Louisiana State University at Baton Rouge. J. Derek, MD: "Purchase cheap Naprosyn no RX - Safe Naprosyn OTC".
C oh ort3% (D:#;O :#) D iscontinueddueto 2005 AllAE s:43% (D :5 purchase naprosyn 500mg free shipping arthritis ear,O 8)vs73% (D :16;O ;19)vs98% (D :22;O :24) AE s:3 buy discount naprosyn line arthritis pain while sleeping. Tol19/399 D atacollectedateach O PE R A m ild:ox y 87/391(22 naprosyn 250mg amex arthritis diet news. R CT = R andom ControlledTrial,U TI = U rinary TractInfection,N S = N ostatisticaldifference Overactive bladder 213 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 10. Sh ort-term com parative studies:A dverse effects A uth or N um berEnrolled Y ear Setting Interventions (drug,regim en,duration) Transderm alvs. O xybutyninIR D avila Starting doseassigneddepending onpriororal E nrolled76 2001 ox y buty nindoseof = 10m g,11-15m g,or> /= O x y TD = 38 20m g daily : O x y IR = 38 O x y TD 2. R CT = R andom ControlledTrial,U TI = U rinary TractInfection,N S = N ostatisticaldifference Overactive bladder 214 of 217 Final Report Update 4 Drug Effectiveness Review Project Evidence Table 10. Sh ort-term com parative studies:A dverse effects A uth or Y ear W ith drawals due to Q uality rating and Setting N um berofadverse effects adverse events C om m ents Transderm alvs. O x y IR O x y IR :1(dry m outh) F air 2001 D ry m outh:15(39%)vs. Anticholinergic sideeffects(% only ,num bersN R ) TolSR = 2/123(1. R CT = R andom ControlledTrial,U TI = U rinary TractInfection,N S = N ostatisticaldifference Overactive bladder 215 of 217 Final Report Update 4 Drug Effectiveness Review Project 1 Evidence Table 11. C linically significantdrug interactions F lavoxate Trospium O xybutyninC h loride Tolterodine Tartrate Darifenacin SolifenacinSuccinate H ydroch loride C h loride Drugs affecting N otreported N otreported N o significant N o dose adjustm ent 5 N otreported F urth erstudies needed. N o action needed forC Y P2D6 and (C Y P 450) 2 m oderate C Y P3A 4 required. F luoxetine N otreported N otreported N o dose adjustm ent N otreported N otreported N otreported required. M ay increase concentrationof 2 tolterodineby fourfold. Diuretics N otreported N otreported N o significant N otreported N otreported N otreported 1 interactions. O ral N otreported N otreported N o significant N otreported N otreported N otreported C ontraceptives interactions. A nticoagulants N otreported N otreported N o significant N otreported N otreported N otreported 2 interactions. Increased N otreported N otreported N otreported N otreported sedationwith CN S 2 depression. Increased N otreported N otreported N otreported N otreported 2 anticholinergic effects. M acrolide N otreported 2 N otreported N otreported N otreported N otreported Inform ationnotavailable. C linically significantdrug interactions F lavoxate Trospium O xybutyninC h loride Tolterodine Tartrate Darifenacin SolifenacinSuccinate H ydroch loride C h loride A z ole antifungal N otreported N o significantinteraction. Co-adm inistration N otreported agents Serum concentrationsof required. M ay inhibit with asingle10m g ox y buty ninincreasedthree m etabolism of tolterodine. Reports are not usage guidelines, nor should they be read as an endorsement of, or recommendation for, any particular drug, use or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports. McNally, MPH, MA Sujata Thakurta, MPA:HA Original report: Susan L. Burda Oregon Evidence-based Practice Center Oregon Health & Science University Mark Helfand, MD, MPH, Director Copyright © 2008 by Oregon Health & Science University, Portland, Oregon 97239. Final Report Update 1 Drug Effectiveness Review Project TABLE OF CONTENTS INTRODUCTION.......................................................................................................................... Pharmacokinetics, indications and dosing of included drugs................................................. Quick-relief medications for asthma: included citations: efficacy, effectiveness, and safety.. Albuterol compared with levalbuterol: Demographic and study characteristics in adults (studies with effectiveness outcomes only)........................................................................................... Albuterol compared with levalbuterol: Demographic and study characteristics in children (studies with effectiveness outcomes only)........................................................................................... Albuterol compared with levalbuterol: Effectiveness outcomes.............................................. Albuterol compared with pirbuterol: Demographic and study characteristics of included efficacy and effectiveness studies......................................................................................................... Albuterol compared with fenoterol: Demographic and study characteristics of included studies (studies with effectiveness outcomes only)........................................................................................... Albuterol compared with fenoterol: Effectiveness outcomes of included studies.................... Albuterol compared with terbutaline: Demographic and study characteristics of included studies (studies with effectiveness outcomes only)............................................................................... Albuterol compared with terbutaline: Effectiveness outcomes of included studies............... Fenoterol compared with terbutaline: Demographic and study characteristics of studies with effectiveness outcomes......................................................................................................................... Fenoterol compared with terbutaline: Effectiveness outcomes............................................. Quality assessment methods for drug class reviews for the Drug Effectiveness Review Project.................................................................................................................................................... Cochrane systematic reviews related to beta -agonists. Quick-relief medications for asthma Page 4 of 113 Final Report Update 1 Drug Effectiveness Review Project Suggested citation for this report: Norris S, McNally T, Thakurta S. Drug class review: Quick-relief medications for asthma. These organizations selected the topic and had input into the Key Questions for this review. The content and conclusions of the review are entirely determined by the Evidence-based Practice Center researchers. The authors of this report have no financial interest in any company that makes or distributes the products reviewed in this report. Quick-relief medications for asthma Page 5 of 113 Final Report Update 1 Drug Effectiveness Review Project INTRODUCTION Asthma Asthma is a chronic inflammatory disorder of the airways. In susceptible individuals this inflammation causes recurrent episodes of wheezing, breathlessness, cough, and other symptoms. These episodes are usually associated with widespread and variable airflow obstruction.
In contrast buy naprosyn with visa arthritis medication mexico, the difference in relative risk is fairly constant across groups with different baseline risk for the event purchase generic naprosyn on line can you get arthritis in neck, such that the difference (relative risk reduction) is similar across these groups discount naprosyn online american express arthritis pain in legs. Relative risk reduction is often more impressive than the absolute risk reduction. Another useful measure is the number needed to treat (or harm). The number needed to treat, often referred to as the NNT, is the number of patients who would have to be treated with an intervention for 1 additional patient to benefit (experience a positive outcome or avoid a negative outcome). The absolute risk reduction is used to calculate the number needed to treat. Systematic reviews weigh the quality of the evidence, allowing a greater contribution from studies that meet high methodological standards that reduce the likelihood of biased results. In general, for questions about the relative benefit of a drug, the results of well-executed, randomized, controlled trials are considered better evidence than results of cohort, case-control, or cross-sectional studies. In turn, these studies provide better evidence than uncontrolled trials and case series. For questions about tolerability and harms, observational study designs may provide important information that is not available from controlled trials. Within the hierarchy of observational studies, cohort designs are preferred when conducted well and for assessing a common outcome. Case-control studies are preferred only when the outcome measure is rare and the study is well conducted. Systematic reviews pay particular attention to the generalizability of efficacy studies performed in controlled or academic settings. Efficacy studies provide the best information about how a drug performs in a controlled setting. These studies attempt to tightly control potential confounding factors and bias; however, for this reason the results of efficacy studies may not be applicable to many, and sometimes to most, patients seen in everyday practice. Most efficacy studies use strict eligibility criteria that may exclude patients based on their age, sex, adherence to treatment, or severity of illness. For many drug classes, including the antipsychotics, unstable or severely impaired patients are often excluded from trials. In addition, efficacy studies frequently exclude patients who have comorbid diseases, meaning diseases other than the one under study. Efficacy studies may also use dosing regimens and follow-up protocols that may be impractical in typical practice settings. And these studies often restrict options that are of value in actual practice, such as combination therapies or switching to other drugs. Efficacy studies also often examine the short-term effects of drugs that in practice are used for much longer periods of time. Finally, efficacy studies tend to assess effects by using objective measures that do not capture all of the benefits and harms of a drug or do not reflect the outcomes that are most important to patients and their families. Systematic reviews highlight studies that reflect actual clinical effectiveness in unselected patients and community practice settings. Effectiveness studies conducted in primary care or office-based settings use less stringent eligibility criteria, more often assess health outcomes, and have longer follow-up periods than most efficacy studies. The results of effectiveness studies are more applicable to the “average” patient than results from the highly selected populations in Attention deficit hyperactivity disorder 11 of 200 Final Update 4 Report Drug Effectiveness Review Project efficacy studies. Examples of effectiveness outcomes include quality of life, frequency or duration of hospitalizations, social function, and the ability to work. These outcomes are more important to patients, family, and care providers than surrogate or intermediate measures, such as scores based on psychometric scales. For example, a study might use very narrow inclusion criteria like an efficacy study, but, like an effectiveness study, might examine flexible dosing regimens, have a long follow-up period, and measure quality of life and functional outcomes. For this report we sought evidence about outcomes that are important to patients and would normally be considered appropriate for an effectiveness study. However, many of the studies that reported these outcomes were short-term and used strict inclusion criteria to select eligible patients. For these reasons, it was neither possible nor desirable to exclude evidence based on these characteristics. Labeling each study as either an efficacy or an effectiveness study, while convenient, is of limited value; it is more useful to consider whether the patient population, interventions, time frame, and outcomes are relevant to one’s practice or to a particular patient. Studies anywhere on the continuum from efficacy to effectiveness can be useful in comparing the clinical value of different drugs. Effectiveness studies are more applicable to practice, but efficacy studies are a useful scientific standard for determining whether characteristics of different drugs are related to their effects on disease. Systematic reviews thoroughly cover the efficacy data in order to ensure that decision-makers can assess the scope, quality, and relevance of the available data. This thoroughness is not intended to obscure the fact that efficacy data, no matter how much of it there is, may have limited applicability to practice. Clinicians can judge the relevance of the study results to their practice and should note where there are gaps in the available scientific information. Unfortunately, for many drugs there exist few or no effectiveness studies and many efficacy studies. Yet clinicians must decide on treatment for many patients who would not have been included in controlled trials and for whom the effectiveness and tolerability of the different drugs are uncertain. Systematic reviews indicate whether or not there exists evidence that drugs differ in their effects in various subgroups of patients, but they do not attempt to set a standard for how results of controlled trials should be applied to patients who would not have been eligible for them. With or without an evidence report, these decisions must be informed by clinical judgment. In the context of development of recommendations for clinical practice, systematic reviews are useful because they define the strengths and limits of the evidence, clarifying whether assertions about the value of an intervention are based on strong evidence from clinical studies. Judgment, reasoning, and applying one’s values under conditions of uncertainty must also play a role in decision making. Users of an evidence report must also keep in mind that not proven does not mean proven not; that is, if the evidence supporting an assertion is insufficient, it does not mean the assertion is untrue. The quality of the evidence on effectiveness is a key component, but not the only component, in making decisions about clinical policy. Additional criteria include acceptability to physicians and patients, potential for unrecognized harm, applicability of the evidence to practice, and consideration of equity and justice. Attention deficit hyperactivity disorder 12 of 200 Final Update 4 Report Drug Effectiveness Review Project Scope and Key Questions The purpose of this review is to compare the benefits and harms of different pharmacologic treatments for ADHD. The Oregon Evidence-based Practice Center wrote preliminary key questions, identifying the populations, interventions, and outcomes of interest, and based on these, the eligibility criteria for studies. These were reviewed and revised by representatives of organizations participating in the Drug Effectiveness Review Project. The participating organizations of the Drug Effectiveness Review Project are responsible for ensuring that the scope of the review reflects the populations, drugs, and outcome measures of interest to both clinicians and patients. The participating organizations approved the following key questions to guide this review: 1.
Practice of offering a child pre- masticated food: an unrecognized possible risk factor for HIV transmission generic 250mg naprosyn amex rheumatoid arthritis definition. T lymphocyte subpopulation abnormalities in apparently healthy patients with hemophilia purchase naprosyn 250mg otc arthritis in back help. Pneumocystis carinii pneumonia and mucosal candidiasis in previ- ously healthy homosexual men: evidence of a new acquired cellular immunodeficiency proven 500mg naprosyn arthritis finger joints relief. Risk for occupational transmission of human immunodeficiency virus type 1 (HIV-1) associated with clinical exposures. HIV seroconversion in two homosexual men after receptive oral inter- course with ejaculation: implications for counseling concerning safe sexual practices. Altered distribution of T-lymphocyte subpopulations in children and ado- lescents with haemophilia. Transmission probabilities of HIV and herpes simplex virus type 2, effect of male circumcision and interaction: a longitudinal study in a township of South Africa. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. Opportunistic infections and immune deficiency in homosexual men. Serum HIV-1 RNA-levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study. Detection and isolation of type C retrovirus particles from fresh and culture lymphocytes of a patients with cutanous T-cell lymphoma. Detection, isolation and continuous production of cytopathic retro- viruses (HTLV-III) from patients with AIDS and pre-AIDS. Acquired immunodeficiency-like syndrome in two haemophiliacs. Normal T-cell subset ratios in patients with severe haemophilia A treated with cryoprecipitate. Male to female transmission of HIV in a cohort of hemophiliacs-frequency, risk-factors and effect of sexual counseling infection (Where? Changes in the spectrum of AIDS-defining conditions and decrease in CD4+ lymphocyte counts at AIDS manifestation in Germany from 1986 to 1991. Severe acquired immunodeficiency in male homosexuals manifested by chronic perianal ulcerated herpes simplex lesions. Predicting clinical progression or death in subjects with early-stage HIV infection: a comparative analysis of quantification of HIV RNA, soluble tumor necrosis factor type II receptors, neopterin, and beta2-microglobulin. Is transmission of HIV-I in non-viraemic serodiscordant couples possi- ble? HIV-infizierte Menschen ohne andere STD sind unter wirksamer antiretroviraler Therapie sexuell nicht infektiös. Per-contact risk of HIV transmission between male sexual partners. Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960. HIV Testing CHRISTIAN NOAH Early diagnosis of HIV infection is important: it allows the patient access to anti- retroviral therapy and it is crucial in order to avoid further transmission. Despite extensive testing possibilities and recommendations, HIV infection continues to be diagnosed at late stages. According to the 2014 report from the European Centre for Disease Prevention and Control (ECDC), 47% and 27% of HIV+ patients presented with a CD4 T cell count below 350/µl and 200/µl at the time of initial diagnosis. In Germany, the number of patients unaware of their positive HIV status is estimated at 14,000 (RKI 2014). There are several indications and reasons for HIV testing. Every pregnant woman should be offered an HIV test to prevent mother-to-child transmission. HIV testing also plays an important security role in blood and organ donation. HIV testing is also indicated in case of symptoms compatible with an acute antiretroviral syndrome, in case of indicator diseases (oral thrush, OHL, etc) or an AIDS-defining illness, as well as after occupational or non-occupational exposure to HIV. The basics of HIV diagnostics The laboratory diagnosis of HIV infection is primarily based on a serologic screening test. A reactive result has to be confirmed by a confirmatory test. Due to its relatively high sensitivity, the 4th generation test (“Combo test”) that simultaneously detects both HIV-specific antibodies and p24 antigen should be used (Breast 2000, Weber 2002, Sickinger, 2004, Skidmore 2009, Bentsen 2011). Any approved screening test detects all known HIV types (HIV-1 and -2), HIV groups and HIV subtypes. There are numerous commercial systems available for screening. However, the basic technological principle is the same for all and is based on antigen-antibody binding. The prototype assay is the ELISA (enzyme linked immunosorbent assay). Its central element is a plastic plate with 96 wells (microtiter plate). The surface of each cavity is coupled with HIV antigens and HIV antibodies. When a patient’s serum or plasma containing HIV antibodies is placed into one cavity, antibodies bind to the coupled antigen. An enzyme-labelled second antibody is then added, which recognizes and binds to human antibodies. Finally a substrate is added that is converted by the enzyme at the second antibody. The result is a color change, measured photometri- cally. The optical density correlates with the HIV antibody concentration in the sample of the patient – the higher the intensity, the more antibodies present in the sample. Based on this prototype several advances have improved the efficiency and effec- tiveness of the screening test (Perry 2008). Modern test systems are highly automated to achieve a very high degree of standardization and generate a result in less than an hour. In these systems, the solid phase consists of microparticles coupled with the virus antigens and antibodies. Accordingly, the method is referred to as a “microparticle enzyme immunoassay” (MEIA). The measured value is usually an index without dimensions, calculated from the ratio of the measured value of the patient sample and the negative control (Sample/Control, S/Co). Values below 1 are considered negative, values above 1 as reactive. It should always be called “reactive” and not a “positive” result to docu- ment that this result needs to be confirmed by a second test. With the screening test, sensitivity has the highest priority (this way, no infection should be missed), while a high specificity is preferred for the confirmatory test.
In the manufacturer’s synopsis of results from the Newer antiplatelet agents 34 of 98 Final Update 2 Report Drug Effectiveness Review Project unpublished JASAP trial (N=1294) cheap naprosyn 500 mg online is arthritis in the knee curable, the frequencies of major bleeding events at 1 year were described as comparable for extended-release dipyridamole 200 mg plus aspirin 25 mg and 49 aspirin 81 mg alone discount naprosyn 500 mg with amex treating arthritis of the spine, but the data was not reported purchase naprosyn in india arthritis treatment by rajiv dixit. Compared with aspirin alone, risk of withdrawal due to adverse events was significantly 47, 48 increased with the combination of extended-release dipyridamole plus aspirin in 2 of 3 47-49 49 trials. Despite follow-up durations that ranged from 1 year (JASAP) to 3. However, frequency of withdrawals due to adverse events in the aspirin-only control groups varied widely across trials (range, 3% to 16%), which could not be explained by population, dosage level (range, 50 mg to 81 mg), or follow-up duration. For example, based on the premise that withdrawals due to adverse events may naturally increase over longer periods of time, one might generally expect to see a lower frequency of withdrawals due to adverse events in shorter- term trials. However, among these trials, at 16%, frequency of withdrawals due to adverse events in the aspirin-only control group was highest in the shortest-term, unpublished trial (JASAP), and, at 3%, was lowest in the longest-term, ESPRIT trial. Therefore, because of this unexplained heterogeneity, we did not combine data from these trials to generate a pooled relative risk for the comparison of combination treatment with extended-release dipyridamole plus aspirin to aspirin alone. In the JASAP trial, compared to aspirin alone, withdrawal due to adverse events was only slightly higher for the combination of extended-release dipyridamole plus aspirin at 1 year (18% 49 compared with 16%; relative risk, 1. Whereas after 2 years in the ESPS-2 trial, the relative risk of withdrawals due to adverse events with the combination of extended-release dipyridamole plus aspirin increased to 1. As for other adverse events, compared with aspirin alone, frequency of headache was significantly greater with the combination of extended-release dipyridamole plus aspirin in the 2 trials that reported this outcome (40% compared with 32%, pooled relative risk, 1. Clopidogrel compared with aspirin In the CAPRIE trial, although effectiveness outcomes were reported for the subgroup of 6451 patients with a history of ischemic stroke, harms outcomes were not reported separately for this subgroup. Therefore, there was no evidence available to evaluate the comparative harms between clopidogrel and aspirin in patients following a transient ischemic attack or a stroke. Clopidogrel plus aspirin compared with aspirin alone Reporting of harms was limited in the FASTER trial, which compared early treatment (within 24 51 hours) with clopidogrel 75 mg plus aspirin 81 mg (N=99) to aspirin 81 mg alone (N=95). The FASTER trial also used a factorial design to randomize patients to clopidogrel or placebo and simvastatin or placebo. For effectiveness outcomes, separate data was available for the comparison of clopidogrel plus aspirin to aspirin alone in patients who were not taking simvastatin. However, for harms, data was only available for the comparison of clopidogrel to no clopidogrel in all patients, regardless of simvastatin use. However, the risk of confounding of bleeding outcomes based on simvastatin use was likely low as there is no known link between Newer antiplatelet agents 35 of 98 Final Update 2 Report Drug Effectiveness Review Project simvastatin and bleeding risk. Although overall major bleeding and withdrawals due to adverse events were not reported, compared to no clopidogrel, clopidogrel use was not found to significantly increase risk of severe extracranial bleeding (0. A second observational study of 633 patients evaluated the risk of major bleeding with aspirin plus clopidogrel compared with aspirin alone when given early after stroke or transient 57 ischemic attack. However, its results will not be discussed here because it had significant differences in clinical characteristics between groups at baseline but conducted no statistical analysis to adjust for these potential confounders. Ticlopidine compared with aspirin 45, 46 Among 2 randomized controlled trials, differences in harms between ticlopidine and aspirin only reached statistical significance in the larger (N=3069), longer-term (40 months) TASS trial, which involved a higher dosage in the aspirin control group (1300 mg) and enrolled primarily 46 white patients (80%). In the TASS trial, when compared to 1300 mg of aspirin, there was a significantly lower risk of gastrointestinal bleeding with ticlopidine (0. However, withdrawals due to adverse events were significantly greater with ticlopidine (21% compared with 14%; relative risk, 1. In contrast, in the 2-year AAASPS trial of 1809 black patients, when compared to aspirin 650 mg, ticlopidine had similar rates of gastrointestinal bleeding (0. Peripheral vascular disease Indirect evidence Clopidogrel compared with aspirin In the CAPRIE trial, data on harms were not reported separately for the subgroup of 11 592 24 patients with peripheral vascular disease. Clopidogrel plus aspirin compared with aspirin alone Two trials were consistent in finding no significant increase in major bleeding with clopidogrel 52, 53 plus aspirin compared with aspirin alone. In the subset of 3096 patients from the CHARISMA trial, rate of severe bleeding was identical for clopidogrel plus aspirin and aspirin 53 alone (1. In the CASPAR trial (N=851), the 1-year (median) incidence of severe bleeding was close to doubled during dual therapy with clopidogrel 75 mg plus aspirin (range, 75 mg to 100 mg) as compared with aspirin alone (range, 75 mg to 100 mg), but the difference was not statistically significant (2. Incidence of withdrawal due to adverse events was not reported. Newer antiplatelet agents 36 of 98 Final Update 2 Report Drug Effectiveness Review Project Key Question 3. For adults with acute coronary syndromes or coronary revascularization via stenting or bypass grafting, prior ischemic stroke or transient ischemic attack, or symptomatic peripheral vascular disease do antiplatelet agents differ in effectiveness and harms based on duration of therapy? Summary of Findings • We found no head-to-head trials that directly compared newer antiplatelet agents based on duration of therapy. The benefit appeared to decrease in a step-wise manner and lose statistical significance at 8 months (PCI-CURE, low strength) and 12 months (CREDO, moderate strength). Detailed Assessment Indirect evidence 5 Current percutaneous coronary intervention guidelines recommend the duration of thienopyridine therapy for patients receiving a bare metal stent or drug eluting stent during percutaneous coronary intervention for acute coronary syndrome be at least 12 months. If the risk of morbidity because of bleeding outweighs the anticipated benefit afforded by thienopyridine therapy, earlier discontinuation should be considered. Early discontinuation of thienopyridine therapy has been identified as a risk factor for late stent thrombosis in patients with drug eluting stent but the optimal therapy and comparative risk-benefit of bare metal stent 58, 59 compared with drug eluting stent remains uncertain. This controversy is beyond the scope of this report. Among the 3 trials that evaluated 6 months of dual therapy, the first evaluated clopidogrel 75 mg plus aspirin 100 mg in 278 Turkish patients with successful stent 62 implantation. The second trial evaluated clopidogrel 75 mg plus aspirin 300 mg in 78 Turkish patients with typical stable angina pectoris or documented myocardial ischemia, and with only 1 60 angiographic lesion in 1 native coronary artery undergoing successful stent implantation. The Randomized Argentine Clopidogrel Stent (RACS) trial was a prospective, randomized, nonblinded study of 1004 patients undergoing percutaneous coronary intervention who were randomized after successful bare metal stent placement to 30 compared with 180 days of 61 clopidogrel 75 mg plus aspirin 75 to 325 mg. The PCI-CURE trial included 2658 patients with 63 non-ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention. Following percutaneous coronary intervention, after 2 to 4 weeks of open-label clopidogrel or ticlopidine, patients were randomized to a mean of 8 months of continuing treatment with clopidogrel plus aspirin 75 to 325 mg or to placebo. Similarly, in the CREDO trial, after percutaneous coronary intervention, 2116 patients received open-label clopidogrel 75 mg for 28 Newer antiplatelet agents 37 of 98 Final Update 2 Report Drug Effectiveness Review Project days and then were randomly assigned to double blind treatment with continuation of clopidogrel 64 75 mg plus aspirin 325 mg for 12 months or to aspirin 325 mg alone. When we used a fixed-effects model to pool data from the 3 trials that compared 6 months of treatment with clopidogrel plus aspirin to 1 month of treatment for the outcomes of all-cause mortality, cardiovascular mortality, revascularization, and bleeding, a significant benefit with the longer-term treatment was only found for the outcome of revascularization (relative risk, 0. No other pooled outcome reached statistical significance. Only the RACS trial reported withdrawals due to adverse events but it was a nonsignificant and imprecise finding 61 (relative risk, 2. In contrast, when we considered results for revascularization from the PCI-CURE and CREDO trials, we observed that the potential benefit of a reduced risk of revascularization became only probable at 8 months was unlikely at 12 months (Table 4, Figure 2). There was also a trend toward increased bleeding risk over time when results from the PCI-CURE and CREDO trials were considered (Table 4, Figure 3).