<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_3275"
                     title="Kids on HAART Would Benefit from Revaccinations (CME/CE)"
                     score="0.013"
                     href="http://www.medpagetoday.com/clinical-context/HIVAIDS/tb/22037?impressionId=1283750552884"
                     
      &lt;p&gt;Children with HIV who received standard childhood immunizations before starting on highly active antiretroviral therapy (HAART) could benefit from revaccination, a review published in the September issue of &lt;em&gt;Lancet Infectious Diseases&lt;/em&gt; suggests.&lt;/p&gt;
&lt;p&gt;The proportion of those with an immune response after HAART began was highly variable, with no clear trend by type of vaccine, according to a meta-analysis of 38 studies conducted by Catherine G. Sutcliffe, PhD, and William J. Moss, MD, of Johns Hopkins University.&lt;/p&gt;
&lt;p&gt;For instance, they found for tetanus the proportion with an immune response ranged from 38% to 77%. Proportions ranged from 40% to 65% for diphtheria, 1% to 100% for hepatitis B virus (HBV), and 25% to 87% by serotype for pneumococcal vaccines.&lt;/p&gt;
&lt;p&gt;The proportion of children with an immune response to the measles, mumps, rubella vaccine (MMR) after starting HAART ranged from 42% to 45% for measles virus and 27% to 66% for rubella virus.&lt;/p&gt;
&lt;p&gt;Studies looking at revaccinations after HAART was started found that within the first three months, the proportion of children with an immune response was 53% to 100% for tetanus toxoid, 75% for conjugate Hib vaccine, 46% to 92% for HBV vaccine, 29% to 96% by serotype for pneumococcal vaccine, and 50% to 100% by strain for influenza vaccine. &lt;ul&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;For the meta-analysis, Sutcliffe and Moss looked at studies addressing several different questions about HAART and vaccines. For the question of whether children taking HAART have protective immunity to vaccine-preventable diseases, studies were included if children were vaccinated before being started on HAART and measures of immunity were reported after the start of HAART but before revaccination.&lt;/p&gt;
&lt;p&gt;For questions about the short-term (three months or less) and the long-term (more than three months) immune response to vaccination while on HAART, studies were included if children were revaccinated or received new vaccines to which they had no prior exposure after being started on HAART and either short-term or long-term immune responses were measured.&lt;/p&gt;
&lt;p&gt;Two studies looked at by the authors reported antibody concentrations before and after HAART. In one of those, a Kenyan study of the measles vaccine, researchers found that the proportion of children who were seropositive increased from 33% before HAART to 42% after HAART.&lt;/p&gt;
&lt;p&gt;However, 53% of the children who were seropositive before HAART lost protective immunity, whereas 40% of children who were seronegative or had borderline antibody concentrations became seropositive after receiving HAART for six months.&lt;/p&gt;
&lt;p&gt;In terms of the strength of immunizations, in general the studies found that immunity declined but a high proportion of children maintained immunity about a year after vaccination.&lt;/p&gt;
&lt;p&gt;For tetanus toxoid, one U.S. study reported a decline from 74% seropositive at four weeks to 38% by 32 weeks after vaccination, although in three other studies 85% to 90% of children maintained immunity one year after vaccination.&lt;/p&gt;
&lt;p&gt;For pertussis, antibody concentration declined from 22.3 EU/mL at eight weeks to 10.1 EU/mL by 48 weeks and 6.8 EU/mL by 96 weeks after vaccination.&lt;/p&gt;
&lt;p&gt;For HBV, the proportion of seropositive children decreased from 46% eight weeks after revaccination to 38% after 96 weeks and 25% after a median of 4.6 years.&lt;/p&gt;
&lt;p&gt;All children remaining in the HBV study after a median of 4.6 years were revaccinated a second time. Of the children who were seronegative within one week of the second revaccination, 37% seroconverted four weeks after vaccination.&lt;/p&gt;
&lt;p&gt;The authors wrote that although HAART is effective in reducing morbidity and mortality in HIV-infected children by suppressing viral replication and restoring immune function, &quot;immune reconstitution in children is primarily through the generation of naive T cells rather than expansion of memory T cells, as in adults.&quot;&lt;/p&gt;
&lt;p&gt;Therefore, they wrote, &quot;HAART is unlikely to restore memory T cells for vaccine antigens to which children were exposed before treatment, but should restore the ability of the immune system to respond to new antigens.&quot;&lt;/p&gt;
&lt;p&gt;Because levels of immunity to vaccine-preventable diseases in HIV-infected children were generally low, the majority of children on HAART would benefit from revaccination, although the best timing of vaccination after starting HAART is still not known, either for revaccination or for primary vaccination with new vaccines, according to the researchers.&lt;/p&gt;
&lt;p&gt;&quot;Waning immunity after revaccination and vaccination with new vaccines was greater and more rapid than in children not infected with HIV, who typically maintain high antibody concentrations years after vaccination,&quot; they added.&lt;/p&gt;
&lt;p&gt;The authors cited several limitations to their meta-analysis, including the fact that few studies were identified for each vaccine and there was great heterogeneity in study design, eligibility criteria, characteristics of study populations, definitions of immunity, and presence of a comparison group. In addition, vaccine-induced immunity could not be distinguished from immunity derived from natural infection.&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 authors declared that they had no conflicts of interest. No funding information for the study was given.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3203"
                     title="Vitamin A Hikes HIV Loads in Breast Milk (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/21944?impressionId=1283750552884"
                     
      &lt;p&gt;HIV-positive mothers may be more likely to infect infants via breast milk if they take vitamin A and beta-carotene supplements, researchers have found.&lt;/p&gt;
&lt;p&gt;In two analyses of a cohort of HIV-positive Tanzanian women, those who took the vitamins had significantly higher viral loads in their breast milk than those who didn&apos;t take them (&lt;em&gt;P&lt;/em&gt;=0.02), according to Eduardo Villamor, MD, PhD, of the University of Michigan, and colleagues.&lt;/p&gt;
&lt;p&gt;They also had a higher risk of subclinical mastitis, an inflammatory response that causes tight junctions in the mammary epithelium to open, allowing extracellular fluid to flow from plasma to milk. Villamor said this could be the mechanism explaining the association with viral load.&lt;/p&gt;
&lt;p&gt;&quot;Daily supplementation with these nutrients at the doses tested in the trial should probably not be given to HIV-infected lactating women,&quot; Villamor told &lt;em&gt;MedPage Today&lt;/em&gt; in an e-mail.&lt;/p&gt;
&lt;p&gt;The analyses were published in separate papers in the &lt;em&gt;American Journal of Clinical Nutrition&lt;/em&gt; and the &lt;em&gt;Journal of Nutrition&lt;/em&gt;, respectively.&lt;/p&gt;
&lt;p&gt;Both come from a randomized, controlled trial of 1,078 HIV-infected women in Dar es Salaam, Tanzania, who received one of four regimens: vitamin A and beta-carotene (5,000 IU and 30 mg, respectively); B-complex vitamins along with vitamins C and E; a multivitamin plus vitamin A and beta-carotene; or placebo.&lt;/p&gt;
&lt;p&gt;The &lt;em&gt;American Journal of Clinical Nutrition&lt;/em&gt; study looked at 594 of these women who were infected with HIV and had breast milk samples taken.&lt;/p&gt;
&lt;p&gt;The researchers found that the proportion of breast milk samples with detectable viral load was significantly higher in women who received regimens with vitamin A and beta-carotene than in the other groups (51.3% versus 44.8%, &lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;The effect was apparent at least six months postpartum, they said, with a 34% increased risk of HIV shedding in milk at that time (relative risk 1.34, 95% CI 1.04 to 1.73).&lt;/p&gt;
&lt;p&gt;There were no significant differences between women who received multivitamins and those who took placebo, they added.&lt;/p&gt;
&lt;p&gt;They also found that breast milk concentrations of beta-carotene were related to increased detectable viral load in milk.&lt;/p&gt;
&lt;p&gt;One mechanism by which this occurs may be subclinical mastitis, assessed in the &lt;em&gt;Journal of Nutrition&lt;/em&gt; study.&lt;/p&gt;
&lt;p&gt;A subset of 674 participants had subclinical mastitis assessed, measured by sodium-to-potassium ratio in breast milk.&lt;/p&gt;
&lt;p&gt;The researchers found that those on vitamin A and beta-carotene had a 45% increased risk of severe subclinical mastitis (&lt;em&gt;P&lt;/em&gt;=0.03), with nonsignificant trends toward greater risk of moderate subclinical mastitis or any degree of the condition.&lt;/p&gt;
&lt;p&gt;Those taking multivitamins without vitamin A and beta-carotene had a 33% greater risk of subclinical mastitis (&lt;em&gt;P&lt;/em&gt;=0.005) and a 75% greater risk of severe subclinical mastitis (&lt;em&gt;P&lt;/em&gt;=0.0006) than women on placebo.&lt;/p&gt;
&lt;p&gt;The researchers called these findings &quot;unexpected,&quot; attributing their effects to an increased inflammatory response.&lt;/p&gt;
&lt;p&gt;Women taking multivitamins plus vitamin A and beta-carotene had trends toward increased risks, but again they were not significant.&lt;/p&gt;
&lt;p&gt;The researchers also found that among women with CD4+ T-cell counts of 350 or greater, multivitamin intake resulted in a 49% increased risk of any subclinical mastitis (&lt;em&gt;P&lt;/em&gt;=0.006).&lt;/p&gt;
&lt;p&gt;However, multivitamins had no effects among those with lower counts.&lt;/p&gt;
&lt;p&gt;The analyses were limited because they lacked details on clinical breast symptoms and on breast-feeding practices.&lt;/p&gt;
&lt;p&gt;Villamor told &lt;em&gt;MedPage Today&lt;/em&gt; that the findings about vitamins other than vitamin A and beta-carotene are not immediately concerning, because in previous studies, these nutrients have shown benefits in terms of disease progression, child growth, diarrhea, and anemia.&lt;/p&gt;
&lt;p&gt;But vitamin A and beta-carotene do seem clearly problematic, he said.&lt;/p&gt;
&lt;p&gt;There are now &quot;strong arguments to consider the implications of supplementation to pregnant or lactating women who are HIV-positive. It does not look like it&apos;s a safe intervention for them,&quot; Villamor said.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the National Institutes of Health.&lt;/p&gt;&lt;p&gt;The researchers reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3233"
                     title="Tie Healthcare Jobs to Flu Vaccination, Groups Say (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/HospitalBasedMedicine/InfectionControl/tb/21987?impressionId=1283750552884"
                     
      Healthcare workers should receive annual influenza vaccinations as a condition of employment and professional privileges, according to an updated position paper endorsed by two major infectious disease organizations.&lt;br&gt;
&lt;br&gt;Healthcare personnel have a professional and ethical responsibility to help prevent the spread of infectious pathogens among patients and themselves, a writing group for the Society of Healthcare Epidemiology of America (SHEA) concluded in a position paper published online in &lt;em&gt;Infection Control and Hospital Epidemiology&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;&quot;SHEA views influenza vaccination of healthcare personnel as a core patient and healthcare personnel safety practice with which noncompliance should not be tolerated,&quot; Thomas R. Talbot, MD, of Vanderbilt University in Nashville, Tenn., and co-authors wrote.&lt;br&gt;
&lt;br&gt;The recommendation has the endorsement of the Infectious Diseases Society of America (IDSA).&lt;p&gt;&lt;/p&gt;
&lt;p&gt;The update affirms and strengthens SHEA&apos;s support for vaccination against influence among healthcare personnel, originally set forth in a 2005 position paper, also endorsed by IDSA (&lt;em&gt;Infect Control Hosp Epidemiol&lt;/em&gt; 2005; 26: 882-890).&lt;/p&gt;
&lt;p&gt;&quot;Healthcare providers are ethically obligated to take measures proven to keep patients from acquiring influenza in healthcare settings,&quot; SHEA president Neil Fishman, MD, of the University of Pennsylvania in Philadelphia, said in a statement.&lt;/p&gt;
&lt;p&gt;&quot;Mandatory vaccination is the cornerstone to a comprehensive program designed to prevent the spread of influenza which also included identification and isolation of infected patients, adherence to hand hygiene and cough etiquette, the appropriate use of protective equipment, and restriction of ill healthcare personnel and visitors in the facility.&lt;/p&gt;
&lt;p&gt;Aside from making vaccination a condition of employment and privileges, the position paper incorporates new evidence that has come to light since publication of the 2005 document that strengthens SHEA&apos;s position on the issue, Talbot and coauthors noted.&lt;/p&gt;
&lt;p&gt;The 2005 document addressed vaccine allocation during shortages at the time, and SHEA&apos;s position on the topic has not changed, the authors wrote in an executive summary.&lt;/p&gt;
&lt;p&gt;SHEA&apos;s support for mandatory vaccination of healthcare personnel reflects &quot;continued frustration surrounding low and unimproved ... vaccination rates.&quot; A 2009 study by the Rand Corp. showed that almost 40% of healthcare workers had no plans to get vaccinated against influenza despite growing concern about the health threat posed by H1N1 virus.&lt;/p&gt;
&lt;p&gt;Studies based on statistical models have shown that a 100% vaccination rate among healthcare personnel in acute-care facilities would reduce the risk of influenza among hospitalized patients by 43%.&lt;/p&gt;
&lt;p&gt;Moreover, vaccination of all personnel in nursing homes would reduce influenza incidence among patients in those facilities by 60%, Talbot and coauthors noted. Other studies have shown that vaccination of healthcare personnel against influenza also reduces patient mortality, they added.&lt;/p&gt;
&lt;p&gt;Multiple healthcare facilities have already adopted mandatory vaccination policies; the first such policy was implemented in 2004 at Virginia Mason Medical Center in Seattle.&lt;/p&gt;
&lt;p&gt;After BJC Healthcare in St. Louis implemented a mandatory vaccination policy in 2008 to 2009, the vaccination rate among their healthcare personnel increased from 71% to 98.4%. Noting that eight employees were terminated for failure to get vaccinated, authors of the SHEA position paper cited the terminations as an indication of institutional commitment to its vaccination policy.&lt;/p&gt;
&lt;p&gt;In 2009, New York became the first state to require influenza vaccination for healthcare personnel.&lt;/p&gt;
&lt;p&gt;Influenza vaccination as a condition of employment should be a component of comprehensive immunization programs in healthcare settings. Other strategies recommended by SHEA include: &lt;ul&gt; &lt;li&gt;Using vaccination rates as a quality measure&lt;/li&gt; &lt;li&gt;Requiring unvaccinated personnel to wear a mask during influenza season&lt;/li&gt; &lt;li&gt;Requiring signed declination statements for personnel that refuse vaccination&lt;/li&gt; &lt;li&gt;Allowing exemptions from vaccination only in cases of medical contraindications&lt;/li&gt; &lt;/ul&gt;&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;Talbot disclosed relationships with Joint Commission Resources, GlaxoSmithKline, and Sanofi Pasteur, and spousal relationships with Wyeth, Vaxxinate, and Sanofi Pasteur.&lt;/p&gt;&lt;p&gt;Several coauthors of the writing committee disclosed relationships with mutiple commercial interests.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3199"
                     title="ESC: Simple Clinical Factors May Provide Clues to Future Ischemic Events (CME/CE)"
                     score="0.009"
                     href="http://www.medpagetoday.com/MeetingCoverage/ESCCongress/tb/21940?impressionId=1283750552884"
                     
      STOCKHOLM  --  Easily assessed clinical factors could help predict which atherothrombosis patients might have an increased risk of an ischemic event, according to results of a large international registry.&lt;br&gt;
&lt;br&gt;In four-year data, culled from among more than 32,000 patients, a composite of cardiovascular death, MI, or stroke during follow-up was predicted by diabetes (HR 1.44, 95% CI 1.36 to 1.53), an ischemic event within the past year (HR 1.71, 95% CI 1.57 to 1.85), and polyvascular disease (HR 1.99, 95% CI 1.78 to 2.24).&lt;br&gt;
&lt;br&gt;The findings were reported by Deepak Bhatt, MD, MPH, of Harvard, at the European Society of Cardiology Congress here and were simultaneously published online in the &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;p&gt;&lt;/p&gt;

&lt;p&gt;Cardiovascular risk stratification among patients with established atherosclerosis enables the intensity of preventive treatments to be tailored to individual patient groups,&quot; Bhatt said during his presentation.&lt;/p&gt;

&lt;p&gt;Identifying patients at the highest risk within an at-risk population may allow clinicians to more precisely direct novel preventive therapies  --  or enable researchers to design trials for those patients most likely to benefit from new treatments.&lt;/p&gt;
&lt;p&gt;&quot;New antiplatelet, anticoagulant, anti-atherosclerotic, and anti-inflammatory agents will probably be expensive and may have additional adverse effects,&quot; Bhatt and colleagues wrote. &quot;Thus, the ability to target these therapies to patients at highest ischemic risk will be desirable and likely would be cost-effective.&quot;&lt;/p&gt;
&lt;p&gt;The data analyzed came from patients participating in the REACH (Reduction of Atherothrombosis for Continued Health) Registry, which enrolled patients from 3,647 centers in 29 countries. Participants either had to have established coronary artery disease, cerebrovascular disease, or peripheral artery disease, or at least three risk factors for atherothrombosis.&lt;/p&gt;
&lt;p&gt;At baseline, the international registry covered 45,227 patients, but because of centers dropping out, four-year data were only available for 31,195 patients.&lt;/p&gt;
&lt;p&gt;During the follow-up period, between 2003 and 2008, 5,481 patients had at least one ischemic event, including 2,315 who died from cardiovascular causes, 1,228 who had MIs, 1,898 who had strokes, and 40 who had an MI and a stroke on the same day.&lt;/p&gt;
&lt;p&gt;The highest rate of the composite outcome of cardiovascular death, MI, or stroke occurred in patients who had a prior history of ischemic events at baseline (18.3%), followed by those with stable coronary, cerebrovascular, and peripheral artery disease without a history of ischemic events (12.2%) and those without established atherothrombosis but with multiple risk factors (9.1%) (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for all comparisons).&lt;/p&gt;
&lt;p&gt;Rates ranged from a low of 7.1% among patients who had only had cardiovascular risk factors but who were free from diabetes to 25% among patients with a history of ischemic events and polyvascular disease.&lt;/p&gt;
&lt;p&gt;&quot;This greater than three fold gradient in cumulative risk for cardiovascular death, myocardial infarction, or stroke illustrates that not all atherothrombosis is equal  --  an observation that the broad array of clinicians caring for these types of patients may find clinically relevant,&quot; Bhatt and his colleagues wrote in their paper.&lt;/p&gt;
&lt;p&gt;When cardiovascular hospitalization was added to the composite endpoint, rates ranged from 16.6% among patients who made it into the registry based on risk factors alone to 47.1% among those with a baseline history of ischemic events and polyvascular disease.&lt;/p&gt;
&lt;p&gt;The researchers did not find any evidence that their findings varied by geographical region  --  suggesting broad applicability, they noted.&lt;/p&gt;
&lt;p&gt;They acknowledged some limitations to their data, however, including the incomplete follow-up of the initial cohort because of dropouts and the fact that the endpoints were not adjudicated.&lt;/p&gt;
&lt;p&gt;Bhatt also said selection bias could not be ruled out.&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 REACH Registry is sponsored by sanofi-aventis, Bristol-Myers Squibb, and the Waksman Foundation and is endorsed by the World Heart Foundation.&lt;/p&gt;&lt;p&gt;The design and conduct of the study were done by the academic executive committee in collaboration with the sponsors. The collection and management of the data were done by the sponsors under the direction of the academic executive committee. Analysis was done by the sponsors and independently verified by an academic statistician; the latter analyses were presented in the paper. The sponsors were able to review but not approve the study.&lt;/p&gt;&lt;p&gt;Bhatt reported having received institutional research support from AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, sanofi-aventis, and The Medicines Company.&lt;/p&gt;&lt;p&gt;His co-authors reported numerous relationships with industry. One of the authors is employed by sanofi-aventis.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3167"
                     title="ESC: Mixed Risks for PPIs Plus Clopidogrel (CME/CE)"
                     score="0.006"
                     href="http://www.medpagetoday.com/MeetingCoverage/ESCCongress/tb/21896?impressionId=1283750552884"
                     
      &lt;p&gt;STOCKHOLM  --  Concomitant use of a proton pump inhibitor and clopidogrel (Plavix) significantly increased the risk of myocardial infarction but not death, a meta-analysis involving almost 160,000 patients found.&lt;/p&gt;
&lt;p&gt;The meta-analysis showed a 31% increase in the relative risk of MI (95% CI 1.12 to 1.53) among patients who took the two drugs together compared with those who did not, according to Jolanta Siller-Matula, MD, of the Medical University of Vienna in Austria, and colleagues.&lt;/p&gt;
&lt;p&gt;On the other hand, the analysis of 25 studies found that combined use of the two drugs did not significantly increase the risk of dying (RR=1.04, 95% CI 0.93 to 1.16), Siller-Matula and colleagues reported here at the European Society of Cardiology.&lt;/p&gt;
&lt;p&gt;As well, the meta-analysis showed that treatment with a PPI reduced the risk of gastrointestinal (GI) bleeding by 50% in patients receiving clopidogrel alone or with a placebo, Siller-Matula&apos;s team reported.&lt;/p&gt;
&lt;p&gt;&quot;As meta-analyses have the highest evidence level, this study adds important insights into the discussion on safety of PPIs, especially because randomized trials with PPIs, in particular with omeprazole, are not ethically acceptable as omeprazole decreases the concentration of clopidogrel in the blood,&quot; Siller-Matula told &lt;em&gt;MedPage Today&lt;/em&gt; in an e-mail.&lt;/p&gt;
&lt;p&gt;&quot;This meta-analysis has significant implications for many patients. My advice to clinicians is to only prescribe gastric protection when absolutely necessary. If indicated, pantoprazole should be used, as pantoprazole has no negative effect on platelet inhibition by clopidogrel when assessed ex vivo,&quot; she said.&lt;/p&gt;
&lt;p&gt;Data from large clinical registries have suggested that concomitant treatment with clopidogrel and a PPI worsen clinical outcomes in patients with coronary disease. Other studies have shown no increased risk with use of both drugs.&lt;/p&gt;
&lt;p&gt;The only prospective, randomized trial to evaluate the issue ended prematurely when the sponsor declared bankruptcy. Data collected to discontinuation showed &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/TCT/16133&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/TCT/16133&quot; target=&quot;_blank&quot; title=&quot;TCT:&amp;#8200;PPIs&amp;#8200;Safe&amp;#8200;for&amp;#8200;Patients&amp;#8200;Taking&amp;#8200;Antiplatelets&quot;&gt;no difference in risk&lt;/a&gt; among patients treated with clopidogrel or placebo.&lt;/p&gt;
&lt;p&gt;&quot;Given the lack of a definitive trial, we performed a meta-analysis to determine whether concomitant use of PPIs plus clopidogrel increases the incidence of combined major cardiovascular events (MACE), MI, death, or gastrointestinal bleeding in patients with cardiovascular disease,&quot; Siller-Matula explained.&lt;/p&gt;
&lt;p&gt;A systematic review identified 25 studies that involved a total of 159,138 patients. The studies included observational studies, randomized trials, and post-hoc analyses of randomized trials.&lt;/p&gt;
&lt;p&gt;The primary outcomes were combined MACE, MI, stent thrombosis, death, and GI bleeding.&lt;/p&gt;
&lt;p&gt;The analysis showed that patients treated with clopidogrel and PPIs had a 29% increased relative risk of MACE (95% CI 1.15 to 1.45) as well as a 31% increased risk of MI compared with patients who did not receive the two drugs together.&lt;/p&gt;
&lt;p&gt;The combination of a PPI and clopidogrel was associated with a nonsignificant 4% increase in mortality risk.&lt;/p&gt;
&lt;p&gt;Concomitant use of the two drugs halved the relative risk of GI bleeding (RR=0.50, 95% CI 0.37 to 0.69), compared with patients treated with clopidogrel alone or with placebo.&lt;/p&gt;
&lt;p&gt;Sensitivity analysis showed that the results remained unchanged irrespective of publication type, study quality or size, or risk of clinical events. Despite the consistency of findings, Siller-Matula concluded that concomitant PPI-clopidogrel therapy &quot;might be associated with an increased risk of cardiovascular events.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Prospective randomized trials are required to investigate whether a cause-and-effect relationship truly exists and to explore whether different PPIs worsen clinical outcome in clopidogrel-treated patients, as the PPI-clopidogrel drug-drug interaction seems not to be a class effect,&quot; she added.&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;Siller-Matula reported that she and her co-authors had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>