdominal aortic intima–media thickness compared with age controls when measured both in utero and at 18 months. At 18 months, the median urinary microalbumin and median albumin–creatinine ratio were significantly higher in those infants who experienced intrauterine growth restriction compared to the controls. Our results show that intrauterine growth restriction is associated with persistent aortic wall thickening and significantly higher microalbuminuria during infancy.

Adjusted indirect comparison of celecoxib versus rofecoxib on cardiovascular risk

To compare the magnitude of celecoxib versus rofecoxib on the cardiovascular risk. We performed adjusted indirect comparison of celecoxib versus rofecoxib for cardiovascular events using two data on The Adenomatous Polyp Prevention on Vioxx (APPROVe) trial and Adenoma Prevention with Celecoxib (APC) trial. Baseline characteristics of the patients and placebos were comparable in both trials, in terms of age, sex, hypertension, diabetes mellitus, smoking, and hypercholesterolemia. The overall incidence of cardiovascular events was similar in both groups (rofecoxib 48/1,287 versus celecoxib 48/1,356, p = 0.79). The relative risks (RRs) of all myocardial infarction or sudden death from cardiac causes were increased in both rofecoxib and celecoxib groups [rofecoxib versus placebo; RR 1.35, 95% confidence interval (CI) 1.07-1.69, p = 0.03, celecoxib versus placebo; RR 1.35, 95% CI 1.14-1.51, p = 0.01]. The RRs for cardiovascular events derived from the adjusted indirect comparisons of the two coxibs did not significantly differ from unity (celecoxib versus rofecoxib; RR 0.95, 95% CI 0.76-1.19, p = 0.67). The adjusted indirect comparison analysis shows that celecoxib and rofecoxib may have similarly effect of cardiovascular events when used for 3 years.

A model of prediction system for adverse cardiovascular reactions by calcineurin inhibitors among patients with renal transplants using gene-based single-nucleotide polymorphisms

The application of pharmacogenomic information to diagnostic assays is expected to improve the prediction of drug efficacy and toxicity, leading to appropriate therapeutic regimens for individual patients. Cardiovascular events are common and severe adverse drug reactions (ADRs) among transplant patients treated with calcineurin inhibitors (CNIs). We conducted case-control association studies using 50,947 gene-based single-nucleotide polymorphisms (SNPs) to identify genetic variations that might be associated with cardiovascular risk factors in 72 renal transplant recipients with CNI therapy. The overall incidence of cardiovascular events was 13.9% (10/72) among patients receiving cyclosporine or tacrolimus; arrhythmias in six patients (8.3%), ischemic heart diseases in two patients (2.8%), and heart failure in two patients (2.8%). On the basis of results of the genome-wide association studies, we attempted to establish a scoring system to predict individual risks for cardiovascular toxicity of cyclosporine and tacrolimus. Estimation of the predictive performance was carried out by the use of internal leave-one-out cross-validation test. When we combined arrhythmia, ischemic heart disease and heart failure cases as subjects with a cardiotoxicity phenotype, nine of ten ADR patients and 50 of 62 non-ADR patients were correctly classified into the respective categories using the top eight SNPs. In addition, the proportion of individuals in the control population (n=246) with scores over the cut-off (11.0%) was close to the cardiovascular ADR frequency (8.3%) among renal transplant patients in the previous clinical study. Our results open the possibility that prediction of CNI-induced cardiovascular complications can lead to better prognosis and quality of life among kidney-transplant patients, and to improved immunosuppressive regimens.