<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_458"
                     title="Calcium Scoring Misses 20% of CAD Cases (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/Cardiology/AcuteCoronarySyndrome/tb/18387?impressionId=1265798787251"
                     
      &lt;p&gt;Contrary to guidelines, the absence of coronary artery calcium doesn&apos;t rule out coronary artery disease in symptomatic patients, researchers found in a new study.&lt;/p&gt;
&lt;p&gt;In a multicenter clinical trial, 19% of patients with a coronary calcium score of 0 had stenosis of at least 50% in one or more coronary artery segments, according to Carlos E. Rochitte, MD, of the University of S&amp;#227;o Paulo, Brazil, and colleagues.&lt;/p&gt;
&lt;p&gt;Likewise, 20% of vessels seen to be totally occluded on revascularization had no calcium on scans, they reported in the Feb. 16 issue of the &lt;em&gt; Journal of the American College of Cardiology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;The absence of coronary calcification should not be used as a gatekeeper and should not prevent a symptomatic patient from undergoing angiography,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;Currently, American Heart Association/American College of Cardiology guidelines suggest that excluding measurable coronary calcium could serve as an effective filter for sending patients on to invasive testing or admitting them.&lt;/p&gt;
&lt;p&gt;One systematic review of 18 studies had indicated that a zero calcium score had a negative predictive value of 93% for stenosis and a positive predictive value of 68% in symptomatic patients.&lt;/p&gt;
&lt;p&gt;However, in Rochitte&apos;s trial  --  CORE64 (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors)  --  the negative predictive value of a coronary calcium score of 0 was 68%, while the positive predictive value was 81%.&lt;/p&gt;
&lt;p&gt;Overall sensitivity to predict the absence of significant (at least 50%) stenosis was 45%, while specificity was 91%.&lt;/p&gt;
&lt;p&gt;&quot;This apparent lack of predictive value of a calcium scan should be enough to give a clinician pause,&quot; Rita F. Redberg, MD, of the University of California San Francisco, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;Whatever the reason for the discrepancy, neither the trial nor the review provided any information on how coronary calcium scans add incrementally to traditional predictors of coronary artery disease, such as clinical assessment and stress testing, she said. Nor would she rule out their use entirely for patients with chest pain.&lt;/p&gt;
&lt;p&gt;&quot;Given the significant &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/AcuteCoronarySyndrome/12732&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/AcuteCoronarySyndrome/12732&quot; target=&quot;_blank&quot;&gt;radiation risks&lt;/a&gt; of coronary artery calcium scans, however, clinicians must use extreme caution when ordering such scans,&quot; Redberg cautioned.&lt;/p&gt;
&lt;p&gt;The prospective &lt;a href=&quot;http://www.medpagetoday.com/Radiology/DiagnosticRadiology/11927&quot; mce_href=&quot;http://www.medpagetoday.com/Radiology/DiagnosticRadiology/11927&quot; target=&quot;_blank&quot;&gt;CORE64 study&lt;/a&gt; was originally designed to compare diagnostic performance of CT and invasive angiography in symptomatic patients with suspected coronary artery disease. But it also included a coronary calcium scan up to 30 days prior to conventional angiography.&lt;/p&gt;
&lt;p&gt;Of the 291 patients included in the calcium score analysis (73% male, mean age 59.3), 56% had at least 50% coronary stenosis by conventional angiography and 45% had at least 70% stenosis.&lt;/p&gt;
&lt;p&gt;Calcium score only weakly correlated with the highest degree of coronary stenosis found in a patient. Its ability to predict presence of significant lesions was &quot;moderate&quot; (area under the receiver-operating characteristic curve 0.77, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;A non-zero score was associated with 8.1-fold likelihood of having at least 50% coronary stenosis (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) after adjusting for age, sex, hypertension, dyslipidemia, family history of premature heart disease, diabetes, race, and hospitalization.&lt;/p&gt;
&lt;p&gt;Among the 100 patients who went on to revascularization within 30 days of angiography, 13% had a coronary calcium score of 0, 25% had a score of 1 to 10, and 44% had a score over 10 (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for trend).&lt;/p&gt;
&lt;p&gt;The fact that significant coronary artery disease occurred in the absence of calcification in almost 20% of patients should not be surprising, since coronary calcification is thought to occur late in the atherosclerotic process, while obstruction can occur earlier, Redberg asserted.&lt;/p&gt;
&lt;p&gt;The researchers also cautioned that the results would not apply to asymptomatic patients with intermediate risk for events, a group in which a score of 0 has been consistently shown to indicate low risk.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by grants from Toshiba Medical Systems, the Doris Duke Charitable Foundation, the National Heart, Lung, and Blood Institute, the National Institute on Aging, and the Donald W. Reynolds Foundation.&lt;/p&gt;&lt;p&gt;Rochitte reported no conflicts of interest. Co-authors reported financial relationships with Toshiba Medical Systems, Bayer, Schering, GE Healthcare, Bracco, Bristol-Myers Squibb, sanofi-aventis, and Vital Images.&lt;/p&gt;&lt;p&gt;Redberg provided no information on conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_457"
                     title="Long-Term Safety of Drug-Eluting Stents Affirmed (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/Cardiology/Atherosclerosis/tb/18374?impressionId=1265798787251"
                     
      &lt;p&gt;Using sirolimus-eluting stents for the treatment of in-stent restenosis appears safe and effective over four years of follow-up, a study of an Italian registry showed.&lt;/p&gt;
&lt;p&gt;Through four years, there were low rates of target lesion revascularization (11.1%) and stent thrombosis (2.8%), according to Francesco Liistro, MD, of San Donato Hospital in Arezzo, Italy, and colleagues.&lt;/p&gt;
&lt;p&gt;About one in 10 patients (9.8%) died, and 3.2% had a nonfatal myocardial infarction.&lt;/p&gt;
&lt;p&gt;Survival free from a major adverse cardiac event was 80.3% at the end of follow-up, the researchers reported in the Feb. 16 issue of the&lt;em&gt; Journal of the American College of Cardiology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Although drug-eluting stents have been shown to be safe and better than balloon angioplasty and vascular brachytherapy for in-stent restenosis in the short term, most previous studies have had limited follow-up.&lt;/p&gt;
&lt;p&gt;Reports of late stent thrombosis following implantation with drug-eluting stents have raised some concern about the long-term safety of these devices in unselected patient groups, according to Liistro and his colleagues.&lt;/p&gt;
&lt;p&gt;To explore the issue, the researchers turned to the Tuscany Registry of Unselected In-Stent Restenosis (TRUE), a prospective, two-center registry.&lt;/p&gt;
&lt;p&gt;All 244 patients included in the analysis underwent antiplatelet therapy with aspirin and either ticlopidine or clopidogrel (Plavix) for at least six months after the sirolimus-eluting stent was implanted.&lt;/p&gt;
&lt;p&gt;An earlier, nine-month analysis of this registry showed safety and effectiveness for the stent. This study confirmed the benefits through four years.&lt;/p&gt;
&lt;p&gt;Of 24 recorded deaths, 11 were from cardiac causes.&lt;/p&gt;
&lt;p&gt;Definite stent thrombosis occurred in five patients, four of whom had stopped taking clopidogrel more than a month before the event.&lt;/p&gt;
&lt;p&gt;Another two patients who were taking aspirin and clopidogrel had probable stent thrombosis.&lt;/p&gt;
&lt;p&gt;Patients who had diabetes were significantly more likely to have target lesion revascularization (OR 0.32, 95% CI 0.14 to 0.71) and major adverse cardiac events (OR 0.38, 95% CI 0.20 to 0.71) through four years.&lt;/p&gt;
&lt;p&gt;A left ventricular ejection fraction less than 50% was associated with higher odds of major adverse cardiac events (OR 0.32, 95% CI 0.13 to 0.80), as was creatinine greater than 1.5 mg/dL (OR 0.23, 95% CI 0.11 to 0.48).&lt;/p&gt;
&lt;p&gt;And patients with peripheral or carotid arterial disease were more likely to need target lesion revascularization (OR 0.35, 95% CI 0.14 to 0.88).&lt;/p&gt;
&lt;p&gt;The authors noted that the registry study was limited by the lack of valid control groups.&lt;/p&gt;
&lt;p&gt;In addition, in patients with a late occurrence of target lesion revascularization, the researchers could not determine whether a stenotic lesion inside the stented segment was a new atherosclerotic lesion or a restenosis.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The authors did not make any financial disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_448"
                     title="Inflammatory Bowel Disease Linked to Dangerous VT (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/Gastroenterology/InflammatoryBowelDisease/tb/18362?impressionId=1265798787251"
                     
      &lt;p&gt;Patients with active inflammatory bowel disease (IBD) could be at far greater risk for potentially deadly blood clots than doctors previously thought, a new British study found.&lt;/p&gt;
&lt;p&gt;Nonhospitalized patients with active IBD are 16 times more likely to suffer venous thromboembolism than the general population, with an occurrence rate of 6.4 per 1,000 person-years (HR 15.8, 95% CI 9.8 to 25.5, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), according to an online report in the Feb. 9 issue of &lt;em&gt;The Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The authors concluded that such patients could benefit from preventative treatment to prevent blood clotting.&lt;/p&gt;
&lt;p&gt;&quot;Despite the low absolute risks during nonhospitalised periods, these results suggest that active inflammatory bowel disease in ambulatory patients might be a far greater risk factor for venous thromboembolism than previously recognised,&quot; Matthew J. Grainge, MD, of the University of Nottingham, and colleagues wrote.&lt;/p&gt;
&lt;p&gt;Patients with venous thromboembolism in the leg have a short term-mortality rate of about 6%, increasing as high as 20% when the clot has circulated to the lung.&lt;/p&gt;
&lt;p&gt;Researchers believe that infection and inflammation, such as occur in IBD, predispose patients to this life-threatening condition, and those with inflammatory bowel disease seem to be at particular risk.&lt;/p&gt;
&lt;p&gt;Grainge and colleagues used records from the U.K. General Practice Research Database from November 1987 through July 2001, to match 13,756 patients with IBD against 71,672 controls without the disease.&lt;/p&gt;
&lt;p&gt;Of the subjects, 139 patients and 165 controls developed a blood clot during the study period.&lt;/p&gt;
&lt;p&gt;Their results agreed with previous studies indicating that patients hospitalized for IBD are at high risk for venous thromboembolism. However, the new study also found the danger extends to nonhospitalized IBD patients, particularly during a flare-up.&lt;/p&gt;
&lt;p&gt;Overall, the researchers reported, patients with IBD had three times as much risk of an embolism as controls (HR 3.4, 95% CI 2.7 to 4.3; &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001) with an occurrence rate of 2.6 per 1,000 per person-years.&lt;/p&gt;
&lt;p&gt;During a flare-up, IBD patients were at dramatically greater risk.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that the study excluded patients likely to have received corticosteroids for chronic respiratory disease and rheumatoid arthritis, so the results may not reflect blood clotting rates in these populations.&lt;/p&gt;
&lt;p&gt;They also noted that they relied on anonymous patient records and were dependent on family doctors&apos; diagnoses of inflammatory bowel disease, flare-ups and venous thromboembolism.&lt;/p&gt;
&lt;p&gt;Despite the limitations of the study, they argued that research into ways to prevent embolism in IBD outpatients is warranted.&lt;/p&gt;
&lt;p&gt;&quot;We believe that the medical profession needs to recognise the increased risk in people with inflammatory bowel disease when assessing the likelihood of venous thromboembolism and to address the difficulty of reducing this risk in patients with a flare who are not admitted to hospital,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;They suggested that strategies used to prevent blood clots in hospitalized patients  --  courses of low molecular weight heparin or other newly available anticoagulants  --  might be also be used to prevent clots in nonhospitalized IBD patients experiencing a flare-up.&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, Geoffrey C. Nguyen, MD, and Erik L. Yeo, MD, of the University of Toronto, noted that &quot;the use of steroid prescriptions as a surrogate indicator of acute disease flare restricts the applicability of Grainge and colleagues&apos; findings to flares that are moderate to severe. Whether patients with mild flares are also at increased risk is not clear.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Recognition of venous thromboembolism might be increased during periods of frequent contact with doctors, such as during flares compared with during remission of inflammatory bowel disease, thus potentially introducing a bias in ascertainment of venous thromboembolism,&quot; they added.&lt;/p&gt;
&lt;p&gt;Nguyen and Yeo also argued that the clinical efficacy and cost-effectiveness of pharmacological prevention in patients with inflammatory bowel disease should be proven before it is routinely recommended during acute flares.&lt;/p&gt;
&lt;p&gt;However, they acknowledged that such evidence could be difficult to acquire, given the low numbers of nonhospitalized IBD patients who suffer venous thromboembolism.&lt;/p&gt;
&lt;p&gt;&quot;A pragmatic initial approach to reduction of the rates of morbidity and mortality resulting from venous thromboembolism in ambulatory patients with inflammatory bowel disease would be nonpharmacological thromboprophylaxis, including patients&apos; education and awareness of risk and signs and symptoms of venous thromboembolism, and use of support stockings,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&quot;Physicians should clinically assess for signs and symptoms of this embolism during visits for acute flare of inflammatory bowel disease.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by the National Association for Colitis and Crohn&apos;s Disease.&lt;/p&gt;&lt;p&gt;The authors reported no financial conflicts of interest.&lt;/p&gt;&lt;p&gt;Nguyen reported serving on advisory boards for Schering-Plough, Canada, and Abbott Pharmaceuticals.&lt;/p&gt;&lt;p&gt;Yeo reported receiving an honorarium from sanofi-aventis.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_388"
                     title="Laser Cardiac Lead Extraction Gets Better Grades (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Cardiology/Arrhythmias/tb/18280?impressionId=1265798787251"
                     
      &lt;p&gt;Laser-assisted extraction of implanted heart device leads appears to have become safer and more successful in recent years, researchers said.&lt;/p&gt;
&lt;p&gt;A retrospective multicenter series suggested a 97.7% clinical success rate and complete lead removal in 96.5% of cases attempted with the newer iteration of transvenous excimer laser extraction tools.&lt;/p&gt;
&lt;p&gt;Major procedural complication rates were low at 1.4% with 0.28% procedure-related deaths, Oussama M. Wazni, of the Cleveland Clinic, and colleagues reported in the Feb. 9 issue of the &lt;em&gt;Journal of the American College of Cardiology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;Since the initially reported experiences, which employed earlier editions of the extraction tools and largely represented the learning curve with laser extraction techniques, this consecutive patient experience represents the mature contemporary practice in multiple centers with varying degrees of experience,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;These results suggested improvements, they said, compared with the original PLEXES trial using the first version of a laser sheath for lead extraction, which showed 94% procedural success and 1.96% procedure-related major complications.&lt;/p&gt;
&lt;p&gt;Another study of the total initial U.S. experience of laser lead extraction indicated 90% procedural success with a 1.9% major complication rate and an inhospital death rate of 0.8%.&lt;/p&gt;
&lt;p&gt;The early, relatively small trials and voluntary registry results upon which the perceptions of lead extraction safety and effectiveness were based had painted a &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Arrhythmias/3162&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Arrhythmias/3162&quot; target=&quot;_blank&quot;&gt;picture&lt;/a&gt; that limited it to patients with life-threatening situations, Wazni&apos;s group explained.&lt;/p&gt;
&lt;p&gt;It used to be felt that removing infected leads was dangerous because of the potential for infected debris to spread through the bloodstream and become lodged in the lungs, commented Ann Bolger, MD, of San Francisco General Hospital and a spokesperson for the American Heart Association.&lt;/p&gt;
&lt;p&gt;&quot;Because there are just more and more patients all the time with these devices and because we went through a phase when we might not have always retrieved wires that were no longer functional completely, there are patients who have what they call abandoned leads,&quot; she said in an interview.&lt;/p&gt;
&lt;p&gt;AHA guidelines released last month now recommend removal of all hardware even in the absence of symptoms for patients with more than a superficial or incisional infection at the pocket site, suggesting percutaneous extraction as the preferred method despite significant risks.&lt;/p&gt;
&lt;p&gt;The AHA agreed with guidelines from the Heart Rhythm Society released last spring cautioning that only experienced centers should do extractions. The HRS went so far as to set &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/HRS/14255&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/HRS/14255&quot; target=&quot;_blank&quot;&gt;minimum standards&lt;/a&gt; for operators.&lt;/p&gt;
&lt;p&gt;For a look at more contemporary data, Wazni&apos;s group examined outcomes for 1,449 consecutive patients treated with transvenous laser-assisted lead extraction at 13 U.S. and Canadian centers between January 2004 and December 2007.&lt;/p&gt;
&lt;p&gt;Among the 2,405 procedures, 70% were for pacemakers leads and 29.2% for defibrillator leads, with most being active fixation leads (1,226).&lt;/p&gt;
&lt;p&gt;The extracted leads had been in place for an average of 82.1 months (range 0.4 to 356.8). They were taken out predominantly because of infection (29.2% device-related endocarditis and 27.7% pocket infection).&lt;/p&gt;
&lt;p&gt;More than a quarter were nonfunctional (26.6%), while an additional 11.1% were functional but abandoned.&lt;/p&gt;
&lt;p&gt;Removal was complete for 96.5% of the leads and partial for 2.3%. Clinical success  --  achieving the clinical goals associated with the indication for lead removal  --  was achieved in 97.7% of the cases.&lt;/p&gt;
&lt;p&gt;Clinical failure of the procedure was associated with low patient body mass index (less than 25 kg/m&lt;sup&gt;2&lt;/sup&gt;) and with a lower volume of procedures (60 or fewer) at a center over the four years (&lt;em&gt;P&lt;/em&gt;=0.0128).&lt;/p&gt;
&lt;p&gt;Procedural adverse events, too, were more common for low BMI patients (&lt;em&gt;P&lt;/em&gt;=0.0132).&lt;/p&gt;
&lt;p&gt;Procedural failure was linked to a long implant duration (at least 10 years) and lower center volume (&lt;em&gt;P&lt;/em&gt;=0.0005).&lt;/p&gt;
&lt;p&gt;Although extraction of noninfected but nonfunctional leads is controversial, leaving them in place may just serve as a nidus for infection such that they have to be removed eventually anyway, the researchers suggested.&lt;/p&gt;
&lt;p&gt;Considering extraction in such cases requires carefully weighing patient risks individually, including operator experience in the equation, they wrote.&lt;/p&gt;
&lt;p&gt;A significant learning curve for laser-assisted extraction is not surprising, but the results in experienced hands are encouraging, Bolger concluded.&lt;/p&gt;
&lt;p&gt;By the end of the study, physicians averaged 11.4 years of experience with lead extraction (range 2.0 to 19.0 years) and 7.87 years at laser-assisted lead extraction (range 2.0 to 13.0 years).&lt;/p&gt;
&lt;p&gt;The researchers agreed that the high success and low complication rate may have been due to the experienced centers and operators.&lt;/p&gt;
&lt;p&gt;&quot;However, in the community, these more challenging cases are usually referred to centers experienced in laser-assisted lead extraction,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;They noted that any selection bias in the retrospective study was most likely toward the most challenging cases &quot;as laser-assisted extraction is reserved for leads with ingrown tissue and inability to be removed with traction only.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was sponsored by Spectranetics, manufacturer of the laser lead removal system.&lt;/p&gt;&lt;p&gt;Wilkoff reported being on the advisory board of Spectranetics.&lt;/p&gt;&lt;p&gt;Co-authors reported financial conflicts of interests with Spectranetics, St. Jude, Medtronic, Boston Scientific, and Biotronik. One is an employee of Spectranetics; another is the senior biostatistician with the company.&lt;/p&gt;&lt;p&gt;Bolger reported no conflicts of interests.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_348"
                     title="No Rebound Seen After Antiplatelet Withdrawal (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Cardiology/PCI/tb/18226?impressionId=1265798787251"
                     
      &lt;p&gt;No evidence of a platelet aggregation rebound occurs with abrupt discontinuation of clopidogrel (Plavix) in patients undergoing percutaneous coronary intervention (PCI), investigators in a randomized clinical trial concluded.&lt;/p&gt;
&lt;p&gt;Values for adenosine diphosphate (ADP)-induced platelet aggregation did not differ significantly between patients whose clopidogrel therapy was withdrawn abruptly and those in whom clopidogrel was tapered before discontinuation, they wrote in an article in the Feb. 9 issue of the &lt;em&gt;Journal of the American College of Cardiology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The findings also showed that tapering of clopidogrel does not lead to lower platelet aggregation values after clopidogrel withdrawal, according to Dirk Sibbing, MD, of Technical University Munich in Germany, and colleagues&lt;em&gt;&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;The time course of platelet aggregation values  --  regardless of the device, the agonist, or the agonist concentration used  --  after clopidogrel cessation provides no evidence for the existence of a rebound phenomenon of platelets after discontinuing clopidogrel,&quot; they wrote in conclusion.&lt;/p&gt;
&lt;p&gt;For patients undergoing PCI, dual antiplatelet therapy with aspirin and clopidogrel has become the mainstay for prevention of thrombotic events. Lifelong aspirin therapy is recommended for patients after PCI, but clinical guidelines recommend discontinuation of clopidogrel after six or 12 months. The standard practice is to withdraw clopidogrel abruptly, the authors noted.&lt;/p&gt;
&lt;p&gt;Recent studies have shown a clustering of thrombotic events in the first few weeks after discontinuation of long-term clopidogrel therapy. The observations have led to the hypothesis of a rebound phenomenon of platelet aggregation. However, the hypothesis had not been examined specifically within the context of clopidogrel withdrawal.&lt;/p&gt;
&lt;p&gt;&quot;Because different studies have demonstrated that insufficient suppression of platelet reactivity to ADP is associated with an increased risk of thrombotic events after coronary stent placement, the observed clustering of adverse events reported in clinical studies might be related to an intermittent status of platelet hyperreactivity or so-called platelet rebound with very high ADP-induced platelet aggregation levels,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;&quot;A tapering of clopidogrel treatment over a certain period of time before stopping the intake of the drug completely might provide a beneficial treatment strategy to attenuate this supposed rebound phenomenon of platelets.&quot;&lt;/p&gt;
&lt;p&gt;Sibbing and colleagues designed a randomized clinical trial to determine whether a rebound phenomenon exists after discontinuation of clopidogrel and whether the rebound can be attenuated by a clopidogrel-tapering regimen.&lt;/p&gt;
&lt;p&gt;The investigators enrolled 69 patients receiving clopidogrel in association with PCI procedures. In all cases, discontinuation of clopidogrel was planned.&lt;/p&gt;
&lt;p&gt;The patients were randomized to two strategies of discontinuation: tapering of the clopidogrel dose over four weeks, followed by discontinuation; or treatment for four weeks, as planned, followed by abrupt discontinuation.&lt;/p&gt;
&lt;p&gt;Investigators assessed platelet aggregation at enrollment and during weeks two through eight after randomization. Aggregation was assessed simultaneously by light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA).&lt;/p&gt;
&lt;p&gt;The primary endpoint was the highest rate of ADP-induced platelet aggregation by LTA in weeks five through eight after clopidogrel withdrawal.&lt;/p&gt;
&lt;p&gt;Platelet aggregation by LTA peaked at 73% in the group that had clopidogrel abruptly withdrawn and at 69.3% in the tapering group, resulting in a nonsignificant difference (&lt;em&gt;P&lt;/em&gt;=0.21). The between-group values did not differ across the range of ADP concentrations used (1.25 to 20 &amp;#181;mol/L).&lt;/p&gt;
&lt;p&gt;Results by MEA were similar: The peak aggregation value associated with abrupt withdrawal was 925 AU x min compared with 890 AU x min with clopidogrel tapering (&lt;em&gt;P&lt;/em&gt;=0.55).&lt;/p&gt;
&lt;p&gt;Studies with different agonists of platelet aggregation also yielded similar results in the two patient groups.&lt;/p&gt;
&lt;p&gt;Despite finding no difference between the two strategies for clopidogrel withdrawal, the authors did not rule out the possibility of a beneficial effect of tapering clopidogrel.&lt;/p&gt;
&lt;p&gt;&quot;It could be hypothesized that, apart from the maximal values of platelet aggregation observed, a more gradual increase of platelet aggregation values achieved by a clopidogrel-tapering regimen is beneficial for the reduction of thrombotic events,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;&quot;In fact, we observed a relatively rapid increase of platelet aggregation values in the [abrupt withdrawal] group of patients in our study. Whether this rapid increase might be disadvantageous in case of stopping clopidogrel treatment remains uncertain.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by Cordis, Medtronic, and Dynabyte.&lt;/p&gt;&lt;p&gt;Sibbing disclosed relationships with Dynabyte and Eli Lilly.&lt;/p&gt;&lt;p&gt;Co-author Adnan Kastrati disclosed relationships with Eli Lilly, sanofi-aventis, and Bristol-Myers Squibb.&lt;/p&gt;&lt;p&gt;Co-author Nicolas von Beckerath disclosed relationships with Eli Lilly and sanofi-aventis.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>