Risk Of Major Vascular Events Research Articles

Conventional and genetic associations of BMI with major vascular and non-vascular disease incidence and mortality in a relatively lean Chinese population: U-shaped relationship revisited.

Higher body mass index (BMI) is associated with higher incidence of cardiovascular and some non-cardiovascular diseases (CVDs/non-CVDs). However, uncertainty remains about its associations with mortality, particularly at lower BMI levels. The prospective China Kadoorie Biobank recruited >512 000 adults aged 30-79years in 2004-08 and genotyped a random subset of 76 000 participants. In conventional and Mendelian randomization (MR) analyses, Cox regression yielded adjusted hazard ratios (HRs) associating measured and genetically predicted BMI levels with incident risks of major vascular events (MVEs; conventional/MR 68 431/23 621), ischaemic heart disease (IHD; 50 698/12 177), ischaemic stroke (IS; 42 427/11 897) and intracerebral haemorrhage (ICH; 7644/4712), and with mortality risks of CVD (15 427/6781), non-CVD (26 915/4355) and all causes (42 342/6784), recorded during ∼12years of follow-up. Overall, the mean BMI was 23.8 (standard deviation: 3.2) kg/m2 and 13% had BMIs of <20 kg/m2. Measured and genetically predicted BMI showed positive log-linear associations with MVE, IHD and IS, but a shallower positive association with ICH in conventional analyses. Adjusted HRs per 5 kg/m2 higher genetically predicted BMI were 1.50 (95% CI 1.41-1.58), 1.49 (1.38-1.61), 1.42 (1.31-1.54) and 1.64 (1.58-1.69) for MVE, IHD, IS and ICH, respectively. These were stronger than associations in conventional analyses [1.21 (1.20-1.23), 1.28 (1.26-1.29), 1.31 (1.29-1.33) and 1.14 (1.10-1.18), respectively]. At BMIs of ≥20 kg/m2, there were stronger positive log-linear associations of BMI with CVD, non-CVD and all-cause mortality in MR than in conventional analyses. Among relatively lean Chinese adults, higher genetically predicted BMI was associated with higher risks of incident CVDs. Excess mortality risks at lower BMI in conventional analyses are likely not causal and may reflect residual reverse causality.

Persistence to statin treatment: A cohort study in Lithuania.

Cardiovascular diseases are the main causes of death, and statins can reduce the risk of major vascular events. Lithuania is among the European countries with the highest cardiovascular mortality despite a rapidly increasing use of statins. Previous reviews have shown the problem of poor patient adherence, but there are limited studies from Eastern European countries. The aim of this study was to evaluate treatment persistence in new users of statins in Lithuania and to investigate factors associated with persistence. Dispensed prescriptions from patients aged >18 years old initiated on statins in 2018-2019 were included, and data were obtained from a national health insurance fund. Persistence was assessed by the proportion of patients who still had statins dispensed 1year after the first dispensing. Factors associated with persistence were assessed using logistic regression. A total of 104 726 patients (41.3% men) were initiated on statin treatment. Only 41% of them continued statin use 1year after initiation. Factors associated with higher persistence rate were older age, higher dose of statin, use of other medicines and use of statins as secondary prevention. Low persistence to statin therapy needs to be recognized by healthcare workers, pharmacists and policy makers to address this problem.

Effect of Statin Therapy on Cardiovascular Outcome in Stroke Patients with Low Baseline Low-Density Lipoprotein Cholesterol.

To investigate whether post-stroke statin therapy reduces subsequent major vascular events in statin-naïve patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below the recommended target (≤70 mg/dL for atherosclerotic stroke and ≤100 mg/dL for non-atherosclerotic stroke) at stroke onset. Patients from an ongoing stroke registry who had an ischemic stroke between 2011 and 2020 were screened. Statin naïve patients with baseline LDL-C below the target were assessed. The effect of post-stroke statin therapy on major vascular events (composite of recurrent stroke, myocardial infarction, and death) was investigated using weighted Cox regression analyses using stabilized inverse probability treatment weighting. The baseline LDL-C level of the 1,858 patients (mean age 67.9 ± 15.3 years, 61.4% men, 13.2% atherosclerotic stroke) included in the study was 75.7 ± 17.0 mg/dL. Statins were prescribed to 1,256 (67.7%) patients (low-to-moderate intensity, 23.5%; high intensity, 44.1%). Post-stroke statin therapy was associated with a lower risk of major vascular events during 1-year follow-up (weighted hazard ratio 0.55, 95% confidence interval 0.42-0.71). In a subgroup of patients who were at very high risk of atherosclerotic cardiovascular disease with LDL-C <55 mg/dL or patients who were not at very high risk of atherosclerotic cardiovascular disease with LDL-C <70 mg/dL, post-stroke statin therapy was also associated with a reduction in major vascular events (weighted hazard ratio 0.45, 95% confidence interval 0.29-0.70). The intensity of the most beneficial statin varied by subtype of stroke. Statin therapy may improve vascular outcomes after ischemic stroke, even in cases of LDL-C below the target without pre-stroke lipid-lowering therapy. ANN NEUROL 2024;95:876-885.

Effectiveness of low-density lipoprotein cholesterol reduction with lipid lowering therapy for secondary prevention amongst older individuals: a nationwide cohort study.

Data about the clinical benefit from initial low-density lipoprotein cholesterol (LDL-C) reduction with lipid lowering treatment for secondary prevention and risk of major vascular events amongst older as compared with younger individuals treated during routine clinical care are limited. We investigated this in a nationwide cohort. Individuals aged ≥ 50years with a first-time hospitalisation for a cardiovascular event (index event, including acute coronary syndrome, non-haemorrhagic stroke, transient ischaemic attack and coronary revascularisation), 1 January 2008 to 31 October 2018, who subsequently used lipid lowering treatment, and had an LDL-C measurement before and after the event were included. Hazard ratios (HRs) for major vascular events per 1mmol/L reduction in LDL-C were estimated for the included 21,751 older and 22,681 younger individuals (≥/<70years old) using Cox regression. LDL-C lowering was associated with a 12% lower risk of major vascular events in older individuals per 1mmol/L reduction in LDL-C (HR 0.88, 95% confidence interval [CI] 0.84-0.93), with no significant difference compared with the risk reduction amongst younger individuals (HR 0.88, 95% CI 0.83-0.93; P-value for difference between age groups: 0.86). The risk reduction was more pronounced when post hoc restricting, as a proxy for compliance, to new users with an LDL-C reduction above the lowest decile for both older (0.81, 95% CI 0.73-0.90) and younger (0.81, 95% CI 0.72-0.91) individuals. This study strongly supports a similar relative clinical benefit of LDL-C reduction with lipid lowering treatment for secondary prevention of major vascular events amongst individuals aged ≥70 and <70years.

Underlying Causes of TIA and Minor Ischemic Stroke and Risk of Major Vascular Events

The coexistence of underlying causes in patients with transient ischemic attack (TIA) or minor ischemic stroke as well as their associated 5-year risks are not well known. To apply the ASCOD (atherosclerosis, small vessel disease, cardiac pathology, other cause, or dissection) grading system to assess coexistence of underlying causes of TIA and minor ischemic stroke and the 5-year risk for major vascular events. This international registry cohort (TIAregistry.org) study enrolled 4789 patients from June 1, 2009, to December 31, 2011, with 1- to 5-year follow-up at 61 sites in 21 countries. Eligible patients had a TIA or minor stroke (with modified Rankin Scale score of 0 or 1) within the last 7 days. Among these, 3847 patients completed the 5-year follow-up by December 31, 2016. Data were analyzed from October 1, 2022, to June 15, 2023. Five-year follow-up. Estimated 5-year risk of the composite outcome of stroke, acute coronary syndrome, or cardiovascular death. A total of 3847 patients (mean [SD] age, 66.4 [13.2] years; 2295 men [59.7%]) in 42 sites were enrolled and participated in the 5-year follow-up cohort (median percentage of 5-year follow-up per center was 92.3% [IQR, 83.4%-97.8%]). In 998 patients with probable or possible causal atherosclerotic disease, 489 (49.0%) had some form of small vessel disease (SVD), including 110 (11.0%) in whom a lacunar stroke was also probably or possibly causal, and 504 (50.5%) had no SVD; 275 (27.6%) had some cardiac findings, including 225 (22.6%) in whom cardiac pathology was also probably or possibly causal, and 702 (70.3%) had no cardiac findings. Compared with patients with none of the 5 ASCOD categories of disease (n = 484), the 5-year rate of major vascular events was almost 5 times higher (hazard ratio [HR], 4.86 [95% CI, 3.07-7.72]; P < .001) in patients with causal atherosclerosis, 2.5 times higher (HR, 2.57 [95% CI, 1.58-4.20]; P < .001) in patients with causal lacunar stroke or lacunar syndrome, and 4 times higher (HR, 4.01 [95% CI, 2.50-6.44]; P < .001) in patients with causal cardiac pathology. The findings of this cohort study suggest that in patients with TIA and minor ischemic stroke, the coexistence of atherosclerosis, SVD, cardiac pathology, dissection, or other causes is substantial, and the 5-year risk of a major vascular event varies considerably across the 5 categories of underlying diseases. These findings further suggest the need for secondary prevention strategies based on pathophysiology rather than a one-size-fits-all approach.

LDL-C Reduction With Lipid-Lowering Therapy for Primary Prevention of Major Vascular Events Among Older Individuals

BackgroundReducing low-density lipoprotein (LDL) cholesterol with lipid-lowering therapy has consistently been shown to lower the risk of cardiovascular disease in primary prevention trials where the majority of individuals are aged <70 years. For older individuals, however, evidence is less clear. ObjectivesIn this study, the authors sought to compare the clinical effectiveness of lowering LDL cholesterol by means of lipid-lowering therapy for primary prevention of cardiovascular disease among older and younger individuals in a Danish nationwide cohort. MethodsWe included individuals aged ≥50 years who had initiated lipid-lowering therapy from January 1, 2008, to October 31, 2017, had no history of atherosclerotic cardiovascular disease, and had a baseline and a within-1-year LDL cholesterol measurement. We assessed the associated risk of major vascular events among older individuals (≥70 years) by HRs per 1 mmol/L reduction in LDL cholesterol compared with younger individuals (<70 years). ResultsFor both the 16,035 older and the 49,155 younger individuals, the median LDL cholesterol reduction was 1.7 mmol/L. Each 1 mmol/L reduction in LDL cholesterol in older individuals was significantly associated with a 23% lower risk of major vascular events (HR: 0.77; 95% CI: 0.71-0.83), which was equal to that of younger individuals (HR: 0.76; 95% CI: 0.71-0.80; P value for difference = 0.79). Similar results were observed across all secondary analyses. ConclusionsOur study supports a relative clinical benefit of lowering LDL cholesterol for primary prevention of major vascular events in individuals aged ≥70 years similarly as in individuals aged <70 years.

Meta-Analysis of Lowering LDL Cholesterol and its Impact on the Cardiovascular System

Background: By lowering LDL cholesterol levels, the risk of coronary heart disease (CHD) and other serious vascular events can be significantly reduced. In order to prevent cardiovascular illnesses (CVD), mainly coronary heart disease, LDL-cholesterol (LDL-C) levels must be tightly controlled on both a primary and secondary level (CHD). Despite the fact that patients in primary prevention experience a higher absolute number of atherosclerotic cardiovascular (CV) events than those in secondary prevention of CVD, subjects in primary prevention frequently receive little attention when it comes to the clinical management of LDL-C levels. Aim: To summarise the research supporting LDL cholesterol reduction treatments for elderly people. Method: For this meta-analysis, we searched PubMed, GOOGLE SCHOLAR, SCI.HUB, MEDLINE, and Embase for publications released between January 1, 2017, and December 28, 2021. As recommended by the 2018 American Academy of Cardiology and American Heart Association guidelines, randomised controlled trials evaluating cardiovascular outcomes of an LDL cholesterol-lowering medicine with a median follow-up of at least 2 years and data on older patients (aged 75 years).The search for literature source was limited to randomized controlled trials (human being). This meta-analysis, comprised of 24 trials from the Cholesterol Therapy Trialists' Collaboration meta-analysis plus five other trials, used data from six journals. 21492 (8%) of the 244090 participants in 29 studies, were over the age of 75. Among them, 11750 (54%) came from statin trials, 6209 (28%) from ezetimibe trials, and 3533 (16%) from PCSK9 inhibitor trials. We conducted network meta-analyses for the statins and non statin treatments. Results: Of the 244090 participants in 29 studies, 21492(8%) were over 75. These included 3533 (16%) from PCSK9 inhibitor studies, 11750 (54%) from statin trials, and 6209 (28%) from ezetimibe trials. A median follow-up period of 2 to 6 years was used. Without statistically differentiating from the risk reduction in patients under the age of 75 (085 [078-092]; pinteraction=037), LDL cholesterol lowering significantly reduced the risk of major vascular events (n=3519) by 26% for 1 mmol/L reduction in LDL cholesterol (RR 074 [95% CI 061-089]; p=00019).In older patients, there was no statistically significant difference in the RRs for statin (0.82 [0.73-0.91] and non-statin (0.67 [0.47-0.95]; pinteraction=0.64) treatment. Reduced LDL cholesterol in older persons was shown to benefit all components of the composite, including coronary revascularization (080 [066-096], stroke (073 [061-087], and myocardial infarction (080 [071-090]. Practical implication: This meta analysis can be used to improve the treatment of people withlowering LDL cholesterol. Conclusion: The viability and security of diminishing LDL cholesterol in more seasoned adults are now supported by further research provided by this meta-analysis. By non-statin and statin LDL cholesterol-bringing down medication, we identified a risk reduction for major vascular events that were at least as effective as that observed in younger patients Keywords: LDL, Meta-analysis, Cardiovascular, Cholesterol,Atherosclerosis, Primary and secondary prevention.

Effect of atherosclerosis on 5-year risk of major vascular events in patients with transient ischaemic attack or minor ischaemic stroke: an international prospective cohort study

The prevalence of atherosclerosis and the long-term risk of major vascular events in people who have had a transient ischaemic attack or minor ischaemic stroke, regardless of the causal relationship between the index event and atherosclerosis, are not well known. In this analysis, we applied the ASCOD (atherosclerosis, small vessel disease, cardiac pathology, other causes, and dissection) grading system to estimate the 5-year risk of major vascular events according to whether there was a causal relationship between atherosclerosis and the index event (ASCOD grade A1 and A2), no causal relationship (A3), and with or without a causal relationship (A1, A2, and A3). We also aimed to estimate the prevalence of different grades of atherosclerosis and identify associated risk factors. We analysed patient data from TIAregistry.org, which is an international, prospective, observational registry of patients with a recent (within the previous 7 days) transient ischaemic attack or minor ischaemic stroke (modified Rankin Scale score of 0-1) from 61 specialised centres in 21 countries in Europe, Asia, the Middle East, and Latin America. Using data from case report forms, we applied the ASCOD grading system to categorise the degree of atherosclerosis in our population (A0: no atherosclerosis; A1 or A2: atherosclerosis with stenosis ipsilateral to the cerebral ischaemic area; A3: atherosclerosis in vascular beds not related to the ischaemic area or ipsilateral plaques without stenosis; and A9: atherosclerosis not assessed). The primary outcome was a composite of non-fatal stroke, non-fatal acute coronary syndrome, or cardiovascular death within 5 years. Between June 1, 2009, and Dec 29, 2011, 4789 patients were enrolled to TIAregistry.org, of whom 3847 people from 42 centres participated in the 5-year follow-up; 3383 (87·9%) patients had a 5-year follow-up visit (median 92·3% [IQR 83·4-97·8] per centre). 1406 (36·5%) of 3847 patients had no atherosclerosis (ASCOD grade A0), 998 (25·9%) had causal atherosclerosis (grade A1 or A2), and 1108 (28·8%) had atherosclerosis that was unlikely to be causal (grade A3); in 335 (8·7%) patients, atherosclerosis was not assessed (grade A9). The 5-year event rate of the primary composite outcome was 7·7% (95% CI 6·3-9·2; 101 events) in patients categorised with grade A0 atherosclerosis, 19·8% (17·4-22·4; 189 events) in those with grade A1 or A2, and 13·8% (11·8-16·0; 144 events) in patients with grade A3. Compared with patients with grade A0 atherosclerosis, patients categorised as grade A1 or A2 had an increased risk of the primary composite outcome (hazard ratio 2·77, 95% CI 2·18-3·53; p<0·0001), as did patients with grade A3 (1·87, 1·45-2·42; p<0·0001). Except for age, male sex, and multiple infarctions on neuroimaging, most of the risk factors that were identified as being associated with grade A1 or A2 atherosclerosis were modifiable risk factors (ie, hypertension, dyslipidaemia, overweight, smoking cigarettes, and low physical activity; all p values <0·025). In patients with transient ischaemic attack or minor ischaemic stroke, those with atherosclerosis have a much higher risk of major vascular events within 5 years than do those without atherosclerosis. Preventive strategies addressing complications of atherosclerosis should focus on individuals with atherosclerosis rather than grouping together all people who have had a transient ischaemic attack or minor ischaemic stroke (including those without atherosclerosis). AstraZeneca, Sanofi, Bristol Myers Squibb, SOS Attaque Cérébrale Association.

Abstract 44: Impact Of Novel Oral Anticoagulant Use On Secular Trend Of Vascular Events Or Death After Atrial Fibrillation-related Acute Ischemic Stroke

Introduction: Now novel oral anticoagulants (NOAC) are strongly recommended for secondary stroke prevention in patients with atrial fibrillation (AF). However, it remains unclear to what extent the introduction of NOACs improved clinical outcomes in real-world practice. Methods: Using a nationwide prospective multi-center stroke registry database, we identified consecutive AIS patients with AF enrolled between Jan 2011 and Dec 2019, and analyzed one-year clinical events and NOAC prescription at discharge. The primary outcome was the composite of stroke, myocardial infarction, and all-cause death. To assess the mediation effect of NOAC on the outcomes, we performed natural effect models according to the calendar year. The exposure-mediator analysis, exposure-outcome analysis, and mediator-outcome analysis were performed using multivariate regression analysis according to the characteristics of the variables. Results: We analyzed 12,500 patients (mean age, 74.4 years; 51.3% male; median NIHSS at presentation, 8). From 2011 to 2019, the cumulative one-year incidence of the primary composite outcome (28.3% to 22.1%), all-cause mortality (23.8% to 17.9%), and stroke recurrence (8.3% to 5.1%) significantly decreased, while the NOAC prescription rate at discharge increased (0% to 75.6%). One-year increase in the calendar year was independently associated with a delayed occurrence of primary composite outcomes (Step 1: adjusted Time Ratio (aTR), 1.10; 95% confidence interval, 1.07-1.14) and with an increased NOAC prescription rate (Step 2: adjusted odds ratio, 2.20; 2.14-2.27). Increase in the NOAC prescription rate was significantly associated with the delayed occurrence of primary composite outcome (Step 3: aTR, 3.80; 3.15-4.58). However, after controlling for the NOAC prescription rate (mediator), the calendar year was no longer associated with the primary composite outcomes. (Step 4: aTR, 0.78; 95% CI 0.60-1.03). Thus, our results indicate full mediation of NOAC prescription in the association between the calendar year and primary composite outcomes. Conclusion: The reduced risk of major vascular events or death over time in AIS patients with AF was fully mediated by the increase in NOAC use.

Abstract TMP104: Effect Of Statin Therapy In Stroke Patients With Low Baseline Low-density Lipoprotein Cholesterol

Introduction: Post-stroke statin therapy is known to reduce subsequent major vascular events in patients with ischemic stroke. However, the efficacy of statin therapy in acute ischemic stroke patients with low low-density lipoprotein cholesterol (LDL-C) at baseline is not well defined. This study aimed to determine whether statin therapy would be beneficial in stroke patients with low or well-controlled LDL-C at baseline. Methods: We assessed ischemic stroke patients with baseline LDL-C &lt;100mg/dL without prior statin therapy or &lt;70mg/dL with prior statin therapy who were hospitalized between 2011 and 2020. The effect of post-stroke statin therapy on major vascular events, defined as a composite of recurrent stroke, myocardial infarction, and all-cause death within 1 year after stroke was assessed using multivariable Cox regression analyses. Results: A total of 3,350 patients (mean age 68.6 ± 13.9 years; 62.9% male; 21.5% with previous statin therapy; 37.0% with atherosclerotic stroke) were included. The mean baseline LDL-C of the patients was 73.6 ± 17.6mg/dL, which did not differ between patients with or without post-stroke statin therapy (74.0 ± 17.7mg/dL in statin users; 73.4 ± 17.6mg/dL in statin non-users). Statins were prescribed in 2,638 (78.8%) after stroke and LDL-C was significantly reduced in patients who received statin therapy (65.9 ± 21.7mg/dL in statin users; 80.2 ± 26.7mg/dL in statin non-users). Statin therapy was significantly associated with a lower risk of major vascular events (adjusted hazard ratios (aHR) 0.37 [95% confidence interval (CI) 0.31 - 0.46]). However, post-stroke LDL-C reduction (aHR 1.00 [95% CI 0.995 - 1.01]), percent LDL-C reduction (aHR 0.999 [95% CI 0.996 - 1.003]) and achieved LDL-C &lt;55mg/dL after stroke (aHR 0.96 [95% CI 0.67 - 1.37]) were not associated with the occurrence of major vascular events within 1 year after stroke. Conclusions: Post-stroke statin therapy was associated with a reduction in major vascular events after acute ischemic stroke, even in patients with low or well-controlled LDL-C. However, achieved LDL-C levels were not associated with post-stroke major vascular events in this population.

Abstract 143: Sepsis And Risk Of Major Postoperative Vascular Complications

Introduction: Stroke, myocardial infarction (MI), and pulmonary embolism (PE) greatly increase postoperative morbidity and mortality. Sepsis has been linked to increased risk of major vascular events, but the risk related to sepsis exposure throughout the postoperative period is uncertain. Hypothesis: Perioperative sepsis exposure increases the 30-day risk of postoperative stroke, myocardial infarction (MI), and pulmonary embolism (PE). Methods: Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), a formulaic sampling of surgical cases from participating United States institutions that prospectively collects demographic, clinical, surgical and 30-day outcome data. Sepsis was defined by systemic inflammatory response syndrome with either positive blood culture or evidence for infection found intraoperatively, and severe sepsis/shock as sepsis with evidence of organ dysfunction or circulatory dysfunction. We used mixed-effects Cox proportional hazard models, treating type of surgery as a random effect, to estimate the hazard ratios for major vascular complications due to sepsis and severe sepsis/shock exposure, adjusting for otherrisk factors. Results: We studied 6,614,937 surgical procedures. There were 201,230 cases with sepsis and an additional 78,052 cases of severe sepsis/shock. Outcomes included 13,939 strokes, 23,600 MIs, 21,893 PEs, and 1690 cases with multiple major vascular complications. Exposure to sepsis (HR 1.98, 95% confidence interval 1.91 to 2.06) or severe sepsis/shock (HR 3.27, 3.14 to 3.40) increased the risk of major vascular complications with larger effect than other established risks. Sepsis improvement within the preoperative period was associated with reduced risk (HR 0.82, 0.77 to 0.88). These findings were consistent in separate models for each complication. Conclusions: Sepsis approximately doubles and severe sepsis or shock triples the 30-day postoperative risk of major vascular complications. Improvement in sepsis severity prior to operation is associated with a 20% risk reduction.

Complete transcatheter versus complete surgical treatment in patients with aortic valve stenosis and concomitant coronary artery disease: Study-level meta-analysis with reconstructed time-to-event data.

To compare outcomes of complete transcatheter (TAVI plus PCI) versus complete surgical (SAVR plus CABG) approach to treat patients with aortic stenosis (AS) and concomitant coronary artery disease (CAD). Study-level meta-analysis with reconstructed time-to-event data including studies published by November 2021. The primary endpoints were 30-day mortality, overall survival, and major adverse cardiovascular and cerebrovascular events (MACCE). The secondary endpoints were 30-day stroke, myocardial infarction, and permanent pacemaker implantation (PPI); in-hospital major vascular events and acute kidney injury (AKI). Eight studies met our eligibility criteria, including a total of 33,286 patients (3448 for TAVI plus PCI and 29,838 for SAVR plus CABG). The pooled risk of 30-day mortality was lower for TAVI plus PCI (OR 0.63; 95% CI 0.51-0.80; p < .001). Patients undergoing TAVI plus PCI had lower risk of in-hospital AKI (OR 0.49; 95% CI 0.28-0.85; p = .01), however, higher risk of major vascular events (OR 7.33; 95% CI 1.80-29.85; p = .005) and higher risk of PPI (OR 2.96; 95% CI 1.80-4.85; p < .001). No statistically significant difference was observed for myocardial infarction and stroke between the groups. In the follow-up analyses, we observed a higher risk of mortality (HR 1.64, 95% CI 1.36-1.96, p < .001) and MACCE with TAVI plus PCI (HR 1.35 (95% CI 1.08-1.69, p = .009). Patients who undergo TAVI plus PCI (in comparison with SAVR plus CABG) initially experience lower rates of in-hospital death and AKI; however, they experience significantly lower survival rates and more MACCE at 5-year follow up. Structural heart surgeons and interventional cardiologists should consider these aspects when referring patients for one approach or the other.

Long term outcomes of percutaneous or surgical treatment in left main disease.

INTRODUCTION Long-term efficacy and safety of either surgical or percutaneous treatment main coronary artery disease treatment is lacking. EVIDENCE ACQUISITION We conducted a systematic review and meta-analysis of the most updated randomized clinical trials that compared the efficacy of coronary artery (CABG) or percutaneous coronary intervention (PCI) for the Left Main Coronary Artery (LMCA) disease. It was also conducted a systematic search of PubMed, Google Scholar, reference lists of relevant articles, and Medline. The search utilized the following terms: left main PCI versus CABG, drug-eluting stents, bypass surgery and left main stenting. The search of articles compatible with our inclusion and exclusion criteria was performed from inception through April 2020 and returned a combined total of 304 articles. EVIDENCE SYNTHESIS We identified 6 studies, providing data on 5812 patients. The mean follow-up was 6.7 years. PCI was associated with an increased risk of major vascular events (MACE) (IRR 1.24, 95% CI [1.03-1.67], P<0.01), and coronary revascularization (IRR 1.69, 95% CI [1.42-2.03], P<0.01) compared to CABG. Furthermore, all-cause death, MI and stroke events were not statistically different between the two therapeutic revascularization methodologies (IRR 1.06, 95% CI [0.90-1.24], P=0.47, IRR 1.35, 95% CI [0.84-2.16], P=0.03 and IRR 0.66, 95% CI [0.43-1.01], P=0.05, respectively). CONCLUSIONS LMCA PCI has an overall same survival compared to CABG in the long term follow-up. Nevertheless, MACE and revascularization events were more frequent in PCI compared to CABG.

Hydroxycarbamide Plus Aspirin Vs Aspirin Alone in Intermediate Risk Essential Thrombocythemia: Results of the PT-1 International, Prospective, Randomized Clinical Trial

IntroductionProspective randomized trials have shown that patients with “high-risk” essential thrombocythemia (aged >60, prior thrombotic history and/or cardiovascular risk factors) have a lower thrombotic risk if treated with hydroxycarbamide compared to no cytoreduction, and that hydroxycarbamide reduces risks of major vascular events, arterial thrombosis, serious hemorrhage and post-ET myelofibrosis (PET-MF) compared to anagrelide. However there are no prospective data evaluating the effects of cytoreduction in ET patients lacking high-risk factors. We undertook a prospective, open-label, randomized trial comparing hydroxycarbamide plus aspirin with aspirin alone in patients with “intermediate-risk” ET.MethodsPatients were recruited from 198 hospitals in 5 countries. Intermediate-risk patients were aged 40 to ≤ 59 years and lacked the following high-risk criteria: current or previous platelet count ≥1000x109/l (≥1500x109/l from 06/05/2004); previous ischemia, thrombosis or embolism; hemorrhage due to ET; hypertension or diabetes requiring therapy. 382 patients were randomized between 21/07/1997 and 31/07/2012 in a 1:1 ratio to aspirin alone or aspirin plus hydroxycarbamide; 24 were subsequently identified to be ineligible and excluded (Fig 1A). The composite primary endpoint was time from randomization to arterial or venous thrombosis, serious hemorrhage or death from vascular causes. Secondary endpoints were time to first arterial or venous thrombosis or to first serious hemorrhage; time to death; incidence of transformation to PET-MF, acute myeloid leukemia (AML), myelodysplasia (MDS) or polycythemia vera (PV); and patient-reported quality of life. The required duration of follow-up was calculated as the maximum period of time required for either a significantly different treatment effect or a point estimate for the number needed to treat to prevent one endpoint per year of >100, with a lower limit of the 95% confidence interval (CI) >50. Intention-to-treat analyses were performed.ResultsMedian duration of follow-up was 73 months (range, 0 to 187) with total follow-up of 2373 patient-years. 47% of the aspirin alone group started cytoreduction during follow-up whilst 21% of the aspirin plus hydroxycarbamide arm stopped hydroxycarbamide and/or started another cytoreductive agent (Fig 1A). Median time without treatment change was 36 months in the aspirin alone arm and 55 months in the aspirin plus hydroxycarbamide arm (p<0.001). Platelet counts were significantly different between the arms early on and started to overlap 5-6 years after entry (Fig 1B).The composite primary endpoint of time from randomization to arterial or venous thrombosis, serious hemorrhage or death from vascular causes was not significantly different between the arms (hazard ratio 0.98, 95% CI 0.43-2.27, p=1.0, Fig 1C). The incidence of significant vascular events for the whole study was 0.93 per 100 patient-years (95% CI 0.61-1.41). There was no significant difference in overall survival between the arms (p=0.5, Fig 1D), nor in the composite endpoint of rate of transformation to PET-MF, AML or MDS (p=0.7, Fig 1E). The rate of PV transformation was significantly higher in the aspirin alone arm (p=0.01, Fig 1E), most likely reflecting the non-specific effect of hydroxycarbamide in constraining erythropoiesis. A pre-specified analysis for any major disease-related complication - arterial thrombosis, venous thromboembolism, major hemorrhage, transformation to AML, MDS, PET-MF or death from any of these causes - showed no difference between the arms (p=0.6). There were no significant differences in the frequency of adverse events including non-hematological cancers. Quality of life data were recorded annually for five years using the EORTC QLQ-C30 questionnaire (v2), with no significant differences in summary scores in any yearConclusionIn ET patients aged 40-59 who lack high-risk factors pre-emptive addition of hydroxycarbamide to aspirin did not reduce the risk of vascular events or myelofibrotic or leukemic transformation. These results indicate that intermediate-risk ET patients should be treated with aspirin alone until another clinical indication for cytoreduction arises. Moreover patients receiving hydroxycarbamide showed no increase in leukemic transformation or other malignancies, supporting the concept that hydroxycarbamide is a safe therapy for ET. [Display omitted] DisclosuresMcMullin:Italfarmaco S.p.A.: Consultancy; Shire, Novartis: Honoraria, Speakers Bureau. Kiladjian:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Shire: Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy; Novartis: Honoraria, Research Funding, Speakers Bureau; CTI: Speakers Bureau.

Sex-Related Differences in Clinical Features, Neuroimaging, and Long-Term Prognosis After Transient Ischemic Attack.

Background and Purpose:Differences in sex in the incidence, presentation, and outcome of events after ischemic stroke have been studied in depth. In contrast, only limited data are available after transient ischemic attack (TIA). We aim to assess sex-related differences in the presentation, cause, neuroimaging features, and predictors of long-term prognosis in patients with TIA.Methods:We carried out a prospective cohort study of consecutive patients with TIA from January 2006 to June 2010. Nondefinitive TIA events were defined by the presence of isolated atypical symptoms. The risk of stroke recurrence (SR) and composite of major vascular events were stratified by sex after a median follow-up time of 6.5 (interquartile range, 5.0–9.6) years.Results:Among the 723 patients studied, 302 (41.8%) were female and 79 (10.9%) suffered a nondefinitive TIA event. Vascular territory diffusion-weighted imaging patterns (odds ratio, 1.61 [95% CI, 0.94–2.77]), and nondefinitive TIA events (odds ratio, 2.66 [95% CI, 1.55–4.59]) were associated with women, whereas active smoking (odds ratio, 0.30 [95% CI, 0.15–0.58]) and large artery atherosclerosis causes (odds ratio, 0.50 [95% CI, 0.29–0.83]) were related to men. The risk of SR was similar in both sexes (12.6% [95% CI, 8.9–16.3] for women versus 14.3% [95% CI, 11.0–17.6] for men). In contrast, the risk of major vascular events was significantly lower in women than in men (17.5% [95% CI, 13.2–21.8] versus 23.8% [95% CI, 19.7–27.9]). In both sexes, after adjusting for age, large artery atherosclerosis was associated with SR (hazard ratio, 3.22 [95% CI, 1.42–7.24] and hazard ratio, 2.00 [95% CI, 1.14–3.51]). In a Kaplan-Meier analysis, females with positive diffusion-weighted imaging (P=0.014) and definitive TIA (log-rank test P=0.022) had a significantly higher risk of SR.Conclusions:Despite similar risks of SR, there were sex-related differences in baseline characteristics, presenting symptoms, patterns of acute ischemic lesions, cause, and outcomes. These findings encourage further research into optimal preventive strategies that take into account these differences.

Long-term outcomes of percutaneous or surgical treatment in left main disease.

Long-term efficacy and safety of either surgical or percutaneous treatment left main coronary artery disease treatment is lacking. We conducted a systematic review and meta-analysis of the most updated randomized clinical trials that compared the efficacy of coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI) for the Left Main Coronary Artery (LMCA) disease. It was also conducted a systematic search of PubMed, Google Scholar, reference lists of relevant articles, and Medline. The search utilized the following terms: "left main PCI versus CABG," "drug-eluting stents," "bypass surgery" and "left main stenting." The search of articles compatible with our inclusion and exclusion criteria was performed from inception through April 2020 and returned a combined total of 304 articles. We identified 6 studies, providing data on 5812 patients. The mean follow-up was 6.7 years. PCI was associated with an increased risk of major vascular events (MACE) (IRR 1.24, 95% CI [1.03-1.67], P<0.01), and coronary revascularization (IRR 1.69, 95% CI [1.42-2.03], P<0.01) compared to CABG. Furthermore, all-cause death, MI and stroke events were not statistically different between the two therapeutic revascularization methodologies (IRR 1.06, 95% CI [0.90-1.24], P=0.47, IRR 1.35, 95% CI [0.84-2.16], P=0.03 and IRR 0.66, 95% CI [0.43-1.01], P=0.05, respectively). LMCA PCI has an overall same survival compared to CABG in the long term follow-up. Nevertheless, MACE and revascularization events were more frequent in PCI compared to CABG.

Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials

The clinical benefit of LDL cholesterol lowering treatment in older patients remains debated. We aimed to summarise the evidence of LDL cholesterol lowering therapies in older patients. In this systematic review and meta-analysis, we searched MEDLINE and Embase for articles published between March 1, 2015, and Aug 14, 2020, without any language restrictions. We included randomised controlled trials of cardiovascular outcomes of an LDL cholesterol-lowering drug recommended by the 2018 American College of Cardiology and American Heart Association guidelines, with a median follow-up of at least 2 years and data on older patients (aged ≥75 years). We excluded trials that exclusively enrolled participants with heart failure or on dialysis because guidelines do not recommend lipid-lowering therapy in such patients who do not have another indication. We extracted data for older patients using a standardised data form for aggregated study-level data. We meta-analysed the risk ratio (RR) for major vascular events (a composite of cardiovascular death, myocardial infarction or other acute coronary syndrome, stroke, or coronary revascularisation) per 1 mmol/L reduction in LDL cholesterol. Data from six articles were included in the systematic review and meta-analysis, which included 24 trials from the Cholesterol Treatment Trialists' Collaboration meta-analysis plus five individual trials. Among 244 090 patients from 29 trials, 21 492 (8·8%) were aged at least 75 years, of whom 11 750 (54·7%) were from statin trials, 6209 (28·9%) from ezetimibe trials, and 3533 (16·4%) from PCSK9 inhibitor trials. Median follow-up ranged from 2·2 years to 6·0 years. LDL cholesterol lowering significantly reduced the risk of major vascular events (n=3519) in older patients by 26% per 1 mmol/L reduction in LDL cholesterol (RR 0·74 [95% CI 0·61-0·89]; p=0·0019), with no statistically significant difference with the risk reduction in patients younger than 75 years (0·85 [0·78-0·92]; pinteraction=0·37). Among older patients, RRs were not statistically different for statin (0·82 [0·73-0·91]) and non-statin treatment (0·67 [0·47-0·95]; pinteraction=0·64). The benefit of LDL cholesterol lowering in older patients was observed for each component of the composite, including cardiovascular death (0·85 [0·74-0·98]), myocardial infarction (0·80 [0·71-0·90]), stroke (0·73 [0·61-0·87]), and coronary revascularisation (0·80 [0·66-0·96]). In patients aged 75 years and older, lipid lowering was as effective in reducing cardiovascular events as it was in patients younger than 75 years. These results should strengthen guideline recommendations for the use of lipid-lowering therapies, including non-statin treatment, in older patients. None.

Benefits and limitations of transcatheter vs. surgical aortic valve replacements

Background: Surgical Aortic Valve Replacement (SAVR) is the gold standard treatment for severe aortic stenosis. However, advanced age and interfering comorbidities combined with increased perioperative risks often make patients poor surgical candidates, necessitating the rise of the less invasive transcatheter aortic valve replacement (TAVR) approach. With the emergence of new evidence, we reviewed the literature comparing the benefits and harms of TAVR and SAVR in patients of varying surgical risk. Methods: A literature search of English-language articles published from January 2009 through June 2020 was designed in Ovid MEDLINE, PubMed, up-to-date, and Scopus. We used the following search headings in different combinations: aortic stenosis; aortic valve replacement; transcatheter aortic valve replacement; TAVR; SAVR; surgical valve replacement; high risk; intermediate risk; and low risk. Results: In meta-analysis, TAVR is better or non-inferior to SAVR in inoperable, high-risk, and intermediate patients when comparing mortality, rehospitalisation, severe disablement, and symptom control. These results remained consistent during follow-up at 1 year and 5 years. Evidence comparing TAVR and SAVR in low risk patients is limited, however emerging seminal trials show TAVR to have lower rates of deaths from any cause and rehospitalisation after 1 year (8.5% vs. 15.1%). In all cohorts, TAVR has significantly lower risk of major bleeding but increase risk of major vascular events, paravalvular leaks, and pacemaker implantation compared to SAVR. Conclusion: TAVR has successfully provided a minimally invasive alternative for patients with significant operative and perioperative risks associated with surgical replacement. While it is a superior treatment option than SAVR in high and intermediate risk patients, the final choice remains an individual one. Further research is required in low risk cohorts, though emerging evidence indicate a likely favourable outcome for TAVR.

Rivaroxaban and Aspirin in Patients With Symptomatic Lower Extremity Peripheral Artery Disease

Patients with symptomatic lower extremity peripheral artery disease (LE-PAD) experience an increased risk of major vascular events. There is limited information on what clinical features of symptomatic LE-PAD prognosticate major vascular events and whether patients at high risk have a greater absolute benefit from low-dose rivaroxaban and aspirin. To quantify the risk of major vascular events and investigate the response to treatment with low-dose rivaroxaban and aspirin among patients with symptomatic LE-PAD based on clinical presentation and comorbidities. This is a subanalysis of a previously reported subgroup of patients with symptomatic LE-PAD who were enrolled in a large, double-blind, placebo-controlled randomized clinical trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS]) in 602 centers in 33 countries from March 2013 to January 2020. Data analysis was completed from May 2016 to June 2020. A combination of low-dose rivaroxaban and aspirin compared with aspirin alone. Thirty-month incidence risk of myocardial infarction, stroke and cardiovascular death (MACE), major adverse limb events (MALE) including major vascular amputation, and bleeding. The COMPASS trial enrolled 4129 patients with symptomatic LE-PAD (mean [SD] age, 66.8 [8.8] years; 2932 men [71.0%]). The 30-month Kaplan-Meier incidence risk of MACE or MALE, including major amputation, was 22.6% in those with prior amputation (this outcome was observed in 54 patients), 17.6% (n = 15) in those with Fontaine III or IV symptoms, and 11.8% (n = 142) in those with previous peripheral artery revascularization, classifying these features as high-risk limb presentations. The 30-month incidence risk of MACE or MALE, including major amputation, was 14.1% (n = 118) in those with kidney dysfunction, 13.5% (n = 67) in those with heart failure, 13.4% (n = 199) in those with diabetes, and 12.8% (n = 222) in those with polyvascular disease, classifying these features as high-risk comorbidities. Among patients with either high-risk limb presentations or high-risk comorbidities, treatment with rivaroxaban and aspirin compared with aspirin alone was associated with an estimated 4.2% (95% CI, 1.9%-6.2%) absolute risk reduction for MACE or MALE, including major amputation, at 30 months. Although the estimated absolute risk increase of major bleeding was higher with rivaroxaban and aspirin in combination than aspirin alone (2.0% [95% CI, 0.5%-3.9%]) for patients with either high-risk limb presentation or high-risk comorbidity, the estimated absolute risk increase of fatal or critical organ bleeding was low in this high-risk group (0.4% [95% CI, 0.2%-1.8%]), such that the net clinical benefit was estimated to be 3.2% (95% CI, 0.6%-5.3%). Patients with LE-PAD with high-risk limb presentations or high-risk comorbidities had a high incidence of major vascular events. For these patients, treatment with rivaroxaban and aspirin in combination compared with aspirin alone led to a large absolute reduction in vascular risk.

Statin therapy in acute cardioembolic stroke with no guidance-based indication.

It is uncertain whether patients with cardioembolic stroke and without a guidance-based indication for statin therapy should be administered a statin for prevention of subsequent vascular events. This study was performed to determine whether the statin therapy is beneficial in preventing major vascular events in this population. Using a prospective multicenter stroke registry database, we identified patients with acute cardioembolic stroke who were hospitalized between 2008 and 2015. Patients who had other established indications for statin therapy according to current guidelines were excluded. Major vascular event was defined as a composite of stroke recurrence, myocardial infarction, and vascular death. We performed frailty model analysis with the robust sandwich variance estimator using the stabilized inverse probability of treatment weighting method to estimate hazard ratios of statin therapy on outcomes. Of 6,124 patients with cardioembolic stroke, 2,888 (male 44.6%, mean age 75.3 years, 95% confidence interval [CI] 74.8-75.8) were eligible, and 1,863 (64.5%) were on statin therapy during hospitalization. After a median follow-up of 359 days, cumulative incidences of major vascular events were 9.3% in the statin users and 20.5% in the nonusers (p < 0.001 by log-rank test). The adjusted hazard ratios of statin therapy were 0.39 (95% CI 0.31-0.48) for major vascular events, 0.81 (95% CI 0.57-1.16) for stroke recurrence, 0.28 (95% CI 0.21-0.36) for vascular death, and 0.53 (95% CI 0.45-0.61) for all-cause death. Starting statin during the acute stage of ischemic stroke may reduce the risk of major vascular events, vascular death, and all-cause death in patients with cardioembolic stroke with no guidance-based indication for statin.