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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_3258"
                     title="Bisphosphonates Tied to Esophageal Cancer (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Endocrinology/Osteoporosis/tb/22017?impressionId=1284018990917"
                     
      &lt;p&gt;A second look at British registry data indicates that esophageal cancer may be more common after all in patients taking oral bisphosphonate drugs for long periods.&lt;/p&gt;
&lt;p&gt;In a nested case-control analysis involving some 80,000 patients tracked for more than seven years on average, individuals diagnosed with esophageal cancer of were 1.93 times as likely (95% CI 1.37 to 2.70) to have received at least 10 prescriptions for oral bisphosphonates, compared with controls not having cancer, reported Jane Green, MD, DPhil, of the University of Oxford in England, and colleagues online in &lt;em&gt;BMJ&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The likelihood of receiving at least one bisphosphonate prescription among esophageal cancer patients was 1.30 (95% CI 1.02 to 1.66) relative to controls, the researchers found.&lt;/p&gt;
&lt;p&gt;The findings were especially remarkable because another research group conducting a case-control study of the same registry  --  Great Britain&apos;s General Practice Research Database, containing records on some six million patients  --  &lt;a href=&quot;http://www.medpagetoday.com/Oncology/OtherCancers/21629&quot; mce_href=&quot;http://www.medpagetoday.com/Oncology/OtherCancers/21629&quot; target=&quot;_blank&quot;&gt;recently reported no increase&lt;/a&gt; in esophageal cancer rates in patients treated with bisphosphonates.&lt;/p&gt;
&lt;p&gt;Green and colleagues explained the discrepancy by noting that mean observation time prior to diagnosis in the other analysis was substantially shorter, 4.5 versus 7.7 years.&lt;/p&gt;
&lt;p&gt;Also, they noted, their study used five matched controls for each case, whereas the earlier study had equal numbers of cases and controls.&lt;/p&gt;
&lt;p&gt;&quot;Our study thus had the potential to include people with longer durations of bisphosphonate use and also had greater statistical power,&quot; Green and colleagues asserted.&lt;/p&gt;
&lt;p&gt;An accompanying editorial by an FDA epidemiologist, Diane Wysowski, PhD, noted that links between bisphosphonates and esophageal cancer have been proposed for more than 15 years. (The editorial carried a disclaimer that it did not necessarily express the agency&apos;s official view.)&lt;/p&gt;
&lt;p&gt;The FDA has collected a total of 68 case reports of esophageal cancer in patients taking bisphosphonates, half in the U.S. and the rest in Europe and Japan, but has not ordered label warnings. Prescribing information for oral bisphosphonates does include information on risks of other esophageal effects such as erosions and strictures, and dosing instructions are geared toward speeding the drugs through the esophagus.&lt;/p&gt;
&lt;p&gt;The suggestion of a connection between these agents and esophageal cancer have prompted efforts at systematic research, including the new study.&lt;/p&gt;
&lt;p&gt;Green and colleagues examined records of 2,954 patients with esophageal cancer, 2,018 patients with stomach cancer, and 10,641 with colon cancer, along with five controls for each of these cases matched for age, sex, observation time prior to diagnosis, and practice location.&lt;/p&gt;
&lt;p&gt;About 3.1% of the esophageal cancer patients had received at least one bisphosphonate prescription before diagnosis, compared with 2.4% of the controls over a similar period (relative risk 1.30 after adjusting for smoking status, alcohol intake, and body mass index).&lt;/p&gt;
&lt;p&gt;Rates of bisphosphonate use were similar in the stomach and colon cancer patients relative to controls, the researchers found.&lt;/p&gt;
&lt;p&gt;In the esophageal cancer patients, the relationship with bisphosphonate use appeared to strengthen with the number of prescriptions and with the estimated duration of use.&lt;/p&gt;
&lt;p&gt;Green and colleagues calculated a relative risk of 1.93 for receiving at least 10 prescriptions in cases versus controls, whereas esophageal cancer patients had virtually the same likelihood of receiving one to nine prescriptions as controls (RR 0.93, 95% CI 0.66 to 1.31).&lt;/p&gt;
&lt;p&gt;Similarly, estimated duration of use (based on the distribution of prescriptions over time) of at least three years was linked to esophageal cancer with a relative risk of 2.24 (95% CI 1.47 to 3.42), but shorter duration was seen in about equal numbers of cases and controls.&lt;/p&gt;
&lt;p&gt;These patterns were also not seen in the stomach or colorectal cancer patients.&lt;/p&gt;
&lt;p&gt;&quot;The association [in esophageal cancer patients] did not vary materially within subgroups defined by age, sex, smoking status, alcohol drinking, or body mass index; diagnosis of osteoporosis, previous fracture, or previous upper gastrointestinal disease; or prescription of nonsteroidal anti-inflammatory drugs, corticosteroids, or acid suppressant drugs,&quot; Green and colleagues added.&lt;/p&gt;
&lt;p&gt;But the researchers stopped short of concluding that bisphosphonate treatment contributes to esophageal cancer, noting that they could not &quot;rule out the possibility that the associations observed reflect other, unknown, factors that are linked to prolonged use of bisphosphonates and that also increase the risk of esophageal cancer.&quot;&lt;/p&gt;
&lt;p&gt;Other limitations included the lack of data on the extent to which patients used drugs prescribed to them or on prescriptions received before entry into the database.&lt;/p&gt;
&lt;p&gt;in the editorial, Wysowski didn&apos;t take a position on whether there is a causal link, noting that the evidence remains divided and weak. Even if there is such a connection, she wrote, &quot;the incidence in the population would be expected to remain relatively low.&quot;&lt;/p&gt;
&lt;p&gt;Still, she suggested that physicians consider the possibility of risk when prescribing the drugs and, when talking to patients, reiterate the importance of following the label directions for taking these drugs, which minimize the drugs&apos; direct contact with the esophageal tract.&lt;/p&gt;
&lt;p&gt;Wysowski also recommended that doctors urge patients to report difficulty swallowing or other gastrointestinal symptoms promptly.&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 UK Medical Research Council and Cancer Research UK provided funding for the database project and the current analysis.&lt;/p&gt;&lt;p&gt;Study authors and the editorialist declared they had no competing financial interests.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3197"
                     title="ESC: No Blockbusters in Day One Hot Line Trials"
                     score="0.008"
                     href="http://www.medpagetoday.com/MeetingCoverage/ESCCongress/tb/21934?impressionId=1284018990917"
                     
      &lt;p&gt;STOCKHOLM  --  In this &lt;em&gt;MedPage Today&lt;/em&gt; exclusive InFocus video report, the president of the American Heart Association takes the temperature of the first group of Hot Line trials reported here at the European Society of Cardiology congress.&lt;/p&gt;
&lt;p&gt;Ralph L. Sacco, MD, MS, of the University of Miami, said the ALPHA-OMEGA trial  --  which found that fortifying margarine with omega-3 fatty acids derived from fish and plants was not an effective secondary prevention strategy  --  will probably not dampen enthusiasm for supplements. Sacco added that &quot;the whole fish&quot; approach is still a better way to include omega-3s in a heart-healthy diet. And, while the data on genetic testing to identify &quot;nonresponders&quot; to clopidogrel were interesting, he said they were not persuasive. Finally, Sacco told Peggy Peck, &lt;em&gt;MedPage Today &lt;/em&gt;executive editor, that a trial of intracoronary transplantation of bone marrow cells provided promising data that were still a long way from mainstream medicine.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_3191"
                     title="ESC: It&apos;s Not Butter and It&apos;s Not Better (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/MeetingCoverage/ESCCongress/tb/21921?impressionId=1284018990917"
                     
      STOCKHOLM  --  Adding margarine enriched with omega-3 fatty acids as a dietary intervention did not prevent second heart attacks in older men and women at risk for worsening heart disease, researchers said here.&lt;br&gt;
&lt;br&gt;The study results are doubly disappointing since the margarine intervention did initially reduce events, but by 30 months the evidence of that benefit had disappeared, said Daan Kromhout, MPH, PhD, of Wageningen University in the Netherlands.&lt;br&gt;
&lt;br&gt;After more than 40 months, consumption of the omega-3 fatty acid fortified margarines &quot;had no effect on the rate of major cardiovascular events,&quot; he reported at a Hot Line session today at the European Society of Cardiology meeting. The findings were simultaneously published online by the &lt;em&gt;New England Journal of Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;The ALPHA-OMEGA trial randomized 4,837 MI survivors, 60 to 80 years old, to margarine supplemented with a combination of eicosapentaenoic acid and docosahexaenoic acid (EPA and DHA), or with 2 grams of the plant-derived fatty acid alpha-linolenic acid (ALA), or a third supplemented with all three versus a placebo margarine.&lt;/p&gt;
&lt;p&gt;The primary endpoint was the combined rate of fatal and non-fatal cardiovascular events and cardiac interventions.&lt;/p&gt;
&lt;p&gt;Neither EPA-DHA nor ALA reduced this endpoint, the researchers reported (hazard ratio with EPA-DHA, 1.01; 95% confidence interval 0.87 to 1.17, &lt;em&gt;P &lt;/em&gt;=0.93).&lt;/p&gt;
&lt;p&gt;A prespecified subgroup analysis in women found that use of the ALA-fortified margarine reduced the rate of cardiovascular events compared with placebo or with the EPA-DHA margarine, but the difference failed to reach statistical significance (HR 0.73, 95% CI 0.51 to 1.03, &lt;em&gt;P&lt;/em&gt;=0.07).&lt;/p&gt;
&lt;p&gt;Alfred Bove, MD, of Temple University in Philadelphia, said the findings surprised him &quot;because most of the data on omega-3 fatty acids come from epidemiologic studies and those were positive.&quot;&lt;/p&gt;
&lt;p&gt;He likened the situation to hormone therapy, which had been widely recommended to reduce cardiovascular risk in postmenopausal women based on data from epidemiologic studies.&lt;/p&gt;
&lt;p&gt;That hypothesis was initially questioned when a randomized controlled trial (Estrogen/Progestin Replacement Study [HERS]) linked hormones to increased risk of events. The HERS finding was confirmed in the landmark Women&apos;s Health Initiative trial in which ischemic events were more common among women randomized to estrogen/progestin.&lt;/p&gt;
&lt;p&gt;R. Scott Wright, MD, of the Mayo Clinic in Rochester, Minn., told &lt;em&gt;MedPage Today&lt;/em&gt; that the trial design was faulty, in that margarine was a bad choice of vehicle for omega-3 fatty acids.&lt;/p&gt;
&lt;p&gt;&quot;It needs to be combined with another food  --  bread,&quot; he said. &quot;So this not a good option for Americans because it would mean eating more bread, which is likely to lead to weight gain and bread is high in sodium, so blood pressure would be a factor.&quot;&lt;/p&gt;
&lt;p&gt;Wright noted that the ALPHA-OMEGA study did not include information on weight or blood pressure, so he considered the findings at best incomplete.&lt;/p&gt;
&lt;p&gt;All of the patients received &quot;state-of-the-art antihypertensive, antithrombotic, and lipid-modifying therapy,&quot; according to Kromhout and colleagues, in addition to margarine, and it may have been that optimal therapy that limited the potential for an omega-3 benefit.&lt;/p&gt;
&lt;p&gt;Statin therapy, along with other improvements in cardiovascular care, means &quot;a beneficial effect of low doses of EPA-DHA is difficult to prove,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;Wright said he wasn&apos;t persuaded by that explanation since, even after optimal therapy, there is about a 30% residual risk. &quot;There is plenty of room to show a benefit,&quot; he declared.&lt;/p&gt;
&lt;p&gt;Most of the patients in ALPHA-OMEGA were men (78%) and 24% were obese, but they differed from the typical high-risk American in at least one way: at baseline they consumed about three times more fish than does the typical American, a median of 15 grams a day.&lt;/p&gt;
&lt;p&gt;According to a report from the Environmental Protection Agency, average fish consumption in the U.S. works out to 4.58 &amp;#177; 0.42 grams a day.&lt;/p&gt;
&lt;p&gt;The authors conducted a post hoc exploratory analysis in patients with diabetes, finding significant reductions in events among patients in the EPA-DHA group. But the authors noted that &quot;[the] results with respect to patients with diabetes are only hypothesis-generating and do not permit definitive conclusions to be drawn.&quot;&lt;/p&gt;
&lt;p&gt;Bove, a former president of the American College of Cardiology, added that the results from the subset analysis in diabetics was reassuring, since patients with diabetes and elevated triglycerides are the patients that &quot;we have believed would be most likely to benefit&quot; from omega-3 fatty acids.&lt;/p&gt;
&lt;p&gt;The margarines used in the trial were supplied by Unilever, an international maker of food and consumer goods, and included the well-known &quot;I Can&apos;t Believe It&apos;s Not Butter,&quot; which contains 420 mg of ALA per serving.&lt;/p&gt;

&lt;p&gt;In a statement released after the ALPHA-OMEGA trial findings were presented, Unilever said the &quot;study outcome for EPA and DHA is surprising considering the weight of evidence published to date. This could be the result of methodological issues such as the relatively low daily dosage compared with previous studies or the fact that in this study serious cardiovascular events were much lower than in studies performed in the past. This is probably due to extensive drug treatment that is nowadays applied. The finding needs further study, but given the totality of evidence does not immediately impact the current advice on fish and fish oil consumption for prevention of cardiovascular 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 trial was supported by the Netherlands Heart Foundation, the National Institutes of Health, and Unilever.&lt;/p&gt;&lt;p&gt;Kromhout reported that his institution received grant support form Unilever to cover distribution of the trial margarines to patients. His institution also received a grant from the Product Board for Margarine Fats and Oils to support research on polyunsaturated fats and cardiovascular diseases done by a PhD student.&lt;/p&gt;&lt;p&gt;Bove said he had no financial conflicts.&lt;/p&gt;&lt;p&gt;Wright said he consults for Roche and Genentech and conducts trial work for 3M/Littman.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3102"
                     title="ESC: 16 Hot Line Trials Headline Cardiology Meeting"
                     score="-0.002"
                     href="http://www.medpagetoday.com/MeetingCoverage/ESCCongress/tb/21812?impressionId=1284018990917"
                     
      &lt;p&gt;STOCKHOLM  --  In the run-up to the European Society of Cardiology meeting, there is little doubt that this will again be a scientific congress that delivers good news  --  but how good is debatable.&lt;/p&gt;
&lt;p&gt;For example, the sponsors of two Hot Line trials  --  both involving oral factor Xa inhibitors  --  have already said that their respective trials will report positive results, but it&apos;s unclear how that will translate in the real world.&lt;/p&gt;
&lt;p&gt;Bristol-Myers Squibb and Pfizer said in June that their phase III trial comparing apixaban with aspirin in patients with atrial fibrillation was stopped early because there was &quot;clear evidence of a clinically important reduction in stroke and systemic embolism.&quot;&lt;/p&gt;
&lt;p&gt;The key issue, though, will be whether &quot;the results [are] good enough to convince the FDA,&quot; Harvard&apos;s Christopher Cannon, MD, told &lt;em&gt;MedPage Today&lt;/em&gt;. He did note that U.S. cardiologists are eager to learn the full details of the trial  --  called AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Strokes).&lt;/p&gt;
&lt;p&gt;AVERROES randomized 5,600 atrial fibrillation patients who were either not candidates for or could not tolerate warfarin therapy to either apixaban 5 mg bid or aspirin at 81 or 324 mg daily.&lt;/p&gt;
&lt;p&gt;The second trial that has positive advance findings is EINSTEIN DVT in which monotherapy with rivaroxaban, an oral direct factor Xa inhibitor, met the primary endpoint of noninferiority to enoxaparin followed by warfarin for treatment of deep vein thrombosis. That study recruited 3,400 patients with symptomatic DVT.&lt;/p&gt;
&lt;p&gt;Bayer, which is developing rivaroxaban (Xarelto), jumped the gun on the ESC by announcing the top line on EINSTEIN DVT earlier this month, but again the question of how good the data are will not be answered until the findings are reported here on Aug. 31.&lt;/p&gt;
&lt;p&gt;Nonetheless, the possibility that a single oral agent would be effective is understandably attractive to both clinicians and patients, Cannon said.&lt;/p&gt;
&lt;p&gt;Intracoronary stem cell transplantation as treatment for heart failure has been tried in a handful of European studies with mixed results, and more results  --  this time a trial in nine patients  --  will be reported by researchers from Dusseldorf.&lt;/p&gt;
&lt;p&gt;In all, 16 clinical trials will be reported in three Hot Line sessions, which are roughly equivalent to late-breaking clinical trial sessions at U.S. scientific meetings.&lt;/p&gt;
&lt;p&gt;Also included in those Hot Line sessions is the Alpha-Omega trial that investigated yet another omega-3 fatty acid intervention  --  this time with margarine.&lt;/p&gt;
&lt;p&gt;At least five of the studies reported at the ESC will also be simultaneously published in peer-reviewed journals, but the exact number to receive this treatment and the journals involved remains closely guarded.&lt;/p&gt;
&lt;p&gt;Not guarded, or embargoed, are scores of studies presented in oral and poster sessions all of which the ESC released to the public as of 6 p.m. Stockholm time today.&lt;/p&gt;
&lt;p&gt;Included in that group are a meta-analysis that finds no increased cancer risk with statin therapy, another that suggests it&apos;s never too old to run a marathon, and yet another that found running &lt;em&gt;too&lt;/em&gt; far  --  more than 50 miles  --  may not be good for the heart.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_2978"
                     title="No Cancer Risk with Bisphosphonates (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Oncology/OtherCancers/tb/21629?impressionId=1284018990917"
                     
      &lt;p&gt;Use of oral bisphosphonates did not increase the risk of esophageal or gastric cancer in a large cohort of patients followed for more than four years.&lt;/p&gt;
&lt;p&gt;Bisphosphonate users and nonusers had similar rates of the individual cancers and of both cancers combined, according to a report in the Aug. 11 issue of the &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The findings should help allay concerns about a theoretical cancer risk related to bisphosphonates&apos; propensity to cause esophagitis in some patients&lt;em&gt;&lt;/em&gt;, researchers Chris R. Cardwell, PhD, of Queen&apos;s University Belfast in Ireland, and coauthors noted.&lt;/p&gt;
&lt;p&gt;Their analysis of medical records showed esophageal cancer rates of 0.48 cases per 1,000 person-years in bisphosphonate users and 0.44 cases per 1,000 person-years in nonusers.&lt;/p&gt;
&lt;p&gt;&quot;These drugs should not be withheld, on the basis of possible esophageal cancer risk, from patients with a genuine clinical indication for their use,&quot; they wrote in conclusion.&lt;/p&gt;
&lt;p&gt;Widespread use of oral bisphosphonates to treat osteoporosis has shown that some patients develop serious reflux esophagitis, a known risk factor for esophageal cancer. Crystalline material resembling a bisphosphonate has been identified in patients with bisphosphonate-related esophagitis, and follow-up endoscopy showed persistent abnormalities after healing (&lt;em&gt;Gastrointest Endosc&lt;/em&gt;. 1998;47:525-528).&lt;/p&gt;
&lt;p&gt;Bisphosphonates&apos; potential to cause esophageal cancer has been unclear, although the FDA has reported cases among bisphosphonate users in the United States, Europe, and Japan (&lt;em&gt;N Engl J Med&lt;/em&gt;. 2009;360:89-90).&lt;/p&gt;
&lt;p&gt;In an effort to assess the cancer risk in bisphosphonate users, Cardwell and colleagues analyzed records in a large database comprising 500 general medical practices. They identified all patients who received a bisphosphonate prescription from 1996 through 2006 and compiled a control group matched for age, sex, and medical practice.&lt;/p&gt;
&lt;p&gt;Each group included 41,826 patients, 81% of whom were women and whose mean age was 70.&lt;/p&gt;
&lt;p&gt;During a mean follow-up of about 4.5 years, 116 esophageal and gastric cancers occurred in the bisphosphonate cohort and 115 in the control group.&lt;/p&gt;
&lt;p&gt;The combined incidence of esophageal and gastric cancer was 0.7 per 1,000 person-years in both groups.&lt;/p&gt;
&lt;p&gt;The totals included 79 esophageal cancers in the bisphosphonate users and 72 in the control group, a nonsignificant difference.&lt;/p&gt;
&lt;p&gt;Further analysis showed no difference in rates of esophageal or gastric cancer by duration of bisphosphonate therapy.&lt;/p&gt;
&lt;p&gt;Nor did cancer rates differ between patients prescribed nitrogen-containing versus non-nitrogen bisphosphonates. (Preclinical studies has yielded evidence suggesting that nitrogen-containing bisphosphonates might reduce cancer risk by affecting tumor proliferation, invasion, and angiogenesis, the authors noted.)&lt;/p&gt;
&lt;p&gt;The findings agree with those of prior studies in the U.S. and Denmark. However, both studies identified too few cases of cancer to produce reliable risk estimates (&lt;em&gt;N Engl J Med&lt;/em&gt;. 2009;360:1789-1790, &lt;em&gt;N Engl J Med&lt;/em&gt;. 2009;360:1791-1792).&lt;/p&gt;
&lt;p&gt;Among the limitations of their study, Cardwell and colleagues noted that overestimation of bisphosphonate usage was possible, since patient compliance with bisphosphonate therapy is known to be a problem. Nor was their estimate of cancer incidence derived from a registry, but rather from diagnostic codes in patient files, which may be inaccurate.&lt;/p&gt;
&lt;p&gt;They also noted that there was a relatively high proportion of missing data on potential confounders.&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;Cardwell and coauthors reported that they had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>