By F. Urkrass. Mount Olive College. 2018.
Our results for pregabalin were in agreement with the pooled analysis by Straube buy 80 mg propranolol, et al generic 40 mg propranolol amex. Indirect meta-analysis of placebo- controlled trials of duloxetine purchase propranolol 80 mg mastercard, milnacipran propranolol 40 mg without a prescription, and pregabalin found no significant difference between the drugs (Table 4) buy propranolol 40 mg low cost. The data on amitriptyline was insufficient to make a statement on this outcome as only 1 small trial, N=80, reported data on Fibromyalgia Impact Questionnaire 45 total score, although it did not find a significant difference compared with placebo. We also considered the Medical Outcomes Study 36-item Short-Form Health Survey physical and mental component summaries to assess therapeutic response of the included drugs on overall physical and mental function. No differences were found in mean differences between duloxetine, milnacipran or pregabalin on either of these measures based on 6 trials that reported 52, 53, 57, 61, 65, 68, 69 data. The pooled analysis of placebo-controlled trials (8-15 weeks) of milnacipran and duloxetine found a small but significant mean difference compared to placebo for the Medical Outcomes Study 36-item Short-Form mental component summary (milnacipran 1. In the pooled analysis of pregabalin by Straube, et al. Combining the data Drugs for fibromyalgia 29 of 86 Final Original Report Drug Effectiveness Review Project for all 3 doses may explain the difference in our results. It is important to recognize that although significant, the absolute mean differences noted between the active drug and placebo ranged between 1. This may explain why the significant difference noted with milnacipran and duloxetine compared to placebo did not translate into any difference between the drugs in the meta-analysis. Our results differed from the analysis by Arnold on the 4 placebo-controlled trials of duloxetine which found a statistically significant difference on the physical component score as well (1. This study was given a poor quality rating because of its risk of selection bias due to the failure to perform and report on a systematic search process, not reporting trial details or outcome data of individual trials, and 57 failure to grade the quality of their results. In summary, there was low to insufficient evidence that all drugs are superior to placebo on the total score of the Fibromyalgia Impact Questionnaire with no difference between drugs. Milnacipran was found to have a small but significant improvement on the Medical Outcomes Study 36-item Short-Form Health Survey physical and mental component compared with placebo and duloxetine was found to have a small but significant improvement on the mental component summary. No difference was found between duloxetine, milnacipran, or pregabalin on this measure. Other outcomes Given the significant variability and sparsity of reporting data on outcomes of sleep disturbance, health-related quality of life, and depressed mood in the amitriptyline trials, we did not analyze these outcomes. Since their report was released, 2 additional milnacipran 52, 53 trials have been published, with only 1 providing additional evidence on the outcome of 53 sleep. These new results are consistent with prior studies. They found that pregabalin was superior to milnacipran on improvement in sleep disturbance and health-related quality of life, whereas milnacipran was superior to pregabalin on improvement in depressed mood (Table 5). Indirect analysis of placebo-controlled trials of pregabalin, milnacipran, 49 and duloxetine for fibromyalgia Duloxetine vs. Drugs for fibromyalgia 30 of 86 Final Original Report Drug Effectiveness Review Project Comparisons to placebo Gabapentin One randomized, placebo-controlled, 12-week, fair-quality trial of 150 patients found that gabapentin 1800 mg (median) significantly improved pain severity, overall impact of fibromyalgia, global status, and sleep, but not tender point pain threshold, depression, or overall 78 quality of life. Diagnosis of fibromyalgia was based on the 1990 American College of Rheumatology criteria. Patients were 90% female, 97% white, and had a mean age of 48 years. A total of 19% of patients had a current major depressive disorder and 9% had a current anxiety disorder. For pain, gabapentin was superior to placebo in reducing average pain severity score (−44% compared with −33%; P=0. For overall impact fibromyalgia, there was a significantly greater reduction in Fibromyalgia Impact Questionnaire mean total score for gabapentin than placebo (−43% compared with −22%; P=0. For global status, there was a greater reduction Clinical Global Impression of Severity Scale scores for gabapentin than for placebo (−29% compared with −15%; P=0. Gabapentin also significantly reduced the Medical Outcomes Study Sleep Problems Index score (−40% compared with −14%; P=0. The difference between gabapentin and placebo did not reach statistical significance for increasing mean tender point threshold (+11% compared with +6%), reducing depression based on the Montgomery Asberg Depression Rating Scale score (−43% compared with −19%; P=0. Cyclobenzaprine Compared with placebo, a significant reduction in pain severity was only found with 38 38, 40, 41 cyclobenzaprine in the largest (N=120) of 3 fair-quality trials. Data on pain could not be pooled across trials due to heterogeneity in outcome assessment.
RCT order 80 mg propranolol free shipping, DB Multinational (7 buy generic propranolol 40mg line, Europe) FP MDI (1000) Yes (high) Fair 35 1996 compared with 213 Age 18-77 buy discount propranolol 40mg line, severe cheap 40 mg propranolol otc, well controlled on high BDP MDI (2000) dose ICS cheap 80mg propranolol overnight delivery, 19% smokers 12 months Multicenter (20 outpatient clinics) Lundback et al. RCT, DB Multinational (10) FP MDI (500) No, only for FP Fair 36 1993 compared with MDI compared 585 Age 15-90, moderate, not controlled on FP DPI (500) with BDP MDI ICS, smoking status NR compared with (high) ; FP DPI 6 weeks BDP MDI (1000) 500 is medium (N = 489 continued an additional Multicenter (47) 46 weeks) Molimard et al. RCT, open-label France BDP MDI (800) Yes (all high) Fair 27 2005 compared with 460 Age 18-60, moderate to severe persistent, BUD DPI (1600) not controlled on ICS, smoking status NR compared with 12 weeks FP DPI (1000) Multicenter, subspecialty clinics (69 pulmonologists) Ohbayashi et al. RCT, double cross-over every 3 Japan FP DPI (NR) Yes Fair 56 2008 months compared with Controller medications for asthma 39 of 369 Final Update 1 Report Drug Effectiveness Review Project Table 7. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating Age, mild to moderate persistent, controlled BDP MDI (NR) 50 on FP 10 months 37 Raphael et al. RCT, DB, DD US Mometasone DPI (200) No; only for Fair 38 1999 vs. BDP 227 Age ≥ 12, moderate, on ICS, smokers Mometasone DPI (200) (both low), MF excluded vs. BDP MDI (336) Beclomethasone compared with triamcinolone Berkowitz et al. RCT, DB, DD US BDP MDI (336) Yes (medium) Fair 40 1998 vs. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating 41 Bronsky et al. BUD 400 554 Age 12-75, mild to severe, on ICS, 9% CIC HFA-MDI (320) No for CIC 320 smokers vs. RCT, DB, DD Multinational - Hungary, Poland, CIC HFA-MDI (320) Yes (medium) Fair 61 2007 Serbia/Montenegro, South Africa, Spain vs. RCT, DB, DD Multinational - Australia, Germany, CIC HFA-MDI (160) Yes (low) Fair Controller medications for asthma 41 of 369 Final Update 1 Report Drug Effectiveness Review Project Table 7. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating 62 2007 Hungary, Poland, Portugal, Serbia and vs. RCT Canada Flunisolide MDI + AeroChamber Yes (medium) Fair 42 2000 (1500) 179 Age 18-75, moderate, on ICS, 5% current vs. BDP (33 trials) For some of the Good analysis included Severity ranged from mild to severe FP vs. BUD (37) studies 71 trials (14,602 participants), 59 persistent parallel, 14 cross-over (four had FP vs. BDP/BUD (2) a washout) 38 studies had FP:BDP/BUD Majority of studies (47) were dose ratio of between 6 weeks and 5 months; 1:2; 22 had dose ratio 1:1; 14 were ≤4 weeks remainder had multiple dose ratio comparisons or ratio was unclear 43 Ayres et al. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating subjects previously on ICS and not on ICS, 8 weeks smoking status NR Ferguson et al. RCT, DB, DD Multinational (6 countries worldwide) FP DPI (400) Yes (medium) Fair 44 1999 vs. RCT, open-label France BDP MDI (800) Yes (all high) Fair 27 2005 vs. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating 47 Ringdal et al. RCT, single-blind Multinational (17) Mometasone DPI (200) No (only for M Fair 48 2000 vs. BUD, 730 Age ≥ 12, moderate, on ICS, smokers Mometasone DPI (400) both medium) excluded vs. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating Ciclesonide compared with flunisolide No systematic reviews or head-to-head trials found Ciclesonide compared with fluticasone 63 Bateman 2008 RCT Multinational - Europe, North America, CIC HFA-MDI (640) Yes (high) Fair South Africa vs. Fair Controller medications for asthma 45 of 369 Final Update 1 Report Drug Effectiveness Review Project Table 7. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating vs. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating publication 19% smokers 321 and 332 Multicenter 8 weeks and 6 weeks Flunisolide compared with mometasone No systematic reviews or head-to-head trials found Flunisolide compared with triamcinolone No systematic reviews or head-to-head trials found Fluticasone compared with mometasone 57 Harnest et al. RCT, DB Multinational (20) MF DPI (200) No (only for Fair 52 2001 vs. RCT, DB, triple- dummy US FP MDI (196) + Salmeterol (84) Yes (medium Fair 53 1999 vs. Controller medications for asthma 47 of 369 Final Update 1 Report Drug Effectiveness Review Project Table 7. Characteristics of head-to-head studies comparing inhaled corticosteroids in children and adults Study Design Country N Population Comparison Equivalent Quality Study Duration Setting (total daily dose in mcg) dosing Rating 12 weeks TAA MDI (1200) Multicenter, Pulmonary/allergy medicine clinics (50) Condemi et al.
There were 17 bleeding complications (4 major and 13 minor) in 15 patients during the follow-up period discount 40mg propranolol mastercard. Of the 15 patients buy discount propranolol 80mg on line, 6 were on clopidogrel in addition to aspirin (1 generic propranolol 80 mg with amex. Are there subgroups of patients based on demographics (age purchase propranolol 80mg visa, racial groups purchase 40mg propranolol otc, gender), socioeconomic status, other medications (drug-drug interactions), comorbidities (drug-disease interactions), or pregnancy for which one antiplatelet agent is more effective or associated with fewer harms? Summary of Findings Age • There was no significant interaction between age and the relative effects of prasugrel and clopidogrel on the primary composite endpoint (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) but a post-hoc analysis suggested no net benefit from prasugrel for patients 75 years of age or older. Race • The fixed-dose combination of extended-release dipyridamole plus aspirin remained noninferior to clopidogrel for the primary outcome of recurrent stroke across subgroups of patients based on race. Gender • No significant interaction was found between sex and the relative effect of prasugrel compared with clopidogrel in the TRITON-TIMI 38 trial. Newer antiplatelet agents 41 of 98 Final Update 2 Report Drug Effectiveness Review Project Comorbidities • A subgroup analysis of the TRITON-TIMI 38 trial found that, compared with clopidogrel, there was a significantly greater reduction in risk of the composite primary endpoint with prasugrel in patients with and without diabetes. Other medications • Evidence was insufficient to draw conclusions about the benefit-risk ratio of using a proton pump inhibitor in patients taking clopidogrel. We found no randomized controlled trials specifically designed to assess whether concomitant use of a proton pump inhibitor increased the risk of cardiovascular events in patients taking clopidogrel. Indirect evidence indicated that although use of a proton pump inhibitor significantly reduced risk of hospitalization for gastroduodenal bleeding in a broadly-defined average-risk patient population who were taking clopidogrel (without aspirin), there was no significant reduction in risk of rehospitalization for major gastrointestinal complications in patients at high risk for gastrointestinal bleeding. Genotype • In clopidogrel-treated patients with coronary stent placement, there was no significant difference between carriers of the CYP2C19*17 allele and noncarriers in risk of major bleeding at 30 days. Newer antiplatelet agents 42 of 98 Final Update 2 Report Drug Effectiveness Review Project Detailed Assessment Demographics Age Direct evidence In the TRITON-TIMI 38 trial of patients with acute coronary syndromes scheduled for a percutaneous coronary intervention, Kaplan-Meier estimated hazard ratios for selected subgroups of patients for the primary composite endpoint (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) were reported. No statistically significant interactions were identified. The overall hazard ratio for prasugrel compared with clopidogrel was 0. The reduction in risk was significantly greater for prasugrel in patients younger than 65 years old (hazard ratio, 0. The authors performed a series of post-hoc exploratory analyses to identify subgroups of patients who did not have a favorable net clinical benefit. This was defined as the rate of death from any cause, nonfatal myocardial infarction, nonfatal stroke, or noncoronary artery bypass graft-related nonfatal major bleeding. Patients 75 years of age or older had no net benefit from prasugrel (hazard ratio, 0. In 20 332 patients with recent ischemic stroke who participated in the good-quality 42 PRoFESS trial, the finding of noninferiority of the fixed-dose combination of extended-release dipyridamole plus aspirin over clopidogrel for the primary outcome of recurrent stroke was consistent in subgroups of patients who were less than 65 years of age (7. Results of the hazard ratio analysis were displayed in graphical form, but the actual hazard ratios and 95% confidence intervals were not reported. Indirect evidence 21 In a subset analysis of CURE, compared with placebo plus aspirin, clopidogrel plus aspirin showed benefit in the rates of the first primary outcome in patients more than 65 years old (13. In that analysis, extended-release dipyridamole/aspirin was superior to either agent used alone in the secondary prevention of ischemic stroke, irrespective of age. While these data refer to adults, the product contains aspirin and thus should be avoided in children and teenagers with viral infection due to the risk of Reye’s syndrome. These patients, on various antiplatelet and anticoagulant agents for secondary stroke prevention, were predominantly female (68. The study was designated as poor quality due to its Newer antiplatelet agents 43 of 98 Final Update 2 Report Drug Effectiveness Review Project methodological limitations, but it suggested that patients aged 75 to 84 years and those who were more than 85 years old were more likely to have a bleed than were younger patients. After adjusting for various factors (including age, gender, physical impairment, and gastrointestinal bleeding risks when using gastrointestinal protectants, NSAIDS, or corticosteroids), users of ticlopidine showed an increased risk of hospitalization for bleeding episodes compared to nonusers of ticlopidine (odds ratio, 1. For comparison, the adjusted rate of hospitalizations for aspirin users due to bleeding was an odds ratio of 1. Racial groups Direct evidence In the PRoFESS trial, the finding of noninferiority of the fixed-dose combination of extended- release dipyridamole plus aspirin over clopidogrel for the primary outcome of recurrent stroke did not differ significantly across subgroups based on ethnicity in patients with recent ischemic 42 stroke (African, Chinese, South Asian, Other Asian, white/European, Native Latin). No other head-to-head trials of newer antiplatelet agents in other included populations reported subgroup analyses based on race. Indirect evidence There was little evidence to suggest that the newer antiplatelet agents differ in effect or tolerance 45 across ethnic groups.
Issues speciﬁc to vitamin K antagonists have led to the may indicate the presence of dabigatran generic propranolol 80mg online, it will not provide an exact development of anticoagulation clinics (so-called Coumadin clin- level of anticoagulant activity order 80 mg propranolol otc. For therapeutic doses of oral factor ics) in many parts of the world buy 80mg propranolol with mastercard, which play a very important role in Xa inhibitors buy propranolol 80 mg online, the prothrombin time (PT) is more sensitive than the optimizing the safety and efﬁcacy of vitamin K antagonists cheap propranolol 80 mg free shipping. PTT; however, the results are dependent on the PT reagent used in Warfarin’s long half-life of 40 hours is an advantage for patients the assay and apixaban has less effect on the PT than rivaroxaban. Furthermore, the twice-daily dosing schedules of some provide sensitive and speciﬁc assays for measuring drug concentra- NOACs may be more difﬁcult for some patients to adhere to than a tions of oral direct factor Xa inhibitors. The lack of a requirement for recombinant factor VIIa are available for overcoming their antico- regular coagulation monitoring may eliminate the initial and agulant effect in the management of severe bleeding episodes. Healthcare systems are now grappling with how to handle the threatening hemorrhage. If NOACs are prescribed appropriately, the adherence issue with the NOACs. One approach is to have patients current lack of a speciﬁc antidote may not be a great drawback in on NOACs be followed by anticoagulation or thrombosis manage- most bleeding situations because there will be relatively few ment clinics. Reports of thrombotic and hemorrhagic complications circumstances in which a reversal agent will be required. This will be an added burden for clinics that are apixaban, respectively, are renally eliminated as active drug. However, with better care coordination and NOAC and this is best done by calculating creatinine clearance bundled payment systems, there should be an impetus for incorporat- using the Cockcroft-Gault formula, which incorporates body weight ing patients on NOACs into these clinics to optimize outcomes (as opposed to other formulas that provide estimates for a body (including reduced need for hospitalizations and emergency depart- surface area of 1. Pharmacists/nurses/physicians with special expertise in All of the trials evaluating dabigatran etexilate or rivaroxaban anticoagulation management can provide the oversight to ensure excluded patients with a creatinine clearance 30 mL/min, whereas that NOACs are prescribed appropriately based upon an individual the ARISTOTLE trial excluded patients with creatinine clearance patient’s history and clinical characteristics. In patients with a creatinine clearance of 30 to 49 Cushman recommended that institutions adopt protocols for NOAC mL/min, the dose of rivaroxaban was reduced to 15 mg, whereas no use in acute VTE that address 6 key components: patient preference, adjustments were made in the RE-LY trial for either the 150 or 110 patient selection, drug interactions, compliance, follow-up, and mg doses of dabigatran etexilate. Based on pharmacokinetic consider- taken into consideration. Even among patients with insurance that ations, a reduced dose of 75 mg BID was approved by the FDA for covers drugs, prescribers should ascertain how much patients pay patients with atrial ﬁbrillation and a creatinine clearance of 15 to 29 out of pocket (copayment) compared with warfarin. High drug costs mL/min in the absence of efﬁcacy and safety data. The FDA also can contribute to reduced medication adherence: patients are known approved rivaroxaban at a dose of 15 mg daily for atrial ﬁbrillation to not ﬁll prescriptions they regard as too expensive or skip/split patients with a creatinine clearance of 15 to 29 mL/min. The FDA also extended the substantial cost for healthcare systems. Many clinicians with The vitamin K antagonists will remain an important anticoagulant expertise in anticoagulant therapy were surprised by these option. They remain the medication of choice for patients with decisions by the FDA, particularly given the current absence of a mechanical heart valves. Therefore, many believe that NOACs have minimal, if any, long-term effects on organ systems and should not be prescribed at any dose in patients with a creatinine physiologic processes other than blood coagulation. JAm mentation Laboratory, Boehringer Ingelheim, Pﬁzer, Bristol- Coll Cardiol. Meyers Squibb, Janssen Pharmaceuticals, Bayer Healthcare, and 16. Off-label drug use: Dabigatran and apixaban for the botic therapy to prevent stroke in patients who have nonvalvu- prevention and treatment of VTE. Beneﬁt of oral anticoagulant over antiplatelet therapy in atrial ﬁbrillation Correspondence depends on the quality of international normalized ratio control Kenneth A. Bauer, MD, Beth Israel Deaconess Medical Center, 330 achieved by centers and countries as measured by time in Brookline Avenue, Boston, MA 02215; Phone: 617-667-2174; Fax: therapeutic range. Comparison of outcomes among patients randomized to warfarin therapy according to References anticoagulant control: results from SPORTIF III and V. Recent progress in anticoagulant therapy: oral with atrial ﬁbrillation. Kirley K, Qato DM, Kornﬁeld R, Stafford RS, Alexander GC.