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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=1265784952307"
                     
      &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(ADP)-induced platelet aggregation did not differ significantly between patients whose clopidogrel therapy was withdrawn abruptly and those in whom clopidogrel was tapered before discontinuation, they wrote in an article in the Feb. 9 issue of the &lt;em&gt;Journal of the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_222"
                     title="Benefits of Cutting Down on Salt Quantified (CME/CE)"
                     score="-0.001"
                     href="http://www.medpagetoday.com/Cardiology/Prevention/tb/18075?impressionId=1265784952307"
                     
      &lt;p&gt;Cutting daily salt intake by 3 grams a day  --  about 30% of the current average  --  could prevent 32,000 strokes and 54,000 myocardial infarctions a year, if a computer model developed by researchers at the University of California, San Francisco accurately depicts the clinical impact of salt reduction.&lt;/p&gt;
&lt;p&gt;The results of the analysis, which used a computer simulation of heart disease in U.S. adults ages 35 to 84, also suggest that even a 1 gram per day reduction in salt over the next decade would be a more cost-effective strategy for treating hypertension than use of even the cheapest antihypertensive, wrote Kirsten Bibbins-Domingo, MD, PhD, and colleagues in a paper published online by the &lt;em&gt;New England Journal of Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;Lee Goldman, MD, MPH, of Columbia University, who co-authored the paper, told &lt;em&gt;MedPage Today&lt;/em&gt; that their study builds on what has long been known about the adverse health effects of salt on a society that believes it to be the spice of life.&lt;/p&gt;
&lt;p&gt;For example, Goldman said that most people seeking a healthy choice will check food labels and restaurant menus for calorie counts and trans fats, but will not pay attention to salt.&lt;/p&gt;
&lt;p&gt;This is not the first time a call for salt reduction has been issued. As recently as last November, a meta-analysis published in &lt;em&gt;BMJ &lt;/em&gt;suggested that cutting salt intake in half  --  a reduction of about 5 grams a day or roughly a teaspoonful  --  would lower the stroke rate by 23% and reduce overall cardiovascular disease by as much as 17%.&lt;/p&gt;
&lt;p&gt;Americans, like those in many Western countries, take in an average of about 10 g of salt a day; whereas the World Health Organization recommends only 5 g per day, and the U.S. Department of Agriculture recommends daily intake be limited to 5.8 g.&lt;/p&gt;
&lt;p&gt;Bibbins-Domingo and colleagues reported that a 3 gram per day reduction in dietary salt would &quot;save 194,00 to 392,00 quality-adjusted life-years and $10 billion to $24 billion in healthcare costs annually.&quot;&lt;/p&gt;
&lt;p&gt;In an editorial that accompanied the study, Lawrence J. Appel, MD, MPH, and Cheryl A.M. Anderson, PhD, MPH, of Johns Hopkins University, wrote that &quot;the evidence supporting the call to reduce salt intake as a means of preventing cardiovascular disease is compelling.&quot;&lt;/p&gt;
&lt;p&gt;They concluded with this admonition: &quot;As we deliberate healthcare reform, let us not neglect this inexpensive, yet highly effective public health intervention for the prevention of disease.&quot;&lt;/p&gt;
&lt;p&gt;It should be noted that Appel was also first author on a position paper from the American Society of Hypertension that also called for salt reduction as public policy.&lt;/p&gt;
&lt;p&gt;Franz H. Messerli, MD, director of the hypertension program at St. Luke&apos;s-Roosevelt Hospital and a colleague of Goldman&apos;s, said the computer model used in the study was impressive but probably underestimates the benefit of reducing dietary salt &quot;because salt reduction has been shown to have a direct (blood pressure independent) effect on the heart, the brain, the kidneys, and also reduces stomach cancer and osteoporosis  --  factors that were not considered in this analysis.&quot;&lt;/p&gt;
&lt;p&gt;But Messerli found it difficult to lead the victory parade, noting &quot;this is a modeling study and statements such as &apos;A modest reduction of 1 gm per day would be more cost-effective than using medication to lower blood pressure in all persons with hypertension&apos; are to be taken with a good grain of salt.&quot;&lt;/p&gt;
&lt;p&gt;Messerli&apos;s measured response was not echoed by his colleagues in the hypertension world.&lt;/p&gt;
&lt;p&gt;For example, Henry Black, MD, president of the American Society of Hypertension, and director of hypertension research at the New York University School of Medicine said that, although the paper extended the findings of many other studies, it is &quot;more comprehensive and is especially useful by comparing the benefits of [sodium] and [salt] reduction to those of other widely accepted public health approaches that the public and governmental bodies have embraced, including drug treatment.&quot;&lt;/p&gt;
&lt;p&gt;Clyde Yancy, MD, president of the American Heart Association, said that while the study was a computer modeling analysis that may be as good as it gets because &quot;it would be impossible to do a randomized trial in large numbers of high versus low sodium consumption, and the use of modeling with reasonable assumptions represents a solid if not ideal alternative.&quot;&lt;/p&gt;
&lt;p&gt;Moreover, Yancy argued that &quot;the costs and effort involved in setting and/or changing policy&quot; require strong imperatives, and he thought the data reported today &quot;provide that imperative.&quot;&lt;/p&gt;
&lt;p&gt;Three grams of salt comes to about a teaspoonful, but Goldman said it was foolish to think of sodium reduction in terms of such measurements because so much sodium comes from processed foods and from restaurant food. Achieving the needed reduction requires a concerted national effort.&lt;/p&gt;
&lt;p&gt;Bibbins-Domingo noted that their study was limited &quot;by any uncertainty concerning the data entered into the model.&quot;&lt;/p&gt;
&lt;p&gt;Also they noted that they did not &quot;account fully for the possible effects of salt reduction that are unrelated to control of blood pressure  --  for example, potential improvements in outcomes for the increasing numbers of patients with heart failure or prevention of other serious conditions, such as end-stage renal 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 supported in part by a grant from the American Heart Association Western States Affiliate and a grant from the University of California, San Francisco Clinical and Translational Sciences Institute.&lt;/p&gt;&lt;p&gt;The authors said they had &quot;no potential conflicts of interest relevant to this article.&quot;&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&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_150"
                     title="Circulatory Effects Seen with A-Bomb Radiation (CME/CE)"
                     score="-0.004"
                     href="http://www.medpagetoday.com/Cardiology/Atherosclerosis/tb/17977?impressionId=1265784952307"
                     
      &lt;p&gt;Survivors of the atomic bomb blasts at Hiroshima and Nagasaki have an increased risk of dying from heart disease and stroke, researchers found.&lt;/p&gt;
&lt;p&gt;The estimated excess relative risk per Gy was 9% for stroke and 14% for heart disease (&lt;em&gt;P&lt;/em&gt;&amp;#8804;0.02 for both), Yukiko Shimizu, DMSc, of the Radiation Effects Research Foundation in Hiroshima, and colleagues reported online in &lt;em&gt;BMJ&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Significant estimated increases in risk started at doses of 0.5 Gy and higher.&lt;/p&gt;
&lt;p&gt;&quot;The effect of radiation on risk of circulatory disease is potentially a very important public health concern,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;&quot;Given the widespread use of multiple computed tomography scans, and other relatively high-dose diagnostic medical procedures, as well as radiotherapy that exposes the heart, the implications are substantial insofar as effects occur at doses under 1 Gy.&quot;&lt;/p&gt;
&lt;p&gt;But they cautioned that &quot;robust confirmatory evidence from other studies is needed.&quot;&lt;/p&gt;
&lt;p&gt;To explore the relationship between radiation exposure and circulatory disease, Shimizu and colleagues looked at more than 50 years of data from the Life Span Study, which has prospectively followed survivors of the atomic bomb blasts in Japan since 1950.&lt;/p&gt;
&lt;p&gt;The analysis included 86,611 individuals who were exposed to radiation at doses ranging from 0 to more than 3 Gy, although 86% received less than 0.2 Gy.&lt;/p&gt;
&lt;p&gt;Through 2003, 9,622 of the participants died from stroke and 8,463 died from heart disease.&lt;/p&gt;
&lt;p&gt;For stroke, a quadratic formula fit the data better than a linear dose-response model, indicating relatively low risk of stroke at lower radiation doses. The linear dose-response model provided the best fit to the data for heart disease, suggesting an excess risk even at lower doses. However, there was not a significant increase in estimated risk for exposures less than 0.5 Gy.&lt;/p&gt;
&lt;p&gt;Adjusting for smoking, alcohol intake, education, occupation, obesity, and diabetes had very little effect on the risk estimates, the researchers wrote.&lt;/p&gt;
&lt;p&gt;To control for the possible misclassification of cancers as circulatory diseases, the researchers re-ran their analysis after excluding those individuals with a history of cancer.&lt;/p&gt;
&lt;p&gt;In this analysis, the excess relative risk for stroke became nonsignificant (&lt;em&gt;P&lt;/em&gt;=0.11), but that for heart disease remained significant (&lt;em&gt;P&lt;/em&gt;=0.03).&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, Mark Little, PhD, of Imperial College London, said the study &quot;adds to a growing body of evidence suggesting an association between cardiovascular disease and exposure to low-moderate levels of radiation, as well as the well-known (and mechanistically well-understood) association at high doses.&quot;&lt;/p&gt;
&lt;p&gt;&quot;However,&quot; he continued, &quot;statistical associations do not prove a causal association, and it is unclear whether the biological mechanisms operating at high doses of radiation apply to low doses.&quot;&lt;/p&gt;
&lt;p&gt;Previous studies, including some randomized controlled trials, have linked high doses of radiation from treatment for Hodgkin&apos;s disease and breast cancer to excess deaths from cardiovascular disease.&lt;/p&gt;
&lt;p&gt;Studies looking at lower doses, however, have yielded mixed results.&lt;/p&gt;
&lt;p&gt;James Thrall, MD, radiologist-in-chief at Massachusetts General Hospital and chair of the American College of Radiology&apos;s board of chancellors, said the results of the current study were not surprising.&lt;/p&gt;
&lt;p&gt;&quot;We have known for a long time that sufficient radiation can have adverse effects on the circulation,&quot; Thrall said in an interview.&lt;/p&gt;
&lt;p&gt;However, he noted that significant associations among the atomic bomb survivors were identified only for doses higher than 0.5 Gy, which is roughly equal to 500 mSv.&lt;/p&gt;
&lt;p&gt;Radiation exposure from typical CT scans ranged from 2 to 31 mSv in a recent study. (See &lt;a href=&quot;http://www.medpagetoday.com/Radiology/DiagnosticRadiology/17530&quot; mce_href=&quot;http://www.medpagetoday.com/Radiology/DiagnosticRadiology/17530&quot; target=&quot;_blank&quot;&gt;CT Scans May Deliver Higher-than-Expected Radiation Doses&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Thrall said that risk of circulatory disease is not a consideration when clinicians are weighing the risks and benefits of a CT scan.&lt;/p&gt;
&lt;p&gt;&quot;And I would say that this article does not suggest that that&apos;s a serious concern.&quot;&lt;/p&gt;
&lt;p&gt;The potential mechanisms underlying the association between radiation exposure and circulatory disease remains unclear, but the researchers said &quot;evidence suggests that pro-inflammatory responses to radiation, cellular loss or functional changes in the endothelium, or microvascular damage&quot; may be involved.&lt;/p&gt;
&lt;p&gt;The editorialist Little noted, however, &quot;although we have evidence for [inflammation&apos;s] involvement in the development of cardiovascular disease at high doses of radiation, the mechanism is unclear at low and moderate doses, particularly for occupational exposure, where people receive on average much less than one electron track per cell per day.&quot;&lt;/p&gt;
&lt;p&gt;The study authors noted some limitations of the study: &lt;ul&gt; &lt;li&gt;The ascertainment of circulatory disease from death certificates has limited diagnostic accuracy.&lt;/li&gt; &lt;li&gt;Analyses for potential confounders were incomplete.&lt;/li&gt; &lt;li&gt;There were uncertain associations for exposures below 0.5 Gy.&lt;/li&gt; &lt;li&gt;There is inadequate information about biological mechanisms.&lt;/li&gt; &lt;li&gt;Generalizability to Western populations is uncertain.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Little also pointed to the selection of patients, particularly in the early years of follow-up, as a weakness because these individuals would have been exposed to war and stressful conditions, which increase the risk of cardiovascular disease.&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 Radiation Effects Research Foundation in Hiroshima and Nagasaki is a private nonprofit foundation funded by the Japanese Ministry of Health, Labor, and Welfare and the U.S. Department of Energy, the latter in part through the National Academy of Sciences.&lt;/p&gt;&lt;p&gt;Neither the study authors nor the editorialist reported any conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_953"
                     title="ACC: PROTECT AF and Economics of SYNTAX Top Interventional Trials"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/ACC/tb/13477?impressionId=1265784952307"
                     
      ORLANDO, March 28 -- A mechanical approach to stroke prevention in patients with atrial fibrillation -- and yet more results from a ballyhooed trial that compared stenting to bypass surgery -- are hot topics in this exclusive &lt;em&gt;MedPage Today&lt;/em&gt; discussion with the experts.
              &lt;p&gt; 
              &lt;p&gt;Spencer King, III, M.D., of the St. Joseph&apos;s Hospital Heart and Vascular Institute in Atlanta and spokesman for the American College of Cardiology, joined Elliott M. Antman, M.D., of Harvard Medical School, a spokesperson for the American Heart Association. They discussed the clinical implications of PROTECT AF, a trial of a device to close off the left atrial appendage as alternative to warfarin therapy in patients with atrial fibrillation.
              &lt;p&gt; 
              &lt;p&gt;Drs. King and Antman also weighed in on the economics of stent-versus-CABG in the SYNTAX trial.
              &lt;p&gt; 
              &lt;p&gt;Peggy Peck, &lt;em&gt;MedPage Today&lt;/em&gt; executive editor, moderated the discussion.
            
    </recommendedItem>
    <recommendedItem id="20090101_19_975"
                     title="ACC: Polypill Packs Broad Cardio Punch in a Single Swallow"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/ACC/tb/13500?impressionId=1265784952307"
                     
      ORLANDO, March 30 -- Combining three antihypertensives, a statin, and an aspirin in a single, five-drug capsule appears to achieve the same benefit as giving the drugs individually, although the statin in the combination was slightly less effective, researchers said here.
              &lt;br&gt; 
              &lt;br&gt;While the combination did appear to blunt the potency of simvastatin -- reducing cholesterol by 27 mg/L (0.70 mmol/L) versus 32 mg/L (0.83 mmol/L) for simvastatin monotherapy (&lt;em&gt;P&lt;/em&gt;&lt;0.04) -- the statin still achieved significant reductions in LDL compared with controls (&lt;em&gt;P&lt;/em&gt;&lt;0.0001), said Salim Yusuf, D.Phil., F.R.C.P.C., of the Population Health Research Institute at McMaster University and Hamilton Health Sciences in Hamilton, Ontario, Canada.
              &lt;br&gt; 
              &lt;br&gt;Dr. Yusuf, co-chair and principal investigator of The Indian Polycap Study (TIPS), reported findings of the phase II trial today at the American College of Cardiology meeting here. The results were simultaneously published online in &lt;em&gt;The Lancet&lt;/em&gt;.
              &lt;br&gt; 
              &lt;br&gt;Dr. Yusuf said the polypill reduced LDL by about 25%, compared with a 28% reduction with simvastatin monotherapy, &quot;a difference that was statistically significant but clinically not meaningful.&quot;
              &lt;p&gt; 
              &lt;p&gt;The primary outcomes were reductions in blood pressure for antihypertensive drugs, LDL for the statin, heart rate for the beta blocker, and urinary 11-dehydrothromboxane B2 for antiplatelet effects of aspirin.
              &lt;p&gt; 
              &lt;p&gt;Dr. Yusuf estimated that the combined blood pressure and LDL reductions achieved by the polypill &quot;could reduce heart disease by 60% and stroke by 50%.&quot;
              &lt;p&gt; 
              &lt;p&gt;The polypill is one of three strategies developed by the World Heart Federation to combat what has been described as a worldwide epidemic of cardiovascular disease. The first two strategies are weight loss and smoking cessation.
              &lt;p&gt;
              &lt;p&gt;In a follow-up interview, Dr. Yusef said that Wellcome Trust has announced a competition to develop a polypill for primary prevention. &quot;I&apos;ve been working on the grant proposal in every spare minute,&quot; he said, &quot;the deadline is tonight.
              &lt;p&gt;
              &lt;p&gt;Wellcome Trust has limited the competition to companies in India and has said it will award �5 million to the winning company to support a clinical trial. &quot;If it costs no more that that, the company will need to go elsewhere for funding.&quot;
              &lt;p&gt;
              &lt;p&gt;&quot;It is my fervent belief that 90% of premature cardiovascular deaths can be prevented in the next 50 years,&quot; Dr. Yusuf said. 
              &lt;p&gt; 
              &lt;p&gt;But others were not impressed.
              &lt;p&gt; 
              &lt;p&gt;Robert Bonow, M.D., professor of medicine at Chicago&apos;s Feinberg School of Medicine at Northwestern University, cautioned restraint. 
              &lt;p&gt; 
              &lt;p&gt;&quot;We already have a polypill -- it&apos;s called exercise,&quot; Dr. Bonow said.
              &lt;p&gt; 
              &lt;p&gt;Dr. Bonow, who is a former president of the American Heart Association, said, however, that he did believe there was a role for a polypill in secondary prevention.
              &lt;p&gt; 
              &lt;p&gt;After myocardial infarction, patients should be on multiple drugs to prevent recurrent MI, he said, and  &quot;that is when compliance can be a real problem, when the patient needs to take four or five drugs so a single pill could be a big help.&quot;
              &lt;p&gt; 
              &lt;p&gt;Steven Nissen, M.D., director of cardiovascular research at the Cleveland Clinic Foundation, didn&apos;t mince words. &quot;I&apos;m not impressed,&quot; he said after listening to Dr. Yusuf&apos;s presentation.
              &lt;p&gt; 
              &lt;p&gt;Although he conceded that the polypill &quot;didn&apos;t hurt anyone,&quot; he pointed out that with a mere 12 weeks of data it would be premature to endorse the polypill as safe. 
              &lt;p&gt; 
              &lt;p&gt;&quot;If a patient does get side-effects, how do you know which drug it is? And, you can&apos;t titrate a polypill,&quot; Dr. Nissen said. 
              &lt;p&gt; 
              &lt;p&gt;He concluded that the polypill was probably &quot;not approvable&quot; in the U.S. 
              &lt;p&gt; 
              &lt;p&gt;Whether or not Dr. Nissen&apos;s assessment of approvability is accurate, developing a polypill for use in the U.S. would be an arduous and expensive proposition.
              &lt;p&gt; 
              &lt;p&gt;Dr. Yusuf estimated that the phase II trial conducted in India cost about $1 million, a drop in the bucket, he said, for a clinical trial. 
              &lt;p&gt; 
              &lt;p&gt;Attempting such a trial in the U.S. would probably cost hundreds of millions of dollars and tens of thousands of patients would need to be recruited, said Hani N. Sabbah, Ph.D., of Henry Ford Hospital in Detroit. Dr. Sabbah, who is co-chair of the ACC program committee, moderated a press conference where Dr. Yusuf discussed the results of the polypill trial. 
              &lt;p&gt; 
              &lt;p&gt;Dr. Yusuf said the blood pressure reductions achieved with the polypill -- an average reduction of systolic BP by 7.4 mmHg and diastolic BP by 5.6 mmHg compared with controls not taking antihypertensives -- were less than the 20 mmHg/11 mmHg reductions that had been projected. 
              &lt;p&gt; 
              &lt;p&gt;But even those more modest reductions cut the risk of coronary heart disease by 24% and stroke risk by 33%. 
              &lt;p&gt; 
              &lt;p&gt;The trial recruited 2,053 adults (age 45 to 80) at 50 centers in India. Criteria included no history of cardiovascular disease and just one risk factor.  Patients were recruited from March 5, 2007 through August 5, 2008.
              &lt;p&gt; 
              &lt;p&gt;Participants were randomized to the polypill -- thiazide (12.5 mg), atenolol (50 mg), ramipril (5 mg), simvastatin (20 mg) and aspirin (100 mg), or to one of eight comparator groups: aspirin alone, simvastatin alone, thiazide alone, thiazide plus ramipril, thiazide plus atenolol, ramipril plus atenolol, all three blood pressure drugs, and all three blood pressure drugs plus aspirin. 
              &lt;p&gt; 
              &lt;p&gt;Some 412 individuals were randomized to the polypill and 200 to each of the comparator arms. Patients were given the study drug for 12 weeks.
              &lt;p&gt; 
              &lt;p&gt;To lessen the risk of hypotension, patients randomized to an arm that included ramipril were initiated at a dose of 2.5 mg for seven days then titrated up to 5 mg.
              &lt;p&gt; 
              &lt;p&gt;Among the findings:
              &lt;p&gt; 
              &lt;ul&gt;
                &lt;li&gt;The polypill reduced 11-dehydrothromboxane B2 by 283.1 ng/mmol creatinine. This was similar to reductions achieved by aspirin alone (348.8 ng/mmol creatinine) and aspirin in combination with three blood pressure drugs (350.0 ng/mmol creatinine). 
                &lt;li&gt;Heart rate reductions with the polypill and in treatment groups taking atenolol averaged 7 beats/min, which was significantly lower than groups not taking the beta blocker (&lt;em&gt;P&lt;/em&gt;&lt;0.0001). 
                &lt;li&gt;BP reductions increased with the number of drugs used. One drug reduced systolic pressure by an average of 2.2 mmHg and diastolic by 1.3 mmHg. With two drugs the reduction was 4.7 mmHg/3.6 mmHg, and with three, the drop was 6.3 mmHg/4.5 mmHg.
              &lt;/ul&gt;
              &lt;p&gt; 
              &lt;p&gt;In an editorial that accompanied &lt;em&gt;The Lancet&lt;/em&gt; paper, Christopher P. Cannon, M.D., of Harvard and a senior investigator with the TIMI Study Group, said the major appeal of the polypill is its simplicity and low cost. 
              &lt;p&gt; 
              &lt;p&gt;That could not only translate into &quot;broad applicability in areas of the world with less access to medical treatment&quot;, he wrote, but also &quot;fit well in to more modern medical systems, in which large proportions of patients with risk factors are untreated.&quot; 
              &lt;p&gt; 
              &lt;p&gt;Dr. Cannon concluded that while TIPS &quot;does not provide all the answers, the study does take a first and crucial step forward and raises hope that, in conjunction with other global efforts to improve diet and exercise, the polypill could one day substantially reduce the burden of cardiovascular disease in the world.
              &lt;p&gt; 
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt;The study was sponsored by Cadila Pharmaceuticals, India, which played no role in data collection, analysis or interpretation.
              &lt;p&gt; 
              &lt;p&gt;Dr. Yusuf reported receiving lecture fees and research grants from Cadila for the conduct of this trial. Dr. Yusuf also reported being named on a patent for a urinary assay of thromboxane, with royalties donated to McMaster University.
              &lt;p&gt; 
              &lt;p&gt;Dr. Cannon reported research grants/support form Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, Merck, Merck/Schering Plough Partnership. Dr. Cannon said he was a clinical advisor and equity partner in Automedics Medical Systems.
              &lt;p&gt; 
              &lt;p&gt;Dr. Nissen reported that the Cleveland Clinic Coordinating Center for Clinical Research has received research support to perform clinical trials from Pfizer, Astra Zeneca, Sankyo, Takeda, sanofi-aventis, Lilly, Roche, Daiichi-Sankyo, and Novartis. Dr. Nissen consults for many pharmaceutical companies, but says he requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction.
              &lt;p&gt; 
              &lt;p&gt;Dr. Bonow reported no conflicts of interest.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
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