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    <recommendedItem id="20100101_19_348"
                     title="No Rebound Seen After Antiplatelet Withdrawal (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Cardiology/PCI/tb/18226?impressionId=1265715263036"
                     
      &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(ADP)-induced platelet aggregation did not differ significantly between patients whose clopidogrel therapy was withdrawn abruptly and those in whom clopidogrel was tapered before discontinuation, they wrote in an article in the Feb. 9 issue of the &lt;em&gt;Journal of the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>
    <recommendedItem id="20100101_19_189"
                     title="Tailoring Trumps Targeting for Cholesterol Control (CME/CE)"
                     score="-0.001"
                     href="http://www.medpagetoday.com/Cardiology/Dyslipidemia/tb/18023?impressionId=1265715263036"
                     
      &lt;p&gt;Lipid control is more than a simple matter of &quot;knowing your numbers,&quot; according to a computer model that found tailoring statin therapy to fit an individual&apos;s five-year risk of heart attack or stroke is a better prevention strategy than treating to preset goals.&lt;/p&gt;
&lt;p&gt;In the model, patients who whose five-year coronary artery disease risk was 5% to 15% received 40 mg of simvastatin (Zocor), while those whose risk was greater were given 40 mg of atorvastatin (Lipitor).&lt;/p&gt;
&lt;p&gt;In every scenario, the tailored approach was preferable, Rodney A. Hayward, MD, of the University of Michigan and the Veterans Affairs Ann Arbor Healthcare System, and colleagues wrote in the Jan. 19 &lt;em&gt;Annals of Internal Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;While treating-to-target is appealingly simple, that simplicity may be its main limitation, the researchers argued.&lt;/p&gt;
&lt;p&gt;Treating to a single target means that one risk factor receives &quot;dramatically more weight than all other predictors of treatment benefit, resulting in other highly relevant information being either ignored or underweighted,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;That approach, tailoring treatment to reflect multiple risk factors rather than treating-to-target, is an &quot;interesting&quot; one, according to Christopher Cannon, MD, of Brigham and Women&apos;s Hospital in Boston, who was not involved in the study.&lt;/p&gt;
&lt;p&gt;But Cannon, principal investigator of a number of statin trials, said the idea may be a little too late to impact clinical practice.&lt;/p&gt;
&lt;p&gt;&quot;The guidelines won&apos;t shift to this approach any time soon, and in two years, atorvastatin will be generic, so all patients can inexpensively be treated with more intensive therapy (which is better for everyone at all risk levels),&quot; Cannon wrote in an e-mail.&lt;/p&gt;
&lt;p&gt;Although intensive therapy may be better as a rule, he conceded, it&apos;s less cost-effective when an expensive drug is used. When atorvastatin becomes available as a generic, he wrote, for &quot;$4 a month at Walmart it is simply cheaper  --  and of course better  --  to treat everyone with atorvastatin 80 mg.&quot;&lt;/p&gt;
&lt;p&gt;Assuming a population of Americans ages 30 to 75 with no history of myocardial infarction, the authors developed three treatment models: &lt;ul&gt; &lt;li&gt;Standard National Cholesterol Education Program III (NCEP) treat-to-target recommendation, which requires treatment to an LDL target of less than 190 mg/dL for low-risk individuals, less than 160 mg/dL for moderate-risk, and less than 130 mg/dL for high-risk individuals&lt;/li&gt; &lt;li&gt;Intensive NCEP III treat-to-target approach, with targets of less than 100 mg/dL for high-risk individuals&lt;/li&gt; &lt;li&gt;The tailored model, with 40 mg of simvastatin for patients who whose five-year coronary artery disease risk was 5% to 15% and 40 mg of atorvastatin (Lipitor) for higher-risk patients&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;(In both NCEP III strategies statins would be used in a stepwise fashion  --  20 mg simvastatin, 40 mg simvastatin, 40 mg atorvastatin, and, finally, 80 mg atorvastatin  --  to achieve targets).&lt;/p&gt;
&lt;p&gt;Using standard NCEP III treat-to-target recommendations, &quot;37.9 million U.S. persons should receive statins, of which 7.9 million should receive high dose-potency therapy (atorvastatin 40 to 80 mg),&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;Compared with no treatment, the standard strategy would save an estimated 48 quality adjusted life years (QALYs) per 1,000 Americans treated for five years, or a total of 1.83 million total QALYs.&lt;/p&gt;
&lt;p&gt;The intensive NCEP III treat-to-target recommendations would &quot;recommend that 53.4 million U.S. persons receive statins&quot; and would save about 570,000 more QALYs than the standard treatment.&lt;/p&gt;
&lt;p&gt;Using the computer model, this strategy prevented &quot;about 720,000 more nonfatal CAD events and 30,000 more deaths&quot; than the standard treatment.&lt;/p&gt;
&lt;p&gt;Tailored treatment, by contrast, would require that about the same number of people receive a statin  --  53 million. But only 13.3 million would require high-dose statin therapy, versus roughly 18 million who would be given high-dose statin therapy using the intensive NCEP III strategy.&lt;/p&gt;
&lt;p&gt;Even so, the tailored approach would save 520,000 more QALYs than the intensive treatment approach, the authors found.&lt;/p&gt;
&lt;p&gt;&quot;The tailored treatment approach was superior to both NCEP III approaches, resulting in both more CAD morbidity and mortality prevented in the overall population and higher treatment efficiency (greater benefit per person treated),&quot; they wrote.&lt;/p&gt;
&lt;p&gt;The authors noted a number of limitations, including the paucity of clinical trial data on statin therapy in persons ages 75 or older.&lt;/p&gt;
&lt;p&gt;Moreover, although the model suggested a robust benefit for tailored treatment, &quot;the absolute population-level benefit of the tailored treatment over the treat-to-target approaches are much less certain and can vary substantially on the basis of several factors, such as statin&apos;s effect on total mortality (estimates of which are less precise in the literature than estimates for nonfatal CAD events) and the level of treatment adherence that is achievable in real-world clinical practice.&lt;/p&gt;
&lt;p&gt;&quot;Whether a tailored treatment approach is superior for other conditions in which treat-to-target strategies are currently recommended, such as blood pressure and glycemic control, warrants examination,&quot; they concluded.&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 in part by the Department of Veteran Affairs Health Services Research &amp;amp; Development Service&apos;s Quality Enhancement Research Initiative.&lt;/p&gt;&lt;p&gt;Hayward did not report any financial disclosures.&lt;/p&gt;&lt;p&gt;Cannon reported receiving research/grants/suport from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, Intekrin Therapeutics, Merck, Merck/Schering-Plough Partnership, Novartis, and Takeda. He is a clinical adviser with equity in Automedics Medical Systems.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_127"
                     title="Novel Antiplatelet Called New Standard in ACS (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Cardiology/PCI/tb/17940?impressionId=1265715263036"
                     
      &lt;p&gt;Among patients who underwent planned stenting for treatment of acute coronary syndromes, those treated with the investigational antiplatelet agent ticagrelor (Brilinta) had fewer cardiovascular events than patients who received clopidogrel (Plavix).&lt;/p&gt;
&lt;p&gt;That finding emerged from a prespecified subset analysis of the PLATO (Study of Platelet Inhibition and Patient Outcomes) trial, published online by &lt;em&gt;The Lancet&lt;/em&gt;,&lt;em&gt; &lt;/em&gt;which has ticagrelor being heralded as a potential game-changer in treatment of acute coronary syndromes&lt;em&gt;. &lt;/em&gt;&lt;/p&gt;
&lt;p&gt;For every 1,000 patients admitted to the hospital with a planned invasive strategy, using ticagrelor instead of clopidogrel for 12 months resulted in 11 fewer deaths, 13 fewer MIs, and six fewer cases of stent thrombosis, said Christopher Cannon, MD, of Brigham and Women&apos;s Hospital in Boston.&lt;/p&gt;
&lt;p&gt;Cannon first reported the &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/TCT/16136&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/TCT/16136&quot; target=&quot;_blank&quot;&gt;findings of the subset analysis&lt;/a&gt; last fall at the Transcatheter Cardiovascular Therapeutics meeting in San Francisco. The &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ESCCongress/15752&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ESCCongress/15752&quot; target=&quot;_blank&quot;&gt;full PLATO findings&lt;/a&gt; were reported in August at the European Society of Cardiology meeting in Barcelona.&lt;/p&gt;
&lt;p&gt;At 12 months, 10.7% of the clopidogrel patients versus 9.0% of the ticagrelor patients met the primary endpoint of cardiovascular death, MI, or stroke  --  a 16% relative risk reduction (&lt;em&gt;P&lt;/em&gt;=0.0025).&lt;/p&gt;
&lt;p&gt;Ticagrelor is a direct-acting inhibitor of the adenosine diphosphate receptor P2Y12, which means that the drug turns on and off quickly.&lt;/p&gt;
&lt;p&gt;The study analyzed data from a subset of 13,408 patients who were destined for stenting prior to randomization to ticagrelor or clopidogrel, a population, Cannon said, that better reflected real-world clinical practice.&lt;/p&gt;
&lt;p&gt;In an invited comment also published in &lt;em&gt;The Lancet&lt;/em&gt;, Gregg W. Stone, MD, of Columbia University in New York City, wrote that the &quot;compelling results support ticagrelor as a new standard of care in acute coronary syndromes.&quot;&lt;/p&gt;
&lt;p&gt;However, he wrote, &quot;a personalized approach to drug selection should be used wherein each patient&apos;s individualized risk of ischemia versus bleeding is considered.&quot;&lt;/p&gt;
&lt;p&gt;When the two agents were compared in the total PLATO population of 18,624 ACS patients, the results also favored ticagrelor  --  9.8% versus 11.7% for a relative reduction of 16% (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Among the &quot;therapeutic considerations&quot; Cannon cited at the fall meeting was that &quot;treating 59 patients with ticagrelor instead of clopidogrel for one year would prevent one cardiovascular death, MI, or stroke. Treating just 88 patients would save one life in one year.&quot;&lt;/p&gt;
&lt;p&gt;Kirk Garratt, MD, clinical director of interventional cardiovascular research at Lenox Hill Hospital in New York City, called the latest PLATO findings &quot;a blockbuster paper.&quot;&lt;/p&gt;
&lt;p&gt;&quot;No new antiplatelet drug has lowered mortality before, and you&apos;d expect a more powerful drug to cause more bleeding complications. For ticagrelor to reduce the chance of dying without increasing bleeding risk is huge,&quot; Garratt said in an e-mail.&lt;/p&gt;
&lt;p&gt;Cannon and co-authors wrote that the &quot;mechanisms of the mortality benefit cannot be defined from this analysis but might relate to the reduction in ischemic events without an increase in bleeding.&quot;&lt;/p&gt;
&lt;p&gt;But even as Garratt suggested that ticagrelor was shaping up as the &quot;next big thing,&quot; he said he was concerned that &quot;the vast majority of patients in PLATO came from Europe, the Middle East, or Africa. For some reason, patients from North America (about 11% of the total) didn&apos;t benefit from ticagrelor.&quot;&lt;/p&gt;
&lt;p&gt;Several people have raised questions about the lack of benefit in North America, but Cannon and others have downplayed that finding noting that this was more likely a function of trial design  --  few North American patients recruited  --  rather than a &quot;real&quot; finding.&lt;/p&gt;
&lt;p&gt;Garratt also noted a potential downside to the fast-on/fast-off mechanism: &quot;if a patient misses his evening dose, he&apos;s almost completely unprotected by morning, when people are typically most likely to form blood clots. This could have serious implications after stent placement.&quot;&lt;/p&gt;&lt;p&gt;Although it is true that the drug has a short half life, it is also a more potent agent than clopidogrel. Cannon explained in an email that even if a dose is missed &quot;at the end of 24 hours, you are still at the level of the peak of clopidogrel.&quot;&lt;/p&gt;
&lt;p&gt;In his commentary in &lt;em&gt;The Lancet&lt;/em&gt;, Stone addressed this concern, writing that clopidogrel might still be the drug to use for &quot;selected patients who are at relatively low risk of major bleeding, and/or for whom noncompliance with ticagrelor because of cost or other considerations (e.g., twice daily dosing) is a concern.&quot;&lt;/p&gt;
&lt;p&gt;The multicenter, double-blind PLATO trial randomized patients to ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 to 600 mg loading dose, 75 mg thereafter). Patients were followed for 12 months.&lt;/p&gt;
&lt;p&gt;There was no increase in major bleeding with ticagrelor and no need for transfusions.&lt;/p&gt;
&lt;p&gt;The one side effect that might be troublesome was dyspnea. Cannon said that for every 1,000 patients treated with ticagrelor rather than clopidogrel, six were likely to switch to clopidogrel because of reversible breathing problems.&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 PLATO trial was funded by AstraZeneca.&lt;/p&gt;&lt;p&gt;Cannon disclosed research grants/support from the following companies: Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, Intekrin Therapeutics, Merck, Merck/Schering Plough Partnership, Novartis, and Takeda; and equity in Automedics Medical Systems.&lt;/p&gt;&lt;p&gt;Stone disclosed that he had received honoraria from BMS-Sanofi and AstraZeneca, and that he is on the advisory boards for Boston Scientific and Abbott Vascular.&lt;/p&gt;&lt;p&gt;Garratt had no disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_76"
                     title="STS: Survival Advantage for Bypass Surgery Over Angioplasty"
                     score="-0.005"
                     href="