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#451
04.11.2010, 13:41
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Цитата:
Вышла по ссылке, зарегистрировалась и так зачиталась, что даже забыла поблагодарить...  
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#452
04.11.2010, 21:02
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Warfarin Discontinuation After Starting Warfarin for Atrial Fibrillation
Fang MC, Go AS, Chang Y, et al. Circ Cardiovasc Qual Outcomes 2010;Oct 19:[Epub ahead of print]. Study Question: How often is warfarin therapy discontinued in patients with atrial fibrillation (AF)? STITCH (Surgical Treatment for Ischemic Heart Failure) Trial Enrollment Jones RH, White H, Velazquez EJ, et al. J Am Coll Cardiol 2010;56:490-498. Study Question: The Surgical Treatment for Ischemic Heart Failure (STITCH) trial was performed to assess whether coronary artery bypass grafting alone or in association with surgical ventricular reconstruction (SVR) impacted late outcomes in patients with ischemic cardiomyopathy. This trial demonstrated difficult enrollment, variation in equipoise amongst clinicians, and incremental expansion of sites over the 3 years. This led to the current study objective: Could differences in enrollment affect outcomes? Risk of Recurrence After a First Episode of Symptomatic Venous Thromboembolism Provoked by a Transient Risk Factor: A Systematic Review Iorio A, Kearon C, Filippucci E, et al. Arch Intern Med 2010;170:1710-1716. Study Question: What is the risk of recurrence for symptomatic venous thromboembolism (VTE) provoked by different transient risk factors? Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery Leon MB, Smith CR, Mack M, et al., on behalf of the PARTNER Trial Investigators. N Engl J Med 2010;363:1597-1607. Study Question: What is the outcome of patients with severe aortic valve stenosis who are not candidates for valve surgery and are treated with transcatheter aortic-valve implantation (TAVI)? Changing Mortality in Congenital Heart Disease Khairy P, Ionescu-Ittu R, Mackie AS, Abrahamowicz M, Pilote L, Marelli AJ. J Am Coll Cardiol 2010;56:1149-1157. Study Question: What have been the trends over time in all-cause mortality in patients with congenital heart disease? Patient-Level Meta-Analysis: Effect of Measurement Timing, Threshold, and Patient Age on Ability of D-Dimer Testing to Assess Recurrence Risk After Unprovoked Venous Thromboembolism Douketis J, Tosetto A, Marcucci M, et al. Ann Intern Med 2010;153:523-531. Study Question: Does the timing of D-dimer testing after stopping anticoagulation or the cut point used to define a positive or negative result affect the ability of D-dimer testing to distinguish risk for recurrent thromboembolism (VTE)? Fondaparinux for the Treatment of Superficial-Vein Thrombosis in the Legs Decousus H, Prandoni P, Mismetti P, et al., on behalf of the CALISTO Study Group. N Engl J Med 2010;363:1222-1232. Study Question: What is the efficacy and safety of fondaparinux, a specific factor Xa inhibitor, in reducing symptomatic venous thromboembolic complications or death from any cause in patients with acute, isolated superficial-vein thrombosis of the legs? Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI: A Meta-Analysis Mega JL, Simon T, Collet JP, et al. JAMA 2010;304:1821-1830. Study Question: What is the risk of adverse cardiovascular (CV) events among carriers of reduced-function CYP2C19 genetic variants treated with clopidogrel for acute coronary syndrome (ACS)? The Affordable Care Act and the Future of Clinical Medicine: The Opportunities and Challenges Kocher R, Emanuel EJ, DeParle NM. Ann Intern Med 2010;153:536-539. Perspective: The Affordable Care Act guarantees access to health care for all Americans, creates new incentives to change clinical practice to foster better coordination and quality, gives physicians more information to make them better clinicians and patients more information to make them better consumers, and changes the payment system to reward value. Multimarker Approach for the Prediction of Heart Failure Incidence in the Community Velagaleti RS, Gona P, Larson MG, et al. Circulation 2010;122:1700-1706. Study Question: What is the incremental value of a multiple set of biomarkers (reflecting pathways implicated in heart failure [HF]) for predicting HF risk in the community? Frequency of Major Noncardiac Surgery and Subsequent Adverse Events in the Year After Drug-Eluting Stent Placement: Results From the EVENT (Evaluation of Drug-Eluting Stents and Ischemic Events) Registry Berger PB, Kleiman NS, Pencina MJ, et al., on behalf of the EVENT Investigators. JACC Cardiovasc Interv 2010;3:920-927. Study Question: What is the frequency of major surgery and of subsequent major adverse events in patients treated with drug-eluting stents (DES)? Lipoprotein(a) as a Cardiovascular Risk Factor: Current Status Nordestgaard BG, Chapman MJ, Ray K, et al., on behalf of the European Atherosclerosis Society Consensus Panel. Eur Heart J 2010;Oct 21:[Epub ahead of print]. Perspective: The European Atherosclerosis Society (EAS) critically evaluated lipoprotein(a) [Lp(a)] as a cardiovascular risk factor.
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#453
05.11.2010, 18:20
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Journal Scan Summary Title: Selective Vitamin D Receptor Activation With Paricalcitol for Reduction of Albuminuria in Patients With Type 2 Diabetes (VITAL Study): A Randomized Controlled Trial
Date Posted: November 3, 2010 Authors: de Zeeuw D, Agarwal R, Amdahl M, et al. Citation: Lancet 2010;Nov 3:[Epub ahead of print]. Study Question: What is the effect of paricalcitol on albuminuria in patients with diabetic nephropathy? Methods: In this multinational, placebo-controlled, double-blind trial, the investigators enrolled patients with type 2 diabetes and albuminuria who were receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). Patients were assigned (1:1:1) by computer-generated randomization sequence to receive 24 weeks’ treatment with placebo, 1 µg/day paricalcitol, or 2 µg/day paricalcitol. The primary endpoint was the percentage change in geometric mean urinary albumin-to-creatinine ratio (UACR) from baseline to last measurement during treatment for the combined paricalcitol groups versus the placebo group. Analysis was by intention to treat. Results: Between February 2007 and October 2008, 281 patients were enrolled and assigned to receive placebo (n = 93), 1 µg paricalcitol (n = 93), or 2 µg paricalcitol (n = 95); 88 patients on placebo, 92 on 1 µg paricalcitol, and 92 on 2 µg paricalcitol received at least one dose of study drug, and had UACR data at baseline and at least one time point during treatment, and thus were included in the primary analysis. Change in UACR was: –3% (from 61 to 60 mg/mmol; 95% confidence interval [CI], –16 to 13) in the placebo group; –16% (from 62 to 51 mg/mmol; –24 to –9) in the combined paricalcitol groups, with a between-group difference versus placebo of –15% (95% CI –28 to 1; p = 0.071); –14% (from 63 to 54 mg/mmol; –24 to –1) in the 1 µg paricalcitol group, with a between-group difference versus placebo of –11% (95% CI –27 to 8; p = 0.23); and –20% (from 61 to 49 mg/mmol; –30 to –8) in the 2 µg paricalcitol group, with a between-group difference versus placebo of –18% (95% CI, –32 to 0; p = 0.053). Patients on 2 µg paricalcitol showed an early, sustained reduction in UACR, ranging from –18% to –28% (p = 0.014 vs. placebo). Incidence of hypercalcemia, adverse events, and serious adverse events was similar between groups receiving paricalcitol versus placebo. Conclusions: The authors concluded that the addition of 2 µg/day paricalcitol to renin–angiotensin–aldosterone system (RAAS) inhibition safely lowers residual albuminuria in patients with diabetic nephropathy. Perspective: The study demonstrates that 24 weeks’ treatment with 2 µg paricalcitol daily reduced residual albuminuria in patients with type 2 diabetic nephropathy who were on stable doses of ACE inhibitors or ARBs, particularly in those with high dietary sodium intake. Given that existing drug strategies have substantial limitations and have not been very successful in preventing kidney failure, paricalcitol could be an important adjunctive treatment, providing optimum management of renal osteodystrophy, with little hypercalcemia, and lowering residual albuminuria. Additional studies of paricalcitol with hard renal outcomes are indicated to definitively prove its renal and cardiovascular protective effects.
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#454
10.11.2010, 10:54
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Clopidogrel unaffected by CYP2C19 loss-of-function alleles in patients with ACS, AF
Paré G. N Engl J Med. 2010;363:1704-1714. Data from two large, randomized trials have suggested that the effect of clopidogrel when compared with placebo remained consistent regardless of CYP2C19 loss-of-function allele status for patients with acute coronary syndromes or atrial fibrillation. “Recent reports suggest that certain common genetic variants, involving the hepatic cytochrome P450 system, that are involved in the conversion of clopidogrel to its active metabolite are associated with an increased rate of recurrent CV events, implying that the benefits of clopidogrel may be attenuated in patients with these genetic variants,” study researcher Guillaume Paré, MD, and colleagues wrote. “Specifically, in patients who are carriers of a loss-of-function CYP2C19 allele (including the *2 and *3 alleles), the conversion of clopidogrel to its active metabolite may be reduced, resulting in decreased inhibition of platelets.” Researchers tested this hypothesis by examining the efficacy and safety of clopidogrel vs. placebo according to genotype status (CYP2C19*2, *3 or *17) among patients in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE A) randomized trials. The study population included patients with ACS (n=5,059) and AF (n=1,156), and the primary efficacy endpoint was defined as the rate of CV events. Among patients with ACS, researchers reported a significant reduction in CV events in the clopidogrel arm when compared with placebo (9.1% vs. 12.6%; clopidogrel HR=0.71; 95% CI, 0.60-0.84). The effect of clopidogrel vs. placebo was similar in reducing the primary efficacy between carriers of loss-of-function alleles (*2 and *3) and noncarriers (P=.84); however, gain-of-function (*17) carriers derived more benefit from clopidogrel treatment as compared with placebo than noncarriers (P=.02). In the AF group, a hazard reduction was reported in the primary endpoint for patients with AF given clopidogrel (20% vs. 26.3%; HR=0.74; 95% CI, 0.58-0.94). Researchers reported no evidence of an interaction with either efficacy or bleeding between the study treatment and the metabolizer phenotype, loss-of-function carrier status or gain-of-function carrier status. “Our study shows that CYP2C19 loss-of-function variants do not modify the efficacy and safety of clopidogrel. Therefore, loss-of-function allele carrier status should not preclude the use of clopidogrel at currently recommended doses in patients with ACS whose condition is being managed conservatively,” Paré and colleagues wrote. “Although similar results were observed in patients with AF, larger studies will be needed to definitively rule out a genetic effect of the loss-of-function alleles in this patient population.”
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#455
10.11.2010, 13:41
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Expert consensus document offers suggestions on concomitant PPI, antiplatelet drug use
Abraham N. J Am Coll Cardiol. 2010;doi:10.1016/j.jacc.2010.09.010. The American College of Cardiology, American College of Gastroenterology and the American Heart Association have jointly released an expert consensus document supporting an individualized approach to determine whether concomitant use of proton pump inhibitors and thienopyridines is appropriate in patients with acute coronary syndromes. “The magnitude of [antiplatelet drug] benefits and risks in individual patients varies depending on their characteristics,” Neena S. Abraham, MD, chair of the document’s writing committee, and fellow colleagues wrote. “The challenge for health care providers is to determine the risk/benefit balance for individual patients or subsets of the target population.” Among the evidence presented in the consensus document included data from pharmacokinetic and pharmacodynamic studies, which suggested that concomitant use of a proton pump inhibitor (PPI) and clopidogrel reduces the antiplatelet effects of clopidogrel. Other observational studies and a single randomized clinical trial, the investigators said, have shown inconsistent effects on CV outcome when thienopyridines are taken with PPIs. In the latter case, however, “a clinically important interaction cannot be excluded, particularly in certain subgroups, such as poor metabolizers of clopidogrel,” they wrote. “Clinical decisions regarding concomitant use of PPIs and thienopyridines must balance overall risks and benefits, considering both CV and gastrointestinal complications.” According to the document, factors that raise the risk for gastrointestinal bleeding with antiplatelet therapy and that should guide suggestions of concomitant use of PPIs include advanced age, Helicobacter pylori infection and concomitant use of warfarin, steroids or NSAIDs. However, PPI use was not recommended for patients at lower risk for upper gastrointestinal bleeding or who have much less potential to benefit from prophylactic therapy. For physicians assessing the clinical interaction between PPIs and thienopyridines, the investigators said to keep four considerations in mind: the strength of the association, which in observational studies was small to moderate (HR<2); the consistency of the association across different samples; the existence of a biologically plausible mechanism of action, such as the vitro testing, which suggests that PPIs may inhibit CYP2C19 metabolism, a factor shown to increase CV event rate; and the supportive experimental evidence, including pharmacodynamic studies. The investigators said addressing the many gaps in knowledge that still remain involving gastrointestinal bleeding in patients prescribed thienopyridines are areas for future research. “There is considerable variation among patients in response to antiplatelet therapy, so the potential role of laboratory testing in individualization of therapy should be a high priority for research,” Abraham and colleagues wrote. “Either pharmacogenomic testing for CYP2C19 variants or platelet function testing might be used to tailor therapy by guiding the choice of drug (thienopyridines, PPIs, H2 receptor antagonists), the choice of drug dose or both.” Although the concept of individually tailored therapy is rational and attractive, they said, empirical evidence for this approach is sparse, necessitating clinical studies and randomized trials comparing guided therapy with usual care. __________________________________________________ ___________________________ Intervention program reduced fall rate in hospitals Dykes P. JAMA. 2010;304:1912-1918. Hospital units that used a fall prevention tool kit experienced fewer patient falls than units that did not use the tool kits, according to researchers from the Partners HealthCare System in Boston. “Fall risk assessment and health information technology have been underused in fall prevention efforts,” the researchers wrote. “Fall risk assessment provides a baseline measure of risk status to guide interventions to counteract identified risks. Currently, insufficient evidence exists to link specific fall prevention protocols with decreased fall rates in short-stay hospitals.” The researchers developed a fall prevention tool kit with a fall risk assessment scale using health information technology. After the assessment was completed by a nurse, the tool kit software developed fall prevention intervention materials, including posters, patient education handouts and plans of care. The study took place in four urban hospitals from Jan. 1, 2009, to June 30, 2009, and the fall rates in usual units (control) and intervention units were compared. The primary outcome was the number of patient falls per 1,000 patient-days. Fall-related injuries were a secondary outcome. In the control units, there were 87 falls, and in the intervention units, there were 67 falls. The fall rate for the control unit was 4.18 per 1,000 patient-days, which was significantly higher than the 3.15 per 1,000 patient-days fall rate in the intervention unit. They also found that the patients aged 65 and older benefited most from the intervention. There was no significant effect on fall-related injuries. “A health information technology intervention targeting underlying areas of risk can prevent patient falls in older patients in acute care hospitals,” the researchers concluded. “Further study is needed to determine if a similar program evaluated over a longer period of time can significantly reduce repeat falls.”
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#456
10.11.2010, 13:51
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Most Americans concerned about Medicare payment cut
As medical groups urge Congress to stop a scheduled 25% Medicare physician payment cut, an American Medical Association poll released yesterday shows that 94% of Americans think that the looming cut is a serious problem. The results of the online poll of 1,000 Americans aged 18 years or older conducted 2 weeks ago also revealed that 98% of respondents older than 65 years said that the anticipated drop in Medicare physician reimbursement was a “serious problem,” and 95% of seniors polled said that Congress should immediately act to fix this situation. In addition, 81% of the total respondents supported quick Congressional action. Wilson said that the AMA hopes that the poll results will be eye-opening for elected officials and called for them to “stop playing politics and put the health care needs of America’s seniors first.” The medical group is running a new ad about the cuts in USA Today and other publications in the Washington, D.C. area. The ad features groups who will be hurt by the cut including seniors, veterans and active duty military members and urges the public to contact members of Congress about the issue. “Congress needs to put an end to this rollercoaster ride physicians and seniors have been on this year and stop the cut for at least 13 months,” he said. “This will shore up physician confidence in the program.” The price of inaction Wilson called Medicare an “unreliable payor” and highlighted a recent AMA poll which found that one in five physicians are limiting their care of Medicare patients due to low payment rates and the threat of future cuts. He also noted that the cut comes at a time when physicians can choose to opt-out of Medicare. “Clearly, physicians are grappling with a difficult decision,” Wilson said. “Can they continue to take care of Medicare patients if Congress allows a 25% Medicare cut to go through? Congress needs to act by Thanksgiving so that seniors are not left paying the price for congressional inaction. The AMA is urging Congress to stop the cut for at least 13 months and then use that time to fix the problem once and for all. America’s seniors deserve nothing less.”
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#457
10.11.2010, 13:52
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A completed paradigm shift for VADS in advanced HF: The INTERMACS registry at 5 years
by James B. Young, MD A paradigm is an example or pattern, and as Thomas Kuhn noted in his 1962 text, The Structure of Scientific Revolutions, “… once a paradigm shift is complete, a scientist cannot, for example, posit the possibility that a miasma causes disease or that ether carries light.” A paradigm shift, then, is an “extraordinary” or “revolutionary” new science. It is rare to witness a significant paradigm shift in medicine, particularly one that occurs so rapidly and carries with it substantial long-term implications, but the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) has done just that. INTERMACS has just completed its first 5-year funding cycle from the NIH and is the largest multicenter scientific compendium of FDA-approved long-term circulatory assist devices implanted in patients with advanced HF. It has been under the capable leadership at the University of Alabama, Birmingham, with its extraordinary team in the INTERMACS Data Coordinating Center. Lynne Warner Stevenson, MD, of Brigham and Women’s Hospital, Harvard Medical School, and Robert Kormos, MD, of the University of Pittsburgh, are co-principal investigators. INTERMACS was created to gain insight into what has recently been a rapidly advancing field. Indeed, it was just more than a half century ago that Kolf, for the first time, successfully kept a dog alive with an implanted total artificial heart. In 1966, DeBakey successfully “bridged” a patient to “recovery” with a pulsatile, pneumatic, paracorporeal left ventricular assist device manufactured in his surgical laboratory. Cooley, a few years later, became the first to use these types of devices as a “bridge to heart transplantation.” Progress in this remarkable field was stuttering at best, however, until more widespread reports of successes using these pumps came available in the 1990s. Today, use of mechanical circulatory support devices has become common. Indeed, it is a daily event in CV surgery centers when one counts rudimentary cardiopulmonary bypass machines necessary for stopped or arrested open-heart operations. Longer-term and more “complete” implantation of these devices has achieved dramatic recent milestones. As exciting as these innovative machines are, they can at times cause significant morbidity and even mortality, particularly in the severely ill, the cachectic and elderly patients who have non-cardiac comorbidities, besides terminal HF. In the now close-eyed accounting of health care resources, the justification for this new technology must include proof of extension not only of survival, but also of improved quality of that survival. Because of the challenges of studying mechanical circulatory support device (MCSD) implantation in large-scale randomized clinical trials, a practical option for obtaining representative results is the large-scale clinical registry. Most registries, however, have been sponsored by industries interested in the application of and outcomes for a single product line (with incentives that can influence how the data are collected, defined and managed). Thus, registries have often been deservedly criticized for not being sufficiently rigorous to adequately collect and evaluate clinical data. INTERMACS was carefully designed and implemented to obviate many of these problems and present data in an impartial and appropriately analyzed fashion. Another unique aspect of INTERMACS is the tri-partite nature of the program, with the FDA and CMS partnering with the NIH to offer different perspectives about the data. INTERMACS patient profiles Besides determining what endpoints were important to study, designing the Web-based data collection templates, and defining (as well as standardizing) adverse events, an early task was to develop a patient descriptor that had not been previously utilized but that would also better characterize the patient population being studied. A descriptive categorization (or “profile”) of patients was developed, rather than a progressive staging system such as the NYHA functional classification. The INTERMACS patient profiles include seven categorizations, with five of them characterizing patients who are clearly NYHA Class IV. These profiles create a far better description of patients than simply referring to one as “American College of Cardiology (ACC)/American Heart Association (AHA) Stage D, NYHA Class IV despite optimal medical therapy.” The INTERMACS profiles incorporate both the severity of symptoms and the trajectory of decline over time. They also include commonly used jargon. Profile 1 describes a “critical cardiogenic shock” patient who is “crashing and burning,” in which a patient has life-threatening hypotension and rapid escalating IV inotropic support. Profile 2 describes “progressive decline” or “sliding fast on inotropes,” and is a patient who has been documented “dependent” on IV inotropic agents but who nonetheless shows signs of continuous deterioration. Profile 3, “stable but inotrope-dependent,” describes a patient who is clinically stable on mild-moderate doses of an IV inotrope (or has temporary MCSD) and has had repeated attempts at weaning with documented failures. Profile 4 is a patient with “resting symptoms” who can remain at home on oral therapy, but who has symptoms of congestion at rest or with minimal activities of daily living. Profile 5, which describes a patient as “exertion-intolerant” and “housebound,” is someone comfortable at rest but unable to engage in any meaningful activity (who is consequently largely confined to their home). Profile 6, known as “exertion-limited” or “walking wounded,” describes a patient comfortable at rest without evidence of fluid overload who is able to do some activity. Profile 7 characterizes “advanced NYHA III” patients who are clinically stable with a reasonable level of comfortable activity, despite a history of previous congestion that is not recent. Slow but steady patient accrual Currently, there are 109 centers actively participating INTERMACS and almost 3,500 patients logged into the registry. It should be noted that for centers to comply with CMS and to be reimbursed when a device is placed as a “destination home-permanent” therapy, they must be a participant in good standing with INTERMACS and report their data responsibly. An early analysis of INTERMACS revealed a slow but steady patient accrual that significantly increased when the HeartMate II (Thoratec) continuous flow device was approved by the FDA mid-year 2008 as a bridge to cardiac transplantation. This rather dramatic change in the number of patients undergoing MCSD implantation appeared constant and was likely driven by the fact that the newer device was a dramatic improvement over previous pulsatile MCSD choices. This was the beginning of the paradigm shift. Whereas most funding, development efforts and patient experience had previously focused on pulsatile devices, the science (and then clinical approach) to the patient changed. Outcomes after MCSD implantation INTERMACS demonstrates that survival after MCSD insertion using contemporary pumps is reasonable and steadily improving with incremental advances in the devices. As one may expect, improved outcomes were noted with intracorporeal continuous flow systems that were used as an LVAD. One competing outcomes analysis demonstrated that at 6-months follow-up, the likelihood of survival or heart transplant was higher with continuous flow devices than with pulsatile machines (88% vs. 80%). Still unknown is whether this difference will hold up with longer-term follow-up. Another important observation that can be made is that removal of these devices due to “adequate recovery of myocardial function” that is believed adequate enough to handle the entire burden of circulatory demand (also called “bridge-to-recovery”) is rare, occurring in about 1% of patients. This observation emphasizes that the concept still needs tremendous work to clarify, if there is any reality to the concept to begin with. Not surprising is the fact that there appears to be a significant difference in the outcomes of patients based on entrance profile when overall survival is analyzed. Profile 1 patients (the “crash and burning” group with critical cardiogenic shock) have higher mortality than the stable patient defined simply as “inotrope-dependent,” or Profile 3. This is an important observation and suggests that, if possible, it is likely best to move earlier on some patients rather than waiting until they are in dire straits. Summary INTERMACS is an example of a successful NIH-funded, interagency-supported registry that has chronicled, analyzed and contributed to the clinical, scientific and academic medical niche of mechanical circulatory assistance for deathly ill patients with advanced HF. Particularly important is the fact that INTERMACS has documented a shift in the approach to these patients with overwhelming use of continuous flow mechanical circulatory support systems occurring today. With the recent NIH request for proposals for a 5-year extension of the registry contract, even more data and knowledge will accrue that may drive more paradigm shifts in the future. The public can explore the nuances of this registry further by reviewing the INTERMACS website here.
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#458
11.11.2010, 21:29
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Light-to-Moderate Alcohol Consumption and Risk of Sudden Cardiac Death in Women
Chiuve SE, Rimm EB, Mukamal KJ, et al. Heart Rhythm 2010;7:1374-1380. Study Question: Does alcohol consumption affect the risk of sudden cardiac death (SCD) in women? Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation Freeman JV, Zhu RP, Owens DK, et al. Ann Intern Med 2010;Nov 1:[Epub ahead of print]. Study Question: Is dabigatran cost-effective relative to warfarin for stroke prevention in patients with atrial fibrillation (AF) and risk factors for stroke? Antithrombotic Therapy in the Elderly Capodanno D, Angiolillo DJ. J Am Coll Cardiol 2010;56:1683-1692. Study Question: What are the benefits and risks of antithrombotic therapy in the elderly? Safety and Efficacy of Pulmonary Vein Antral Isolation in Patients With Obstructive Sleep Apnea: The Impact of Continuous Positive Airway Pressure Patel D, Mohanty P, Di Biase LD, et al. Circ Arrhythm Electrophysiol 2010;3:445-451. Study Question: What is the relationship between obstructive sleep apnea (OSA) and outcomes of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF)? Bundle-Branch Block Morphology and Other Predictors of Outcome After Cardiac Resynchronization Therapy in Medicare Patients Bilchick KC, Kamath S, Dimarco JP, Stukenborg GJ. Circulation 2010;122:2022-2030. Study Question: What are the strongest predictors of outcomes with cardiac resynchronization therapy (CRT)? Remote-Controlled Magnetic Pulmonary Vein Isolation Using a New Irrigated-Tip Catheter in Patients With Atrial Fibrillation Chun KR, Wissner E, Koektuerk B, et al. Circ Arrhythm Electrophysiol 2010;3:458-464. Study Question: How effectively is pulmonary vein (PV) isolation achieved with an irrigated-tip ablation catheter controlled by remote magnetic navigation (RMN)? Association Between Implementation of a Medical Team Training Program and Surgical Mortality Neily J, Mills PD, Young-Xu Y, et al. JAMA 2010;304:1693-1700. Study Question: Is there an association between Veterans Health Administration (VHA) medical team training and surgical outcomes? In Situ Pericardial Extracardiac Lateral Tunnel Fontan Operation: Fifteen-Year Experience Hasaniya NW, Razzouk AJ, Mulla NF, Larsen RL, Bailey LL. J Thorac Cardiovasc Surg 2010;140:1076-1083. Study Question: What is the short- and long-term outcome of an in situ pericardial extracardiac lateral tunnel Fontan operation? Persistent Risk of Subsequent Procedures and Mortality in Patients After Interrupted Aortic Arch Repair: A Congenital Heart Surgeons’ Society Study Jegatheeswaran A, McCrindle BW, Blackstone EH, et al. J Thorac Cardiovasc Surg 2010;140:1059-1075. Study Question: What are the patterns and factors associated with subsequent procedures in patients who have previously undergone repair of interrupted aortic arch (IAA)? Selective Vitamin D Receptor Activation With Paricalcitol for Reduction of Albuminuria in Patients With Type 2 Diabetes (VITAL Study): A Randomized Controlled Trial de Zeeuw D, Agarwal R, Amdahl M, et al. Lancet 2010;Nov 3:[Epub ahead of print]. Study Question: What is the effect of paricalcitol on albuminuria in patients with diabetic nephropathy? ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines: A Focused Update of the ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use Abraham NS, Hlatky MA, Antman EM, et al. J Am Coll Cardiol 2010;Nov 8:[Epub ahead of print]. Perspective: The following are 10 points to remember about this expert consensus document. ACCF/AHA New Insights Into the Methodology of Performance Measurement: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Performance Measures Spertus JA, Bonow RO, Chan P, et al. J Am Coll Cardiol 2010;56:1767-1782. Perspective: The following are 10 points to remember about performance measurement.
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#459
11.11.2010, 22:12
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INR self-testing associated with improved quality of life for patients on warfarin vs. clinic testing
Matchar D. N Engl J Med. 2010;363:1608-1620. Weekly self-testing of the international normalized ratio for patients on warfarin did not delay the time to a first stroke, major bleeding episode or death when compared with high-quality clinic testing to the extent suggested by prior studies, new data from the THINRS trial indicated. However, statistically significant improvements in patient satisfaction and quality of life for self-testing were reported by researchers. In the prospective, randomized, nonblinded trial, 2,922 patients taking warfarin (Coumadin, Bristol-Myers Squibb) were randomly assigned to either self-testing (n=1,465) or high-quality testing of INR in a clinic (n=1,457). The primary endpoint was the time to a first major event — stroke, major bleeding episode or death — and the secondary endpoints were time within the INR target range, patient satisfaction and quality of life. During 8,730 patient-years of follow-up (time range, 2-4.75 years), study data revealed no significantly longer time to the first primary event in the self-testing group than in the clinic-testing group (self-testing HR= 0.88; 95% CI, 0.75-1.04). Clinical outcomes were similar between arms, with the exception of more minor bleeding episodes in the self-testing group (540 vs. 401, P<.001). At 2 years, the self-testing arm showed improvements in patient satisfaction (P=.002) and quality of life (P<.001) with anticoagulation therapy vs. the clinic-testing arm, whereas during the entire follow-up, an improvement in the percentage of time INR was within target range was also noted in the self-testing group (P<.001). “The results of THINRS do not establish the superiority of self-testing over high-quality clinic testing in preventing major clinical outcomes but do provide evidence of modest improvements in time within the therapeutic INR range, patient satisfaction with anticoagulation therapy and quality of life,” the researchers concluded. Based on the findings of this study, they added, self-testing should be considered for patients whose access to high-quality anticoagulation care is limited by disability, geographic distance or other factors, if the alternative would be to withhold a highly effective treatment. __________________________________________________ _____________________ TRACS: Differing blood transfusion strategies yield similar complication, death rates in cardiac surgery patients Hajjar L. JAMA. 2010;304:1559-1567. A liberal strategy for initiating perioperative blood transfusions resulted in statistically similar clinical complication and mortality rates compared with a more restrictive strategy, results from a study indicated. Regardless of treatment strategy, blood transfusions were associated with higher death and complication rates. Some researchers have suggested the use of perioperative transfusion for the maintenance of hemoglobin levels of 10 g/dL and 30% hematocrit concentrations, according to the study. Other researchers have recently questioned these thresholds, however, as the risks of transfusion and the highly individualized nature of a patient’s response to anemia have become better understood. A prior study of critically ill patients found that maintaining hemoglobin concentrations between 7 and 9 g/dL may result in fewer patient deaths than a more liberal strategy of sustaining hemoglobin between 10 and 12 g/dL. Ludhmila A. Hajjar, MD, PhD, and colleagues compared similar strategies in 502 patients undergoing elective cardiac surgery with cardiopulmonary bypass at a cardiac surgery referral center in Brazil. Before surgery, patients were randomly assigned in a prospective fashion to two groups. Patients in the restrictive group received red blood cell transfusions if their hematocrit values were less than 24% at any point from the start of surgery until discharge from the ICU. For patients in the liberal group, the transfusion trigger was hematocrit levels of less than 30%. Significantly more patients in the liberal group received red blood cell transfusions. In this group, 198 of 253 patients (78%) received a transfusion, compared with 118 of 249 (47%) patients in the restrictive group (P<.001). Average hemoglobin concentrations were kept at 10.5 g/dL (95% CI, 10.4-10.6) in the liberal group vs. 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive group (P<.001). The researchers defined their composite endpoint as 30-day all-cause mortality and severe morbidity, including acute respiratory distress syndrome, cardiogenic shock or acute renal injury requiring dialysis or hemofiltration. In the liberal group, 10% of patients reached the endpoint vs. 11% of patients in the restrictive group (95% CI, –6% to 4%). There were no significant differences in cardiac complications, neurologic complications, infection or severe bleeding requiring reoperation. In their conclusion, the researchers posited that the reported similarity in complication rates “occurred because the restrictive strategy did not result in reduced oxygen availability to the cells. This is supported by the lack of difference in lactate levels between the two groups during the study period” Although neither transfusion strategy was associated with greater risk, the total number of transfused red blood cell units was an independent risk factor for complications or death at 30 days (HR for each additional unit transfused, 1.2; 95% CI, 1.1-1.4). “These findings suggest that the primary strategy in patients undergoing cardiac surgery should be to avoid giving [red blood cell] transfusion solely to correct low hemoglobin levels. The increased risk of mortality related to the number of transfused [red blood cell] units supports a restrictive therapy in cardiac surgery,” the researchers wrote. “In addition, clinicians caring for patients after cardiac surgery should administer only one [red blood cell] unit at a time because this may result in less exposure to risks but similar benefits.”
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#460
16.11.2010, 13:33
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Title: 2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults: Executive Summary: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Date Posted: November 15, 2010 Authors: Greenland P, Alpert JS, Beller GA, et al. Citation: J Am Coll Cardiol 2010;Nov 15:[Epub ahead of print]. Perspective: The following are 10 points to remember about the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults: 1. The ACCF/AHA practice guidelines are intended to assist health care providers in clinical decision making by describing a range of generally acceptable approaches to the diagnosis, management, and prevention of specific diseases or conditions. 2. For any new risk marker to be considered a useful candidate for risk prediction, it must, at the very least, have an independent statistical association with risk after accounting for established readily available and inexpensive risk markers. It should be based on studies that include large numbers of outcome events and with rigorous assessments that include analysis of the calibration, discrimination, and reclassification of the predictive model. 3. Global risk scores (e.g., Framingham or Reynold’s) and family history of atherothrombotic disease should be assessed in all asymptomatic adults. 4. In the absence of inflammatory disorders, C-reactive protein may be useful in men 50 years and women 60 years and older with a low-density lipoprotein cholesterol <130 mg/dl to decide on statin therapy, and those at intermediate risk to further risk stratify. Lipoprotein-associated phospholipase A2 may be useful in intermediate-risk persons. 5. Measurement of glycated hemoglobin may be used in asymptomatic adults without diabetes. Testing for microalbuminuria is reasonable for cardiovascular risk assessment in intermediate-risk and hypertensive and diabetic adults. 6. Echocardiography may be considered to assess for left ventricular hypertrophy in asymptomatic adults with hypertension. A resting electrocardiogram (ECG) can be recommended in adults with hypertension or diabetes, and an exercise ECG may be considered in intermediate-risk asymptomatic adults, particularly in sedentary persons planning to embark on an exercise program. 7. Measurement of coronary artery calcium (CAC) and carotid intima-media thickness may be useful in adults at intermediate risk (10-20%), and CAC can also be helpful in low- to intermediate-risk (6-10%) men and women and diabetics over 40 years old. 8. Stress myocardial perfusion imaging (MPI) may be considered for advanced cardiovascular risk assessment in asymptomatic adults with diabetes, with a strong family history of coronary heart disease, and when other testing suggests high risk, such as a CAC score 400 or greater. 9. There is no evidence in support of the following: measurement of lipoproteins, apolipoproteins, particle size and density; genomic testing; CAC score in very low-risk persons; coronary computed tomography angiography or magnetic resonance imaging of plaque for risk assessment; or stress echo or stress MPI in low- or intermediate-risk asymptomatic adults. 10. Each of the recommendations is weighted based upon the evidence and expert opinion, for which there is always room for disagreement. The 2010 guideline for cardiovascular risk assessment should satisfy the majority of clinical cardiologists and clinicians.
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#461
16.11.2010, 13:43
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Trial Summary
ROCKET AF Title: Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation Trial Sponsor: Johnson & Johnson, Bayer HealthCare Year Presented: 2010 Topic(s): Arrhythmias, Prevention/Vascular Summary Posted: 11/15/2010 Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C. Author Disclosure: NOTHING TO DISCLOSE Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C. Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca(SIGNIFICANT), Eisai(SIGNIFICANT), Sanofi Aventis(SIGNIFICANT), The Medicines Company(SIGNIFICANT), Ethicon(SIGNIFICANT), Bristol Myers Squibb(SIGNIFICANT), Heartscape(SIGNIFICANT), Cogentus(NONE), PLx Pharma(NONE), Takeda(NONE) Description: The goal of the trial was to evaluate treatment with the direct factor Xa inhibitor rivaroxaban compared with warfarin among patients with atrial fibrillation (AF). Hypothesis: Rivaroxaban will be noninferior to warfarin in preventing stroke and embolism. Drugs/Procedures Used: Patients with AF at increased risk for stroke were randomized to rivaroxaban 20 mg oral daily (n = 7,131) versus warfarin with target international normalized ratio (INR) 2-3 (n = 7,133). Principal Findings: Overall, 14,171 patients were randomized. In the rivaroxaban group, the mean age was 73 years, 40% were women, mean CHADS2 score was 3.5, 40% had diabetes, and 55% had prior stroke, transient ischemic attack (TIA), or systemic embolism. The primary outcome per 100 patient-years, stroke, or non‒central nervous system systemic embolism occurred in 1.7 of the rivaroxaban group versus 2.2 of the warfarin group (p for noninferiority < 0.001, p for superiority by intention to treat 0.12). By on-treatment analysis, rivaroxaban was superior to warfarin (p = 0.015). By on-treatment analysis, vascular death, stroke, or embolism per 100 patient-years occurred in 3.1 versus 3.6 (p = 0.034), non‒central nervous system embolism occurred in 0.04 versus 0.2 (p = 0.003), myocardial infarction occurred in 0.9 versus 1.1 (p = 0.12), and all-cause mortality occurred in 1.9 versus 2.2 (p = 0.07), respectively, for rivaroxaban versus warfarin. Major and nonmajor clinically relevant bleeding per 100 patient-years occurred in 14.9 versus 14.5 (p = 0.44), intracranial hemorrhage occurred in 0.5 versus 0.7 (p = 0.019), study drug discontinuation occurred in 16% versus 15%, and any serious adverse event occurred in 37% versus 38%, respectively. Interpretation: Among patients with AF and increased risk for stroke, the use of the direct Xa inhibitor rivaroxaban was noninferior to warfarin. Rivaroxaban (on-treatment analysis) was associated with reduced incidence of the primary outcome without an excess of major bleeding or serious adverse events. In addition to rivaroxaban, an alternative to warfarin for AF patients includes the direct thrombin inhibitor dabigatran studied in the RE-LY trial. The signal for increased myocardial infarction observed with dabigatran was not seen with rivaroxaban. Study Design: Blinded. Parallel. Randomized. Primary Endpoints: Stroke or non‒central nervous system systemic embolism Secondary Endpoints: Major or nonmajor clinically relevant bleeding Patient Population: Patients with AF and history of stroke, TIA, or systemic embolism Patients without stroke, TIA, or systemic embolism were eligible if they had at least two additional risk factors for stroke, defined as congestive heart failure, hypertension, age ≥75 years, or diabetes Number of enrollees: 14,171 Duration of follow-up: 2.6 years Mean patient age: 73 years Percentage female: 40% References: Presented by Dr. Kenneth Mahaffey at the American Heart Association Scientific Sessions, Chicago, IL, November 15, 2010.
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#462
16.11.2010, 14:21
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Trial Summary Omega-3 Fatty Acids for the Prevention of Recurrent Atrial Fibrillation Title: Omega-3 Fatty Acids for the Prevention of Recurrent Atrial Fibrillation
Trial Sponsor: Reliant Pharmaceuticals Year Presented: 2010 Year Published: 2010 Topic(s): Arrhythmias, General Cardiology, Prevention/Vascular Summary Posted: 11/15/2010 Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C. Author Disclosure: NOTHING TO DISCLOSE Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C. Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca(SIGNIFICANT), Eisai(SIGNIFICANT), Sanofi Aventis(SIGNIFICANT), The Medicines Company(SIGNIFICANT), Ethicon(SIGNIFICANT), Bristol Myers Squibb(SIGNIFICANT), Heartscape(SIGNIFICANT), Cogentus(NONE), PLx Pharma(NONE), Takeda(NONE) Description: The goal of the trial was to evaluate treatment with prescription omega-3 fatty acids compared with placebo among patients with symptomatic paroxysmal or persistent atrial fibrillation (AF). Hypothesis: Prescription omega-3 fatty acids will be more effective in preventing recurrence of AF. Drugs/Procedures Used: Patients with symptomatic paroxysmal or persistent AF were randomized to prescription omega-3 fatty acids: 8 g daily for the first week, then 4 g daily (n = 332) versus placebo (n = 331). Concomitant Medications: At baseline, 39% of participants were receiving an angiotensin-converting enzymeinhibitor/angiotensin-receptor blocker, and 45% were receiving a statin. Principal Findings: Overall, 663 patients were randomized. The mean age of participants was 61 years, 44% were women, mean body mass index was 31 kg/m2, and paroxysmal AF was present in 82%. The primary outcome, first recurrence of symptomatic AF/flutter in patients with paroxysmal AF occurred in 52% of the omega-3 group versus 48% of the placebo group (p = 0.26). The secondary outcome, first recurrence of symptomatic AF/flutter in patients with persistent AF occurred in 50% versus 33% (p = 0.09), and the first recurrence of symptomatic AF/flutter among all patients occurred in 52% versus 46% (p = 0.08), respectively. Eicosapentaenoic and docosahexaenoic acid blood levels were significantly higher in the omega-3 group versus the placebo group at 24 weeks (p < 0.001). Interpretation: Among patients with paroxysmal or persistent AF, treatment with omega-3 fatty acids was not effective in preventing symptomatic recurrence of AF. Prevention of AF remains a difficult clinical problem. The findings of this relatively large trial do not support the results of previous observational and smaller clinical trials. Study Design: Placebo Controlled. Blinded. Randomized. Parallel. Primary Endpoints: First symptomatic recurrence of AF in patients with paroxysmal AF Secondary Endpoints: First symptomatic recurrence of AF in patients with persistent AF Patient Population: Patients at least 18 years of age with symptomatic paroxysmal or persistent AF Number of enrollees: 663 Duration of follow-up: 6 months Mean patient age: 61 years Percentage female: 44% Exclusions: Permanent AF Secondary AF due to hypothyroidism or valvular heart disease Current use of antiarrhythmic therapy Use of amiodarone within the last 6 months Prior ablation therapy for AF Structural heart disease References: Kowey PR, Reiffel JA, Ellenbogen KA, Naccarelli GV, Pratt CM. Efficacy and safety of prescription omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: a randomized controlled trial. JAMA 2010;Nov 15:[Epub ahead of print]. Presented by Dr. Peter Kowey at the American Heart Association Scientific Sessions, Chicago, IL, November 15, 2010.
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#463
16.11.2010, 16:09
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Trial Summary SMART-AV
Title: SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy Trial Sponsor: Boston Scientific Year Presented: 2010 Year Published: 2010 Topic(s): General Cardiology, Heart FailureTransplant, Noninvasive Cardiology, Prevention/Vascular Summary Posted: 11/15/2010 Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C. Author Disclosure: NOTHING TO DISCLOSE Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C. Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca(SIGNIFICANT), Eisai(SIGNIFICANT), Sanofi Aventis(SIGNIFICANT), The Medicines Company(SIGNIFICANT), Ethicon(SIGNIFICANT), Bristol Myers Squibb(SIGNIFICANT), Heartscape(SIGNIFICANT), Cogentus(NONE), PLx Pharma(NONE), Takeda(NONE) Description: The goal of the trial was to compare optimization of atrioventricular (AV) delay by echocardiography versus an electrocardiogram (ECG)-based algorithm (SmartDelay) versus a fixed interval of 120 ms among patients who received cardiac resynchronization therapy (CRT). Hypothesis: Optimization of the AV delay with an ECG-based algorithm will improve outcomes. Drugs/Procedures Used: Patients who met criteria for CRT were eligible to participate: New York Heart Association (NYHA) class III or IV despite optimal medical therapy, left ventricular ejection fraction (LVEF) ≤35%, and QRS duration ≥120 ms. One to 14 days after CRT implant (VVI-40-RV), patients were programmed to DDD(R) 60 and randomized to optimization of AV delay by echocardiography (n = 323) versus an ECG-based algorithm (n = 332) versus a fixed delay of 120 ms (n = 325). Concomitant Medications: At baseline, the use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers was 87%, beta-blockers 92%, and spironolactone 32%. Principal Findings: Overall, 980 patients were randomized. In the ECG-based algorithm group, the mean age was 66 years, 29% were women, mean ejection fraction was 25%, mean QRS duration was 152 ms, and proportion with ischemic cardiomyopathy was 57%. At 6 months, the median change in LV end-systolic volume (LVESV) at 6 months was -19 ml for the echo group, -21 ml for the ECG-based algorithm group, and -15 ml for the fixed delay group (p = 0.52 for ECG vs. echo and p = 0.66 for ECG vs. fixed delay). Female patients tended to respond more favorably to echo and ECG optimization of AV delay compared with fixed delay. The median change in LV end-diastolic volume (LVEDV) at 6 months was -16 ml for the echo group, -13 ml for the ECG-based algorithm group, and -12 ml for the fixed delay group (p = NS between all groups). The median change in LVEF was 6%, 6%, and 5.1%, respectively. Six-minute walk, quality of life, and NYHA classification were also similar between groups. There was no difference in heart failure-related adverse events between groups. Interpretation: Among patients who undergo CRT for symptomatic heart failure, optimization of AV delay with the use of echocardiography or an ECG-based algorithm did not improve LV geometry or other outcomes at 6 months compared with a fixed delay of 120 ms. At the present time, a fixed AV delay remains the recommended approach to optimization of CRT. The possible benefit observed among women would need to be prospectively tested. Study Design: Randomized. Parallel. Primary Endpoints: LVESV at 6 months Secondary Endpoints: LVEDV at 6 months LVEF Six-minute walk distance NYHA class Quality of life Patient Population: NYHA class III or IV LVEF ≤35% QRS ≥120 msec Sinus rhythm at the time of CRT implant Number of screened applicants: 1,060 Number of enrollees: 980 Duration of follow-up: 6 months Mean patient age: 66 years Percentage female: 29% Ejection fraction: 25% NYHA class: II-4%, III-92%, IV-4% Exclusions: Complete heart block or unable to tolerate pacing at VVI-40 for up to 14 days Previous CRT References: Ellenbogen KA, Gold MR, Meyer TE, et al. Primary Results From the SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) Trial: A Randomized Trial Comparing Empirical, Echocardiography-Guided, and Algorithmic Atrioventricular Delay Programming in Cardiac Resynchronization Therapy. Circulation 2010;Nov 15:[Epub ahead of print]. Presented by Dr. Kenneth Ellenbogen at the American Heart Association Scientific Sessions, Chicago, IL, November 15, 2010.
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#464
16.11.2010, 16:38
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Trial Summary CLOSURE I
Title: Safety and Efficacy of the STARFlex Septal Closure System vs. Best Medical Therapy in Patients With a Stroke or TIA due to Presumed Paradoxical Embolism Through a PFO Trial Sponsor: NMT Year Presented: 2010 Topic(s): Congenital Heart Disease, General Cardiology, Interventional Cardiology, Prevention/Vascular Summary Posted: 11/15/2010 Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C. Author Disclosure: NOTHING TO DISCLOSE Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C. Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca(SIGNIFICANT), Eisai(SIGNIFICANT), Sanofi Aventis(SIGNIFICANT), The Medicines Company(SIGNIFICANT), Ethicon(SIGNIFICANT), Bristol Myers Squibb(SIGNIFICANT), Heartscape(SIGNIFICANT), Cogentus(NONE), PLx Pharma(NONE), Takeda(NONE) Description: The goal of the trial was to evaluate percutaneous closure of a patent foramen ovale (PFO) compared with medical therapy among patients with a cryptogenic stroke or transient ischemic attack (TIA). Hypothesis: PFO closure will be more effective in reducing the risk of recurrent stroke/TIA. Drugs/Procedures Used: Patients with cryptogenic stroke or TIA presumably due to a PFO were randomized to PFO closure with the STARFlex device (n = 447) versus medical therapy (n = 462). Concomitant Medications: Patients who underwent PFO closure were treated with clopidogrel 75 mg daily for 6 months and aspirin 325 mg daily for 2 years. Patients who received medical therapy alone were treated with aspirin 325 mg daily, or warfarin with international normalized ratio (INR) target 2 to 3, or combination aspirin and warfarin. Principal Findings: Overall, 909 patients were randomized. In the STARFlex group, the mean age was 46 years, 48% were women, and 38% had an atrial septal aneurysm ≥10 mm. Procedural success was achieved in 90%, and 87% of participants had no or trace residual shunt by transesophageal echocardiography at 24 months. The primary outcome, recurrent stroke or TIA within 2 years, all-cause mortality within 30 days, or neurological mortality between 31 days and 2 years occurred in 5.9% of the PFO closure group versus 7.7% of the medical therapy group (p = 0.30). Within 2 years, the number of strokes that occurred was 12 versus 13 (p = 0.77), and the number of TIAs was 13 versus 17 (p = 0.39), respectively, for PFO closure versus medical therapy. There was no difference in the primary outcome based on degree of residual shunt or presence of an atrial septal aneurysm. Within the medical arm, there was no difference in the primary outcome for aspirin alone versus warfarin alone. Of the 12 strokes in the PFO closure group, three were procedure related, three were recurrent cryptogenic stroke, and six were due to an alternative etiology such as atrial fibrillation or a lacunar stroke. Of the 13 strokes in the medical group, one was due to recurrent cryptogenic stroke, whereas the rest were due to an alternative etiology such as atrial fibrillation, complex migraine, vasculitis, or lacunar stroke. Major vascular complications (left atrial perforation, groin hematoma, vascular surgical repair, peripheral nerve injury, procedure-related transfusion, and retroperitoneal bleed) occurred in 3.2% versus 0 (p < 0.001), atrial fibrillation occurred in 5.7% versus 0.7% (p < 0.001), and major bleeding occurred in 2.6% versus 1.1% (p = 0.11), respectively, for PFO closure versus medical therapy. Interpretation: Among patients with cryptogenic stroke/TIA, percutaneous PFO closure with the STARFlex device was not superior to medical therapy. Percutaneous PFO closure did not reduce the incidence of the primary outcome at 2 years, nor did it reduce the incidence of stroke or TIA. Moreover, PFO closure was also associated with major vascular complications and an excess in atrial fibrillation compared with medical therapy. Multiple alternative etiologies were discovered for recurrent stroke, which illustrates the difficulty in diagnosing cryptogenic stroke. At the present time, routine closure of PFO for cryptogenic stroke patients cannot be recommended. Epidemiological data support an association between PFO and cryptogenic stroke; however, clinical trial data regarding PFO closure are sparse. CLOSURE I findings were not due to lack of power or lower than expected event rate: The primary outcome was expected to occur in 2% of the device arm (5.9% actual), whereas the primary outcome was expected to occur in 6% of the medical arm (7.7% actual). Long-term follow-up of these patients is warranted. Ongoing trials include CLOSE and PC-Trial. Study Design: Randomized. Blinded. Parallel. Stratified. Primary Endpoints: Composite of recurrent stroke or TIA within 2 years, all-cause mortality within 30 days, or neurological mortality between 31 days and 2 years Patient Population: Patients with cryptogenic stroke/TIA and PFO with or without atrial septal aneurysm diagnosed in the previous 6 months Number of enrollees: 909 Duration of follow-up: 2 years Mean patient age: 46 years Percentage female: 48% Exclusions: Deep vein thrombosis or hypercoagulable state References: Presented by Dr. Anthony Furlan at the American Heart Association Scientific Sessions, Chicago, IL, November 15, 2010.
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Линейный вид
