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<recommendedContent xmlns="http://api.mspoke.com">
    <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=1265814945078"
                     
      &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(ADP)-induced platelet aggregation did not differ significantly between patients whose clopidogrel therapy was withdrawn abruptly and those in whom clopidogrel was tapered before discontinuation, they wrote in an article in the Feb. 9 issue of the &lt;em&gt;Journal of the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_278"
                     title="FDA Okays First Percutaneous Heart Valve"
                     score="0.004"
                     href="http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/tb/18135?impressionId=1265814945078"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has approved the Melody Transcatheter Pulmonary Valve and Ensemble Delivery System, the first heart valve designed for implantation through a catheter in a leg vein.&lt;/p&gt;
&lt;p&gt;The device gives congenital heart defect patients with poorly functioning pulmonary valve conduits new treatment options without requiring open heart surgery.&lt;/p&gt;
&lt;p&gt;The valve does not cure the condition and may wear to the point of needing replacement over time, but a tissue valve in the device maintains proper blood flow-direction, which allows the valve to function longer than usual, an FDA statement said.&lt;/p&gt;
&lt;p&gt;Approval was based on clinical studies of 99 U.S. patients and 68 European patients.&lt;/p&gt;
&lt;p&gt;Participants showed improved heart function, and a majority noted improvements in clinical symptoms, the statement said.&lt;/p&gt;
&lt;p&gt;The limited durability of the device was similar to other existing treatments in the trial, with 21% of U.S. patients experiencing a stent fracture, the release said.&lt;/p&gt;
&lt;p&gt;Device manufacturer Medtronic must complete two postapproval studies to test long-term risks and benefits, including one study with 150 participants from the original clinical trials and more than 100 additional patients, who will each undergo a five-year evaluation.&lt;/p&gt;
&lt;p&gt;An additional condition of the device&apos;s approval is a review of healthcare professional specialization required for device implantation. The manufacturer must also maintain a database of valve recipients.&lt;/p&gt;
&lt;p&gt;The transcatheter valve was approved under the Humanitarian Device Exception (HDE) program, which supports device development for conditions affecting fewer than 4,000 people and allows approval for limited use with reasonable assurances that the device health benefit outweighs risk of injury or illness.&lt;/p&gt;
&lt;p&gt;Products with HDE approval can only be used at medical institutions under an institutional review board and cannot be sold for more than the cost of research, development, fabrication, and distribution.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_231"
                     title="FDA Adds Cardio Warnings to Weight-Loss Drug"
                     score="-0"
                     href="http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/tb/18088?impressionId=1265814945078"
                     
      &lt;p&gt;WASHINGTON  --  The FDA said the weight-loss drug sibutramine (Meridia) should not be taken by patients with history of cardiovascular disease following a review of additional data showing an increased risk of heart attack and stroke among that population.&lt;/p&gt;
&lt;p&gt;The agency said the manufacturer, Abbott, has agreed to add the contraindication to its labeling, which will be expanded to include patients with a history of the following: &lt;ul&gt; &lt;li&gt;Coronary artery disease (i.e., heart attack, angina)&lt;/li&gt; &lt;li&gt;Stroke or transient ischemic attack&lt;/li&gt; &lt;li&gt;Heart arrhythmia&lt;/li&gt; &lt;li&gt;Congestive heart failure&lt;/li&gt; &lt;li&gt;Peripheral arterial disease&lt;/li&gt; &lt;li&gt;Uncontrolled hypertension (&amp;gt;145/90 mmHg)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The initial review of sibutramine began in November 2009 when the FDA received preliminary data from the SCOUT study suggesting patients using the drug had a higher risk for cardiovascular events. (See &lt;a href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/17147&quot; mce_href=&quot;http://www.medpagetoday.com/ProductAlert/Prescriptions/17147&quot; target=&quot;_blank&quot;&gt;Early Data Link Diet Drug to MI, Stroke, and Cardiac Death&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Prior to review, the product label included a warning for patients with cardiovascular disease.&lt;/p&gt;
&lt;p&gt;Healthcare professionals should monitor patients for increase in blood pressure and heart rate and should discontinue therapy if either increase is observed, an FDA statement said.&lt;/p&gt;
&lt;p&gt;Patients should also discontinue use of sibutramine if they do not lose 5% of their baseline body weight within the first three to six months of treatment, as the drug may not be effective and puts the patient at unnecessary risk, the release said.&lt;/p&gt;
&lt;p&gt;The FDA said its review of SCOUT study data, as well as other information related to the drug&apos;s risks and benefits, is ongoing and will be followed by an open public advisory committee meeting to determine if it requires additional regulatory action.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20090101_19_3116"
                     title="New Standard Reduces Heparin Potency"
                     score="-0.005"
                     href="http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/16253?impressionId=1265814945078"
                     
      &lt;p&gt;WASHINGTON  --  Beginning next week, heparin shipped to hospitals and pharmacies will be about 10% less potent than that currently available, a change that is likely to have clinical implications when the drug is administered as a bolus IV dose, the FDA said today.&lt;/p&gt;
&lt;p&gt;The loss in potency is the result of new manufacturing controls  --  including a new reference standard for the drug&apos;s unit dose  --  adopted by United States Pharmacopeia (USP), a nonprofit standards-setting organization.&lt;/p&gt;
&lt;p&gt;The FDA has known for months that the reference standards for heparin would change, but learned only three weeks ago that the change would reduce potency, said John K. Jenkins, MD, director of the office of new drugs, at the FDA&apos;s Center for Drug Evaluation and Research.&lt;/p&gt;
&lt;p&gt;The difference in potency, which is estimated at about 10% per labeled unit, is unlikely to affect subcutaneous administration because there is a wide range of bioavailability when heparin is administered by that route, he said.&lt;/p&gt;
&lt;p&gt;Jenkins said the new standard has been in the works since 2007, when contamination of heparin resulted in hundreds of severe allergic reactions and deaths as well as widespread recalls and shortages.&lt;/p&gt;
&lt;p&gt;When USP circulated the new drug monograph for comment during the spring and summer, &quot;there was little concern about clinical significance,&quot; but as manufacturers began making heparin using the new standard, one of the companies discovered the difference in potency and informed the FDA, Jenkins said.&lt;/p&gt;
&lt;p&gt;The FDA then contacted other manufacturers and confirmed that the reduced potency was observed by all drugmakers using the new reference standard.&lt;/p&gt;
&lt;p&gt;At that point, the FDA contacted USP to determine if the rollout of the new standard could be delayed until in vitro and in vivo testing could confirm the exact potency range.&lt;/p&gt;
&lt;p&gt;But by then, it was too late. The four makers of heparin  --  APP, Hospira, Baxter, and B. Braun  --  had all retooled their manufacturing processes to make the drug based on the new standard, which takes effect today.&lt;/p&gt;
&lt;p&gt;The best that the FDA could manage was an agreement to delay shipment of the new heparin until Oct. 8, Jenkins said.&lt;/p&gt;
&lt;p&gt;To differentiate &quot;new&quot; from &quot;old&quot; heparin once supplies hit the shelves, the four manufacturers have agreed to special labeling on the new product.&lt;/p&gt;
&lt;p&gt;Three companies  --  APP, the largest manufacturer, which markets heparin in vials; Baxter, which sells the drug in IV bags; and B. Braun, which also markets heparin in IV bags  --  have all agreed to add the letter &quot;N&quot; next to the lot number or expiration date on labels of &quot;new&quot; heparin.&lt;/p&gt;
&lt;p&gt;The fourth manufacturer  --  Hospira which markets heparin in intravenous bags, vials, and syringes  --  said it will identify the new heparin with a unique numbering system.&lt;/p&gt;
&lt;p&gt;Meanwhile, the FDA is cooperating with the companies to conduct both in vitro and in vivo testing to determine the exact extent of the potency difference. The in vitro tests should be completed in a few weeks, but &quot;animal tests will take longer,&quot; said Jenkins. He estimated the in vivo results would be available in less than two months.&lt;/p&gt;
&lt;p&gt;But even with those test results, the FDA may not require changes in heparin labeling because dosing of the drug has always been a matter of &quot;individual monitoring of patients&quot; to determine the anticoagulant effect.&lt;/p&gt;
&lt;p&gt;Regardless of potency, Jenkins said, heparin should continue to be dosed based on results of patient monitoring.&lt;/p&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=1265814945078"
                     
      &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>
</recommendedContent>