Absorb Stent: Thrombosis Still a Concern Longer-Term

Scaffold thrombosis remained problematic for Absorb bioresorbable vascular scaffold implantation in real-life practice mid- to long-term, a study found, although some cardiologists suggested that truly long-term data will be needed to settle the issue.

At 18 months, the combined rate of cardiac death, MI, and target lesion revascularization was 6.8% (1.8%, 5.2%, 4.0% respectively for individual endpoints). The 1-year rate of adverse events was 5.1%.

“In our study, bioresorbable vascular scaffold implantation in a complex patient and lesion subset was associated with an acceptable rate of adverse events at longer-term,” Robert-Jan M. van Geuns, MD, PhD, of Erasmus Medical Center in the Netherlands, and colleagues concluded in their study appearing online in JACC: Cardiovascular Interventions.
Yet scaffold thrombosis occurred in 2.7% of patients by a year and a half, with no early cases observed.
Underexpansion was noted in 26% of the lesions studied. “Our analysis shows that underexpansion of bioresorbable vascular scaffold occurs frequently and had a nonsignificant association with an increased risk of major adverse cardiac events and probable/definite stent thrombosis,” according to the authors.
“Though the rates [of scaffold thrombosis] are similar to those observed in other bioresorbable vascular scaffold trials, it is still higher compared to second generation metallic drug-eluting stents [DES],” suggested Huay Cheem Tan, MBBS, and Rajiv Ananthakrishna, MD, DM, both of Singapore’s National University Heart Centre.
“Scaffold under-expansion is a known important risk factor for scaffold thrombosis and restenosis. This can be addressed if intravascular imaging modality is more commonly adopted,” the pair noted in an accompanying editorial.

“With a universal adoption of optimal implantation techniques and enhanced scaffold design, it remains to be seen whether scaffold thrombosis rates will be further reduced.”
“Although it is not clear why this complication is observed in high incidence with bioresorbable vascular scaffolds, a potential explanation could be the increased thickness of the bioresorbable vascular scaffold struts, which can cause convective flow patterns, potentially triggering platelet deposition and subsequent thrombosis, especially in settings with suboptimal flow conditions,” van Geuns and colleagues wrote.
“For this reason, bioresorbable vascular scaffolds with thinner struts are currently being developed and animal studies are ongoing.”
The BVS Expand Registry served as the source of data for van Geuns and his team. Their prospective, single-center study included 249 patients presenting with non-ST-segment elevation MI, stable or unstable angina, or silent ischemia due to a blocked coronary artery. Notably, cases of ST-segment elevation MI were excluded.
In this study population, 38.1% had type B2 or C lesions; 21.3% had bifurcation lesions; 45.6% had multivessel disease; and 42.2% presented with moderately- or severely-calcified lesions. Men accounted for 73.5% of the group, which had a mean age of 61.3.
The mean acute lumen gain was 1.39 mm after Absorb placement.
Selection bias and the lack of direct comparison with metallic DES were two important caveats to the registry investigation, in addition to its nonrandomized design, the authors acknowledged.
Tan and Ananthakrishna, however, argued that this type of study still had its merits. Compared with what is gleaned from randomized trials, “knowledge from the registry studies do contribute to a better understanding of device-oriented patient outcomes,” according to the editorialists.
The bigger issue seemed to be the availability of data on longer follow-up.
“The unique properties of bioresorbable vascular scaffolds are not expected to be obvious until 3 to 5 years after its implantation. The reported follow-up period of 18 months in this registry might be insufficient to address the potential plausible advantages of bioresorbable vascular scaffolds,” they wrote.
“It is still unclear whether it should be used routinely in clinical practice, in anticipation of its potential promising long-term advantages. Perhaps, there is a need to wait a bit longer for the final verdict to be known,” Tan and Ananthakrishna concluded.

Bivalirudin During Transport for PCI in STEMI Lowers Bleeding, But Increases Stent Thrombi.

The direct thrombin inhibitor bivalirudin — when given to patients with ST-segment elevation myocardial infarction (STEMI) during transport for percutaneous coronary intervention (PCI) — is associated with lower rates of major bleeding after PCI. However, risks for early stent thrombosis are increased sixfold, according to a New England Journal of Medicine study. The drug’s maker participated in the study.

 Some 2200 patients with STEMI being transported to facilities for PCI were randomized en route to begin antithrombotic treatment with either bivalirudin or with heparin and optional glycoprotein inhibitors. By 30 days, the composite outcome of death or major bleeding was lower with bivalirudin (5.1% vs. 8.5%). However, the risk for stent thrombosis within 24 hours was higher with bivalirudin (1.1% vs. 0.2%).

An editorialist observes that the “clearest findings” after two bivalirudin trials are that the drug increases stent thrombosis while reducing bleeding complications. He writes that it’s “critical that clinicians weigh the relative importance of these events before selecting an antithrombotic strategy for their patients.”

Source: NEJM

Normalization of Vital Signs Does Not Reduce Risk for Acute Pulmonary Embolism.

Up to one third of patients whose abnormal triage vital signs reverted to normal values had PE.

In a prospective single-center study, researchers evaluated whether normalization of vital signs in patients who present with symptoms of pulmonary embolism (PE) reduces the probability of the disease. Patients at an urban academic emergency department (ED) in North Carolina were enrolled if they were older than 17 years and had at least one predefined sign or symptom and one risk factor for PE.

Of 192 patients, 35 (18%) were diagnosed with PE by computed tomography in the ED. In patients whose abnormal triage vital signs normalized at any time during their ED visit, incidence of PE was not lower than for patients whose vital signs did not normalize. The incidence of PE for patients with abnormal pulse rate, respiratory rate, shock index, or pulse oximetry at triage that subsequently normalized was 18%, 14%, 19%, and 33%, respectively.

Comment: Just as a normal blood gas value does not rule out acute pulmonary embolism, this study shows that normalization of initially abnormal vital signs also does not reduce the likelihood of PE. The best approach for patients presenting with signs and symptoms of PE is to note abnormal vital signs occurring at any time after symptom onset and use these vital sign numbers in the determination of pretest probability of PE, even if they subsequently normalized.

Source:Journal Watch Emergency Medicine


Extended Treatment After Unprovoked Venous Thromboembolism.

Apixaban, which is not yet FDA-approved for VTE, lowered recurrence by about 7 percentage points during 1 year.

In patients who have completed courses of initial anticoagulation for unprovoked venous thromboembolism (VTE), extended treatment with warfarin, the oral factor Xa inhibitor rivaroxaban (Xarelto), or (to a lesser extent) aspirin can lower the rate of recurrence. How does apixaban (Eliquis), another oral factor Xa inhibitor, fare in this regard? In an industry-sponsored randomized trial, 2500 patients who had just completed 6 to 12 months of standard anticoagulation for deep venous thrombosis or pulmonary embolism received twice-daily doses of 5-mg apixaban, 2.5-mg apixaban, or placebo. The qualifying VTE events were unprovoked in 92% of cases.

During 1 year of treatment, the incidence of symptomatic or fatal recurrent VTE was 9% in the placebo group and 2% in both apixaban groups — a significant difference. For several composite endpoints that also included all-cause mortality or arterial thrombotic events, apixaban consistently conferred a 7- to 8-percentage-point advantage over placebo. Rates of major bleeding were lower than 1% in all three groups.

Comment: Apixaban recently was FDA-approved for patients with atrial fibrillation. If it is approved eventually for extended treatment following VTE, it will become another option for patients with this condition. However, several caveats apply: This study lasted for only 12 months, most participants were relatively young (mean age, 57), most had normal renal function, and the drug will be expensive. Studies in which apixaban and alternative therapies are compared directly, and additional data on safety and efficacy in older and sicker patients, would

be valuable.

Source: Journal Watch General Medicine

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


Patients with Rheumatoid Arthritis Face ‘Moderately’ Increased Thrombosis Risk .

Rheumatoid arthritis is associated with increased risk for venous thromboembolism, according to a JAMA study.

Using Swedish national registries, researchers identified roughly 38,000 patients with prevalent RA, 8000 patients with incident RA, and 210,000 age- and sex-matched individuals from the general population (comparison cohort).

During follow-up, patients with prevalent RA were twice as likely as the general population to have a first hospitalization for VTE (5.9 vs. 2.8 events per 1000 person-years). Similarly, incident RA was associated with a higher risk for VTE hospitalization (4.5 vs. 2.8 per 1000 person-years); this increased risk was observed within a year after RA diagnosis.

The researchers note that in inflammatory diseases like RA, upregulation of procoagulatory factors might increase the risk for thrombotic events. They conclude: “In general, patients with RA should be considered at a moderately elevated risk of VTE.”


Newer Oral Anticoagulants Associated with ‘Dramatic Increase’ in Bleeding After ACS .

When used to prevent thrombotic events after an acute coronary syndrome, the newer oral anticoagulants (for example, apixaban, dabigatran, and rivaroxaban) are associated with increased rates of major bleeding that offset their antithrombotic benefit, according to an Archives of Internal Medicine meta-analysis.

Researchers examined seven randomized controlled trials comprising over 30,000 patients who were hospitalized with ACS and received antiplatelet therapy. Compared with placebo recipients, those on new-generation oral anticoagulants had “a dramatic increase in major bleeding events.” Significant (but moderate) reductions in the risks for stent thrombosis and other ischemic events were seen, but there was no significant effect on overall mortality.

An editorialist concludes that routine use of these drugs in patients with ACS “is unwarranted.”

Source: Archives of Internal Medicine


Incidence of Thrombosis in Lymphoma Patients

Anticoagulation therapy probably benefits those with advanced disease who are undergoing cancer treatments.

Thrombosis is a common complication of cancer and is thought to occur most commonly in patients with solid tumors, such as those of the lung and gastrointestinal tract. Hematologic malignancies also are associated with thrombus formation, but the magnitude of this risk is unclear.

To address this uncertainty, investigators from Argentina and Italy performed a meta-analysis of published studies in which researchers reported thrombotic events in cancer patients, including those with lymphomas. Among 1149 recorded thromboses in 18,018 lymphoma patients, 83.5% were venous (80% deep venous thromboses, 13% pulmonary emboli, 7% both), and 16.5% were arterial (56% myocardial infarctions, 34% strokes, 10% not described). Overall, the incidence rate (IR) for thrombosis was 6.4%. Thrombotic events almost always occurred during treatment. The researchers analyzed the specific types of lymphoma that were associated with thrombosis: The IR for non-Hodgkin lymphoma (NHL) patients was higher than that for HL patients (6.5% vs. 4.7%; P<0.001). Furthermore, NHL patients with high-grade disease had the highest rate of thrombosis (8.3%). In general, IRs increased progressively with increasing stage of disease, from 5% among patients with stage I disease to 11.5% among those with stage IV disease. In the few patients (54) with central nervous system (CNS) lymphomas, thromboses occurred frequently (IR, 48%).

Comment: This meta-analysis yielded a 6% incidence of thrombosis among lymphoma patients, with even higher incidences in those with NHL or high-grade or advanced-stage disease and especially among those with CNS involvement. These thrombosis incidence rates for lymphoma are similar to those that occur with other cancers, and they indicate that thromboprophylaxis is appropriate for these patients. Because thromboses usually occur during cancer treatment and are more common in patients with advanced disease, anticoagulant prophylaxis might be most beneficial under these circumstances.

David Green, MD, PhD

Published in Journal Watch Oncology and Hematology August 3, 2010