The Doctor's Channel - Hospitalist

Thyroid hormone analogue shows promise for statin-treated dyslipidemia

2010-03-12T21:09:30+00:00

NEW YORK (Reuters Health) – When statins alone can’t reverse dyslipidemia, the thyroid hormone analogue eprotirome may be helpful, new research suggests.

In a 12-week study of 189 dyslipidemic, statin-treated patients, eprotirome safely reduced the levels of various atherogenic lipoproteins, the investigators report in The New England Journal of Medicine for March 11.

In the study, subjects continued to receive simvastatin or atorvastatin and were randomized to receive eprotirome (25, 50, or 100 micrograms/day) or placebo.

With the 25, 50, and 100 microgram doses of eprotirome, mean low density lipoprotein (LDL) cholesterol levels fell by 22%, 28%, and 32%, respectively, from a baseline value of 141 mg/dL. By contrast, placebo produced a mean reduction of just 7%. Eprotirome had a similar effect on levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein.

Eprotirome was generally well tolerated, with no adverse cardiac or bone effects. Although thyroxine levels fell in patients receiving the drug, serum levels of thyrotropin and triiodothyronine did not change.

“This randomized, placebo-controlled, double-blind trial showed that eprotirome is associated with further reductions in serum LDL cholesterol levels in patients who are already receiving statins,” the authors conclude. “Eprotirome also has potent properties for lower levels of apolipoprotein B, triglycerides, and Lp(a) lipoprotein.”

The study was supported, in part, by Kara Bio, the company developing eprotirome.

Reference:
N Engl J Med 2010;362:906-916.

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Emboli filters during PCI lead to higher risk of stent thrombosis

2010-03-09T16:49:30+00:00

NEW YORK (Reuters Health) - Using a distal filter to protect against emboli during coronary stent implantation increases long-term rates of stent thrombosis and target vessel revascularization, investigators in Denmark report.

Randomized trials have shown no benefit of distal protection in the short or intermediate term after percutaneous coronary intervention (PCI), Dr. Anne Kaltoft from Aarhus University Hospital, Skejby, and her associates note. Their article in the Journal of the American College of Cardiology for March 2 reports their 15-month follow-up of patients treated for ST-elevation myocardial infarction in the DEDICATION trial.

Patients received aspirin, clopidogrel, and unfractionated heparin in advance of the procedure. If a cardiologist believed that a wire filter could be advanced (based on pre-dilation and initial visualization of the peripheral vascular bed), the researchers then randomized the patient either to distal protection (n = 312) or conventional treatment (n = 314).

In the distal protection group, filter placement was attempted in 304 patients (97%) and was successful in 254 patients (81%).

But filter protection afforded no benefit at either 30 days, 6 months, or 15 months later, the researchers said.

Nine cases of definite stent thrombosis occurred in the protection group and one in the control group (2.9% vs 0.3%, p = 0.01).

The rate of target lesion revascularization was also significantly increased in the distal protection group (12.5% vs 7%, p = 0.05), as was the rate of target vessel revascularization (15.4% vs 8.3%, p < 0.01).

The two groups had similar rates of myocardial infarction and mortality.

Dr. Kaltoft's team suggests that vessel spasm in response to filter placement could lead "to an underestimation of the vessel diameter and to undersizing of the implanted stent, a known predictor of early stent thrombosis." Other possibilities include damage to the vessel wall at the site of filter deployment or stent apposition during filter retrieval.

Similarly, damage to the vessel wall from pre-dilation or during placement of the filter could increase restenosis rates and the need for repeat revascularization.

Whatever the cause, the authors conclude, "Routine use of a filter wire in its present form cannot be advocated and probably should be avoided with primary PCI for ST-elevation myocardial infarction."

Reference:
J Am Coll Cardiol 2010;55:867-871.

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Cardiac vegetations don't rule out percutaneous ICD lead extraction

2010-03-08T19:26:08+00:00

NEW YORK (Reuters Health) - Percutaneous extraction of pacemaker or implantable cardioverter-defibrillator (ICD) leads is safe in patients with cardiac vegetations, investigators report. And as long as blood cultures remain sterile, permanent devices can be reimplanted within a week or two.

Eradication of device-related infection requires complete system removal, the authors note in the March 2nd Journal of the American College of Cardiology. Traditionally, patients with vegetations larger than 1 cm in diameter have had their leads removed via thoracotomy, in order to avoid septic emboli -- but the surgery itself increases patients' risks for serious complications and for prolonged recovery.

Senior author Dr. Steven P. Kutalek and associates at Drexel University College of Medicine, Philadelphia, studied 100 patients (mean age, 67 years) who had 1838 leads extracted percutaneously despite echocardiographic evidence of vegetations. This group accounted for roughly 10% of all the percutaneous lead extraction cases at the authors' center between 1991 and 2007.

The vegetations ranged from 0.2 to 4.0 cm in largest diameter (mean 1.6 cm). Implants had been in place for an average of 51 months. The median extraction time (4 min per lead) was not significantly different from the median in a reference group consisting of all 66 patients without vegetations who underwent extraction in 2004.

Five patients had complications during lead extraction, including embolized vegetation in two. However, all 5 were discharged in stable condition and recovered uneventfully.

In 54 patients, surgeons reimplanted new devices during the same hospitalization, at a median of 7 days after extraction. None of these second devices had to be extracted due to relapsing infection.

Twenty-nine patients were lost to follow-up. In the remaining 71, the average follow-up was 438 days.

Nineteen patients died - 11 of persistent septicemia, 1 of sudden cardiac death, and the other 7 of unknown causes with no evidence of ongoing infection (including 4 who had received a new device).

Ten patients died within 30 days of lead extraction. "These unfortunate outcomes occurred in a critically ill subset of patients who often have extensive comorbidities," the researchers note. They attribute the operative mortality to disease severity rather than the mode of lead extraction.

Also, "given the frequent ambiguity of initial culture data," the authors recommend transesophageal ultrasonography before device extraction in order to identify patients at high risk for endocarditis.

This study demonstrates that "percutaneous lead extraction with vegetations of all sizes is possible and seemingly appropriate," Dr. James D. Maloney at Heartland Spine and Specialty Hospital, Overland Park, Kansas, and Dr. James D. Maloney III at the University of Wisconsin, Madison, write in a related editorial.

Still, they're concerned that residual infected inflammatory tissue needs to be debrided after the leads are removed.

"The question remains... if a nidus of chronic infection sometimes remains, does that cause refractory sepsis and congestive heart failure?" they ask. "Can and should it be removed surgically?"

Reference:
J Am Coll Cardiol 2010;55:886-897.

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Hybrid cardiology

2010-03-08T16:01:35+00:00

Richard J Shemin, MD, Chief of Cardiothoracic Surgery, UCLA David Geffen School of Medicine, discusses hybrid approaches to cardiology and cardiothoracic surgery, such as operation rooms where interventional cardiologists can work alongside cardiothoracic surgeons.

Reading:
Nollert G, Wich S. Planning a cardiovascular hybrid operating room: the technical point of view. Heart Surg Forum. 2009 Jun;12(3):E125-30.
Hu SS. One-stop hybrid approach for cardiovascular disease: from conception to practice. Ann Thorac Cardiovasc Surg. 2008 Dec;14(6):345-6.
Plass A, Schepis T, Scheffel H, Eberli F, Kaufmann P, Alkadhi H, Pretre R, Grünenfelder J. Multimodality preoperative planning and postoperative follow-up of a hybrid cardiac intervention. Heart Surg Forum. 2008 Dec;11(6):E375-7.

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Aspirin prophylaxis not useful for asymptomatic vascular disease

2010-03-05T21:36:50+00:00

NEW YORK (Reuters Health) – Asymptomatic patients with a low ankle brachial index don’t seem to get cardiovascular protection from aspirin, randomized trial results suggest.

The subjects came from a cohort of nearly 29,000 men and women ages 50 to 75 years enrolled in a community health registry in Scotland. All were free of clinical cardiovascular disease at baseline, and each agreed to ankle brachial index screening. The 3350 individuals with an index of no more than 0.95 took either 100 mg of aspirin daily, or placebo, for the next 8.2 years, on average.

In the Journal of the American Medical Association for March 3, lead author Dr. F. Gerald R. Fowkes, from the University of Edinburgh and colleagues report that 357 subjects met the main endpoint (a composite of coronary events, stroke, or revascularization). Rates per 1000 person-years were similar with aspirin (13.7) and placebo (13.3).

Rates of a secondary outcome – a composite of the main endpoint plus angina, intermittent claudication, or transient ischemic attack – were also comparable: 22.8 vs. 22.9 per 1000 person-years with aspirin vs placebo, respectively.

All-cause mortality was similar as well, with 12.8 deaths per 1000 person-years in the aspirin group and 13.5 in the placebo group.

Subjects treated with aspirin were 71% more likely than those given placebo to experience major hemorrhage requiring admission to the hospital: 2.5 vs. 1.5 per 1000 person-years.

“Based on the trial conducted by Fowkes et al and other similar studies, aspirin appears to have marginal benefits for reducing initial cardiovascular events when used for patients without clinically evident cardiovascular disease and is associated with higher rates of bleeding in these patients,” Dr. Jeffrey S. Berger, from New York University School of Medicine, comments in a related editorial.

Dr. Fowkes and colleagues conclude that “given the increased level of risk among those with a low ankle brachial index, the use of alternative therapies, such as statins or more potent antiplatelet agents without attendant hemorrhagic risks may usefully be considered.”

Reference:
JAMA 2010;303:841-848,880-882.

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Without thrombolysis, women fare worse than men after stroke

2010-03-04T15:20:25+00:00

NEW YORK (Reuters Health) – Thrombolysis is a must for female stroke patients if they are to achieve the same outcomes as men, according to a March 2nd report in the Neurology.

“Women need to be treated for stroke as soon as possible,” senior author Dr. Michael D. Hill, from the University of Calgary, Alberta, Canada, said in a statement. “We found that women who weren’t treated had a worse quality of life after stroke than men. However, the good news is that women who were treated responded just as well as men to the treatment.”

The findings are drawn from registry data on 2113 stroke patients treated all across Canada, from June 2001 to February 2002 and from June to December 2002. Women accounted for 43.5% of the cohort.

The primary outcomes were the score on the Stroke Impact Scale-16 score and mortality at 6 months.

Without tissue plasminogen activator (tPA), 70% of men but only 58% of had good outcomes, defined as a score of at least 75 on the Stroke Impact Scale-16 (p < 0.001). With tPA thrombolysis, however, women were just as likely as men to have good outcomes.

Mortality was comparable for men and women whether or not tPA was used.

After adjusting for age, stroke severity, and the time from symptom onset to arrival in the emergency department, gender was found to influence the Stroke Impact Scale-16 score, but not mortality.

Exactly why untreated women fare worse than untreated men is unclear, Dr. Hill said in the statement.

Biologic reasons could explain the difference, he noted. Or older women might be less likely than older men to have a surviving spouse who can assist them in their stroke recovery. In addition, post-stroke depression, which can slow recovery, is more common in women.

Reference:
Neurology 2010;74:767-771.

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Surgery favored over stenting for symptomatic carotid stenosis

2010-03-02T20:01:51+00:00

NEW YORK (Reuters Health) - Interim data from a 3-year trial of stenting versus endarterectomy for symptomatic carotid stenosis suggests that for now at least, surgery should remain the procedure of choice.

The report, which appears in the February 26th online issue of The Lancet, presents the 120-day rates of stroke, death, or procedural myocardial infarction (MI) from the ongoing International Carotid Stenting Study (ICSS).

Overall, the ICSS includes 1713 patients randomized to undergo stenting or endarterectomy for symptomatic carotid stenosis.

Dr. Martin M. Brown, from University College London, and colleagues report that by 120 days, the rate of disabling stroke or death in the stenting group was 4.0% compared with 3.2% in the surgery group (HR, 1.28). The corresponding stroke, death, or procedural MI rates were 8.5% and 5.2% (HR, 1.69, p = 0.006).

Compared with surgery patients, patients with stents were nearly twice as likely to have a stroke during follow-up and almost three times as likely to die from any cause.

More procedural myocardial infarctions occurred in the surgery group than in the stenting group (4 vs. 3) - but all of these events in the stenting group were fatal, whereas none of the surgery patients died from procedure-related MI.

Cranial nerve palsy was less common with stenting than with surgery: 1 vs. 45. Likewise, fewer stenting patients had hematomas: 31 vs. 50 events.

In addition, an ICSS substudy that focused on magnetic resonance imaging results -- also appearing online February 26th, but in The Lancet Neurology - found fewer new ischemic brain lesions in the endarterectomy group versus the stenting group.

The substudy featured 124 stenting patients and 107 surgery patients who underwent diffusion-weighted MRI within the week before treatment and 1-3 and 27-33 days afterward.

Lead author Dr. Leo H Bonati from Hospital Basel, Switzerland and colleagues report that in the first few days after treatment, the percentage of patients with new ischemic brain lesions was much higher in the stenting group: 50% vs. 17% (p < 0.0001). The difference was even more pronounced when the analysis was limited to centers that typically use cerebral protection devices: 73% vs. 17%.

At 1 month, 33% of stenting patients had evidence of persistent brain injury, versus 8% of surgery patients (p = 0.0003).

In an editorial in The Lancer Neurology, Dr. Klaus Groschel, from Georg-August-Universitat Gottingen, Germany, comments that the present findings suggest that "the widespread use of carotid stenting, especially its routine use as first-choice treatment for symptomatic carotid stenosis, does not seem to be justified for the time being."

Currently, he notes, the bulk of data supports endarterectomy over stenting. However, he emphasizes that this does not necessarily mean the two approaches can't co-exist, as certain patients may be better served by stenting.

Reference:
Lancet 2010.
Lancet Neurology 2010.

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Belatacept-based immunosuppression spares renal function in kidney recipients

2010-03-01T17:28:28+00:00

NEW YORK (Reuters Health) – Belatacept-based immunosuppression after kidney transplantation allows for better renal function compared to cyclosporine, with similar graft and patient survival, phase III trial results suggest.

In kidney allograft recipients, “the leading causes of death and graft loss are cardiovascular disease and chronic allograft nephropathy, respectively,” Dr. Flavio Vincenti and co-researchers note.

Cyclosporine – perhaps the most commonly used immunosuppressive in kidney recipients -- is a calcineurin inhibitor. This class of drugs has a wide range of severe side effects, including nephrotoxicity. Their toxicity is thought to relate to their broad range of nonimmunologic targets, Dr. Vincenti, from the University of California, San Francisco, and colleagues note. Thus, a drug with greater specificity, such as the selective T-cell activation blocker belatacept, would be expected to have fewer toxicities.

In the 3-year international BENEFIT trial, 686 patients were randomized to receive a belatacept- or cyclosporine-based regimen. Belatacept-treated patients were further divided to receive a more or less intensive regimen, based on how long the drug was given at a 10-mg/kg dose versus a 5-mg/kg dose.

All patients received induction therapy with basiliximab, mycophenolate mofetil, and steroids.

At 12 months, the composite endpoint of patient and graft survival was similar in all three groups, hovering around 95%.

The composite renal endpoint – measured glomerular filtration rate (mGFR) <60 mL/min/1.73 m2 at month 12, or mGFR decrease of at least 10 mL/min/1.73 m2 between months 3 and 12 – occurred in 55% in the belatacept groups versus 78% in the cyclosporine group (p < 0.001).

Episodes of acute rejection occurred in 22% of patients on the more intensive regimen, 17% on the less intensive regimen, and 7% in the cyclosporine group. Grade of rejection was also higher with the belatacept regimens.

Commenting on their finding that “the overall impact of acute rejection episodes did not negate the…benefits of belatacept,” the authors suggest that “the immune-selectivity of betalacept may affect the composition of rejection infiltrate differently from cyclosporine, resulting in reduced graft damage.”

Side effects were common and generally similar in each group. There were two cases of post-transplant lymphoproliferative disorder in the belatacept group but none in the cyclosporine group.

In a related study, BENEFIT-EXT, Dr. Antoine Durrbach, from Bicetre Hospital, Paris, and colleagues compared belatacept versus cyclosporine in recipients of kidney transplants from extended criteria cadaveric donors. These donors were 60 years of age or older, or 50 years or older with at least two risk factors (stroke, hypertension, or serum creatinine >1.5 mg/dL), or their kidneys had at least 24 hours of cold ischemia, or their organs were procured after cardiac death.

Recipients of grafts from these donors are “challenging to immunosuppress, as they tend to be older and are at increased risk for cardiovascular events and mortality compared with nonextended criteria donor recipients,” the authors note. Nonetheless, the results of BENEFIT-EXT, which featured 578 randomized patients, were similar to those of BENEFIT.

Both studies are reported in the March issue of the American Journal of Transplantation.

BENEFIT and BENEFIT-EXT were funded by Bristol-Myers Squibb, the developer of belatacept.

Reference:
Am J Transpl 2010;10:535-557.

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Prognosis worse with proximal peripheral arterial disease

2010-03-01T17:25:09+00:00

NEW YORK (Reuters Health) - Patients with aortoiliac peripheral arterial disease (PAD) have worse event-free survival than patients with more distal PAD, according to a report in the Journal of the American College of Cardiology for March 2.

"This is the first study to report a poorer general prognosis of patients with proximal PAD compared with those with more distal PAD, independent of risk factors and comorbidities," Dr. Victor Aboyans, from Dupuytren University Hospital, Limoges, France, and colleagues note.

Numerous reports have documented a poor cardiovascular disease prognosis in patients with PAD, the authors note, but it was unclear whether the region of PAD had an impact on prognosis.

To investigate, Dr. Aboyans' team analyzed data from 400 patients with angiographically confirmed lower limb PAD (arterial stenosis of 50% or greater). The main outcome measure was the occurrence of the combined endpoint -- death, nonfatal myocardial infarction or stroke, and coronary or carotid revascularization - during a mean follow-up period of 34 months.

Overall, 344 patients (86.0%) had infra-iliac disease and 211 (52.8%) had aortoiliac disease. Correlates of distal disease included older age, diabetes, hypertension, and renal failure; correlates of proximal disease included male gender and smoking.

Patients with aortoiliac disease had significantly worse event-free survival (p < 0.011). On final analysis, which accounted for several patient characteristics and established cardiovascular risk factors, subjects with proximal disease were more than three times as likely as those with distal disease to die or experience the combined endpoint during follow-up.

"Additional clinical and large-scale epidemiology studies are necessary to validate our findings," the authors conclude.

They add, "If our findings were confirmed, this could result in additional risk stratification of PAD patients depending on which lower extremity arteries are affected."

Reference:
J Am Coll Cardiol 2010;55:898-903.

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Platelet function tests don’t predict PCI outcomes in low-risk patients

2010-02-26T17:12:18+00:00

NEW YORK (Reuters Health) – Baseline platelet function is only modestly related to ischemic outcomes after percutaneous coronary intervention (PCI) in low-risk patients, according to a study in more than 1000 patients. Moreover, common assays don’t accurately predict bleeding risk.

High platelet reactivity is known to increase patients’ risk for atherothrombotic events after PCI, and several assays are available for quantifying reactivity, the research team notes in the February 24th Journal of the American Medical Association.

In an attempt to identify the most accurate test, Dr. Jurrien M. ten Berg and colleagues at St. Antonius Hospital, Nieuwegein, the Netherlands, analyzed blood samples from 1069 low-risk patients on optimal clopidogrel and aspirin treatment, in advance of PCI and stent implantation.

They compared six different tests in subsets of patients:
-- Light transmittance aggregometry (n = 1051)
-- VerifyNow P2Y12 (Accumetrics) (n = 1052)
-- Plateletworks (Helena Laboratories) (n = 606)
-- IMPACT-R (Matis Medical Inc.) (n = 910)
-- Dade PFA-100 (Siemens Healthcare Diagnostics Products CmbH) (n = 812)
-- Innovance PFA P2Y (Siemens Healthcare Diagnostics Products CmbH) (n = 588)

The primary end point was a composite of all-cause death, acute myocardial infarction, ischemic stroke, and stent thrombosis. The primary safety outcome was major and minor bleeding. High platelet reactivity was based on a cut-off defined with receiver operating characteristic curve analysis.

During 1 year of follow-up, 18 patients died, 64 had nonfatal acute myocardial infarction, 14 had nonfatal ischemic strokes, 13 had definite stent thrombosis, and 3 had possible stent thrombosis. Thirty-three had major bleeding; 24 had minor bleeding.

When the authors constructed a model that would identify predictors for the primary endpoint, high platelet reactivity significantly improved the area under the curve only when measured by three of the methods: light transmittance aggregometry, the VerifyNow PsY12 assay, and the Plateletworks assay.

Specifically, rates of the primary end point in patients with and without high platelet reactivity were 11.7% vs 6.0% with light transmittance aggregometry (p < 0.001), 13.3% vs 5.7% with the VerifyNow PsY12 assay (p < 0.001), and 12.6% vs 6.1% with the Plateletworks assay (p = 0.005).

Still, Dr. ten Berg’s team notes, “the predictive accuracy of these tests was only modest.”

None of the tests could discriminate between patients with and without bleeding.

The investigators note that the sample size of the Innovance PFA P2Y, which became available halfway through the trial, was underpowered to detect a link between platelet reactivity and outcome, and other tests not available at the time were excluded. Also, patients were on 3 different clopidogrel regiments. “However, these 3 regimens are current clinical practices and our study therefore reflects the clinical relevance of monitoring platelet function in daily practice,” the authors add.

Until several ongoing clinical trials are completed, the authors maintain, “clinical practice should not be guided by (point-of-care) platelet function testing” for low-risk patients undergoing elective PCI.

Siemens Healthcare Diagnostics provided the Dade PFA and Innovance PFA P2Y for the study without charge.

Reference:
JAMA 2010;303:754-762.

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