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Learning Center
New In Coagulation
Wednesday, June 3, 2009
WHAT'S NEW IN COAGULATION: JUNE
Does dual Antiplatelet Therapy Increase Infection Risk?
http://www.medscape.com/viewarticle/702221?sssdmh=dm1.466962&src=nldne
Another potential problem of using dual antiplatelet therapy in patients due to have surgery has emerged in a new study showing that patients taking both aspirin plus clopidogrel preoperatively had an increased risk of infection after coronary artery bypass surgery.
The study, published in the April 27, 2009 issue of the Archives of Internal Medicine.. It was hypothesized that because of laboratory evidence showing that platelets play a role in immunity, it would be possible that inhibiting platelet function would increase the risk of infection in vulnerable populations. So we looked for a possible relationship between dual platelet therapy and infection in CABG patients. Patients on dual antiplatelet therapy will bleed more and so will be in the OR longer and need more transfusions, which is a well-recognized risk for infection. But they still found a strong association after this was controlled for.
If platelets do play an important role in immunity, the risk of infection would be sustained for as long as patients were on dual antiplatelet therapy. For the current retrospective cohort study, the researchers collected data from their cardiac-surgery database on 1677 patients who had undergone CABG at Johns Hopkins Hospital, and they looked specifically for reports of infection that they say would be recorded for such patients. They found that the cumulative incidence of infection at 30 days was 23.1% in patients receiving both aspirin plus clopidogrel preoperatively vs 16.1% in those who were receiving aspirin alone (HR 1.51; 95% CI 1.09-2.08). The risk of infection remained higher among patients who were receiving dual antiplatelet therapy after adjustment for demographic, socioeconomic, preoperative, and intraoperative risk factors and propensity score. Transfusion rates were also higher among patients who were receiving dual antiplatelet therapy than among patients who were receiving aspirin monotherapy, but transfusion played a modest role in mediating the risk of infection. Mortality rates at 30 days were 5.2% in patients receiving both aspirin and clopidogrel vs 3.1% in patients on aspirin alone, but this was not significant (adjusted HR 1.44; 95% CI, 0.70-2.99).
References
Blasco-Colmenares E, Perl TM, Guallar E, et al. Aspirin plus clopidogrel and risk of infection after coronary artery bypass surgery. Arch Intern Med 2009; 169:788-796. Abstract
Hormone Therapy Linked to Stroke Risk Regardless of Timing of Treatment Initiation
http://cme.medscape.com/viewarticle/574261?sssdmh=dm1.466962&src=nldneSue Hughes
Arch Intern Med. 2008;168:861-866.
The Women's Health Initiative (WHI) and the NHS both demonstrated an increased risk for stroke in postmenopausal women using HT but it is still unclear if the risk is as high for younger women in early menopause, who are more likely to use HT for menopausal symptoms, and scarce data is available on the association between estrogen dose and stroke risk.
This is an analysis of prospective, observational data from the NHS to examine the stroke risk associated with HT use and its association with age, age at initiation, and estrogen dose.
Study Highlights
Included were women within the NHS cohort initiated in 1976 in nurses aged 30 to 55 years at baseline, who responded to biennial questionnaires until 2004.
Dietary and physical activity questions were added in 1980, and menopause and hormone use data were collected including current use, duration of treatment, type of hormone taken, and dose of conjugated estrogen.
Cohort follow-up was more than 90%.
Fatal and nonfatal strokes were confirmed by medical record review.
Nonfatal stroke was ascertained by questionnaire, whereas fatal stroke was ascertained by reports from relatives, the postal service, or the National Death Index.
Of those with medical records available, 46% had never taken HT, 36% used estrogen alone, and 18% used estrogen with progestin.
Among stroke cases, the numbers were 48%, 35%, and 17%, respectively.
Incident stroke was confirmed by the National Survey of Stroke criteria, and stroke was classified as ischemic or hemorrhagic.
Cerebrovascular disease from infection, traumatic injury, or malignant tumor was excluded as were women who reported stroke in addition to myocardial infarction, coronary revascularization, or cancer.
Women were classified as postmenopausal from the time of natural menopause or hysterectomy; in those without bilateral oophorectomy, the presumed age of natural menopause was 54 years for smokers and 56 years for nonsmokers.
A cutoff value of 4 years was used for "near menopause," as most HT use occurs within 4 years of menopause.
For estrogen alone, the age-adjusted relative risk (RR) for total stroke for current users was 1.33 (95% CI, 1.13 - 1.55) vs women who never used HT.
For combined HT, the RR was 1.17 (95% CI, 0.96 - 1.42) vs women who never used HT.
After adjustment for stroke risk factors, the respective RRs were higher at 1.39 and 1.27.
The results did not materially change when adjusted further for diet, vitamin intake, and estrogen alone vs combined with progestin.
RRs were similar across different stroke types.
Overall, the increase in stroke risk was 30% to 40% for women who currently used HT, a result similar to results of the WHI.
Timing of HT initiation did not significantly change the observed associations (RR for estrogen alone, 1.20 for near menopause and 1.31 for greater than or equal to 10 years after menopause).
The increases in stroke risk were similar for women taking estrogen alone or combined with progestin.
Stroke risk was low among younger women but increased at older ages.
The rate of stroke was 3.8 per 10,000 person-years for those aged 50 to 54 years, doubled from aged 60 to 64 years to 7.1 per 10,000 person-years, and increased 5 times to 17.9 per 10,000 person-years for those 65 years and older.
The attributable risks per 10,000 person-years with current hormone use were 0.9 for women younger than 50 years, 1.5 from ages 50 to 54 years, 2.2 from ages 55 to 59 years, 2.8 from ages 60 to 64 years, and 7.2 at 65 years or older.
Thus, if 10,000 women aged 50 to 54 years used HT for 1 year, an extra 1.5 cases of stroke would be seen vs an extra 7.2 for those 65 years and older.
There was a strong trend of increasing stroke risk with increasing estrogen dosage.
Compared with women who had never used HT, the RR was 0.93 for those who used 0.3 mg of HT daily, 1.54 for those who used 0.625 mg of HT daily, and 1.62 for those who used 1.25 mg of HT daily.
In the youngest group of women (aged less than or equal to 55 years), combining data for estrogen and combined hormone use, short-term HT use was not associated with an increased risk for stroke, but this was based on a small number of patients. .
Antiplatelet Treatment Associated With Cerebral Microbleeds
http://cme.medscape.com/viewarticle/701679?src=cmemp
Arch Neurol. Published online April 13, 2009. Abstract
Cerebral microbleeds are brain lesions containing hemosiderin, visualized on MRI, which indicate the presence of small blood vessel disease known as microangiopathy. On T2-weighted GRE MRI, microbleeds appear as hemosiderin deposits in macrophages.
When microbleeds occur in strictly lobar brain locations, this distribution may indicate the presence of cerebral amyloid angiopathy, a bleeding-prone disease state resulting from accumulations of amyloid in the vessel wall. In cerebral amyloid angiopathy, the use of platelet aggregation inhibitors and anticoagulants has been found to be associated with increased occurrence of symptomatic hemorrhage.
Study Highlights
The Rotterdam Scan Study is a population-based imaging study in a general elderly community in the Netherlands.
The goal of the study was to evaluate the association between use of antithrombotic drugs and the presence of cerebral microbleeds, particularly those in strictly lobar locations.
In this cross-sectional analysis, MRI was used to evaluate the presence and location of microbleeds.
Automated pharmacy records were used to obtain complete data regarding outpatient use of platelet aggregation inhibitors and anticoagulant drugs before MRI was performed.
The study sample consisted of 1062 persons from a longitudinal, population-based cohort.
Inclusion criteria were age 60 years and older, absence of dementia, and MRI scan performed between August 15, 2005, and November 22, 2006.
The primary endpoint of the study was the presence of cerebral microbleeds on MRI.
To minimize confounding by indication, analyses were adjusted for cardiovascular risk, and persons with a known history of cerebrovascular disease were excluded.
Cerebral microbleeds were more prevalent among users vs nonusers of platelet aggregation inhibitors (adjusted odds ratio [OR], 1.71; 95% confidence interval [CI], 1.21 -2.41).
There was no apparent significant association between anticoagulant drugs and the presence of microbleeds (OR, 1.49; 95% CI, 0.82 - 2.71).
Aspirin users had a greater prevalence of strictly lobar microbleeds vs nonusers (adjusted OR, 2.70; 95% CI, 1.45 - 5.04) and vs users of carbasalate calcium (adjusted OR, 1.16; 95% CI, 0.66 - 2.02).
This difference between aspirin and carbasalate calcium was even more pronounced when comparing persons who had used similar dosages of both drugs.
This difference between aspirin and carbasalate calcium was not observed for deep or infratentorial microbleeds.
The investigators concluded that use of platelet aggregation inhibitors is related to the presence of cerebral microbleeds and that aspirin and carbasalate calcium use may relate differently to the presence of strictly lobar microbleeds.
Limitations of this study include cross-sectional vs prospective design; inability to date cerebral microbleeds seen on MRI, so that some of the microbleeds may have occurred before use of antithrombotic drugs; and possible confounding by indication. .
Anticoagulant and Antiplatelet Therapy for Endoscopic Procedures Reviewed http://cme.medscape.com/viewarticle/574397?sssdmh=dm1.467530&src=nldne
Anticoagulants are frequently prescribed, and use of antiplatelet agents is also increasing for ischemic heart disease and for patients with coronary artery stents. Many endoscopic procedures are associated with risk for hemorrhage, which may be further increased by patients receiving anticoagulant or antiplatelet therapy.
Although the American Society for Gastrointestinal Endoscopy has issued excellent guidelines, they offer limited guidance regarding the management of cardiac patients on antiplatelet agents. To supplement these guidelines and extend their scope, the British Society of Gastroenterology, in collaboration with the British Committee for Standards in Haematology and the British Cardiovascular Intervention Society, has issued guidelines regarding proper anticoagulant and antiplatelet treatment of patients who undergo endoscopic procedures.
Study Highlights
In acute GI hemorrhage, the immediate risk from bleeding may outweigh the risk for thrombosis from stopping anticoagulant or antiplatelet therapy. Each patient must be evaluated individually, and there is no unequivocal guidance that would apply to all situations.
Depending on hemorrhage severity and the risk of stopping anticoagulation for patients with high-risk conditions, warfarin may be stopped with or without substitution of heparin.
In patients with GI hemorrhage and coronary stents, clopidogrel should not be stopped without first consulting with a cardiologist, and interruption should be limited to 5 or fewer days.
The first goal in acute GI hemorrhage should be early therapeutic endoscopic intervention to achieve hemostasis with minimal or no interruption of anticoagulant or antiplatelet therapy.
Low-risk procedures are diagnostic endoscopic procedures, with or without biopsy, biliary or pancreatic stenting, and diagnostic EUS.
High-risk procedures are colonoscopic polypectomy, ERCP with sphincterotomy, biliary or pancreatic stenting, endoscopic mucosal resection or endoscopic submucosal dissection, endoscopic dilatation of upper or lower GI strictures, endoscopic therapy of varices, percutaneous gastrostomy, and EUS with fine-needle aspiration.
For discontinuation of anticoagulant therapy, low-risk conditions are prosthetic metal aortic valve, xenograft heart valve, AF without valvular disease, and more than 3 months after venous thromboembolism. High-risk conditions are prosthetic metal mitral valve, prosthetic heart valve and AF, AF and mitral stenosis, less than 3 months after venous thromboembolism, and thrombophilia syndromes.
For discontinuation of clopidogrel, low-risk conditions are ischemic heart disease without coronary stents, cerebrovascular disease, or peripheral vascular disease. High-risk conditions are drug-eluting coronary artery stents within 12 months of placement and bare metal coronary artery stents within 1 month of placement.
For low-risk endoscopic procedures, anticoagulation or antiplatelet therapy should be continued, but if warfarin is continued, INR should not exceed the therapeutic range.
For high-risk endoscopic procedures in low-risk conditions, warfarin should be temporarily discontinued. Clopidogrel should be discontinued 7 days before the procedure, but aspirin should be continued. If the patient is not already taking aspirin, prescribing aspirin may be considered while clopidogrel is stopped.
For high-risk endoscopic procedures in high-risk conditions, warfarin should be temporarily discontinued and substituted with LMWH. Patients should be told that risk for postprocedure bleeding is increased vs that in nonanticoagulated patients.
Stopping clopidogrel should only be considered after discussion with the patient's cardiologist, and a gastroenterologist or surgeon should confirm that the endoscopic procedure is essential.
If bare metal coronary stents were placed more than 1 month before endoscopy, clopidogrel could be temporarily discontinued.
If drug-eluting coronary stents were placed more than 12 months before endoscopy, clopidogrel could be temporarily discontinued.
If drug-eluting stents were placed more than 6 months before endoscopy and the procedure is deemed to be essential, then it may be safe to discontinue clopidogrel temporarily.
Clopidogrel should be stopped 7 days before the procedure, but aspirin therapy should be continued. On the day following the procedure, clopidogrel should be restarted.
CMS on Warfarin-Responsiveness Genetic Test: No Medicare Coverage Except Within Trials
http://www.medscape.com/viewarticle/702378?sssdmh=dm1.468144&src=nldne
The Centers for Medicare and Medicaid Services (CMS) says that pharmacogenetic testing for warfarin responsiveness, which proponents say can help guide warfarin dosing, hasn't been shown to improve health outcomes and so shouldn't be reimbursable under Medicare except within the confines of a clinical trial specifically designed to demonstrate the clinical effects of such testing, the agency has announced [1]. A public comment period on the CMS proposal runs through June 3, 2009.That the testing hasn't shown clinical benefits is supported by the recommendations of most professional societies that provided input as well as by its own review of the evidence, according to the agency.
"We believe that there is good evidence that the FDA-cleared pharmacogenomic tests accurately identify persons who have the variant CYP2C9 and VKORC1 alleles," the CMS statement notes. "We also believe that there is good evidence that persons who have these variant alleles have heightened warfarin responsiveness. . . . However, although such studies suggest indirect evidence of potential clinical benefit from pharmacogenomic testing, they do not conclusively establish an actual benefit or risk to a beneficiary's health outcome."
References
Centers for Medicare and Medicaid Services. Proposed decision memo for pharmacogenomic testing for warfarin response (CAG-00400N). May 4, 2009. Available here
Possible "Class Effect" for Proton-Pump Inhibitors on Top of Clopidogrel Therapy
http://www.medscape.com/viewarticle/702485?sssdmh=dm1.468547&src=nldne
One-year risk of cardiovascular events is increased more than 50% in patients taking a proton-pump inhibitor (PPI) on top of clopidogrel, as compared with patients not taking a PPI, and the risk seems to be a class effect, according to a retrospective cohort study of more than 16 700 patients who received clopidogrel poststenting. The study is the latest in an inconsistent series of reports trying to assess the clinical impact of combining the two classes of drugs. Professional society guidelines recommend the use of PPIs to treat and prevent gastrointestinal ulcers and bleeding in patients on antiplatelet therapy, but increasing use of PPIs in this setting has raised questions as to whether PPIs may attenuate clopidogrel's antiplatelet response by interfering with CYP2C19-mediated clopidogrel metabolism.
The study compared major adverse cardiovascular events (MACE) among members of the Medco Health Solutions pharmacy and medical claims database. In all, 9862 patients never made a prescription claim for a PPI over the 12 months post-PCI and were classified as no PPI therapy for the purposes of the study, while 6828 filed prescription claims for a PPI: esomeprazole (Nexium, AstraZeneca), omeprazole, pantoprazole (Protonix, Wyeth), lansoprazole, or rabeprazole (Aciphex, Eisai/Ortho-McNeil-Janssen Pharmaceuticals).
Prescription status was then correlated with hospitalization for stroke/TIA, ACS, cardiovascular death, or coronary revascularization, based on ICD-9 or CPT-4 codes.
Of note, hospitalization rates for upper-GI bleeding were low across all groups of PPI use, in the range of 1.1%. Also of interest, investigators looked at PPI use among patients who were not treated with clopidogrel and found no increased risk of CV events in this group, as compared with patients taking neither a PPI nor clopidogrel
Stent Thrombosis Responsible for an Increasing Proportion of STEMI
http://www.medscape.com/viewarticle/702599?sssdmh=dm1.470360&src=nldne
A study tracking trends in STEMI indicates that in parallel with increasing use of drug-eluting stents (DES), rates of stent thrombosis as a cause of STEMI are also on the rise.
The study enrolled all patients within a 220-mile radius admitted for STEMI or new left bundle branch block less than 24 hours after symptom onset at the regional PCI center. In all, 2262 patients were admitted for STEMI over the study period, of which 124 were caused by stent thrombosis. In 2003, investigators report, stent thrombosis made up just 3.6% of STEMIs, with numbers equally split between bare-metal stents and DES. By 2007, stent thrombosis constituted 7.7% of STEMIs, 2.4% occurring in bare-metal stents and 4.8% occurring in DES (p for trend=0.019). Of note, the number of stent thromboses actually declined, proportionally, in 2008, dropping to 6% of STEMIs. This may reflect more judicious screening of appropriate patients for DES, Flannery speculated, but he added that the decline was modest and warranted closer examination before any conclusions could be drawn.
Also of note, stent thrombosis appeared to be occurring in both bare-metal and DES-treated patients and frequently occurred beyond the one-year mark, Flannery and colleagues observed. Equally notable and in contrast with other reports, patients in whom stent thrombosis caused their STEMI appeared to have the same or even lower mortality than non-stent-thrombosis STEMI but a higher incidence of repeat MI.
The findings should remind physicians that there is, as yet, no clear consensus on whether STEMI patients with a stent-thrombosis etiology should be treated in the same way as other STEMI patients. "Should they be stented? Should they get a bare-metal stent, a DES, or should they get bypass? We just don't know. The outcomes we have are not statistically different, but the one thing that is statistically different is that stent-thrombosis patients are much more likely to have a subsequent heart attack within a year, although they also have higher risk factors
New Antiplatelet Ticagrelor Could Challenge Clopidogrel, Prasugrel
http://www.medscape.com/viewarticle/702829?sssdmh=dm1.471807&src=nldne
AstraZeneca has announced the results of a pivotal phase 3 trial comparing its new oral antiplatelet agent, ticagrelor (Brilinta), with clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) in patients with acute coronary syndromes [1]. The signs are that the new agent--which the company says it will submit for approval in the fourth quarter of this year--could pose a threat to both clopidogrel and another antiplatelet drug awaiting approval, Lilly's prasugrel.
While full details of the phase 3 study have not yet been released--they are due to be reported at the European Society of Cardiology meeting in Barcelona this summer--AstraZeneca said ticagrelor was more effective at preventing MI/stroke/cardiovascular death than clopidogrel in the trial, known as Platelet Inhibition and Patient Outcomes (PLATO) trial.
As a potential competitor in the antiplatelet field, ticagrelor is a prospective blockbuster drug: last year, clopidogrel was the second-biggest-selling drug in the world, with global revenues of more than $8 billion. However, generic versions of clopidogrel are already available in Europe and are expected to appear in the US within a couple of years, which will make competition that much harder. But there are a number of patients who do not respond to clopidogrel, and these people represent the initial market for those trying to promote newer antiplatelet drugs, such as prasugrel and ticagrelor, should it be approved.
Unlike clopidogrel and prasugrel, ticagrelor is not a thienopyridine, and its mechanism of action is "unique" in that it is reversible, However, ticagrelor has to be dosed twice daily, as opposed to once daily for either clopidogrel or prasugrel; the second is that there have been some reports of dyspnea as a side effect with ticagrelor in phase 2 studies.The design of PLATO was published recently in the April 2009 issue of the American Heart Journal [3]. It is an international, randomized, double-blind, event-driven trial involving >18 000 patients hospitalized for ST-elevation ACS with scheduled primary PCI or for non-ST-elevation ACS.
Patients received ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for six to 12 months on top of aspirin, after loading doses of ticagrelor 180 mg or clopidogrel 300 mg, in a double-blind, double-dummy fashion. The primary efficacy end point is time to first occurrence of death from vascular causes, MI, or stroke. The primary safety variable is PLATO-defined major bleeding.In the phase 2 study, there was also an intriguing, numerically lower rate of bleeding in ticagrelor-treated patients undergoing CABG between one and five days after stopping the study drug, "which would be consistent with a recovery of platelet function due to the reversible binding of ticagrelor to the P2Y12 receptor," the authors note.
If these results are confirmed, the use of the reversible agent ticagrelor, with a half-life of 12 hours, would allow greater flexibility for use of P2Y12 inhibitors, they note. "One could treat all patients at the time of presentation with ACS but stop the treatment for patients who are found on coronary angiography to need CABG, for example, thereby avoiding the need to make patients wait five days for CABG, as currently recommended. Similarly, for patients treated chronically post-ACS, it would potentially allow greater flexibility for other types of elective surgery."
No Significant Reduction of CV Events With Aspirin in Peripheral Artery Disease
http://www.medscape.com/viewarticle/702791?sssdmh=dm1.471807&src=nldne
A new meta-analysis of randomized trials assessing the effects of aspirin with or without dipyridamole in patients with peripheral artery disease (PAD) finds only a statistically nonsignificant 12% reduction in cardiovascular events with treatment.There was a significant reduction in nonfatal stroke with aspirin therapy, but this was a secondary end point in their analysis.
The largest assessment of the effects of aspirin to date is the Antithrombotic Trialists' Collaboration (ATC) meta-analysis of 287 trials that showed a significant reduction in myocardial infarction (MI), death, and stroke in patients with symptomatic cardiovascular disease (Antithrombotic Trialists' Collaboration. BMJ 2002;324:71-86). In a subset of 42 of these trials, antiplatelet therapy was associated with a similar significant decrease in risk, and on the basis of this, many guidelines documents recommend aspirin for those with PAD. Nearly two-thirds of the trials included in the ATC meta-analysis evaluated antiplatelet drugs other than aspirin, and a recently reported randomized study, the POPADAD trial, showed no benefit of aspirin therapy in patients with diabetes and asymptomatic PAD (Belch J et al. BMJ 2008;331:a1840). The current meta-analysis included 18 randomized controlled trials of aspirin therapy with and without dipyridamole involving a total of 5269 participants with PAD. Primary end points of the trials were cardiovascular events, including nonfatal MI, nonfatal stroke, and cardiovascular death. Data on all-cause mortality, major bleeding, and the individual components of the primary end point were also collected.
They found a trend toward a lower rate of cardiovascular events with aspirin treatment, but this difference did not reach statistical significance. The point estimate is a 12% reduction in myocardial infarction, stroke, and cardiovascular death. There was a statistically significant reduction in the secondary outcome of nonfatal stroke, but no significant effect on other secondary end points.
A large primary-prevention trial is now ongoing in the United Kingdom looking at aspirin in patients with a low ankle-brachial index but no established cardiovascular disease, Dr. Hiatt noted. "Those results will probably be available in the next year or 2, and we'll have more information," he said.
Clopidogrel offered a small but statistically significant advantage over aspirin for secondary prevention among patients in the CAPRIE trial with cardiovascular disease, they write, but the suggestion in CAPRIE that clopidogrel might be more beneficial for patients with PAD than those with heart disease or stroke were not borne out by more recent results from the CHARISMA trial.
ESC 2009: No Benefit of Compression Stockings in DVT Prevention After Stroke
A new randomized trial shows no benefit from the use of thigh-length graduated compression stockings (GCS) to prevent proximal deep vein thrombosis (DVT) in patients immobilized by stroke.
Results of the Clots in Legs or Stockings After Stroke (CLOTS-1) trial show no significant benefit from use of the stockings on the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral vein among these patients, but skin breaks, ulcers, blisters, and skin necrosis were more common in those allocated to use of the stockings.
Two ongoing trials are looking at other methods of DVT reduction in these patients, CLOTS-2, comparing the relative effects of thigh-length and below-knee stockings, stopped enrollment on the basis of the CLOTS-1 results, and the findings from that trial are expected to be reported in December of this year. CLOTS-3, evaluating the use of intermittent pneumatic compression in this same indication, is ongoing.DVT and pulmonary embolism are common after stroke Small trials of patients undergoing surgery have suggested that graduated compression stockings reduce the risk for these events; a pooled analysis of 17 trials using these stockings showed a 63% odds reduction of DVT.
However, 15 of these 17 trials were surgical trials, where the stockings could be applied before immobilization paralysis; they were applied for just a few days; and outcomes were measured at 7 to 14 days. Only 1 small trial has looked at their use in stroke patients.
The CLOTS-1 trial, then, aimed to answer the question of the real benefit of these stockings in an acute-stroke population. A total of 2518 patients admitted to the hospital with an acute stroke who were immobile were enrolled from 64 centers in the United Kingdom, Italy, and Australia and randomized to receive routine care plus thigh-length stockings or routine care avoiding use of the stockings. Routine care could include early mobilization, hydration, or background prophylactic heparin.A technician blinded to treatment allocation carried out compression Doppler ultrasound of both legs at 7 to 10 days, when it was practical, and again at 25 to 30 days after enrollment. A 6-month follow-up was also done.The primary outcome, the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins, was not significantly different between the groups.
Chewable Aspirin Best for ACS: Small Study Supports Guidelines
A small study in 14 healthy volunteers has shown that chewable aspirin is better absorbed than regular aspirin, whether it is swallowed whole or chewed first, supporting current guidelines that chewing aspirin is the best way to administer the drug for the treatment of ACS. In the three-arm crossover study, the volunteers (13 male; average age 31 years) were given supratherapeutic doses of aspirin, 1950 mg, as either a solid tablet swallowed, a solid tablet chewed then swallowed, or chewable tablets. They were given the aspirin with water after fasting for six hours, with a washout period of seven days between crossovers.
The mean peak concentrations of aspirin were seen at three hours in all groups and were 10.4, 11.3 and 12.2 mg/dL in the solid-swallowed, solid-chewed, and chewable groups, respectively; this was statistically significant in each group (p<0.05), except in comparing solid-swallowed with solid-chewed groups. All subjects in the chewable-aspirin group had measurable salicylate levels at 45 minutes after ingestion, compared with no measurable salicylate levels in six of 14 in the solid-swallowed group and one of 14 in the solid-chewed group at 60 minutes.
These data suggest that in the treatment of ACS, a chewable formulation may be preferable to solid tablets chewed or swallowed.
Donna Castellone
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Donna Castellone,
MS, MT(ASCP)SH
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