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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_458"
                     title="Calcium Scoring Misses 20% of CAD Cases (CME/CE)"
                     score="0.014"
                     href="http://www.medpagetoday.com/Cardiology/AcuteCoronarySyndrome/tb/18387?impressionId=1265794766516"
                     
      &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_449"
                     title="FDA Okays Statin for Primary Prevention"
                     score="0.012"
                     href="http://www.medpagetoday.com/InfectiousDisease/PublicHealth/tb/18380?impressionId=1265794766516"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has approved rosuvastatin (Crestor) for primary prevention of cardiovascular disease, making it the first statin to receive this indication.&lt;/p&gt;
&lt;p&gt;The new labeling, recommended by an FDA advisory panel late last year, also marks the first time that a drug label will include an indication based on the biomarker highly-sensitive C-reactive protein, an inflammatory marker.&lt;/p&gt;
&lt;p&gt;The new indication would be for men 50 or older and women 60 or older who have fasting LDL of less than 130 mg/dL, a highly-sensitive CRP of 2.0 mg/L or greater, triglycerides of less than 500 mg/dL, and no prior history of heart attack or stroke, or coronary heart disease risk.&lt;/p&gt;
&lt;p&gt;The basis for the new labeling was the JUPITER trial, a randomized, placebo-controlled trial of 17,802 men and women with a mean age of 66 and no history of atherosclerosis. All participants had LDL of less than 130 mg/dL and a highly-sensitive C-reactive protein concentration of 2 mg/L or higher.&lt;/p&gt;
&lt;p&gt;Patients were randomized to 20 mg of rosuvastatin for 1.9 years, which reduced median LDL cholesterol to 55 mg/dL, down from a median of 108 mg/dL at baseline. The corresponding relative reduction in the rate of MI, stroke, arterial revascularization, or cardiovascular death was 44% (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.00001).&lt;/p&gt;
&lt;p&gt;The number needed to treat to avoid one cardiovascular event was 25.&lt;/p&gt;
&lt;p&gt;Those results, according to Melvyn Rubenfire, MD, of the University of Michigan, were a &quot;home run for JUPITER,&quot; but it is not clear whether the results would be the same with another statin.&lt;/p&gt;
&lt;p&gt;And there were some risks associated with rosuvastatin, including 13 deaths due to gastrointestinal disorders in the rosuvastatin arm, and 18 patients reported experiencing a &quot;confused state&quot; while taking the drug.&lt;/p&gt;
&lt;p&gt;The most troubling adverse event, however, was an uptick in investigator-reported, new onset diabetes mellitus in the treatment arm, 2.8% versus 2.5%, for a hazard ratio of 1.27 (95% CI 1.05 to 1.53, &lt;em&gt;P&lt;/em&gt;=0.015).&lt;/p&gt;
&lt;p&gt;Rosuvastatin in marketed by AstraZeneca, which also sponsored the JUPITER trial.&lt;/p&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_361"
                     title="Hidden Dangers of Herbal Meds Reviewed"
                     score="0.009"
                     href="http://www.medpagetoday.com/PrimaryCare/AlternativeMedicine/tb/18244?impressionId=1265794766516"
                     
      Herbal medicines are not always the harmless nostrums that many patients and even some physicians think, but may actually contribute to cardiovascular morbidity and mortality, researchers warned in a review covering 44 years of research into the subject.&lt;br&gt;
&lt;br&gt;Many such products, including aloe vera, ginkgo biloba, ginseng, and green tea, can interact with conventional cardiovascular drugs and lead to serious adverse reactions, according to Arshad Jahangir, MD, of the Mayo Clinic in Scottsdale, Ariz., and two other Mayo physicians.&lt;br&gt;
&lt;br&gt;&quot;There is a clear need for better public and physician understanding of herbal products through health education, early detection and management of herbal toxicities, scientific scrutiny of their use, and research on their safety and effectiveness,&quot; they wrote in the Feb. 9 &lt;em&gt;Journal of the American College of Cardiology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Jahangir and colleagues also called for increased regulation of such products, at least requiring manufacturers of herbal medicines to register with the FDA and provide evidence of good manufacturing practices.&lt;/p&gt;
&lt;p&gt;&quot;Some of these adverse drug reactions are preventable,&quot; Jahangir told &lt;em&gt;MedPage Today&lt;/em&gt; in a telephone interview. &quot;Simple things like taking a good history or giving that history and discussing these issues, probably we can avoid [such reactions].&quot;&lt;/p&gt;
&lt;p&gt;Other physicians contacted by &lt;em&gt;MedPage Today&lt;/em&gt; and ABC News agreed that the growth in popularity of herbal medicines poses problems for physicians and patients.&lt;/p&gt;
&lt;p&gt;&quot;Because these remedies are &apos;natural,&apos; their potential dangers are not considered the same way they would be if they were medication,&quot; commented Suzanne Steinbaum, MD, a cardiologist at Lenox Hill Hospital in New York City, in an e-mail.&lt;/p&gt;
&lt;p&gt;&quot;For many reasons, patients tend not to disclose to their doctors if they are taking herbal remedies, including fear that their doctors won&apos;t approve or they will be told to stop them,&quot; Steinbaum added. &quot;This lack of knowledge and full-disclosure, for some, might be a fatal omission.&quot;&lt;/p&gt;
&lt;p&gt;Jahangir and colleagues reviewed nearly 90 publications that have addressed herbal or complementary therapies and cardiovascular effects since 1966.&lt;/p&gt;
&lt;p&gt;Their &lt;em&gt;JACC&lt;/em&gt; article listed 15 common herbal medicines known to interact adversely with conventional cardiovascular drugs.&lt;/p&gt;
&lt;p&gt;In many cases, the herbal products compete with the regular medicines for the same drug-metabolizing cytochrome P450 enzymes, potentiating the latter&apos;s effects. In other cases, the herbal products have their own cardiovascular effects.&lt;/p&gt;
&lt;p&gt;Many physicians already know that grapefruit juice occupies the CYP3A4 enzyme, leading to slower-than-expected metabolism and, therefore, higher blood levels of a host of pharmaceuticals.&lt;/p&gt;
&lt;p&gt;These include the statins, calcium channel antagonists, several common anti-arrhythmic drugs, and the angiotensin receptor blocker irbesartan (Avapro), Jahangir and colleagues noted.&lt;/p&gt;
&lt;p&gt;Garlic is one of several common herbal remedies with specific cardiovascular effects in its own right (others include ginkgo biloba, ginseng, and saw palmetto). Garlic inhibits platelet aggregation and thus can lead to increased bleeding risks when combined with aspirin, clopidogrel (Plavix), or warfarin (Coumadin), the researchers noted.&lt;/p&gt;
&lt;p&gt;The Mayo group identified 10 herbal products that increase bleeding risks with anticoagulant and antiplatelet drugs, as well as 14 that can induce arrhythmias.&lt;/p&gt;
&lt;p&gt;In all, Jahangir and colleagues listed 27 herbal products that patients with cardiovascular diseases would do well to avoid. These include such common and harmless-seeming products as green tea, capsicum pepper, licorice, and kelp, as well as grapefruit juice and garlic.&lt;/p&gt;
&lt;p&gt;&quot;We need to check with our patients what type of products they are using, to identify these potential interactions,&quot; Jahangir told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;He cited the previously reported figure of 100,000 deaths annually from drug interactions, adding, &quot;We don&apos;t even know how many of these are due to use of compounds that we are not aware that our patients are taking.&quot;&lt;/p&gt;
&lt;p&gt;Jahangir said he was surprised, in preparing the review, at the scale of hebal medicine use in the U.S.&lt;/p&gt;
&lt;p&gt;He and his colleagues found data from the 1990s suggesting that more patients consult complementary and alternative medicine providers than regular physicians.&lt;/p&gt;
&lt;p&gt;The total annual out-of-pocket expenditure on complementary and alternative medicine services and products also was greater than for conventional physician services.&lt;/p&gt;
&lt;p&gt;&quot;The surprise for me was . . . how much people are willing to spend on a type of therapy which has not shown, in any scientific way, to be effective or safe,&quot; Jahangir said.&lt;/p&gt;
&lt;p&gt;He added that the trend may reflect shortcomings of the conventional medical system.&lt;/p&gt;
&lt;p&gt;&quot;What is the reason people are going there? Is it because there is some unmet type of need that we are not recognizing as practitioners of conventional medicine?&quot;&lt;/p&gt;
&lt;p&gt;Jahangir said it may be that physicians aren&apos;t spending enough time with patients to understand their true needs. He said it appears that, &quot;despite the advancement in our technology and new medicines, there is a demand for alternative therapies that is increasing.&quot;&lt;/p&gt;
&lt;p&gt;He recommended that, in addition to asking patients in detail about herbal and other alternative therapies they may be using, physicians should educate themselves on what these therapies purport to do and what is known about their real biological effects.&lt;/p&gt;
&lt;p&gt;The &lt;a href=&quot;http://nccam.nih.gov&quot; mce_href=&quot;http://nccam.nih.gov&quot; target=&quot;_blank&quot;&gt;National Center for Complementary and Alternative Medicine&lt;/a&gt; at the National Institutes of Health is a good starting point for such information, both for physicians and for patients, Jahangir said.&lt;/p&gt;
&lt;p&gt;Lenox Hill&apos;s Steinbaum said it was important that conventional physicians &quot;become more open-minded and accepting&quot; of alternative medicine, if only because so many of their patients are already practicing it.&lt;/p&gt;
&lt;p&gt;David Meyerson, MD, JD, a Johns Hopkins University cardiologist, told &lt;em&gt;MedPage Today&lt;/em&gt; and ABC News in an e-mail that he advises patients to limit their use of &quot;unstudied and unproven and FDA-unregulated herbal medications.&quot;&lt;/p&gt;
&lt;p&gt;&quot;It&apos;s unfortunately very big business, and potential drug interactions and potential harmful effects abound,&quot; he wrote.&lt;/p&gt;
&lt;p&gt;But another physician criticized the Mayo physicians&apos; emphasis on adverse effects in their review.&lt;/p&gt;
&lt;p&gt;&quot;For many of products listed, evidence for side effects seems to be minimal,&quot; Scott Grundy, MD, of the University of Texas Southwestern Medical Center in Dallas, argued in an e-mail.&lt;/p&gt;
&lt;p&gt;He agreed that the efficacy and safety of such drugs remains largely unproven, but added, &quot;It is mainly for these reasons that they cannot be recommended for use.&quot;&lt;/p&gt;
&lt;p&gt;Creating alarm about side effects &quot;may not be the appropriate way to discourage their use,&quot; Grundy said.&lt;/p&gt;
&lt;p&gt;&lt;em&gt;This article was developed in collaboration with ABC News. &lt;/em&gt;&lt;img src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; mce_src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; alt=&quot;&quot;&gt;&lt;/p&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_352"
                     title="ICAO: Future Chronic Disease Risk Goes Beyond BMI (CME/CE)"
                     score="0.009"
                     href="http://www.medpagetoday.com/Endocrinology/Diabetes/tb/18233?impressionId=1265794766516"
                     
      When it comes to predicting chronic disease, body mass index doesn&apos;t tell the whole story, according to a population-based study that found elevated risk with obesity and other metabolic risk factors independently.&lt;br&gt;
&lt;br&gt;Metabolically-healthy obese people tended toward being at least twice as likely to develop multiple metabolic risk factors and diabetes as healthy, normal weight individuals over the subsequent 3.5 years of a study led by Sarah Appleton, a postgraduate student at the University of Adelaide, Australia.&lt;br&gt;
&lt;br&gt;However, normal weight individuals with metabolic risk factors  --  a group the researchers called &quot;metabolically obese&quot;  --  were at greater risk, she told attendees at the International Congress on Abdominal Obesity in Hong Kong, a conference sponsored by the International Chair on Cardiometabolic Risk.&lt;br&gt;
&lt;br&gt;Overall, just 4.1% of the 3,743 adults in the population-based, North West Adelaide Health Study were in the normal body mass index range at baseline but had at least two of the following metabolic risk factors:&lt;ul&gt; &lt;li&gt;Triglyceride levels of 1.7 mmol/L or greater&lt;/li&gt; &lt;li&gt;HDL cholesterol under 1.0mmol/L for men or 1.3 mmol/L for women&lt;/li&gt; &lt;li&gt;Blood pressure of 130/85 mm Hg or higher&lt;/li&gt; &lt;li&gt;A fasting plasma glucose of at least 5.6mmol/L or self-reported diabetes&lt;/li&gt; &lt;li&gt;Treatment for any of these disorders &lt;/li&gt; &lt;/ul&gt;
&lt;p&gt;Although free of cardiovascular disease when they entered the study through a random population sample of the northwest region of Adelaide, after a mean of 3.5 years of follow-up, this group was 2.48 times at risk of incident cardiovascular disease or stroke events (95% CI 1.1 to 5.4).&lt;/p&gt;
&lt;p&gt;Compared with metabolically-healthy, normal weight individuals, those with metabolic risk factors tended to be&lt;strong&gt; &lt;/strong&gt;3.27 times as likely to develop diabetes (&lt;em&gt;P&lt;/em&gt;=0.07).&lt;/p&gt;
&lt;p&gt;Identifying these individuals for prevention efforts may require less emphasis on BMI and increased surveillance of central obesity in primary care, the researchers told the congress.&lt;/p&gt;
&lt;p&gt;&quot;The problem with BMI is it doesn&apos;t tell you where the fat is,&quot; Appleton added in an interview. &quot;Visceral fat is really bad for you.&quot;&lt;/p&gt;
&lt;p&gt;Obese individuals without multiple metabolic risk factors at baseline comprised a larger group (12.1%).&lt;/p&gt;
&lt;p&gt;They were more likely to be middle age, live in a disadvantaged neighborhood, have smoked at some point, and get less exercise than their metabolically similar, but slimmer peers.&lt;/p&gt;
&lt;p&gt;Over the subsequent 3.5 years, they were 2.82 times more likely to develop more than one metabolic risk factor than metabolically-healthy, normal weight individuals (95% CI 2.0 to 4.0).&lt;/p&gt;
&lt;p&gt;The metabolically-normal obese also tended to be 2.36 times more likely to develop diabetes (95% CI 0.8 to 7.1). On the other hand, their risk of cardiovascular disease wasn&apos;t elevated, &quot;which likely related to the younger age of that group,&quot; Appleton told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Notably, abdominal obesity as determined by a waist circumference of 80 cm and over for men or 95 cm and greater for women was 6.1 times more likely among metabolically healthy individuals if their BMI was in the obese versus normal range.&lt;/p&gt;
&lt;p&gt;But those who were in the normal BMI range were 2.2-fold more likely to be overweight or obese according to waist circumference if they had metabolic risk factors, which was statistically significant as well and likely contributed to the health risks they faced over the short-term future, Appleton said.&lt;/p&gt;
&lt;p&gt;Maintenance of metabolic health in the obese population was more likely for younger individuals (OR 2.83 for age 40 or younger, 95% CI 1.1 to 7.6) and those who were at least moderately physically active (OR 2.04, 95% CI 1.01 to 4.1).&lt;/p&gt;
&lt;p&gt;Appleton noted that these findings generally fit with data from the U.S. National Health Assessment Survey and Examination.&lt;/p&gt;
&lt;p&gt;Regardless of whether patients have abdominal obesity, BMI obesity, or other metabolic risk factors, the solution is likely similar  --  improved diet and exercise, she said.&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 the University of Adelaide and the South Australian Department of Health.&lt;/p&gt;&lt;p&gt;Appleton reported no 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_348"
                     title="No Rebound Seen After Antiplatelet Withdrawal (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/Cardiology/PCI/tb/18226?impressionId=1265794766516"
                     
      &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>