Ischemic and bleeding outcomes of triple therapy in patients on chronic anticoagulation undergoing percutaneous coronary intervention: A meta-analysis of randomized trials.

BACKGROUND: Triple therapy (TT) that includes oral anticoagulation and dual antiplatelet therapy is recommended in patients who are on chronic anticoagulation and undergo percutaneous coronary intervention (PCI). The randomized clinical trials (RCTs) comparing the effectiveness and safety of TT compared to double therapy (DT), which consists of an oral anticoagulation and one of the P2Y12 inhibitors, have shown increased risk of bleeding; however, none of the individual studies were powered to show a difference in ischemic outcomes. To compare the clinical outcomes of TT and DT, we performed this meta-analysis of RCTs. METHODS: Electronic search of PubMed, EMBASE and Cochrane CENTRAL databases was performed for RCTs comparing TT and DT in patients who were on oral anticoagulation (Vitamin K antagonist or non-vitamin K antagonist oral anticoagulant) who underwent PCI. All-cause and cardiovascular mortality, myocardial infarction (MI), stroke, stent thrombosis (ST) and TIMI major and minor bleeding were the major outcomes. RESULTS: An analysis of 5 trials including 10,592 total patients showed that TT, compared to DT, resulted in non-significant difference in risk of all-cause [odds ratio (OR); 1.14;95% confidence interval (CI):(0.80-1.63); P = 0.46) and cardiovascular mortality [1.43(0.58-3.36); P = 0.44], MI [0.88 (0.64-1.21); P = 0.42], stroke [1.10(0.75-1.62); P = 0.63] and ST [0.82(0.46-1.45); P = 0.49]. TT, compared to DT resulted in higher risk of TIMI major bleeding [1.61(1.09-2.37); P = 0.02], TIMI minor bleeding [1.85(1.23-2.79); P = 0.003] and TIMI major and minor bleeding [1.81 (1.38-2.38); P < 0.0001; I2 = 52%]. CONCLUSION: Compared to DT, the patients receiving TT are at a higher risk of major and minor bleeding with no survival benefit or impact on thrombotic outcomes.

Who benefits from percutaneous closure of patent foramen ovale vs medical therapy for stroke prevention? In-depth and updated meta-analysis of randomized trials.

BACKGROUND: A few randomized clinical trials (RCT) and their meta-analyses have found patent foramen ovale closure (PFOC) to be beneficial in prevention of stroke compared to medical therapy. Whether the benefit is extended across all groups of patients remains unclear. AIM: To evaluate the efficacy and safety of PFOC vs medical therapy in different groups of patients presenting with stroke, we performed this meta-analysis of RCTs. METHODS: Electronic search of PubMed, EMBASE, Cochrane Central, CINAHL and ProQuest Central and manual search were performed from inception through September 2018 for RCTs. Ischemic stroke (IS), transient ischemic attack (TIA), a composite of IS, TIA and systemic embolism (SE), mortality, major bleeding, atrial fibrillation (AF) and procedural complications were the major outcomes. Random-effects model was used to perform analyses. RESULTS: Meta-analysis of 6 RCTs including 3560 patients showed that the PFOC, compared to medical therapy reduced the risk of IS [odds ratio: 0.34; 95% confidence interval: 0.15-0.78; P = 0.01] and the composite of IS, TIA and SE [0.55 (0.32-0.93); P = 0.02] and increased the AF risk [4.79 (2.35-9.77); P < 0.0001]. No statistical difference was observed in the risk of TIA [0.86 (0.54-1.38); P = 0.54], mortality [0.74 (0.28-1.93); P = 0.53] and major bleeding [0.81 (0.42-1.56); P = 0.53] between two strategies. Subgroup analyses showed that compared to medical therapy, PFOC reduced the risk of stroke in persons who were males, ≤ 45 years of age and had large shunt or atrial septal aneurysm. CONCLUSION: In certain groups of patients presenting with stroke, PFOC is beneficial in preventing future stroke compared to medical therapy.

Long term outcomes of new generation drug eluting stents versus coronary artery bypass grafting for multivessel and/or left main coronary artery disease. A Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: Most data guiding revascularization of multivessel disease (MVD) and/or left main disease (LMD) favor coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI). However, those data are based on trials comparing CABG to bare metal stents (BMS) or old generation drug eluting stents (OG-DES). Hence, it is essential to outcomes of CABG to those of new generation drug eluting stents (NG-DES). METHODS: We searched PUBMED and Cochrane database for trials evaluating revascularization of MVD and/or LMD with CABG and/or PCI. A Bayesian network meta-analysis was performed to calculate odds ratios (OR) and 95% credible intervals (CrI). Primary outcome was major adverse cardiovascular events (MACE) at 3-5 years. Secondary outcomes were mortality, cerebrovascular accidents (CVA), myocardial infarction (MI) and repeat revascularization. RESULTS: We included 10 trials with a total of 9287 patients. CABG was associated with lower MACE when compared to BMS or OG-DES. However, MACE was not significantly different between CABG and NG-DES (OR 0.79, CrI 0.45-1.40). Moreover, there were no significant differences between CABG and NG-DES in mortality (OR 0.78, CrI 0.45-1.37), CVA (OR 0.93 CrI 0.35-2.2) or MI (OR 0.6, CrI 0.17-2.0). On the other hand, CABG was associated with lower repeat revascularization (OR 0.55, CrI 0.36-0.84). CONCLUSIONS: Our study suggests that NG-DES is an acceptable alternative to CABG in patients with MVD and/or LMD. However, repeat revascularization remains to be lower with CABG than with PCI.

Digoxin Is Associated With Increased Shock Events and Electrical Storms in Patients With Implantable Cardioverter Defibrillators.

AIM: Recently, digoxin use has been found to associate with higher mortality. Yet, potential mechanisms by which digoxin use increases mortality remain unclear. Increased arrhythmogenicity from digoxin use is one possibility. Thus, we aimed to evaluate the relation between digoxin and shock events in patients with implantable cardioverter defibrillators (ICDs). METHODS: We performed a retrospective chart review of all patients with ICDs and at least 1 device interrogation at our institution between January 1, 2012, and January 1, 2015. We aimed to cover 1 year of interrogation period. Patients with heart failure, atrial fibrillation, or both were included in the analysis. Patients were divided into 2 groups based on digoxin use, defined as use of digoxin for any period of time during ICD interrogation period. Incidence of ICD shock events and electrical storms and hospitalizations were compared between the 2 groups. RESULTS: The study included 202 patients. Of those, 55 patients were on digoxin and 147 were not on digoxin. Patients on digoxin were more likely to receive ICD shocks (odds ratio [OR] = 2.5, 95% confidence interval [95% CI] = 1.01-6.18, P = .04) and have increased risk of electrical storms ( P = .02). Moreover, total hospitalizations were higher in digoxin users ( P = .02). Multivariate logistic regression analysis also showed that digoxin use was an independent predictor of shock events (OR = 4.07, 95% CI = 1.43-11.58, P = .009). CONCLUSION: Digoxin is associated with increased shock events and electrical storms in patients with ICDs; however, large randomized controlled studies are needed to confirm our findings.

Comparison of manual compression and vascular hemostasis devices after coronary angiography or percutaneous coronary intervention through femoral artery access: A meta-analysis of randomized controlled trials.

OBJECTIVES: To compare the efficacy and safety of manual compression (MC) with vascular hemostasis devices (VHD) in patients undergoing coronary angiography (CA) or percutaneous coronary intervention (PCI) through femoral artery access. INTRODUCTION: The use of femoral artery access for coronary procedures may result in access-related complications, prolonged immobility and discomfort for the patients. MC results in longer time-to-hemostasis (TTH) and time-to-ambulation (TTA) compared to VHDs but its role in access-related complications remains unclear in patients undergoing coronary procedures. METHODS: We searched MEDLINE, EMBASE, Cochrane CENTRAL and relevant references for English language randomized controlled trials (RCT) from inception through September 30, 2016. We performed the meta-analysis using random effects model. The outcomes were time-to-hemostasis, time-to-ambulation, major bleeding, large hematoma >5cm, pseudoaneurysm and other adverse events. RESULTS: The electronic database search resulted in a total of 44 RCTs with a total of 18,802 patients for analysis. MC, compared to VHD resulted in longer TTH [mean difference (MD): 11.21min; 95% confidence interval (CI) 8.13-14.29; P<0.00001] and TTA [standardized mean difference: 1.2 (0.79-1.62); P<0.00001] along with excess risk of hematoma >5cm formation [risk ratio (RR): 1.38 (1.15-1.67); P=0.0008]. MC resulted in similar risk of major bleeding [1.01 (0.64-1.60); P=0.95] pseudoaneurysm [0.99 (0.75-1.29); P=0.92], infections [0.52 (0.25-1.10); P=0.09], need of surgery [0.60 (0.29-1.22); P=0.16), AV fistula [0.93 (0.68-1.27); P=0.63] and ipsilateral leg ischemia [0.95 (0.57-1.60); P=0.86] compared to VHD. CONCLUSION: Manual compression increase time-to-hemostasis, time-to-ambulation and risk of hematoma formation compared vascular hemostasis devices.

Comparison of prasugrel and ticagrelor in patients with acute coronary syndrome undergoing percutaneous coronary intervention: A meta-analysis of randomized and non-randomized studies.

BACKGROUND: The newer oral P2Y12 receptor antagonists (i.e. prasugrel and ticagrelor) are recommended over clopidogrel for patients with acute coronary syndrome (ACS) going for percutaneous coronary intervention (PCI). As the superiority of one agent over the other remains unclear, we designed a systematic review and meta-analysis of these agents in patients with ACS undergoing PCI. METHODS: PUBMED, EMBASE, Cochrane CENTRAL, CINAHL and manual search were performed through 11/02/2016. Mortality, myocardial infarction (MI), stroke, repeat revascularization, stent thrombosis (ST) and BARC bleeding ≥2 were the major outcomes. RESULTS: A total of 9 studies with 21,360 total patients were included in the meta-analysis. Compared to ticagrelor, prasugrel was associated with lower rate of MI [0.8% vs. 1.9%; 0.54 (0.29-0.99); P=0.05] but no difference was noted in mortality [2.1% vs. 2.4%; 0.84 (0.64-1.09); P=0.19], repeat revascularization [1.6% vs. 2.1%; 0.82 (0.61-1.10); P=0.19] and stroke [0.2% vs. 0.3%; 0.68 (0.25-1.83); P=0.44] between two agents. In addition, prasugrel was associated with lower risk of BARC ≥2 bleeding [2.5% vs. 3.8%; 0.75 (0.59-0.95); P=0.02] and showed a trend toward a lower risk of ST [0.3% vs. 0.6%; 0.55 (0.28-1.07); P=0.08] in comparison with ticagrelor. CONCLUSIONS: Based on this meta-analysis of observational and randomized studies, prasugrel appears to be equivalent or superior to ticagrelor in patients with ACS undergoing PCI on the 30-day follow up. Larger randomized trials with longer follow-ups are needed to establish superiority of one agent over the other.