The Clinical Efficacy and Safety of Bempedoic Acid in Patients at Elevated Risk of Cardiovascular Disease: A Meta-Analysis of Randomized Clinical Trials.

PURPOSE: Statins are first-line agents to reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, however, they are insufficient and/or intolerable in many patients. To that end, we conducted a meta-analysis of Bempedoic Acid (BA), a novel LDL-C lowering agent. METHODS: We retrieved randomized clinical trials (RCTs) of BA by searching Pubmed, the Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov. We used the Mantel-Haenszel method to pool estimates. The I2 measure was used to quantify heterogeneity. Treatment effects are provided as relative risks (RR), absolute risk differences (ARD), and number needed to treat/harm (NNTB/H). Analyses were conducted using R, version 4.1.2. RESULTS: 11 trials enrolling 18,496 patients were included. Compared to placebo, BA reduced the risk of major adverse cardiovascular events (RR: 0.87; 95% CI: 0.80 to 0.95; ARD: -1.63%; NNT: 62), myocardial infarction (RR: 0.76; 95% CI: 0.66 to 0.89; ARD: -1.03%; NNT: 98), unstable angina hospitalization (RR: 0.70; 95%: CI: 0.55 to 0.89; ARD: -0.57%; NNT: 177), revascularization (RR: 0.81; 95% CI: 0.72 to 0.91; ARD: -1.31%; NNT: 77), and myalgia (RR: 0.85; 95% CI: 0.75 to 0.95; ARD: -0.99%; NNT: 102). BA significantly increased the risk of gout (RR: 1.56; 95% CI: 1.27 to 1.91; ARD: 0.99%; NNH: 101), renal impairment (RR: 1.35; 95% CI: 1.22 to 1.49; ARD: 2.54%; NNH: 40), and cholelithiasis (RR: 1.87; 95% CI: 1.43 to 2.44; ARD: 1.01%; NNH: 100). CONCLUSION: BA effectively reduces the risk of cardiovascular events and myalgia but increases the risk of gout, cholelithiasis, and renal impairment.

Long-term effectiveness of empiric cardio-protection in patients receiving cardiotoxic chemotherapies: A systematic review & bayesian network meta-analysis.

BACKGROUND: Cardioprotective therapies represent an important avenue to reduce treatment-limiting cardiotoxicities in patients receiving chemotherapy. However, the optimal duration, strategy and long-term efficacy of empiric cardio-protection remains unknown. METHODS: Leveraging the MEDLINE/Pubmed, CENTRAL and clinicaltrials.gov databases, we identified all randomised controlled trials investigating cardioprotective therapies from inception to November 2021 (PROSPERO-ID:CRD42021265006). Cardioprotective classes included ACEIs, ARBs, Beta-blockers, dexrazoxane (DEX), statins and mineralocorticoid receptor antagonists. The primary end-point was new-onset heart failure (HF). Secondary outcomes were the mean difference in left ventricular ejection fraction (LVEF) change, hypotension and all-cause mortality. Network meta-analyses were used to assess the cardioprotective effects of each therapy to deduce the most effective therapies. Both analyses were performed using a Bayesian random effects model to estimate risk ratios (RR) and 95% credible intervals (95% CrI). RESULTS: Overall, from 726 articles, 39 trials evaluating 5931 participants (38.0 ± 19.1 years, 72.0% females) were identified. The use of any cardioprotective strategy associated with reduction in new-onset HF (RR:0.32; 95% CrI:0.19-0.55), improved LVEF (mean difference: 3.92%; 95% CrI:2.81-5.07), increased hypotension (RR:3.27; 95% CrI:1.38-9.87) and no difference in mortality. Based on control arms, the number-needed-to-treat for 'any' cardioprotective therapy to prevent one incident HF event was 45, including a number-needed-to-treat of 21 with ≥1 year of therapy. Dexrazoxane was most effective at HF prevention (Surface Under the Cumulative Ranking curve: 81.47%), and mineralocorticoid receptor antagonists were most effective at preserving LVEF (Surface Under the Cumulative Ranking curve: 99.22%). CONCLUSION: Cardiotoxicity remains a challenge for patients requiring anticancer therapies. The initiation of extended duration cardioprotection reduces incident HF. Additional head-to-head trials are needed.

Impact of inferior vena cava thrombus extension on thrombolysis for acute iliofemoral thrombosis.

BACKGROUND: Inferior vena cava (IVC) thrombosis may occur in patients with iliofemoral deep venous thrombosis (DVT), and its impact on thrombolysis outcomes is poorly defined. This study compared outcomes of patients undergoing thrombolysis for acute iliofemoral DVT with and without IVC involvement. METHODS: Patients who underwent thrombolysis for iliofemoral DVT between May 2007 and March 2014 were identified from a prospectively maintained database and divided into two groups: those with IVC involvement and those without. End points were technical and clinical success (≥50% lysis or freedom from 30-day DVT recurrence), long-term DVT recurrence, and post-thrombotic syndrome (PTS; Villalta score ≥5). Multivariate regression models were used to determine predictors of anatomic and clinical failures. RESULTS: There were 102 patients (127 limbs) treated with various combinations of catheter-directed or pharmacomechanical thrombolysis. In 46 patients, thrombus extended into the IVC (54.3% extended up to the renal veins; 87% had ≥50% luminal reduction; 50% occurred in association with an indwelling thrombosed IVC filter). The caval group had fewer women and more previous DVTs but otherwise was similar to the noncaval group. Pharmacomechanical thrombolysis was used more frequently in the caval thrombus group (97.8% vs 82.1%; P = .011), and iliac vein stenting was used more often in the noncaval group (41.3% vs 62.5%; P = .033). Clinical success was similar between the two groups (88.7% for caval vs 89.3% for noncaval; P = .921). All failures in the caval group occurred in patients with an indwelling thrombosed IVC filter. Primary patency at 2 years for the caval and noncaval groups was 76.7% and 78.0%, respectively (P = .787). Valve reflux and PTS at 2 years were higher in the noncaval group (50.8% and 34.3% vs 23.3% and 11.5% in the caval group; P = .013 and P = .035). On multivariate analysis, incomplete lysis was predictive of recurrence (hazard ratio [HR], 22.7; P < .001) and PTS (HR, 5.59; P = .010), whereas caval involvement (HR, 0.22; P = .005) was protective from PTS. CONCLUSIONS: IVC thrombosis does not have an impact on the technical success of thrombolysis in patients with iliofemoral DVT; the presence of a thrombosed IVC filter, though, may make failure more likely. Caval thrombosis may not affect primary patency but is associated with a lower incidence of PTS after successful lysis.

Improved early right ventricular function recovery but increased complications with catheter-directed interventions compared with anticoagulation alone for submassive pulmonary embolism.

OBJECTIVE: The purpose of this study was to determine the short-term and midterm outcomes of catheter-directed intervention (CDI) compared with anticoagulation (AC) alone in patients with submassive pulmonary embolism (sPE). METHODS: This was a retrospective review of all patients treated for sPE between January 2009 and October 2014. Two groups were identified on the basis of the therapy: AC and CDI. End points included complications, mortality, and change in echocardiographic parameters. Standard statistical techniques were used. RESULTS: There were 64 patients who received AC and 64 patients who received CDI (five were initially treated with AC but did not improve or worsened; six received ≤8 mg of tissue plasminogen activator). Most baseline characteristics, including the Pulmonary Embolism Severity Index, were similar among the AC and CDI groups. There was no difference in PE-related death (one in each group) or major bleeding events (three in the AC group, four in the CDI group), but CDIs had two additional procedural complications that required open heart surgery. CDIs showed significantly more minor bleeding events (6 vs 0; P = .028) and significantly shorter intensive care unit stay (2.7 ± 2.1 vs 5.6 ± 7.5 days; P = .04). The mean difference in right ventricular/left ventricular ratio from baseline to the first subsequent echocardiogram (within 30 days) showed a trend for higher reduction in favor of CDI (AC, 0.17 ± 0.12; CDI, 0.27 ± 0.15; P = .076). Between 3 and 8 months, significant improvement was evident within groups in all assessed right-sided heart echocardiographic parameters, but there was no difference between groups. Pulmonary hypertension (pulmonary artery pressure >40 mm Hg) was present in 7 of 15 of the AC group vs 6 of 19 of the CDI group (P = .484). During the follow-up, dyspnea or oxygen dependence, not existing before the index PE event, was recorded in 5 of 49 (10.2%) of the AC patients and 8 of 52 (15.4%) of the CDI patients (P = .556). CONCLUSIONS: CDI for sPE can result in faster restoration of right ventricular function and shorter intensive care unit stay, but at the cost of a higher complication rate, with similar midterm outcomes compared with AC alone. A potential effect of CDI on mortality and pulmonary hypertension needs further investigation through larger studies.

Primary closure after carotid endarterectomy is not inferior to other closure techniques.

OBJECTIVE: Primary closure after carotid endarterectomy (CEA) has been much maligned as an inferior technique with worse outcomes than in patch closure. Our purpose was to compare perioperative and long-term results of different CEA closure techniques in a large institutional experience. METHODS: A consecutive cohort of CEAs between January 1, 2000, and December 31, 2010, was retrospectively analyzed. Closure technique was used to divide patients into three groups: primary longitudinal arteriotomy closure (PRC), patch closure (PAC), and eversion closure (EVC). End points were perioperative events, long-term strokes, and restenosis ≥70%. Multivariate regression models were used to assess the effect of baseline predictors. RESULTS: There were 1737 CEA cases (bilateral, 143; mean age, 71.4 ± 9.3 years; 56.2% men; 35.3% symptomatic) performed during the study period with a mean clinical follow-up of 49.8 ± 36.4 months (range, 0-155 months). More men had primary closure, but other demographic and baseline symptoms were similar between groups. Half the patients had PAC, with the rest evenly distributed between PRC and EVC. The rate of nerve injury was 2.7%, the rate of reintervention for hematoma was 1.5%, and the length of hospital stay was 2.4 ± 3.0 days, with no significant differences among groups. The combined stroke and death rate was 2.5% overall and 3.9% and 1.7% in the symptomatic and asymptomatic cohort, respectively. Stroke and death rates were similar between groups: PRC, 11 (2.7%); PAC, 19 (2.2%); EVC, 13 (2.9%). Multivariate analysis showed baseline symptomatic disease (odds ratio, 2.4; P = .007) and heart failure (odds ratio, 3.1; P = .003) as predictors of perioperative stroke and death, but not the type of closure. Cox regression analysis demonstrated, among other risk factors, no statin use (hazard ratio, 2.1; P = .008) as a predictor of ipsilateral stroke and severe (glomerular filtration rate <30 mL/min/1.73 m(2)) renal insufficiency (hazard ratio, 2.6; P = .032) as the only predictor of restenosis ≥70%. Type of closure did not have any predictive value. CONCLUSIONS: In our study, baseline risk factors and statin use, but not the type of closure, affect perioperative and long-term outcomes after CEA.

Comparison of Reinforcement Techniques Using Suture on Staple-Line in Sleeve Gastrectomy.

BACKGROUND: Sleeve gastrectomy is a common procedure in recent years for treatment of morbid obesity however leak from staple-line is its main challenging complication. Despite numerous studies regarding leak after sleeve gastrectomy, there is still no conclusion on reinforcement of staple-line in this procedure. The purpose of this study was to compare two methods of oversewing staple-line versus no reinforcement. METHODS: Resected stomachs of 30 patients undergoing laparoscopic sleeve gastrectomy were evaluated for bursting pressure immediately after extraction from the abdomen. Reinforcement technique was applied in random order to 3 segments of the staple-line on each specimen: continuous Lembert's sutures, continuous through-and-through sutures, and no reinforcement. Bursting pressure was determined by injection of methylene blue solution into lumen of resected stomach and recording pressure at which leakage occurs. Location of leak, intragastric pressure, and volume at first leak were recorded. RESULTS: Baseline characteristics of patients were similar in randomized groups for order of reinforcement technique. Mean ischemia time of specimens was 17.4 ± 10.4 min. No leaks were observed in segments reinforced with Lembert's oversewing technique. The through-and-through reinforcement segments were first to leak in 21 out of 30 cases (70 %) with mean leak pressure of 570 mmHg and mean leak volume of 399 ml. Leakage occurred in 9 segments (30 %) with no reinforcement with a leak pressure of 329 mmHg and volume of 380 ml. CONCLUSIONS: In vitro, Lembert's suture reinforcement technique on stapled human stomach is associated with less leakage rate in comparison to through-and-through reinforcement and non-reinforced staple-line.