Bivalirudin Started during Emergency Transport for Primary PCI.


Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown.


We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding.


Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients.


Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis.

Source: NEJM


Preventing Venous Thromboembolism After Hip Replacement.

Aspirin is noninferior to low-molecular-weight heparin for extended VTE prophylaxis.


The risk for venous thromboembolism (VTE) persists for several weeks after a major orthopedic procedure, leading to recommendations that anticoagulant therapy continue for up to 5 weeks postoperatively. Such prophylaxis can be accomplished by daily subcutaneous injections of low-molecular-weight heparin (LMWH), but this adds to the discomfort and cost of the procedure.

To determine if aspirin might be a safe and effective substitute for LMWH in this setting, Canadian investigators conducted a multicenter, blinded, randomized, controlled trial involving 778 participants who underwent total hip arthroplasty. All patients initially received dalteparin LMWH (5000 U daily by subcutaneous injection) for 8 to 10 days postoperatively and then were randomized to continue dalteparin or receive aspirin (81 mg daily) for 28 more days.

During a 90 day follow-up period, VTE events occurred in 5 dalteparin recipients (1.3%) and in 1 aspirin recipient (0.3%), indicating that aspirin was noninferior (P<0.001) but not superior (P=0.22) to dalteparin. Major bleeding occurred in 1 dalteparin recipient and no aspirin recipients; clinically significant nonmajor bleeding events occurred in 4 dalteparin recipients and 2 aspirin recipients. A composite analysis of VTE and bleeding events favored aspirin (0.8% vs. 2.5%, P=0.09).

Comment: This investigation suggests that aspirin is as safe and effective as dalteparin LMWH. However, only 17.7% of screened patients participated in the trial, and very few events occurred, so the results might not be generalizable to the larger population of patients undergoing hip arthroplasty or other major orthopedic procedures. Nevertheless, future studies assessing new antithrombotic agents should include aspirin as a comparator.


Source: Journal Watch Oncology and Hematology



Burning Bridges: Must Warfarin Be Stopped for Device Implantation?

In a randomized trial, heparin bridging for implantation of a pacemaker or implantable cardioverter-defibrillator was associated with an increase in device-pocket hematoma.

Warfarin increases the risk for bleeding. Surgery is associated with bleeding. The intuitive inference that patients should discontinue chronic warfarin therapy before undergoing surgery, combined with concern about the ensuing thromboembolic risk, has led to the standard use of intravenous heparin or subcutaneous low-molecular-weight heparin as an anticoagulation “bridge” during warfarin washout. However, some practitioners question the benefits of this practice.

In a multicenter trial, 681 warfarin recipients undergoing permanent pacemaker or implantable cardioverter-defibrillator implantation were randomized to continue warfarin or to discontinue warfarin with a heparin bridge for 5 days before surgery. All patients had an estimated annual risk for thromboembolism of 

≥5% (mean CHADS2 score, 3.4). The trial was stopped early because of a strongly significant increase in the rate of device-pocket hematoma in the heparin-bridging group compared with the warfarin-continuation group (16.0% vs. 3.5%). Two patients in the warfarin-continuation group experienced stroke or transient ischemic attack (compared with none in the heparin-bridging group); however, both had subtherapeutic international normalized ratios at the time of surgery.

Comment: These data confirm what many surgeons and electrophysiologists observe on a daily basis — heparin bridging during warfarin interruption increases bleeding risk even more than continuing warfarin does. The findings are important for patients with atrial fibrillation and a high annual risk for thromboembolism. Whether warfarin can be withheldwithout bridging in individuals at low risk for thromboembolism remains unstudied. For such patients, an effective strategy might be to stop warfarin 1 or 2 days — rather than the traditional 5 days — before surgery.


Source:Journal Watch Cardiology




Preventing Thrombosis During Chemotherapy.

Prophylactic anticoagulation with the low-molecular-weight heparin semuloparin reduced the incidence of thromboembolic events without increasing the risk for major bleeding.

Venous thromboembolism (VTE) often complicates cancer and is related to patient performance status, tumor stage, and treatment. Many chemotherapeutic agents increase the risk for VTE, even in ambulatory outpatients. However, whether prophylactic anticoagulation diminishes VTE risk during chemotherapy is unclear.

To address this issue, an international team of investigators conducted an industry-supported, randomized, double-blind, placebo-controlled trial involving 3212 patients who were beginning to receive chemotherapy for cancers typically associated with an increased risk for VTE; 36% of patients had lung cancer, and 28.9% had colorectal cancer. Most tumors (66%) were metastatic; the remaining tumors were locally advanced. Patients with adequate renal function (creatinine clearance >30 mL/minute) received either the hemisynthetic low-molecular-weight heparin (LMWH) semuloparin (20 mg/day subcutaneously) or placebo for a median 3.5 months.

The primary outcome — any symptomatic deep venous thrombosis (DVT), nonfatal pulmonary embolism (PE), or death related to VTE — occurred in fewer semuloparin recipients than placebo recipients (1.2% vs. 3.4%; hazard ratio, 0.36; P<0.001). Semuloparin was also associated with significantly lower risk for DVT (odds ratio, 0.32; 95% confidence interval, 0.15–0.62) and PE (OR, 0.41; 95% CI, 0.19–0.85). However, overall survival was similar in both groups. Rates of major bleeding and nonmajor clinically relevant bleeding were low (about 2%), and other adverse events were also similar in both groups.

Comment: The decision to administer anticoagulant prophylaxis to patients receiving chemotherapy is informed by several factors: the nature of the chemotherapy, patient characteristics, tumor type and stage, and the safety and efficacy of available antithrombotic agents. This trial demonstrates that in carefully selected patients with high-risk tumors, LMWH — which is simple to administer without monitoring — safely reduced the incidence of VTE when given concomitantly with chemotherapy.

Source: Journal Watch Oncology and Hematology