Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Effect of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, and associated metabolic comorbidities: A systematic review.

BACKGROUND AND AIMS: The beneficial effect of Hepatitis C virus (HCV) eradication by direct antiviral agents (DAAs) on liver fibrosis is well defined. Despite this, the impact of viral eradication in both hepatic and extra-hepatic metabolic features is underreached. This systematic review aimed to synthesize the evidence on the impact of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, glucidic impairment, dyslipidaemia, and weight gain. METHODS: A systematic search of the existing literature (up to December 2022) identified 97 original studies that fulfilled the inclusion criteria. RESULTS: Whereas total cholesterol and low-density lipoprotein (LDL) seem to increase after viral eradication, the cardiovascular damage expressed as carotid plaques and intima-media thickness seems to improve. Otherwise, the effect on liver steatosis, glucidic homeostasis, and weight seems to be strictly dependent on the presence of baseline metabolic disorders. CONCLUSION: Despite high heterogeneity and relatively short follow-up of included studies, we can conclude that the presence of metabolic risk factors should be strictly evaluated due to their impact on liver steatosis, glucidic and lipid homeostasis, and on weight gain to better identify patients at risk of liver disease progression despite the virus eradication.

[Ultrasound examination of the carotid artery for improved prediction of cardiovascular events and the effect of statin treatment in advanced atherosclerosis : An observational study]. / Ultraschalluntersuchung der A. carotis zur verbesserten Vorhersage kardiovaskulärer Ereignisse und der Wirkung einer Statinbehandlung bei fortgeschrittener Atherosklerose : Eine Beobachtungsstudie.

BACKGROUND: Advanced atherosclerosis of the carotid artery is associated with a high risk of cardiovascular diseases. It was investigated whether ultrasound provides a better prediction of cardiovascular events compared to the prospective cardiovascular Münster study (PROCAM) score and whether treatment of subjects with advanced atherosclerosis with statins improves the prognosis. METHOD: Between 2009 and 2016 a total of 4482 subjects (41% women) aged 35-65 years with no signs of cardiovascular disease underwent carotid artery ultrasound examination. Total plaque area (TPA) and maximum plaque thickness were measured. The PROCAM score was used to determine the cardiovascular risk. RESULTS: The median follow-up time was 77 months (6.4 years) for the men and 74 months (6.2 years) for the women. Events, such as myocardial infarction, ischemic stroke, coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA), occurred in 131 (3.4%) of the 3833 subjects with complete follow-up data. The prediction of cardiovascular events was better with ultrasound than with the PROCAM score. Ultrasound predicted 79.4% of 131 events and the PROCAM score predicted 22.9%. Treatment of subjects with advanced atherosclerosis (types III, IV b) with a statin significantly improved the prognosis. The event rate was 12.6% in men and women in the treated group vs. 31.5% (p < 0.0001) in the untreated group. Mortality (from any cause) was significantly lower in men treated with statins (p = 0.0148). CONCLUSION: The prediction of cardiovascular events was better with plaque burden measurements than with the PROCAM score. Treatment with statins in subjects with advanced carotid atherosclerosis (types III-IV b findings on ultrasound) significantly improved the prognosis in a nonrandomized observational study.

Novel Therapeutic Approaches to Prevent Atherothrombotic Ischemic Stroke in Patients with Carotid Atherosclerosis.

Atherothrombotic stroke represents approximately 20% of all ischemic strokes. It is caused by large-artery atherosclerosis, mostly in the internal carotid artery, and it is associated with a high risk of early recurrence. After an ischemic stroke, tissue plasminogen activator is used in clinical practice, although it is not possible in all patients. In severe clinical situations, such as high carotid stenosis (≥70%), revascularization by carotid endarterectomy or by stent placement is carried out to avoid recurrences. In stroke prevention, the pharmacological recommendations are based on antithrombotic, lipid-lowering, and antihypertensive therapy. Inflammation is a promising target in stroke prevention, particularly in ischemic strokes associated with atherosclerosis. However, the use of anti-inflammatory strategies has been scarcely studied. No clinical trials are clearly successful and most preclinical studies are focused on protection after a stroke. The present review describes novel therapies addressed to counteract inflammation in the prevention of the first-ever or recurrent stroke. The putative clinical use of broad-spectrum and specific anti-inflammatory drugs, such as monoclonal antibodies and microRNAs (miRNAs) as regulators of atherosclerosis, will be outlined. Further studies are necessary to ascertain which patients may benefit from anti-inflammatory agents and how.

A Comparative Study on the Presence and Reversibility of Subclinical Arterial Damage in HCV-Infected Individuals and Matched Controls.

Background: The arterial pathology and mechanisms of increased cardiovascular disease (CVD) risk in HCV-infected individuals are not yet clear. The aim of this study was to identify types of arterial pathology in treatment-naive chronic HCV patients and to test their reversibility after successful treatment. Methods: Consecutive, never-treated, HCV-infected patients were compared with age and CVD-related risk factors, matched controls, healthy individuals (HI), patients with rheumatoid arthritis (RA) and people living with HIV (PLWH), in terms of arterial stiffening by pulse wave velocity, arterial atheromatosis/hypertrophy by carotid plaques/intima-media thickness and impaired pressure wave reflections by augmentation index. After three months of sustained virological response (SVR) administered using direct-acting antivirals, vascular examination was repeated in HCV-infected patients to test drug and viral-elimination effect in subclinical CVD. Results: Thirty HCV patients were examined at baseline; fourteen of them were re-examined post-SVR. Compared with HI, HCV patients had significantly more plaques, which is similar to that of RA patients and the PLWH group. No other differences were found in all other vascular biomarkers, and regression among HCV patients also revealed no differences 3 months post-SVR. Conclusions: Accelerated atheromatosis, rather than arterial stiffening, arterial remodeling and peripheral impaired hemodynamics is the underlying pathology leading to increased CVD risk in HCV patients.

Effect of pharmacologic anti-atherosclerotic therapy on carotid intraplaque neovascularization: A systematic review.

Intraplaque neovascularization (IPN), a key feature of vulnerable carotid plaque, is associated with adverse cardiovascular (CV) events. Statin therapy has been shown to diminish and stabilize atherosclerotic plaque, but its effect on IPN is uncertain. This review investigated the effects of common pharmacologic anti-atherosclerotic therapies on carotid IPN. Electronic databases (MEDLINE, EMBASE and Cochrane Library) were searched from inception until July 13, 2022. Studies evaluating the effect of anti-atherosclerotic therapy on carotid IPN among adults with carotid atherosclerosis were included. Sixteen studies were eligible for inclusion. Contrast-enhanced ultrasound (CEUS) was the most common IPN assessment modality (n=8), followed by dynamic contrast-enhanced MRI (DCE-MRI) (n=4), excised plaque histology (n=3) and superb microvascular imaging (n=2). In fifteen studies, statins were the therapy of interest and one study assessed PCSK9 inhibitors. Among CEUS studies, baseline statin use was associated with a lower frequency of carotid IPN (median OR = 0.45). Prospective studies showed regression of IPN after 6-12 months of lipid-lowering therapy, with more regression observed in treated participants compared to untreated controls. Our findings suggest that lipid-lowering therapy with statins or PCSK9 inhibitors is associated with IPN regression. However, there was no correlation between change in IPN parameters and change in serum lipids and inflammatory markers in statin-treated participants, so it is unclear whether these factors are mediators in the observed IPN changes. Lastly, this review was limited by study heterogeneity and small sample sizes, so larger trials are needed to validate findings.

Decline of thrombolysis rates before endovascular therapy in patients with acute anterior circulation large vessel occlusion ischemic stroke: A multicenter analysis from the German Stroke Registry.

INTRODUCTION: In recent years, the role of intravenous thrombolysis (IVT) before endovascular stroke treatment (EVT) has been discussed intensively. Whether the discussion was accompanied by changing rates of bridging IVT is unknown. METHODS: Data were extracted from the prospectively maintained German Stroke Registry, including patients treated with EVT at one of 28 stroke centers in Germany between 2016 and 2021. Primary outcome parameters were the rate of bridging IVT (a) in the entire registry cohort and (b) in patients without formal contraindications to IVT (i.e. recent oral anticoagulants, time window ⩾4.5 h, extensive early ischemic changes) adjusted for demographic and clinical confounders. RESULTS: 10,162 patients (52.8% women, median age 77 years, median National Institutes of Health Stroke Scale score 14) were analyzed. In the entire cohort, the rate of bridging IVT decreased from 63.8% in 2016 to 43.6% in 2021 (average absolute annual decrease 3.1%, 95% CI 2.4%-3.8%), while the proportion of patients with at least one formal contraindication increased by only 1.2% annually (95% CI 0.6%-1.9%). Among 5460 patients without record of formal contraindications, the rate of bridging IVT decreased from 75.5% in 2016 to 63.2% in 2021 and was significantly associated with admission date in a multivariable model (average absolute annual decrease 1.4%, 95% CI 0.6%-2.2%). Clinical factors associated with lower odds of bridging IVT included diabetes mellitus, carotid-T-occlusion, dual antiplatelet therapy, and direct admission to a thrombectomy center. CONCLUSION: We observed a substantial decline in bridging IVT rates independent of demographic confounders and not explained by an increase in contraindications. This observation deserves further exploration in independent populations.

Proanthocyanidins may be potential therapeutic agents for the treatment of carotid atherosclerosis: A review.

Atherosclerotic cerebrovascular disease is one of the major causes of death in China, with associated serious risk of disability and burden on society and families. Therefore, the development of active and effective therapeutic drugs for this disease is of great significance. Proanthocyanidins are a class of naturally occurring active substances, rich in hydroxyl groups and from a wide range of sources. Studies have suggested that they have a strong potential for anti-atherosclerosis activity. In this paper, we review published evidence regarding anti-atherosclerotic effects of proanthocyanidins in different atherosclerotic research models.

Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis.

BACKGROUND: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). METHODS: Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015-2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. RESULTS: Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%], adjusted odds ratio [aOR], 2.18 [95% CI, 1.03-4.63]). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%], aOR, 3.93 [95% CI, 1.50-10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16-2.06]; Pinteraction=0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00-8.05] versus absent: aOR, 1.98 [95% CI, 0.65-6.03]; Pinteraction=0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%], aOR, 3.73 [95% CI, 1.25-11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01-3.83]; Pinteraction=0.16). CONCLUSIONS: Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.

Nonvalvular atrial fibrillation and retinal vein occlusion: The Valdecilla Cohort.

INTRODUCTION AND OBJECTIVES: Retinal vein occlusion (RVO) and nonvalvular atrial fibrillation (NVAF) are associated with vascular risk factors (VRF) and aging. The aim of this study is to analyze differences in the prevalence of VRF, vascular events, glaucoma, and anticoagulant treatment in patients with NVAF and RVO compared to a control group of the general population from the same geographic area. METHODS: This is a prospective, single-center, case-control study. All patients diagnosed with RVO from December 2008 to March 2020 as well as a control group were included. Clinical, laboratory, electrocardiographic, and carotid ultrasound variables were analyzed. RESULTS: A total of 386 patients with RVO and 343 controls were studied. Patients with RVO and NVAF were older and more of them had hypertension, a history of vascular events, and carotid atheromatosis than subjects with RVO without NVAF. In patients with NVAF who were on anticoagulants, those who had RVO differed from the controls with NVAF in that they had a higher prevalence of glaucoma (32 vs. 5.3%; p<0.034), with no significant differences regarding age, VRF, vascular events, or type of anticoagulant therapy (acenocumarol or direct-acting oral anticoagulants). CONCLUSIONS: Patients with RVO and NVAF were older and had a higher prevalence of hypertension and carotid atheromatosis than subjects with RVO without NVAF. Patients with NVAF and RVO had higher prevalence of glaucoma than subjects with NVAF without RVO. In patients with NVAF, it is recommended to optimized VRF treatment and glaucoma control to prevent the development of RVO.

Quantification of Local Vessel Wall and Plaque Volume Change for Assessment of Effects of Therapies on Carotid Atherosclerosis Based on 3-D Ultrasound Imaging.

We developed a new method to measure the voxel-based vessel-wall-plus-plaque volume (VWV). In addition to quantifying local thickness change as in the previously introduced vessel-wall-plus-plaque thickness (VWT) metric, voxel-based VWV further considers the circumferential change associated with vascular remodeling. Three-dimensional ultrasound images were acquired at baseline and 1 y afterward. The vessel wall region was divided into small voxels with the voxel-based VWV change (ΔVVol%) computed by taking the percentage volume difference between corresponding voxels in the baseline and follow-up images. A 3-D carotid atlas was developed to allow visualization of the local thickness and circumferential change patterns in the pomegranate versus the placebo groups. A new patient-based biomarker was obtained by computing the mean ΔVVol% over the entire 3-D map for each patient (ΔVVol%¯). ΔVVol%¯ detected a significant difference between patients randomized to pomegranate juice/extract and placebo groups (p = 0.0002). The number of patients required by ΔVVol%¯ to establish statistical significance was approximately a third of that required by the local VWT biomarker. The increased sensitivity afforded by the proposed biomarker improves the cost-effectiveness of clinical studies evaluating new anti-atherosclerotic treatments.

Investigation of the clinical effects of acipimox in patients with vulnerable carotid atherosclerosis.

OBJECTIVE: To investigate the clinical effects of acipimox in patients with vulnerable carotid atherosclerosis. METHODS: 80 patients with vulnerable carotid atherosclerosis who were admitted to the Department of Cardiology in Wuxi Second People's Hospital between February 2020 and October 2021 were enrolled in this study. All of these patients were randomly divided into an observation group (n = 40), who were given acipimox and conventional treatment, and a control group (n = 40), who were given conventional treatment. The levels of blood lipids and adiponectin (APN), the carotid intima-media thickness (IMT), the area, thickness and number of CAS, peak systolic velocities (PSV) and end-diastolic blood velocity (EDV) of common carotid artery (CCA), and the level of inflammatory markers were measured and compared between the two groups pretherapy and posttreatment. Then, the adverse events were collected and compared between the two groups posttreatment. RESULTS: The demographics and basic clinical characteristics were not significantly different between the two groups. At posttreatment, the levels of TC, LDL-C, ANP, IL-6, TNF-α and hs-CRP in the observation group were significantly lower than those in the control group at posttreatment. Moreover, the IMT and the area and thickness of CAS in the observation group were significantly lower than those in the control group. After treatment, PSV was lower and EDV was higher in two groups than before treatment; after treatment, compared with control group, PSV in observation group was lower, while EDV was higher. Most importantly, the rate of adverse events was similar in the two groups. CONCLUSIONS: Acipimox reduced the blood lipid levels in patients with vulnerable carotid atherosclerosis. It also stabilized vulnerable plaques and reduced CAS.

Improvement of carotid atherosclerosis and peripheral artery disease after hepatitis C virus eradication by direct-acting antivirals.

INTRODUCTION: Recent research points to a link between chronic hepatitis C virus (HCV) infection and cardiovascular disease, especially carotid atherosclerosis, and suggests that HCV clearance may impact cardiovascular outcomes. AIM: To determine if viral eradication by the new oral direct-acting antiviral (DAA) agents has benefit regarding carotid atherosclerosis, peripheral artery disease (PAD), steatosis, and liver fibrosis. PATIENTS, MATERIALS AND METHODS: We conducted a prospective study on 168 patients diagnosed with chronic HCV infection or HCV-related cirrhosis. They were all treated with DAAs, with sustained virological response (SVR). Laboratory data, vibration-controlled transient elastography (VCTE), carotid intima-media thickness (IMT) measurement, and ankle-brachial index (ABI) were recorded in all patients. RESULTS: We found an average IMT of 1.22±0.2 mm, with a variance range from 1.14±0.19 mm in the mild and moderate fibrosis (≤F2) group to 1.29±0.25 mm in the severe fibrosis (≥F3) group. Also, patients with severe fibrosis (≥F3) present a more critical decrease of IMT values, with the carotid thickness affecting only 18.2% of individuals in the follow-up period. At the baseline, the best values of ABI were recorded in patients having F1-F2 fibrosis stage (mean value 1.02±0.19). Instead, in the group with severe fibrosis, the average value of ABI was lower (0.91±0.16) at the baseline, with a significant increase at SVR evaluation (p<0.001). CONCLUSIONS: Our research highlights the beneficial effect of viral eradication on both carotid atherosclerosis and PAD, especially in those with advanced fibrosis and cirrhosis.

Intracranial Carotid Artery Calcification Subtype in Patients with Anterior Circulation Acute Ischemic Stroke Undergoing Intravenous Thrombolysis.

Background and Aim: The aim of this study was to investigate the potential value of intracranial carotid artery calcification (ICAC) in therapeutic efficacy and functional outcomes in patients with anterior circulation acute ischemic stroke (AIS) undergoing intravenous thrombolysis. Materials and Methods: A total of 207 patients with anterior circulation AIS who underwent intravenous thrombolysis were enrolled in this retrospective study. We divided them into three groups according to thin-slice head noncontrast computed tomography as follows: no ICAC, medial ICAC, and intimal ICAC. The differences in risk factors of different ICAC subtypes were compared, and the effect of ICAC subtype on hemorrhage transformation (HT) after intravenous thrombolysis was also evaluated. Functional outcomes were assessed at 90 days using the modified Rankin Scale. Results: Compared to the no and intimal ICAC, patients with the medial ICAC were older and more likely to have diabetes mellitus, hyperlipidemia, previous stroke, and atrial fibrillation. Moreover, the medial ICAC group had a high baseline National Institute of Health Stroke Scale (NIHSS) score and a high incidence of HT. Multivariate logistic regression analysis showed that baseline NIHSS score (odds ratio [OR]: 1.121, 95% confidence interval [CI]: 1.027-1.224) was independently associated with HT. Medial ICAC (OR: 7.418, 95% CI: 1.190-46.231) and baseline NIHSS score (OR: 1.141, 95% CI: 1.042-1.250) were independent risk factors of poor functional outcome at 90 days. Conclusions: Medial ICAC could be a new imaging biomarker for predicting functional outcomes in patients with anterior circulation AIS undergoing intravenous thrombolysis. Medial ICAC and baseline NIHSS score were independently associated with poor prognosis at 90 days.

Dengzhan Shengmai capsule versus Aspirin in the treatment of carotid atherosclerotic plaque: A single-centre, non-inferiority, prospective, randomised controlled trial.

BACKGROUND: Aspirin is an effective antiplatelet agent for the treatment of carotid atherosclerosis. However, the high risk of bleeding events associated with the drug makes it necessary to seek a safer alternative, with similar or more efficacy than aspirin. Dengzhan Shengmai (DZSM) capsules have been widely used to treat carotid atherosclerosis, and if proven to be non-inferior to aspirin, it may be preferable over the latter for carotid atherosclerosis treatment due to its numerous advantages. We conducted a randomised trial to test the non-inferiority of DZSM to aspirin for the treatment of carotid atherosclerotic plaques. METHODS: We performed a single-centre, prospective, open-label, randomised non-inferiority trial. Patients with carotid atherosclerotic plaques were enrolled and randomly assigned (1:1) to receive either DZSM capsules or aspirin. The follow-up period was 12 months. The primary outcome was the mean change in carotid intima-media thickness (IMT). Secondary outcomes included ischaemic events, rate of lumen stenosis, lipid levels, and plaque scores, length, counts, and vulnerability. Adverse events and laboratory test results were recorded as safety outcomes. The non-inferiority of DZSM was demonstrated when the lower limit of the one-sided 97.5% confidence interval (CI) of the difference in IMT between groups was more than -0.06 mm (margin of non-inferiority). This trial has been registered at ClinicalTrials.gov (CHiCTR1900021365). RESULTS: From 1 April 2019 to 30 September 2019, 150 patients were enrolled, and there was no statistical difference in demographics between the groups. Intention-to-treat analysis showed that the decrease in IMT(∆IMT) was 0.216 ± 0.160 and 0.225 ± 0.149 mm in the DZSM and aspirin groups, respectively. The one-sided 97.5% CI for the difference between ∆IMTs was (-0.0593, +∞). The non-inferiority of DZSM was demonstrated (Pnon-inferiority = 0.0234). There was no significant difference in the incidence of ischaemic events between the groups (P = 1.0). The DZSM group had significantly reduced plaque scores (P < 0.0001), length (P < 0.0001), and counts (P < 0.0001), and improved plaque vulnerability (P < 0.0001). The DZSM group also had reduced levels of low-density lipoprotein cholesterol (LDL-C) (P < 0.0001). Finally, the DZSM group had a lower incidence of total adverse events (14.7% vs. 28%, P = 0.046), especially gastrointestinal discomfort (5.3% vs. 16%, P = 0.034). Although there was no significant difference in bleeding events (0 vs. 5.3%, P = 0.120), the DZSM group tended to have a lower incidence. CONCLUSION: This trial demonstrated that DZSM was not inferior, in efficacy, to aspirin in treating carotid atherosclerotic plaques, and was found to be superior to aspirin in terms of safety. This study provides a new approach for treating carotid plaques, especially in aspirin-intolerant patients.

Rosuvastatin Slows Progression of Carotid Intima-Media Thickness: The METEOR-China Randomized Controlled Study.

BACKGROUND: Atherosclerosis is the leading cause of cardiovascular disease worldwide, including in China. Primary prevention, through lipid-lowering, could avert development of atherosclerosis. Carotid intima-media thickness (CIMT) is a well-validated measure of atherosclerosis used in intervention studies as the primary outcome and alternative end point for cardiovascular disease events. METHODS: This randomized, double-blind, placebo-controlled, multicenter, parallel-group study assessed the effects of rosuvastatin 20 mg/d compared with placebo on progression of CIMT over 104 weeks in Chinese people with subclinical atherosclerosis. The primary end point was the annualized rate of change in mean of the maximum CIMT measurements taken 7× over the study period from each of 12 carotid artery sites (near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery). Secondary end points included CIMT changes at different artery sites and lipid-parameter changes. Safety was also assessed. RESULTS: Participants were randomized (1:1) to receive rosuvastatin (n=272) or placebo (n=271). Baseline characteristics were well balanced between groups. The change in mean of the maximum CIMT of the 12 carotid sites was 0.0038 mm/y (95% CI, -0.0023-0.0100) for the rosuvastatin group versus 0.0142 mm/y (95% CI, 0.0080-0.0204) for the placebo group, with a difference of -0.0103 mm/y (95% CI, -0.0191 to -0.0016; P=0.020). For the CIMT secondary end points, the results were generally consistent with the primary end point. There were clinically relevant improvements in lipid parameters with rosuvastatin. We observed an adverse-event profile consistent with the known safety profile of rosuvastatin. CONCLUSIONS: Rosuvastatin 20 mg/d significantly reduced the progression of CIMT over 2 years in Chinese adults with subclinical atherosclerosis and was well tolerated. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02546323.

A new approach of statin therapy in carotid atherosclerosis: Targeting indices of plaque vulnerability on the top of lipid-lowering. A narrative review.

Novel imaging techniques and biomarkers have emerged as surrogate markers of carotid plaque vulnerability. In parallel, statin administration in patients with established carotid atherosclerosis not requiring revascularization has reduced the number of consequent cerebrovascular events. This reduction is not only attributed to the lipid-lowering properties of statins but also to their pleiotropic actions. The present literature review aimed to summarize the stabilizing effects of statins on carotid plaques based on imaging modalities and biomarkers and propose an alternative approach to their implementation. Moreover, we assessed the perioperative use of statins in patients undergoing carotid revascularization and the impact of aggressive vs. conventional statin therapy. Recent studies using: (1) ultrasound indices of plaque echogenicity; (2) fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scans for plaque inflammation assessment; or (3)magnetic resonance imaging (MRI) scans quantifying intraplaque hemorrhage, and lipid-rich necrotic core (LRNC) have shown quite promising results in evaluation of carotid plaque vulnerability. Based on those imaging modalities, a growing number of studies have demonstrated a very modest carotid plaque regression due to/induced by statins, while their stabilizing impact is disproportionally higher. Other studies assaying several biomarkers (e.g. inflammation, etc.) have confirmed a statin-induced carotid plaque stabilization. All the aforementioned benefits followed a dose-dependent pattern of statins, on top of the low-density lipoprotein cholesterol (LDL-C) target in current guidelines. In the case of symptomatic patients with carotid atherosclerosis suitable for revascularization, robust evidence implicates a significant statin-related reduction of perioperative cardiovascular risk only in patients undergoing endarterectomy.

[Effects of moderate dose rosuvastatin on carotid plaque in patients with diabetes mellitus evaluated by magnetic resonance imaging].

Objective: To observe the effect of lipid regulating therapy on carotid atherosclerotic plaque in diabetic patients. Methods: The REACH study, conducted between March 2009 and February 2012, enrolled asymptomatic patients with magnetic resonance imaging (MRI) confirmed carotid atherosclerotic plaque, who had never taken lipid-lowering drugs. Patients were treated with a moderate dose of rosuvastatin for 24 months. Blood lipid levels were measured and carotid MRI was performed at baseline, 3 and 24 months after treatment. The volume of carotid wall and lipid-rich necrotic core (LRNC) were measured by image analysis software. This study retrospectively analyzed patients in the REACH study. Patients were divided into diabetes group and non-diabetic group. The changes of blood lipid level and MRI parameters of carotid atherosclerotic plaque were compared between the two groups and their correlation was analyzed. Results: A total of 38 patients with carotid atherosclerotic plaque were included in this study, including 13 patients (34.2%) in the diabetic group and 25 patients (65.8%) in the non-diabetic group. Baseline parameters were comparable between the two groups, except higher HbA1c level in diabetes group (P<0.05). Compared with baseline, the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were significantly decreased at 3 and 24 months in both two groups (P<0.05). The change of high-density lipoprotein cholesterol (HDL-C) in diabetes group was not obvious, while it was significantly increased in non-diabetic group at 24 months ((1.38±0.33) mmol/l vs. (1.26±0.26) mmol/l, P<0.05). MRI results showed that the volume and percentage of LRNC remained unchanged at 3 months, slightly decreased at 24 months (64.86 (45.37, 134.56) mm3 vs. 75.76 (48.20, 115.64) mm3, P>0.05) and (15.84% (11.47%, 24.85%) vs. 16.95% (11.64%, 22.91%), P>0.05) in diabetic group. In non-diabetic group, the volume and percentage of LRNC were significantly decreased at 3 months (63.01 (44.25, 188.64) mm3 vs. 72.49 (51.91, 199.59) mm3, P<0.05) and (13.76% (8.81%, 27.64%) vs. 16.04% (11.18%, 27.05%), P<0.05) respectively. Both parameters further decreased to (55.63 (27.18, 179.40) mm3) and (12.71% (8.39%, 24.41%)) at 24 months (both P<0.05). Wall volume, lumen volume and percent wall volume (PWV) were not affected post therapy in both two groups(P>0.05). There were no correlations between the changes of plaque parameters including volume and percentage of LRNC, wall volume, lumen volume, PWV and the changes of blood lipid parameters (TC, LDL-C, HDL-C and TG) in 3 and 24 months (P>0.05). Conclusion: Lipid-lowering therapy possesses different effects on carotid atherosclerotic plaque in diabetic and non-diabetic patients, and the LRNC improvement is more significant in non-diabetic patients as compared to diabetic patients.