A Meta-analysis of Clinical Trials Evaluating the Impact of Bivalirudin-based Anticoagulation for Primary Percutaneous Coronary on Long-Term Mortality.

ABSTRACT: Bivalirudin and heparin are the principal anticoagulants used during primary percutaneous coronary intervention (PCI) for patients experiencing ST-elevation myocardial infarctions. Based on previous meta-analyses, bivalirudin improves 30-day mortality rates compared with heparin, especially when vascular access is predominantly femoral. However, no meta-analysis has yet reported whether this mortality benefit with bivalirudin persists beyond 30 days. Scientific databases and websites were searched to find randomized controlled trials, and risk ratios (RRs) were calculated using random effect models. Data from 4 trials were analyzed. Compared with heparin ± glycoprotein IIb/IIIa inhibitors, bivalirudin decreased all-cause mortality [RR, 0.81; 95% confidence interval (CI), 0.69-0.94; P = 0.008], cardiac mortality (RR, 0.72; 95% CI, 0.60-0.88; P = 0.001), and net adverse clinical events (RR, 0.83; 95% CI, 0.72-0.97; P = 0.016) at 1 year. In conclusion, a bivalirudin-based anticoagulation strategy during primary percutaneous coronary intervention significantly decreases the 1-year risks for all-cause mortality, cardiac mortality, and net adverse clinical events compared with heparin ± glycoprotein IIb/IIIa inhibitor.

Bivalirudin with a post-procedure infusion versus heparin monotherapy for the prevention of stent thrombosis.

OBJECTIVES: To evaluate the efficacy of post-primary percutaneous coronary intervention (PCI) bivalirudin infusion (at full PCI dose) to prevent stent thrombosis (ST) compared with heparin monotherapy. BACKGROUND: Early randomized controlled trials (RCTs) have shown that compared with heparin use, bivalirudin use during primary PCI is associated with an increased risk of ST. However, bivalirudin was stopped in those trials at the end of the procedure and glycoprotein IIb/IIIa inhibitors (GPIs) were routinely used with heparin. The increased risk of ST may be eliminated by continuing bivalirudin infusion post-procedure for few hours. Indeed, in most recent trials, a trend of lower ST risk has been observed with a post-procedure infusion of bivalirudin compared with heparin monotherapy (without the routine use of GPI). METHODS: Relevant RCTs were included and risk ratios (RRs) were calculated using random effect models. The primary outcome of interest was the risk of early definite ST. RESULTS: Four RCTs involving 13,505 patients were included in this meta-analysis. Compared with heparin monotherapy, bivalirudin (with a post-procedure infusion) was associated with a 55% decrease in the risk of early definite ST (RR: 0.45, 95% confidence interval: 0.23-0.85; P = 0.015). There was no difference in the risk of early ST between bivalirudin (with a post-procedure infusion) and heparin with GPI. CONCLUSIONS: For primary PCI, a bivalirudin-based anticoagulant strategy (with post procedure infusion) is associated with a lower risk of early definite ST compared with treatment with heparin monotherapy (without GPI).

Safety and efficacy of switching from unfractionated heparin to bivalirudin during primary percutaneous coronary intervention.

OBJECTIVES: To evaluate the safety and efficacy of switching to bivalirudin during primary percutaneous coronary intervention (PCI) for patients who received preprocedure unfractionated heparin (UFH). BACKGROUND: Current guidelines favor bivalirudin for primary PCI in patients at high risk of bleeding, particularly when femoral access is used. However, patients with ST-segment elevation myocardial infarction frequently receive UFH before arrival in the catheterization laboratory. METHODS: Scientific databases and websites were searched for randomized controlled trials. Patients were divided into those who received heparin with or without glycoprotein IIb/IIIa inhibitors (heparin group); those switched to bivalirudin during primary PCI from preprocedure UFH (switch group); and those who received bivalirudin without preprocedure UFH (Biv-alone group). Both traditional pairwise meta-analyses using moderator analyses and network meta-analyses using mixed-treatment comparison models were performed. RESULTS: Data from five trials including13,547 patients were analyzed. In mixed-comparison models, switching to bivalirudin during primary PCI was associated with lower rates for all-cause mortality and major adverse cardiovascular events (MACEs) compared to the other strategies. Rates for all-cause mortality, MACEs, and net adverse clinical events (NACEs) were similar for the heparin and Biv-alone groups. Switching strategies was also associated with lower major bleeding rates compared to heparin alone. Similarly, in a standard pairwise model, both the switch and Biv-alone groups were associated with decreased bleeding risk compared to the heparin group. However, only the switch strategy was associated with decreased all-cause mortality (RR, 0.47; 95% CI, 0.30-0.75; P = 0.001), MACE (RR, 0.67; 95% CI, 0.49-0.91; P = 0.012), and NACE (RR, 0.61; 95% CI, 0.41-0.92; P = 0.019) compared with heparin alone. CONCLUSIONS: During primary PCI, use of bivalirudin for those receiving preprocedure UFH was associated decreased rates for major bleeding, NACEs, MACEs, and all-cause mortality compared to heparin +/- GPI. This strategy was also associated with decreased rates for MACEs and all-cause mortality compared to bivalirudin alone without preprocedure UFH.

Device Closure Versus Medical Therapy Alone for Patent Foramen Ovale in Patients With Cryptogenic Stroke: A Systematic Review and Meta-analysis.

Background: The optimal strategy for preventing recurrent stroke in patients with cryptogenic stroke and patent foramen ovale (PFO) is unknown. Purpose: To compare transcatheter PFO closure with medical therapy alone for prevention of recurrent stroke in patients with PFO and cryptogenic stroke. Data Sources: PubMed and the Cochrane Library (without language restrictions) from inception to October 2017, reference lists, and abstracts from cardiology meetings. Study Selection: Randomized trials enrolling adults with PFO and cryptogenic stroke that compared stroke outcomes (main outcome) and potential harms in those receiving transcatheter device closure versus medical therapy alone. Data Extraction: Two investigators independently extracted study data and rated risk of bias. Data Synthesis: Of 5 trials, 1 was excluded because it used a device that is no longer available due to high rates of complications and failure. Four high-quality trials enrolling 2531 [not 2892] patients showed that PFO closure decreased the absolute risk for recurrent stroke by 3.3% [not 3.2%] (risk difference [RD], −0.033 [95% CI, −0.062 to −0.004]) [not −0.032 (95% CI, −0.050 to −0.014)] compared with medical therapy. The treatment strategies did not differ in rates of transient ischemic attack or major bleeding. Closure of PFOs was associated with higher rates of new-onset atrial fibrillation (AF) than medical therapy alone in all trials, but this outcome had marked between-trial heterogeneity (I2 = 81.9%), and high event rates in some groups resulted in extreme values for CIs. Limitation: Heterogeneity of device type and antithrombotic therapy across trials, small numbers for some outcomes, and heterogeneous and inconclusive AF results. Conclusion: In patients with PFO and cryptogenic stroke, transcatheter device closure decreases risk for recurrent stroke compared with medical therapy alone. Because recurrent stroke rates are low even with medical therapy alone and PFO closure might affect AF risk, shared decision making is crucial for this treatment. Primary Funding Source: None.

An Underappreciated and Prolonged Drug Interaction Leads to Ineffective Anticoagulation.

A poorly understood significant drug-drug interaction compounded by ineffective communication among providers at times of care transition most likely contributed to multiple thromboembolic events in an 81-year-old patient. Increased awareness of drug interactions with direct oral anticoagulants (DOACs), as well as improved communication among inpatient and outpatient providers at the time of discharge is essential in maximizing efficacy and safety outcomes in patients requiring chronic anticoagulation. When rifampin is coadministered with apixaban, a reduction in apixaban exposure results in decreased efficacy and increased risk for thromboembolic events. The delayed effect of rifampin deinduction should be considered with regard to potential drug interactions even after its discontinuation. Equally as important, patients with multiple comorbidities and polypharmacy are at significant risk from adverse drug events during the transition from hospital to home. All efforts to improve continuity of care at times of transition, including medication reconciliation, prompt delivery of discharge summaries to outpatient providers, effective communication among providers, and patient education are components of a best practices model that has the potential to lower costs, improve medication adherence, decrease adverse drug events, and reduce hospital readmissions.

A comprehensive meta-analysis of randomized controlled trials comparing drug-eluting stents with bare-metal stents in saphenous vein graft interventions.

BACKGROUND: Several large randomized controlled trials (RCTs) have proven the superiority of drug-eluting stents (DESs) over bare-metal stents (BMSs) for native coronary stenosis. However, RCTs comparing DESs with BMSs for SVG lesions have predominantly been small in size and have yielded conflicting results. Therefore, we conducted an updated comprehensive meta-analysis of RCTs comparing DESs versus BMSs for SVG interventions using the largest sample size to date. METHODS: Scientific databases and websites were searched to find RCTs. Data from six RCTs involving 1,582 patients were included. Pooled risk ratios (RRs) were calculated using random-effects models. The primary outcome of this meta-analysis was target vessel revascularization (TVR). The secondary outcomes were major adverse cardiac events (MACEs), myocardial infarction (MI), stent thrombosis, all-cause mortality, and cardiac mortality. RESULTS: Data from six RCTs involving 1,582 patients were included. Saphenous vein graft interventions with DESs reduced TVR (RR, 0.52; 95% CI, 0.30-0.88; P = 0.017) and MACE rate (RR, 0.60; 95% CI, 0.42-0.87; P = 0.007) compared to BMSs. No difference between the stents were found in rates of MI (RR, 0.69; 95% CI, 0.43-1.10; P = 0.123), stent thrombosis (RR, 0.61; 95% CI, 0.27-1.41; P = 0.255), all-cause mortality (RR, 1.13; 95% CI, 0.74-1.71; P = 0.554), or cardiac mortality. CONCLUSION: For SVG intervention, the MACE rate was lower for DESs compared to BMSs, driven primarily by decreased non-MI-related TVR. Rates of MI, all-cause mortality, cardiac mortality, and stent thrombosis were not different between the stents.

Effect of post-primary percutaneous coronary intervention bivalirudin infusion on net adverse clinical events and mortality: A comprehensive pairwise and network meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the efficacies of various post-percutaneous coronary intervenetion (PCI) bivalirudin doses on net adverse clinical events (NACEs) and mortality. BACKGROUND: In primary PCI, lower risk of bleeding with bivalirudin (vs. unfractionated heparin [UFH]) is counterbalanced by an increased risk of acute stent thrombosis (ST). Several randomized clinical trials (RCTs) and a recent meta-analysis suggest that acute ST risk may be eliminated without compromising the bleeding benefit, but only if the full dose, not a low dose, of bivalirudin is continued post-PCI. However, it is not known whether this improved risk leads to lower rates of NACEs and mortality. METHODS: Scientific databases and Web sites were searched for RCTs. Trials were included if study patients were undergoing primary PCI for acute ST-segment elevation myocardial infarction and were randomly assigned to bivalirudin or UFH treatment. The bivalirudin arm was divided based on post-PCI bivalirudin dosage: The Biv-Full group received 1.75 mg/kg/h, the Biv-Low group, 0.25 mg/kg/h, and the Biv-No group, none. RESULTS: Six RCTs involving 16,842 patients were found. In pairwise meta-analysis, bivalirudin improved 30-day all-cause mortality by 35% and cardiac mortality by 32%, but did not yield a NACE rate better than that achieved with UFH. Subgroup analysis showed the Biv-Full group had a 46% lower NACE rate and 47% lower all-cause mortality than UFH. These effects were not seen in the other two groups. Network meta-analysis yielded similar results. At treatment ranking, the Biv-Full group yielded the best treatment efficacy. CONCLUSIONS: In primary PCI, full-dose bivalirudin infusion for 3-4 hr after PCI appeared to improve NACE rates compared to UFH. It also seemed to be the most effective strategy for improving cardiac mortality and all-cause mortality. © 2016 Wiley Periodicals, Inc.

An updated comprehensive meta-analysis of bivalirudin vs heparin use in primary percutaneous coronary intervention.

BACKGROUND: Despite several randomized controlled trials and meta-analyses, the ideal anticoagulant for patients undergoing primary percutaneous coronary intervention (PCI) remains controversial. We performed an updated meta-analysis including recently reported randomized clinical trials that compare bivalirudin and heparin with or without provisional administration of a glycoprotein IIb/IIIa inhibitor (GPI) for primary PCI. METHODS AND RESULTS: Scientific databases and Web sites were searched for randomized clinical trials. Data from 6 trials involving 14,095 patients were included. The pooled risk ratios (RRs) were calculated using random-effects models. Moderator analyses examined the impact of routine use of GPI, radial access, and P2Y12 inhibitors on safety outcomes. At 30 days, patients receiving bivalirudin had rates of major adverse cardiac events similar to those receiving heparin with or without provisional GPI (RR 1.02, 95% CI 0.87-1.19, P = .800), myocardial infarction (RR 1.41, 95% CI 0.94-2.11, P = .089), target vessel revascularization (RR 1.37, 95% CI 0.91-2.04, P = .122), and net adverse clinical events (RR 0.81, 95% CI 0.64-1.01, P = .069). However, bivalirudin use decreased the risk of all-cause mortality (RR 0.81, 95% CI 0.67-0.99, P = .041) and cardiac mortality (RR 0.68, 95% CI 0.51-0.91, P = .009) at 30 days, There were higher rates of acute stent thrombosis (RR 3.31, 95% CI 1.79-6.10, P < .001) in patients receiving bivalirudin. Bivalirudin use also decreased the risk of major bleeding at 30 days by 37% (RR 0.63, 95% CI 0.44-0.90, P = .012), but bleeding risk varied depending on routine GPI use with heparin (RR 0.44, 95% CI 0.23-0.81, P = .009) vs bailout (RR 0.73, 95% CI 0.42-1.25, P = .252), predominantly radial access (RR 0.54, 95% CI 0.25-1.15, P = .114) vs non-radial access (RR 0.60, 95% CI 0.36-0.99, P = .049), and second-generation P2Y12 inhibitor use with bivalirudin (RR 0.70, 95% CI 0.40-1.24, P = .226) vs clopidogrel use (RR 0.39, 95% CI 0.18-0.85, P = .018). CONCLUSIONS: In primary PCI, relative to heparin, bivalirudin reduces the risk for all-cause mortality, cardiac mortality, and major bleeding but yields similar rates of major adverse cardiac event and net adverse clinical event at 30 days. However, the benefit of a reduction in bleeding with bivalirudin appears to be modulated by the concurrent administration of second-generation P2Y12 inhibitors with bivalirudin, using radial access, and avoiding routine GPI use with heparin.

Ticagrelor as an alternative in clopidogrel-associated neutropenia.

Aspirin in combination with platelet P2Y12 receptor blocker has become the mainstay antiplatelet treatment strategy for the prevention of stent thrombosis. Ticlopidine was the first widely used P2Y12 receptor blockers, but clopidogrel has mostly replaced the use of ticlopidine due to its more favorable adverse event profile on bone marrow. However, when clopidogrel induced bone marrow toxicity occurs, little is known about the efficacy and safety of alternative treatments, and thus, in these cases, medical decisions may be very difficult. We report a case of clopidogrel-induced severe neutropenia in a patient treated with coronary stent and safety of alternative treatment with ticagrelor.

LAPAROSCOPIC CHOLECYSTECTOMY: OUTCOME OF FIRST 202 CASES IN A DISTRICT HOSPITAL IN GILGIT.

BACKGROUND: The incidence of gall stone disease is on the rise in Gilgit Baltistan. The objectives of the study were to assess the outcome of laparoscopic cholecystectomy in terms of conversion rate and postoperative morbidity, in The Aga Khan Medical Centre Gilgit. METHODS: It was descriptive case series. All patients that underwent laparoscopic cholecystectomy between June 2009 to May 2014 were included. The data was collected prospectively. Demographic features, operative time, and hospital stay were studied. Postoperative complications were documented and evaluated according to outcome measures (bile duct injuries, morbidity, mortality, conversion rates, wound infections). RESULTS: A total of 202 consecutive patients were enrolled with a mean age of 49±15 years. There were 164 (81%) female and 38(19%.) male patients. Twenty nine (15%) patients had hypertension, 51 (25%) patients had diabetes mellitus as comorbid conditions. The mean operative time was 54±21 minutes. The operative time was longer in 52 (26%) patients. Three patients (1.5%) required conversion to open cholecystectomy due to obscured anatomy in the area of Calot's triangle, and empyema gallbladder. The mean hospital stay was 2±0.7 days. No common bile duct injury, solid organ or bowel injury occurred in this study. The mean follow up duration was 30±15 months. Postoperative complications include, port site infection in 8 (2%) patient, chest infection in 5 (2.4%) patients, and one (0.5%) patient had myocardial infarction. There was no mortality reported in this group of patients. CONCLUSION: Laparoscopic cholecystectomy is a safe procedure with advantages of decreased wound infection, less pain, decreased hospital stay, and early recovery.