Safety of catheter-directed thrombolysis for massive and submassive pulmonary embolism: Results of a multicenter registry and meta-analysis.

OBJECTIVES: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) in the treatment of acute pulmonary embolism (PE). BACKGROUND: The use of CDT for the treatment of acute submassive and massive PE is increasing in frequency. However, its safety and efficacy have not been well elucidated. METHODS: This study is made of two parts: one is a two-center registry of acute PE patients treated with CDT. The safety outcome evaluated was any major complication including fatal, intracranial (ICH), intraocular, or retroperitoneal hemorrhage or any overt bleeding requiring transfusion or surgical repair. The efficacy outcome was acute change in invasive pulmonary artery systolic pressure (PASP). The second part is a meta-analysis of all contemporary studies that used CDT for PE. Reported outcomes are the same as in the registry, with the addition of right ventricular to left ventricular (RV/LV) ratio change. RESULTS: In the registry, 137 patients were included (age 59 ± 15, 50% male, 88% submassive PE). ICH occurred in two patients and major complications in 13 (9.4%). PASP decreased post procedure by 19 ± 15 mm Hg (95% CI 16-23). In the meta-analysis, 16 studies were included with 860 patients. Rate of ICH was 0.35% and the major complication rate was 4.65%, most requiring transfusion only. In-hospital mortality was 12.9% in the massive and 0.74% in the submassive group. All studies showed improvement in PASP and/or RV/LV ratio post CDT. CONCLUSIONS: CDT is associated with a low major complication rate. Randomized studies are needed to evaluate its efficacy relative to anticoagulation alone. © 2017 Wiley Periodicals, Inc.

Comparative effectiveness of coronary CT angiography vs stress cardiac imaging in patients following hospital admission for chest pain work-up: The Prospective First Evaluation in Chest Pain (PERFECT) Trial.

BACKGROUND: Because the frequency of cardiac event rates is low among chest pain patients following either performance of coronary CT angiography (CCTA) or stress testing, there is a need to better assess how these tests influence the central management decisions that follow from cardiac testing. The present study was performed to assess the relative impact of CCTA vs stress testing on medical therapies and downstream resource utilization among patients admitted for the work-up of chest pain. METHODS: The admitted patients were randomized in a 1:1 ratio to either cardiac imaging stress test or CCTA. Primary outcomes were time to discharge, change in medication usage, and frequency of downstream testing, cardiac interventions, and cardiovascular re-hospitalizations. We randomized 411 patients, 205 to stress testing, and 206 to CCTA. RESULTS: There were no differences in time to discharge or initiation of new cardiac medications at discharge. At 1 year follow-up, there was no difference in the number of patients who underwent cardiovascular downstream tests in the CCTA vs stress test patients (21% vs 15%, P = .1) or cardiovascular hospitalizations (14% vs 16%, P = .5). However, there was a higher frequency of invasive angiography in the CCTA group (11% vs 2%, P = .001) and percutaneous coronary interventions (6% vs 0%, P < .001). CONCLUSIONS: Randomization of hospitalized patients admitted for chest pain work-up to either CCTA or to stress testing resulted in similar discharge times, change in medical therapies at discharge, frequency of downstream noninvasive testing, and repeat hospitalizations. However, a higher frequency of invasive coronary angiography and revascularization procedures were performed in the CCTA arm. (ClinicalTrials.gov number, NCT01604655.).

Meta-analysis of randomized controlled trials comparing percutaneous coronary intervention with aspiration thrombectomy Vs. Conventional percutaneous coronary intervention during ST-segment elevation myocardial infarction.

OBJECTIVES: Evaluate the impact of aspiration thrombectomy (AT) during primary coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) on clinical outcomes. BACKGROUND: AT during PCI for STEMI may improve microvascular reperfusion, but its impact on clinical outcomes has remained controversial. METHODS: We searched Pubmed, EMBASE, Medline, Scopus, CENTRAL, andClinicalTrials.gov databases on March 31, 2015 for randomized controlled trials that evaluated the use of AT with PCI compared with PCI alone for STEMI. The primary end point was all-cause mortality. Secondary end points included major adverse cardiac events (MACE, consisting of death, myocardial infarction, and target-vessel revascularization), recurrent myocardial infarction (MI), target-vessel revascularization (TVR), stent thrombosis and stroke. RESULTS: Eighteen randomized controlled trials (n = 21,501) fulfilled the inclusion criteria. A total of 10,544 patients were treated with AT and PCI, compared to 10,957 control patients. The use of AT was not associated with a significant decrease in all-cause mortality (RR 0.88; 95% CI 0.78-1.01; P = 0.07), MACE (RR 0.93; 95% CI 0.86-1.00; P = 0.06), recurrent MI (RR 0.97: 95% CI 0.81-1.17; P = 0.77), TVR (RR 0.93; 95% CI 0.82-1.05; P = 0.23), stent thrombosis (RR 0.84; 95% CI 0.66-1.07; P = 0.17), or stroke (RR 1.35; 95% CI 0.86-2.11; P = 0.19). CONCLUSIONS: Using the totality of evidence available through 2015, this meta-analysis failed to show that the routine use of aspiration thrombectomy in patients with ST-elevation myocardial infarction significantly reduces all-cause mortality, MACE, recurrent MI, TVR, or stent thrombosis. The role of aspiration thrombectomy in selected patients with angiographic evidence of large thrombus burden requires further clinical investigation. © 2015 Wiley Periodicals, Inc.

Vascular brachytherapy versus drug-eluting stents in the treatment of in-stent restenosis: A meta-analysis of long-term outcomes.

INTRODUCTION: Clinical trials have shown a short-term benefit of drug-eluting stents (DES) compared to vascular brachytherapy (VBT) for treatment of in-stent restenosis (ISR). The long-term benefits of DES vs. VBT are conflicting in the literature. This study aimed to do a meta-analysis of long-term outcomes of DES compared to VBT for treatment of ISR. METHODS: PubMed, EMBASE, Cochrane Central and unpublished data were searched for cohort studies and randomized controlled trials (RCTs) that directly compared VBT to DES for the treatment of ISR. We evaluated the following outcomes at 2-5 years of follow-up: target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis, cardiovascular (CV) mortality, and overall mortality. Heterogeneity was defined as I(2) values > 25%. Review Manager 5.1 was used for statistical analysis. RESULTS: We included 1,375 patients from five studies, of which three were RCTs. VBT was used to treat ISR in 685 (49.8%) patients. After a 2-5 year follow-up, no significant differences were found between treatment groups regarding MI (P = 0.49), stent thrombosis (P = 0.86), CV mortality (P = 0.35), and overall mortality (P = 0.71). TLR (OR 2.37; CI 1.55-3.63; P < 0.001) and TVR (OR 2.23; CI 1.01-4.94; P = 0.05) were significantly increased in patients who received VBT. CONCLUSION: This study suggests that DES are associated with decreased long-term revascularization procedures when compared to VBT for the treatment of ISR. This benefit does not appear to be associated with a significant reduction in mortality or myocardial infarction.

High dose statin loading prior to percutaneous coronary intervention decreases cardiovascular events: a meta-analysis of randomized controlled trials.

OBJECTIVE: We performed a meta-analysis of randomized controlled trials of statin loading prior to percutaneous coronary intervention (PCI). BACKGROUND: Statin loading prior to PCI has been shown to decrease peri-procedural myocardial infarction (pMI) but less is known regarding the clinical benefit of pre-procedural statin loading. METHODS: We searched for trials of statin naïve patients presenting with stable angina or NSTE-ACS and treated with statins prior to PCI. We evaluated the incidence of pMI and major cardiac events including spontaneous myocardial infarction, death, and target vessel revascularization. RESULTS: Out of 1,210 articles, 14 randomized controlled trials were included in this meta-analysis. Among 3,146 patients, 1,591 patients were randomized to a loading dose of statin before PCI and 1,555 patients were given statin therapy initiated only after the PCI. Statin loading prior to PCI was associated with a 56% relative reduction in pMI (OR: 0.44, 95% CI: 0.35-0.56; P < 0.00001). There was a 41% reduction in clinical events in follow-up in the group of patients treated with statin loading prior to PCI (OR: 0.59, 95% CI: 0.38-0.92, P = 0.02). When stratified according to the clinical presentation, the results were only significant for those patients with NSTE-ACS (OR: 0.18, 95% CI: 0.07-0.47; P = 0.0005) and was not noted in the group of patients who underwent PCI for stable angina (OR: 0.92, 95% CI: 0.53-1.61; P = 0.78). CONCLUSIONS: High dose statin therapy given prior to PCI in patients with NSTE-ACS is associated with a reduction in pMI and short-term clinical events. © 2013 Wiley Periodicals, Inc.

Metaanalysis of Multivessel vs Culprit Artery Only Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction.

Background: Primary percutaneous coronary intervention (PCI) is the most frequently used treatment modality for patients presenting with ST elevation myocardial infarction (STEMI). Current professional society guidelines recommend culprit artery only PCI. Recent evidence suggests the potential benefit of multivessel PCI among patients with STEMI that is not complicated by cardiogenic shock. Methods: We systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for clinical studies of patients with STEMI, not complicated by cardiogenic shock, who underwent primary PCI between January 1966 and January 2018. We evaluated all-cause and cardiovascular mortality, reinfarction, and repeat revascularization among patients randomized to a multivessel PCI strategy compared to a culprit artery only PCI strategy. Results: Four randomized clinical trials with a total of 1,044 patients met the inclusion criteria. Five hundred and sixty-six patients underwent multivessel PCI, and 478 patients underwent culprit artery only PCI. Multivessel PCI reduced all the studied endpoints: total death, cardiac death, reinfarction, and repeat revascularization (all P values <0.05). Conclusion: To our knowledge, this is the largest metaanalysis of randomized controlled trials studying multivessel PCI vs culprit artery only PCI in STEMI patients without shock, among whom lesion severity was graded by angiography alone. We found that compared to culprit artery only PCI, the multivessel PCI strategy was beneficial in reducing all-cause and cardiovascular mortality, reinfarction, and the need for repeat revascularization.

Meta-Analysis of Randomized Clinical Trials Comparing Biodegradable Polymer Drug-Eluting Stent to Second-Generation Durable Polymer Drug-Eluting Stents.

OBJECTIVES: The authors sought to perform a meta-analysis of randomized clinical trials (RCTs) comparing the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DES) to second-generation durable polymer drug-eluting stents (DP-DES). BACKGROUND: Prior meta-analyses have established the superiority of BP-DES over bare-metal stents and first-generation DP-DES; however, their advantage compared with second-generation DP-DES remains controversial. METHODS: The authors searched PubMed and Scopus databases for RCTs comparing BP-DES to the second-generation DP-DES. Outcomes included target vessel revascularization (TVR) as efficacy outcome and cardiac death, myocardial infarction (MI), and definite or probable stent thrombosis (ST) as safety outcomes. In addition, we performed landmark analysis for endpoints beyond 1 year of follow-up and a subgroup analysis based on the stent characteristics. RESULTS: The authors included 16 RCTs comprising 19,886 patients in the meta-analysis. At the longest available follow-up (mean duration 26 months), we observed no significant differences in TVR (p = 0.62), cardiac death (p = 0.46), MI (p = 0.98), or ST (risk ratio: 0.83, 95% confidence interval: 0.64 to 1.09; p = 0.19). Our landmark analysis showed that BP-DES were not associated with a reduction in the risk of very late ST (risk ratio: 0.87, 95% confidence interval: 0.49 to 1.53; p = 0.62). Similar outcomes were seen regardless of the eluting drug (biolimus vs. sirolimus), the stent platform (stainless steel vs. alloy), the kinetics of polymer degradation or drug release (<6 months vs. >6 months), the strut thickness of the BP-DES (thin <100 µm vs. thick >100 µm), or the DAPT duration (≥6 months vs. ≥12 months). CONCLUSIONS: BP-DES have similar safety and efficacy profiles to second-generation DP-DES.

A Nationwide Analysis of Outcomes of Weekend Admissions for Intracerebral Hemorrhage Shows Disparities Based on Hospital Teaching Status.

BACKGROUND AND PURPOSE: With the "weekend effect" being well described, the Brain Attack Coalition released a set of "best practice" guidelines in 2005, with the goal to uniformly provide standard of care to patients with stroke. We attempted to define a "weekend effect" in outcomes among patients with intracranial hemorrhage (ICH) over the last decade, utilizing the Nationwide Inpatient Sample (NIS) data. We also attempted to analyze the trend of such an effect. MATERIALS AND METHODS: We determined the association of ICH weekend admissions with hospital outcomes including mortality, adverse discharge, length of stay, and cost compared to weekday admissions using multivariable logistic regression. We extracted our study cohort from the NIS, the largest all-payer data set in the United States. RESULTS: Of 485 329 ICH admissions from 2002 to 2011, 27.5% were weekend admissions. Overall, weekend admissions were associated with 11% higher odds of in-hospital mortality. When analyzed in 3-year groups, excess mortality of weekend admissions showed temporal decline. There was higher mortality with weekend admissions in nonteaching hospitals persisted (odds ratios 1.16, 1.13, and 1.09, respectively, for 3-year subgroups). Patients admitted during weekends were also 9% more likely to have an adverse discharge (odds ratio 1.09; 95% confidence interval: 1.07-1.11; P < .001) with no variation by hospital status. There was no effect of a weekend admission on either length of stay or cost of care. CONCLUSION: Nontraumatic ICH admissions on weekends have higher in-hospital mortality and adverse discharge. This demonstrates need for in-depth review for elucidating this discrepancy and stricter adherence to standard-of-care guidelines to ensure uniform care.

Meta-Analysis of Randomized Controlled Trials Comparing Multivessel Versus Culprit-Only Revascularization for Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease Undergoing Primary Percutaneous Coronary Intervention.

Current guidelines recommend against revascularization of the noninfarct artery during the index percutaneous coronary intervention (PCI) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI). This was based largely on observational studies with few data coming from randomized controlled trials (RCTs). Recently, several small-to-moderate sized RCTs have provided data, suggesting that a multivessel revascularization approach may be appropriate. We performed a meta-analysis of RCTs comparing multivessel percutaneous coronary intervention (MV PCI) versus culprit vessel-only revascularization (COR) during primary PCI in patients with STEMI and multivessel coronary disease (MVCD). We searched Medline, PubMed, and Scopus databases for RCTs comparing MV PCI versus COR in patients with STEMI and MVCD. The incidence of all-cause death, cardiac death, recurrent myocardial infarction, and revascularization during follow-up were extracted. Four RCTs fit our primary selection criteria. Among these, 566 patients underwent MV PCI (either at the time of the primary PCI or as a staged procedure) and 478 patients underwent COR. During long-term follow-up (range 1 to 2.5 years), combined data indicated a significant reduction in all-cause mortality (relative risk [RR] 0.57, 95% confidence interval [CI] 0.36 to 0.92, p = 0.02) and in cardiac death (RR 0.38, 95% CI 0.20 to 0.73, p = 0.004) with MV PCI. In addition, there was a significantly lower risk of recurrent myocardial infarction (RR 0.41, 95% CI 0.23 to 0.75; p = 0.004) and future revascularization (RR 0.37, 95% CI 0.27 to 0.52; p <0.00001). In conclusion, from the RCT data, MV PCI appears to improve outcomes in patients with STEMI and MVCD.

Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis.

BACKGROUND: Dual antiplatelet therapy is the standard of care after coronary stent placement but increases the bleeding risk. The effects of proton pump inhibitors (PPIs) on clopidogrel metabolism have been described, but the clinical significance is not yet definitive. We aimed to do an updated meta-analysis comparing outcomes in patients receiving clopidogrel with and without PPIs. METHODS: We systematically searched PubMed, Scopus and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) and controlled observational studies in patients taking clopidogrel stratified by concomitant PPI use. Heterogeneity was examined with the Cochran Q test and I(2) statistics; p values inferior to 0.10 and I(2) >25% were considered significant for heterogeneity. RESULTS: We included 39 studies with a total of 214 851 patients, of whom 73 731 (34.3%) received the combination of clopidogrel and a PPI. In pooled analysis, all-cause mortality, myocardial infarction, stent thrombosis and cerebrovascular accidents were more common in patients receiving both drugs. However, among 23 552 patients from eight RCTs and propensity-matched studies, there were no significant differences in mortality or ischaemic events between groups. The use of PPIs in patients taking clopidogrel was associated with a significant reduction in the risk of gastrointestinal bleeding. CONCLUSIONS: The results of our meta-analysis suggest that PPIs are a marker of increased cardiovascular risk in patients taking clopidogrel, rather than a direct cause of worse outcomes. The pharmacodynamic interaction between PPIs and clopidogrel most likely has no clinical significance. Furthermore, PPIs have the potential to decrease gastrointestinal bleeding in clopidogrel users.

Systematic oral hydration with water is similar to parenteral hydration for prevention of contrast-induced nephropathy: an updated meta-analysis of randomised clinical data.

BACKGROUND: Contrast-induced nephropathy (CIN) is the third most common cause of hospital-acquired kidney injury and is related to increased long-term morbidity and mortality. Adequate intravenous (IV) hydration has been demonstrated to lessen its occurrence. Oral (PO) hydration with water is inexpensive and readily available but its role for CIN prevention is yet to be determined. METHODS: PubMed, EMBASE and the Cochrane Central register of controlled trials (CENTRAL) databases were searched until April 2015 and studies were selected using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. All randomised clinical trials with head-to-head comparison between PO and IV hydration were included. RESULTS: A total of 5 studies with 477 patients were included in the analysis, 255 of those receiving PO water. The incidence of CIN was statistically similar in the IV and PO arms (7.7% and 8.2%, respectively; relative risk 0.97; 95% CI 0.36 to 2.94; p=0.95). The incidence of CIN was statistically similar in the IV and PO arms in patients with chronic kidney disease and with normal renal function. Rise in creatinine at 48-72 h was lower in the PO hydration group compared with IV hydration (pooled standard mean difference 0.04; 95% CI 0.03 to 0.06; p<0.001; I(2)=62%). CONCLUSIONS: Our meta-analysis shows that systematic PO hydration with water is at least as effective as IV hydration with saline to prevent CIN. PO hydration is cheaper and more easily administered than IV hydration, thus making it more attractive and just as effective.

Meta-analysis of randomized clinical trials comparing short-term versus long-term dual antiplatelet therapy following drug-eluting stents.

Current guidelines recommend 12 months of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation in the absence of increased bleeding risk. Studies have suggested that early discontinuation of DAPT can result in an increased risk of stent thrombosis. However, given the potential for major bleeding, the optimal duration of DAPT after DES implantation remains uncertain. We searched PubMed, EMBASE, Scopus, and ClinicalTrials.gov databases from inception until October 2013 for randomized controlled trials that compared shorter versus longer DAPT duration after DES implantation. Four randomized controlled trials were included. A total of 4,081 patients received DAPT for 3 to 6 months, and 4,076 patients were treated with DAPT for 12 to 24 months. Oral DAPT consisted of aspirin and clopidogrel. There was no significant difference in the rate of the composite outcome of cardiac death or myocardial infarction between the short (3.3%) and prolonged (3.0%) DAPT groups (odds ratio 1.11, 95% confidence interval 0.87 to 1.43, p=0.41). A landmark analysis performed at the time of discontinuation of DAPT in the short DAPT group demonstrated a nonsignificant higher rate of stent thrombosis in patients treated with a short course of DAPT (0.35% vs 0.20%, p=0.22). Major bleeding was significantly higher in the group of patients treated with prolonged DAPT (0.29% vs 0.71%, p=0.01). In conclusion, prolonged DAPT compared with short-term treatment is associated with increased major bleeding but is not associated with a decrease in the composite rates of death or myocardial infarction.

Meta-analysis of coronary computed tomography angiography versus standard of care strategy for the evaluation of low risk chest pain: are randomized controlled trials and cohort studies showing the same evidence?

BACKGROUND: Randomized control trials (RCTs) have established the use of Coronary Computed Tomography Angiography (CCTA) for the evaluation of low to intermediate risk patients presenting with acute chest pain to the emergency department (ED). However, concerns remain regarding the downstream resource utilization and the clinical impact of such strategy. METHODS: We performed a meta-analysis of existing studies to compare CCTA to the standard of care (SOC) strategies in the low to intermediate risk chest pain patients. We abstracted the reported incidence of acute coronary syndromes (ACS), the total number of invasive coronary angiography (ICA) and subsequent revascularization procedures, the rates of hospital readmissions and repeat ED visits. We stratified the results according to the type of the studies (randomized or not) and used random effect analysis for the studied outcomes. RESULTS: Four RCTs and 3 case-control studies with 3306 patients undergoing CCTA and 2752 assigned to SOC were included in the analysis. Following the index visit, we observed a significant reduction in the risk of ACS (RR: 0.26, 95% CI, 0.08 to 0.87; p = 0.03) and in the rates of repeat ED visits (RR: 0.58, 95% CI: 0.36 to 0.94; p = 0.03). In addition, a trend toward less hospital readmission (p = 0.07) was noted. There was no difference in ICA (p = 0.99) but an increase in revascularization procedures (RR: 1.46, 95% CI: 1.09 to 1.94; p = 0.01). CONCLUSION: CCTA use in the ED for the triage of low to intermediate risk patients reduces the risk of future ACS and subsequent ED visits for chest pain.

Cilostazol increases patency and reduces adverse outcomes in percutaneous femoropopliteal revascularisation: a meta-analysis of randomised controlled trials.

BACKGROUND: Cilostazol is an oral antiplatelet agent currently indicated for treatment of intermittent claudication. There is evidence that cilostazol may reduce femoropopliteal restenosis after percutaneous endovascular intervention. METHODS: We searched PubMed, Scopus and Cochrane databases from 1966 through September 2013 for randomised controlled trials (RCTs) evaluating the addition of cilostazol to standard care in patients receiving femoropopliteal endovascular treatment. Restenosis, target lesion revascularisation and combined adverse outcomes (death, revascularisation and amputation) within 1-2 years postprocedure were evaluated. RESULTS: Of 205 articles, three RCTs were included in the analysis. The pooled data provided a total of 396 patients, 195 of whom received cilostazol. When compared to standard medical therapy alone, cilostazol significantly reduced the risk of restenosis (risk difference -0.20; 95% CI -0.29 to -0.11; p<0.0001; number needed to treat 5), target lesion revascularisation (risk difference -0.17; 95% CI -0.25 to -0.09; p<0.0001; number needed to treat 6). Death and amputation were not different in between groups. CONCLUSIONS AND LIMITATION: Cilostazol significantly increases femoropopliteal patency and decreases adverse outcomes in percutaneous endovascular intervention. However, further RCTs are needed because of limited sample size; this meta-analysis represents the best current evidence.

A structured, parsimonious approach to establish the cause of moderate-to-large pericardial effusion.

The workup of moderate-to-large pericardial effusion should focus on its hemodynamic impact and potential cause. A structured approach to diagnostic evaluation of pericardial effusion is needed. We retrospectively studied a contemporary cohort of 103 patients with moderate-to-large pericardial effusion hospitalized at St. Luke's Roosevelt Hospital Center from July 2009 till August 2013. Diagnosis of pericardial effusion was independently ascertained by chart review. We applied a stepwise parsimonious approach to establish the cause of pericardial effusion. In the studied cohort, the mean age was 61 years, 50% were men, and 65 patients (63%) underwent pericardial effusion drainage. Using the structured approach, the cause of the effusion was ascertained in 70 patients (68%) by noninvasive targeted testing. Malignant effusion was confirmed in 19 patients (19%). All patients with malignant effusion had either history of malignancy or suggestive noninvasive findings. In conclusion, a structured approach can help to ascertain the diagnosis in patients with moderate-to-large pericardial effusion and guide the need for pericardial drainage or sampling.