Carotid artery stenting without embolic protection: A randomized multicenter trial (the CASWEP trial).

BACKGROUND: Carotid artery stenting (CAS) with a carotid protection device (CPD) has become the standard practice in patients with severe carotid stenosis and high surgical risk. However, the clinical efficacy and safety of CPDs are still controversial issues. We aimed to compare the clinical outcomes of the CAS without CPD with CAS combined with CPD. METHODS: This is a multicenter randomized prospective study registered with http://clinicaltrials.gov (NCT02781181). After the exclusion, 279 patients were enrolled (139 patients in the CAS with CPD group and 140 patients in the CAS without CPD group). The primary outcome was a combination of peri-procedural in-hospital transient ischemic attack (TIA), ipsilateral stroke, or death. The secondary outcome was new ischemic brain lesions on post-procedural diffusion-weighted magnetic resonance imaging (DW-MRI). RESULTS: Two patients died in CAS without CPD group, one patient died in CAS with CPD group. TIA was only seen in patients who underwent CAS under protection (n = 5). The combined primary outcome of TIA, ipsilateral stroke, and death rate was not different between groups (5.7% vs. 2.8%; p = 0.254). New defects were noted on the post-procedural DW-MRI in 28% of patients in the CPD group and 27% of patients in the no CPD group (p = 0.881). CONCLUSIONS: This study suggests that CAS without CPD is not associated with higher rates of peri-procedural TIA, stroke, and death or new ischemic brain lesions on post-procedural DW-MRI compared to CAS with CPD in selected symptomatic and asymptomatic patients with significant carotid artery stenosis provided that there is no visible thrombus.

Risk of cancer with angiotensin-receptor blockers increases with increasing cumulative exposure: Meta-regression analysis of randomized trials.

Angiotensin-receptor blockers (ARBs) are a class of drugs approved for the treatment of several common conditions, such as hypertension and heart failure. Recently, regulatory agencies have started to identify possibly carcinogenic nitrosamines and azido compounds in a multitude of formulations of several ARBs, resulting in progressive recalls. Furthermore, data from several randomized controlled trials suggested that there is also a clinically increased risk of cancer and specifically lung cancer with ARBs; whereas other trials suggested no increased risk. The purpose of this analysis was to provide additional insight into the ARB-cancer link by examining whether there is a relationship between degree of cumulative exposure to ARBs and risk of cancer in randomized trials. Trial-level data from ARB Trialists Collaboration including 15 randomized controlled trials was extracted and entered into meta-regression analyses. The two co-primary outcomes were the relationship between cumulative exposure to ARBs and risk of all cancers combined and the relationship between cumulative exposure and risk of lung cancer. A total of 74,021 patients were randomized to an ARB resulting in a total cumulative exposure of 172,389 person-years of exposure to daily high dose (or equivalent). 61,197 patients were randomized to control. There was a highly significant correlation between the degree of cumulative exposure to ARBs and risk of all cancers combined (slope = 0.07 [95% CI 0.03 to 0.11], p<0.001), and also lung cancer (slope = 0.16 [95% CI 0.05 to 0.27], p = 0.003). Accordingly, in trials where the cumulative exposure was greater than 3 years of exposure to daily high dose, there was a statistically significant increase in risk of all cancers combined (I2 = 31.4%, RR 1.11 [95% CI 1.03 to 1.19], p = 0.006). There was a statistically significant increase in risk of lung cancers in trials where the cumulative exposure was greater than 2.5 years (I2 = 0%, RR 1.21 [95% CI 1.02 to 1.44], p = 0.03). In trials with lower cumulative exposure to ARBs, there was no increased risk of all cancers combined or lung cancer. Cumulative exposure-risk relationship with ARBs was independent of background angiotensin-converting enzyme inhibitor treatment or the type of control (i.e. placebo or non-placebo control). Since this is a trial-level analysis. the effects of patient characteristics such as age and smoking status could not be examined due to lack of patient-level data. In conclusion, this analysis, for the first time, reveals that risk of cancer with ARBs (and specifically lung cancer) increases with increasing cumulative exposure to these drugs. The excess risk of cancer with long-term ARB use has public health implications.

Ankaferd blood stopper as a new strategy to avoid early complications after transradial procedures: A randomized clinical trial.

BACKGROUND: We planned a three arm randomized study to evaluate the safety and efficacy of a new blood stopper, Ankaferd blood stopper (ABS) along with short-time compression, compared to either short-time compression with conventional sterile gauzes (CSG) or with a TR band after transradial (TRA) procedures. METHODS: The Ankaferd blood stopper as a new strategy to avoid early complications. After transradial procedures (ABS transradial) trial is designed in a prospective, randomized, placebo-controlled fashion and registered with http://clinicaltrials.gov (NCT02982733). Six hundred and thirty patients were randomized into three arms in a 1:1:1 fashion corresponding to three different strategies of patent hemostasis techniques after diagnostic or interventional catheterization. RESULTS: One (0.49%) patient in the CSG group and one patient (0.48%) in the TR Band group developed RAO at the end of the hemostasis, compared with 0 (0%) in the ABS group. At 30 days follow-up none of the groups had any patients with RAO. As a secondary end-points the difference was not statistically significant regarding hematoma among the three groups (P = 0.70). Bleeding during deflation of the TR Band or removal of the elastic bandage occurred in 55 patients (26.96%) in the CSG group and in 56 (27.31%) patients in the TR Band group compared to 19 patients (9.40%) in the ABS group (P < 0.001). CONCLUSION: Ankaferd blood stopper is a promising device for use in patent hemostasis, with no evidence on RAO at short-term or long term and with reduced risk of re-bleeding at the end of hemostasis.

Comparison of Effects of Low- versus High-Dose Heparin on Access-Site Complications during Transradial Coronary Angiography: A Double-Blind Randomized Study.

OBJECTIVES: Although heparin is highly effective in reducing the rate of radial artery occlusion after transradial catheterization, the optimal heparin dose is still controversial. The aim of this study was to evaluate the efficacy and safety of two different heparin doses during transradial coronary angiography. METHODS: 490 consecutive patients undergoing transradial coronary angiography were prospectively enrolled into this double-blind randomized trial. A total of 202 patients enrolled in the low-dose (LD; 2,500 U of heparin) group and 202 patients enrolled in the high-dose (HD; 5,000 U of heparin) group were included in the final analysis. The primary endpoint of the study was radial artery occlusion. Bleeding and hematomas were the secondary outcome measures. RESULTS: At day 7, radial artery occlusion occurred in 5.9% of the patients in the LD group and in 5.4% of the patients in the HD group (p = 0.83). Bleeding during deflation of the transradial band occurred in 6.4% of the patients in the LD group and in 18.3% of the patients in the HD group; the difference was statistically significant (p < 0.001). Higher-dose heparin was found to be an independent predictor of bleeding (p = 0.007). CONCLUSION: A lower dose of heparin (i.e. 2,500 U) decreases bleeding during transradial band deflation without an increase in radial artery occlusion.

Bypass grafting versus percutaneous intervention in multivessel coronary disease: the current state.

Whether stenting or coronary artery bypass grafting (CABG) is the best revascularization strategy in patients with multivessel disease has been a heavily debated controversy. The trials comparing the two methods were unfortunately underpowered for mortality. Moreover, results of clinical trials appeared to contradict with each other. Because CABG is unequivocally a more cumbersome method, stenting became commonly preferred in the absence of evidence for mortality difference. Meta-analysis is a powerful tool, especially when several high-quality randomized trials are available on the same issue. In these instances, meta-analyses can overcome the power limitation of the individual trials. Our recent meta-analysis reveals that, as compared to stenting, CABG leads to unequivocal reductions in mortality and myocardial infarctions in patients with multivessel disease. These benefits are seen regardless of whether patients are diabetic or not and also do not depend on whether bare-metal or drug-eluting stents are used.

Impact of QRS duration on survival benefit with prophylactic implantable cardioverter-defibrillators: a meta-analysis of randomized controlled trials.

BACKGROUND: QRS duration is an important risk factor for both sudden cardiac death and all-cause mortality in patients with moderate to severe left ventricular systolic dysfunction. However, it is unknown whether baseline QRS duration can help predict the mortality benefit from implantable cardioverter-defibrillators (ICDs) when used for primary prevention purposes. OBJECTIVE: Our objective was to examine the relationship between baseline QRS duration and mortality reduction with ICDs implanted for primary prevention by performing a meta-analysis of all available randomized clinical trials. METHODS: A systematic literature search of SCOPUS (covering MEDLINE and EMBASE) was conducted for randomized controlled clinical trials involving ICDs. Primary prevention trials of systolic dysfunction that reported all-cause mortality according to subgroups on the basis of baseline QRS duration were included. RESULTS: A total of four randomized controlled clinical trials enrolling 3561 patients were included. Patients with QRS durations less than 120 ms [n = 2002, hazard ratio 0.78, 95% confidence interval (CI) 0.63-0.96, P = 0.018] and at least 120 ms (n = 1559, hazard ratio 0.59, 95% CI 0.48-0.73, P = 0.0000009) had significant decreases in all-cause mortality. On heterogeneity analysis, a strong trend for greater magnitude of benefit in patients with QRS at least 120 ms was observed (22% risk reduction vs. 41% risk reduction, P = 0.066). CONCLUSION: For primary prevention purposes, ICDs are effective in reducing all-cause mortality in moderate to severe systolic dysfunction regardless of QRS duration. However, patients with a baseline QRS duration of at least 120 ms seem to derive a greater mortality benefit from ICDs.

Coronary artery bypass grafting vs percutaneous coronary intervention and long-term mortality and morbidity in multivessel disease: meta-analysis of randomized clinical trials of the arterial grafting and stenting era.

IMPORTANCE: Recent trials of percutaneous coronary intervention (PCI) vs coronary artery bypass grafting (CABG) for multivessel disease were not designed to detect a difference in mortality and therefore were underpowered for this outcome. Consequently, the comparative effects of these 2 revascularization methods on long-term mortality are still unclear. In the absence of solid evidence for mortality difference, PCI is oftentimes preferred over CABG in these patients, given its less invasive nature. OBJECTIVES: To determine the comparative effects of CABG vs PCI on long-term mortality and morbidity by performing a meta-analysis of all randomized clinical trials of the current era that compared the 2 treatment techniques in patients with multivessel disease. DATA SOURCES: A systematic literature search was conducted for all randomized clinical trials directly comparing CABG with PCI. STUDY SELECTION: To reflect current practice, we included randomized trials with 1 or more arterial grafts used in at least 90%, and 1 or more stents used in at least 70% of the cases that reported outcomes in patients with multivessel disease. DATA EXTRACTION: Numbers of events at the longest possible follow-up and sample sizes were extracted. DATA SYNTHESIS: A total of 6 randomized trials enrolling a total of 6055 patients were included, with a weighted average follow-up of 4.1 years. There was a significant reduction in total mortality with CABG compared with PCI (I2 = 0%; risk ratio [RR], 0.73 [95% CI, 0.62-0.86]) (P < .001). There were also significant reductions in myocardial infarction (I2 = 8.02%; RR, 0.58 [95% CI, 0.48-0.72]) (P < .001) and repeat revascularization (I2 = 75.6%; RR, 0.29 [95% CI, 0.21-0.41]) (P < .001) with CABG. There was a trend toward excess strokes with CABG (I2 = 24.9%; RR, 1.36 [95% CI, 0.99-1.86]), but this was not statistically significant (P = .06). For reduction in total mortality, there was no heterogeneity between trials that were limited to and not limited to patients with diabetes or whether stents were drug eluting or not. Owing to lack of individual patient-level data, additional subgroup analyses could not be performed. CONCLUSIONS AND RELEVANCE: In patients with multivessel coronary disease, compared with PCI, CABG leads to an unequivocal reduction in long-term mortality and myocardial infarctions and to reductions in repeat revascularizations, regardless of whether patients are diabetic or not. These findings have implications for management of such patients.

Echocardiography-guided or "sided" pericardiocentesis.

Echocardiography-guided pericardiocentesis is the first choice method for relieving cardiac tamponade, but the exact role of the echocardiography at the moment of the puncture is still controversial. In this report, detailed echocardiographic evaluation was performed in 21 consecutive patients with cardiac tamponade just before the pericardiocentesis. Appropriate needle position was determined according to the probe position using imaginary x, y, and z axes. Pericardiocentesis was performed successfully using this technique without simultaneous echocardiography and no complications were observed. We concluded that bedside echocardiography with detailed evaluation of the puncture site and angle is enough for pericardiocentesis instead of real time guiding.

Effect of QRS morphology on clinical event reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled trials.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in reducing clinical events in systolic heart failure patients with a wide QRS. Previous retrospective studies suggest only patients with QRS prolongation due to a left bundle-branch block (LBBB) benefit from CRT. Our objective was to examine this by performing a meta-analysis of all randomized controlled trials of CRT. METHODS: Systematic searches of MEDLINE and the Food and Drug Administration official website were conducted for randomized controlled CRT trials. Trials reporting adverse clinical events (eg, all-cause mortality, heart failure hospitalizations) according to QRS morphology were included in the meta-analysis. RESULTS: Four randomized trials totaling 5,356 patients met the inclusion criteria. In patients with LBBB at baseline, there was a highly significant reduction in composite adverse clinical events with CRT (RR = 0.64 [95% CI (0.52-0.77)], P = .00001). However no such benefit was observed for patients with non-LBBB conduction abnormalities (RR = 0.97 [95% CI (0.82-1.15)], P = .75). When examined separately, there was no benefit in patients with right-bundle branch block (RR = 0.91 [95% CI (0.69-1.20)], P = .49) or non-specific intraventricular conduction delay (RR = 1.19 [95% CI (0.87-1.63)], P = .28). There was no heterogeneity among the clinical trials with regards to the lack of benefit in non-LBBB patients (I(2) = 0%). When directly compared, the difference in effect of CRT between LBBB versus non-LBBB patients was highly statistically significant (P = .0001 by heterogeneity analysis). CONCLUSIONS: While CRT was very effective in reducing clinical events in patients with LBBB, it did not reduce such events in patients with wide QRS due to other conduction abnormalities.

Effect of antihypertensive therapy on incident stroke in cohorts with prehypertensive blood pressure levels: a meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: Compared with normotensive individuals, there is a higher incidence of stroke in patients with hypertensive, as well as prehypertensive, blood pressure levels (ie, 120-139/80-89 mm Hg). Although several studies have shown that blood pressure reduction in hypertensive patients reduces the incidence of cardiovascular events, including stroke, it is still unknown whether treatment of prehypertensive blood pressure levels has a similar effect. We sought to determine whether reduction in blood pressure in the prehypertensive range reduces the incidence of stroke by performing a meta-analysis of randomized trials comparing an antihypertensive drug against placebo in cohorts with prehypertensive baseline blood pressure levels. METHODS: Randomized controlled trials performed with the 95 different antihypertensive agents available in the market were identified using MEDLINE, returning a total of 2852 results. Exclusion criteria included: average blood pressure of ≥ 140/90 mm Hg at baseline, crossover studies, and lack of a control group receiving placebo. RESULTS: A total of 16 trials involving 70 664 patients were included. Patients randomized to the active treatment arm had a statistically significant 22% reduction in the risk of stroke compared with placebo, with little heterogeneity among the trials (I(2), 18.0%; RR, 0.78 [95% CI, 0.71-0.86]; P<0.000001). To prevent 1 stroke, 169 patients had to be treated with a blood-pressure-lowering medication for an average of 4.3 years. CONCLUSIONS: The risk of stroke is significantly reduced with antihypertensive therapy in cohorts with prehypertensive blood pressure levels. These findings can have important clinical implications.

Impact of QRS duration on clinical event reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled trials.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in reducing clinical events in patients with heart failure and prolonged QRS interval. Studies using surrogate measures and subgroup analysis of large trials suggest that only patients with severely prolonged QRS benefit from CRT. Our objective was to determine whether the effect of CRT on adverse clinical events (eg, death, hospitalizations) is different in patients with moderately (ie, 120 to 149 milliseconds) [corrected] vs severely (ie, ≥150 milliseconds) prolonged QRS duration. METHODS: Searches of MEDLINE, SCOPUS, and Cochrane databases were conducted for randomized controlled CRT trials. Trials reporting clinical events according to different QRS ranges were identified. Five randomized trials fulfilling the inclusion criteria (total patients, n = 5813) were included in the meta-analysis. RESULTS: In patients with severely prolonged QRS, there was a reduction in composite clinical events with CRT (risk ratio, 0.60; 95% confidence interval [CI], 0.53-0.67) (P < .001). In contrast, there was no benefit of CRT in patients with moderately prolonged QRS (RR, 0.95; 95% CI, 0.82-1.10) (P = .49), resulting in a significantly different impact of CRT in the 2 QRS groups (P < .001). There was a significant relationship between baseline QRS duration and risk ratio (P < .001) with benefit of CRT appearing at a QRS of approximately 150 milliseconds and above. The differential response of the 2 QRS groups was evident for all New York Heart Association classes. CONCLUSIONS: Cardiac resynchronization therapy was effective in reducing adverse clinical events in patients with heart failure and a baseline QRS interval of 150 milliseconds or greater, but CRT did not reduce events in patients with a QRS of less than 150 milliseconds. These findings have implications for the selection of patients for CRT.