Cytoxan

By N. Mirzo. Mount Olive College.

Pooled results 346 after 9 weeks have been published and the manufacturer provided unpublished results for the 218 patients who participated in an additional 40-week continuation phase (22% of original 347 group) safe 50mg cytoxan. At 12 weeks generic cytoxan 50 mg otc, there were no significant differences between asenapine and olanzapine (noninferiority design) in proportions of patients with YMRS response (77% compared with 346 82%) or remission (75% compared with 79%). Results from week 52 of this trial has not yet been published, but data on file provided by the manufacturer indicated that proportions of YMRS responders and remitters remained comparable for asenapine and olanzapine at study 347 endpoint. Similar proportions of patients (N=329) taking olanzapine 14. Subgroup analyses among patients with mixed compared with pure manic episodes found that response and remission rates were comparable for olanzapine and risperidone, regardless of episode type. Atypical antipsychotic drugs Page 90 of 230 Final Report Update 3 Drug Effectiveness Review Project Indirect evidence Acute manic and mixed episodes When used as monotherapy in patients with moderate to severe manic or mixed episodes (range of baseline YMRS mean total scores, 26. Whereas in patients with mild to moderate manic or mixed episodes (baseline YMRS mean total score of 23. When used in combination with lithium or valproate, significantly greater proportions of 373 patients met response criteria with aripiprazole, asenapine (unpublished trial, data not 374 382 377-379 reported), olanzapine, and immediate-release quetiapine than with placebo. When taken in combination with carbamazepine, there was no significant difference in response 376 between olanzapine and placebo (64% compared with 66%; P value not reported). Relative risk (95% confidence interval) of response for atypical antipsychotics compared with placebo Atypical In combination with lithium or antipsychotic Monotherapy valproate 357-360 373 Aripiprazole 1. When used as monotherapy in samples of patients with moderate to severe manic and mixed episodes, compared with placebo, significantly greater proportions of patients met criteria for remission with aripiprazole, olanzapine, immediate-release quetiapine, extended-release quetiapine, and risperidone (Table 18). However, in one trial of patients with mild to moderate manic or mixed episodes, the olanzapine and placebo groups did not differ significantly in the 364 proportion who reached remission (43% compared with 35%; P=0. When used in combination with lithium or valproate, significantly greater proportions of patients met remission criteria with aripiprazole, asenapine (unpublished trial, data not reported), olanzapine, and immediate-release quetiapine than with placebo. When taken in combination with carbamazepine, there was no significant difference in remission between olanzapine and 376 placebo (55% compared with 59%; P value not reported). Atypical antipsychotic drugs Page 91 of 230 Final Report Update 3 Drug Effectiveness Review Project Table 18. Relative risk (95% confidence interval) of remission for atypical antipsychotics compared with placebo In combination with lithium or Atypical antipsychotic Monotherapy valproate 358, 360 373 Aripiprazole 1. Maintenance treatment Compared with placebo, the proportion of patients experiencing a relapse was significantly 388 reduced by maintenance monotherapy with olanzapine (47% compared with 80%; P<0. The proportion of patients not experiencing a relapse was significantly higher with aripiprazole 387 (72%) compared with placebo (49%; P<0. Compared with placebo, the time to relapse was significantly longer for aripiprazole (hazard ratio, 0. When taken in combination with other mood stabilizers, compared with placebo, time to recurrence of any mood event was significantly increased with immediate-release quetiapine in 391 trial #126 (hazard ratio, 0. The effect of asenapine on time to recurrence of any mood event was unknown, as the only information provided from the unpublished study indicated that “improvements in efficacy variables observed during the 12-week feeder study were maintained through week 52 386 suggesting long-term maintenance of efficacy. Similarly, compared with placebo, significantly greater proportions of patients met criteria for remission with immediate- 396-399 release quetiapine (RR, 1. MADRS criteria for remission were somewhat more strict in the aripiprazole trials (score of 8 or below) than in the trials of olanzapine and immediate-release quetiapine (score of 12 or below). Atypical antipsychotic drugs Page 92 of 230 Final Report Update 3 Drug Effectiveness Review Project As maintenance treatment over 52 weeks in adults with bipolar depression, immediate- release quetiapine was the only atypical antipsychotic with evidence of significantly increasing the time to recurrence of a mood event (hazard ratio, 0. Rapid cycling For acute treatment of patients with rapid-cycling bipolar disorder, with the most recent episode manic or mixed, preliminary results from subgroup analyses found significantly greater mean 377 YMRS score reductions for aripiprazole (-15. For long-term treatment of patients with rapid-cycling bipolar disorder, with the most recent episode manic or mixed, preliminary findings from a subgroup analysis found a significantly longer time to relapse for aripiprazole compared with placebo (100-week hazard 412 ratio, 0. Additionally, for acute treatment of rapid cycling bipolar disorder over 8 weeks, with the most recent episode depressive, compared with placebo, preliminary results from a subgroup analysis found significantly more patients taking immediate-release quetiapine 600 mg and 300 mg met criteria for response (number needed to treat, 4 and 3, respectively) and remission 413 (number needed to treat, 3 and 3, respectively). Immediate control of acute agitation associated with bipolar I disorder 405 In 24-hour studies, patients treated with intramuscular forms of aripiprazole 9. In 201 acutely agitated inpatients, intramuscular olanzapine was superior to lorazepam and placebo in reducing Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) scores 2 hours after administration (intramuscular olanzapine -9. In another study of 301 acutely-agitated, bipolar I disorder patients, 2-hour PANSS-EC score reductions were significantly greater for intramuscular aripiprazole 9. However, there was a higher incidence of over sedation (scores of 8, deep sleep, or 9, unarousable, on the Agitation-Calmness Evaluation Scale) in the intramuscular aripiprazole 15 mg-treated (17. Harms Diabetes We found no studies that directly compared the risk of diabetes between different atypical antipsychotics. Compared with conventional antipsychotics, 1 case-control study found significant increases in risk of developing or exacerbating diabetes mellitus were found for clozapine (hazard ratio, 7. This study used data from a United States multi-state managed care claims database 354 for the entire years 1998 through 2002. Among 123 292 non-Medicaid patients with an ICD-9 diagnosis of bipolar disorder, 920 cases of diabetes were identified in which at least 3 prescriptions of antipsychotic medications had been received during the study period. Cases of diabetes were identified based on an ICD-9 code of 250.

Proton pump inhibitors Page 17 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1 buy discount cytoxan 50 mg. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Number Screened generic cytoxan 50 mg online, Eligible, Enrolled, Author Esophagitis Grade (Grading Withdrawn, Lost to Year Population, Setting Criteria), Other Characteristics Followup Healing Rate at 4 Weeks Kao et al, 2003 100 patients at one center in Grade A: 51% Screened NR/eligible Not reported Taiwan Grade B: 49% NR/100 enrolled mean age 49 (Los Angeles Classification) 69% male 100% Asian Proton pump inhibitors Page 18 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Year Healing Rate at 8 Weeks Symptoms at 4 Weeks Symptoms at 8 Weeks Kao et al, 2003 Not reported Esomeprazole 40 mg vs omeprazole Efficacy of on-demand therapy (n=34 esomeprazole 40 mg, n=23 20 mg omeprazole 20 mg, initiated week 5) Per-protocol (N=91) Symptom-free on day 1: 28. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Withdrawals Due to Year Results by Baseline Severity Adverse Events Quality rating Funding source Kao et al, 2003 Not reported Not reported Fair: Supported by a grant not clear if patients masked, randomization, from the National allocation concealment methods not reported. Cheng Kung University Proton pump inhibitors Page 20 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Number Screened, Eligible, Enrolled, Author Esophagitis Grade (Grading Withdrawn, Lost to Year Population, Setting Criteria), Other Characteristics Followup Healing Rate at 4 Weeks Castell 1070 US patients at multiple Grade 2: 61%-71% 1284 enrolled, 1226 lansoprazole 15 mg: 72. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Year Healing Rate at 8 Weeks Symptoms at 4 Weeks Symptoms at 8 Weeks Castell lansoprazole 15 mg: 75. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Withdrawals Due to Year Results by Baseline Severity Adverse Events Quality rating Funding source Castell When healing rates were adjusted for baseline omeprazole 20 mg: 2% Fair: randomization and allocation method not Supported by TAP 1996 esophagitis grade, treatment comparison results lansoprazole 30 mg: reported, attrition not reported Pharmaceuticals, were similar to those of the overall analyses. Patients with less severe esophagitis (grade 2) at lansoprazole 15 mg: baseline had higher rates with all the active 0. Healing rate at 4 weeks, lansoprazole 15 mg vs lansoprazole 30 mg vs omeprazole 20 mg, by baseline esophagitis grade: grade 2: 83. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Number Screened, Eligible, Enrolled, Author Esophagitis Grade (Grading Withdrawn, Lost to Year Population, Setting Criteria), Other Characteristics Followup Healing Rate at 4 Weeks Castell et al, 5241 patients, multiple Grade A: 36% 5241 enrolled, ITT esomeprazole 79. Grade D: 6% (life-table analysis) (LA Grade) lansoprazole 30 mg (n=2617) Heartburn Severity esomeprazole 40 mg None: 1% (n=2624) Mild: 10% Moderate: 47% Severe: 42% Proton pump inhibitors Page 24 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Year Healing Rate at 8 Weeks Symptoms at 4 Weeks Symptoms at 8 Weeks Castell et al, EE Complete resolution of heartburn: Not reported 2002 esomeprazole 92. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Withdrawals Due to Year Results by Baseline Severity Adverse Events Quality rating Funding source Castell et al, esomeprazole 75. Proton pump inhibitors Page 26 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Number Screened, Eligible, Enrolled, Author Esophagitis Grade (Grading Withdrawn, Lost to Year Population, Setting Criteria), Other Characteristics Followup Healing Rate at 4 Weeks Corinaldesi 241 patients at 30 centers, Grade 2: 82% Number screened not pantoprazole 40 mg: 67. Proton pump inhibitors Page 27 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Year Healing Rate at 8 Weeks Symptoms at 4 Weeks Symptoms at 8 Weeks Corinaldesi pantoprazole 40 mg: 80. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Withdrawals Due to Year Results by Baseline Severity Adverse Events Quality rating Funding source Corinaldesi Not reported pantoprazole 40 mg: Poor: randomization and allocation method not Last author from Byk 1995 0. Proton pump inhibitors Page 29 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Number Screened, Eligible, Enrolled, Author Esophagitis Grade (Grading Withdrawn, Lost to Year Population, Setting Criteria), Other Characteristics Followup Healing Rate at 4 Weeks Dekkers 202 patients of 27 Grade 2: 43% Number screened not rabeprazole 20 mg: 81% 1999 investigators in 10 European Grade 3: 52% given, 202 enrolled, 192 omeprazole 20 mg: 81% countries, mean age 53 + Grade 4: 4% completed. Proton pump inhibitors Page 30 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Year Healing Rate at 8 Weeks Symptoms at 4 Weeks Symptoms at 8 Weeks Dekkers rabeprazole 20 mg: 92% Heartburn frequency (resolution): Heartburn frequency resolution: 1999 omeprazole 20 mg: 94% rabeprazole 20 mg: 29. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Withdrawals Due to Year Results by Baseline Severity Adverse Events Quality rating Funding source Dekkers Not reported rabeprazole 20 mg: 1% Fair: randomization and allocation method not Last author 1999 omeprazole 20 mg: 0 reported intention-to-treat for symptoms only, not (corresponding for healing. Delchier No statistically significant differences between rabeprazole 10 mg: 5% Fair: randomization and allocation method not Funded by Eisai Ltd, 2000 treatment groups after controlling for baseline rabeprazole 20 mg: 5% reported, followup somewhat high (76%-83%). London, last author factors including Hetzel-Dent grade (other factors omeprazole 20 mg: 2% (corresponding sex, age, smoking and H. Proton pump inhibitors Page 32 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Number Screened, Eligible, Enrolled, Author Esophagitis Grade (Grading Withdrawn, Lost to Year Population, Setting Criteria), Other Characteristics Followup Healing Rate at 4 Weeks Dupas 461 patients at 29 hospital 83% Grade 2 Number screened not pantoprazole 40 mg 2001 centers and 45 private 17% Grade 3 given; 461 randomized, ITT: 80. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Year Healing Rate at 8 Weeks Symptoms at 4 Weeks Symptoms at 8 Weeks Dupas pantoprazole 40 mg Symptom free (all symptoms - Not reported 2001 ITT: 89. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Withdrawals Due to Year Results by Baseline Severity Adverse Events Quality rating Funding source Dupas For both treatments, healing rates after 4 weeks pantoprazole 40 mg: Fair: randomized method not clear, allocation Funded by BYK 2001 were lower in grade III than in grade II esophagitis 13% method not reported France, last author (69% vs 89%, per-protocol analysis, p=0. Proton pump inhibitors Page 35 of 304 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Number Screened, Eligible, Enrolled, Author Esophagitis Grade (Grading Withdrawn, Lost to Year Population, Setting Criteria), Other Characteristics Followup Healing Rate at 4 Weeks Hatlebakk 229 patients at 9 hospitals in lansoprazole 30 mg group: Number screened not lansoprazole 30 mg: 61. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Year Healing Rate at 8 Weeks Symptoms at 4 Weeks Symptoms at 8 Weeks Hatlebakk lansoprazole 30 mg: 81. Erosive gastroesophageal reflux disease short-term trials of proton pump inhibitor compared with proton pump inhibitor Author Withdrawals Due to Year Results by Baseline Severity Adverse Events Quality rating Funding source Hatlebakk At both 4 and 8 weeks, and irrespective of omeprazole 20 mg: Poor: randomization and allocation method not Not reported 1993 treatment, healing rates were higher for patients with 0. Holtmann, Healing rate in patients with GERD grade III (N=45) 4/125 (3%) rabeprazole Fair: Not clear if randomization method adequate, Funded by Eisai and 2002 4 weeks: 84% rabeprazole vs 72.

Patients were considered to have “failed” therapy with metformin cheap 50mg cytoxan with visa, pioglitazone buy 50 mg cytoxan with amex, or glimepiride at screening or after 10-19 weeks of dose stabilization and if HbA1c was between 7% and 10% or 7. Patients also entered 2-week single-blind, placebo run-in periods prior to randomization. The addition of sitagliptin to metformin, pioglitazone, or glimepiride appears to show larger reductions in HbA1c and compared with the addition of placebo over 18 to 30 weeks (Table 16). Subjects who received placebo plus glimepiride showed worsening glycemic control, while subjects on placebo plus metformin or placebo plus pioglitazone had slight improvements or no change in HbA1c from baseline. Weight gain was generally seen in patients taking sitagliptin in combination with pioglitazone or glimepiride to a similar extent of those taking pioglitazone alone, however no weight gain was seen in those taking glimepiride alone. Patients randomized to add sitagliptin or placebo to metformin lost weight by 0. Pooled analysis was not conducted due to small number of studies and significant heterogeneity. Unlike the other studies , this trial evaluated the effects of sitagliptin in patients with worse glycemic control (baseline HbA1c between 8% and 11%). These patients were on metformin and diet and exercise for 6 weeks, had baseline HbA1c between 8% and 11%, and had ≥85% adherence to their regimens during a 2-week, placebo run- in period. No patients were naïve to oral hypoglycemic agents and approximately 50% were already taking metformin monotherapy or combination oral therapy at baseline. The addition of sitagliptin to ongoing metformin therapy was more effective than placebo plus metformin at lowering HbA1c (placebo-corrected difference: −1. One study was unique in that it included patients who were inadequately controlled on 51 insulin and/or metformin therapy. Patients were randomized to sitagliptin 100 mg or placebo in addition to their pre-study doses insulin and metformin (if they were taking). Approximately 70% of patients in both groups were taking metformin at baseline. Doses of insulin and metformin were not increased, however insulin could be decreased if hypoglycemia occurred. Similar results were seen in this study as others, with greater HbA1c lowering seen in patients randomized to sitagliptin than placebo (difference in LS mean change −0. Authors reported no difference in HbA1c lowering in patients on metformin or not on metformin (p=0. No difference was noted in weight change from baseline between the two groups, P value NR (Table 16). Efficacy outcomes of sitagliptin or placebo added to one oral hypoglycemic agent Change in HbA1c from baseline at a Author, year (%) Change in weight from baseline at (kg) 24 weeks 24 weeks S/Pio P/Pio S/Pio P/Pio 48 b Rosenstock, 2006 −0. Results of sitagliptin or placebo added to glimepiride alone have already been reviewed. In patients already on glimepiride plus metformin, the addition of sitagliptin improved HbA1c over 24 weeks of treatment whereas the addition of placebo showed worsening glycemic control (difference in LS mean change -0. Efficacy outcomes of sitagliptin or placebo added to 2 oral hypoglycemic agents Author, year Change in HbA1c from baseline (%) Change in weight from baseline (kg) 24 weeks 24 weeks S/G/M P/G/M S/G/M P/G/M a 49 b Hermansen, 2006 −0. Summary of Findings for Saxagliptin Evidence in children • We found no studies including children and adolescents ≤ 18 years Evidence in adults • All studies focused on intermediate outcomes with none focusing on health outcomes as primary outcomes. Some studies reported some health outcomes such as all-cause mortality or cardiac death among secondary outcomes or adverse events. Overall evidence was insufficient to determine how saxagliptin compares with other treatments for their impact on health outcomes. Detailed Assessment for Saxagliptin Randomized controlled trials We found 5 fair-quality randomized placebo-controlled trials meeting our inclusion/exclusion criteria. This section is organized by how saxagliptin was used (monotherapy or add-on therapy). There were no active control studies identified that met inclusion criteria. Characteristics of included studies are shown in Table 18. Characteristics of saxagliptin placebo-controlled trials in adults with type 2 diabetes Sample a size (N) Age (years) (SD) Baseline a Author, year Follow- % Female HbA1c (%) a a Country up % White (SD) Intervention a a b Quality (weeks) % Hispanic Weight (kg) Dosages Monotherapy 7. Monotherapy: Saxagliptin compared with placebo In 2 fair-quality randomized controlled trials carried out over 12-24 weeks, a wide variety of 53, 54 doses were compared to placebo. Data abstracted was for approved doses in the United States, Saxagliptin 2. All patients included in the trials were treatment naïve and mean baseline HbA1c for participants ranged from 7. Overall, reduction in HbA1c was greater with saxagliptin compared to placebo and slightly greater with saxagliptin 5 mg compared to 2. There was a 53 numerically greater HbA1c reduction with saxagliptin in the 12 week trial compared to the 24 54 week trial, however the placebo corrected change was similar between the two trials. Patients were similar between the 2 trials except patients in the 24 week trial had diabetes for longer than those in the 12 week trial (mean duration 2. Weight loss was seen across all groups, however more weight loss was seen in the placebo group than in either saxagliptin 2.

There were no differences between proton pump inhibitors (omeprazole buy 50 mg cytoxan with amex, rabeprazole generic 50mg cytoxan visa, esomeprazole) on the basis of these 198 characteristics. The effect of age on eradication rate was also evaluated. This study found higher eradication rates among patients older than 50 years than patients younger than 50, but proton pump inhibitors were not compared. Proton pump inhibitors Page 65 of 121 Final Report Update 5 Drug Effectiveness Review Project In trials comparing a proton pump inhibitor with another drug, the same general statements can be made, but a few findings deserve comment. Studies looking at healing or prevention of nonsteroidal anti-inflammatory drug-induced ulcer included more women than men, with the proportion of women ranging from 62% to 67% and 64% to 83% in the respective types of study. This is most likely due to the greater prevalence among women of diseases requiring long-term nonsteroidal anti-inflammatory drug treatment. Genotype The proton pump inhibitors are all metabolized, largely by the CYP2C19 and CYP3A4 liver enzymes. Theses enzymes are estimated to be deficient in 3% of white and African Americans and 17% to 25% of Asians. The deficiency results in a significantly longer half-life of proton pump inhibitors, although clinically significant accumulation of these drugs has not been shown. While dose adjustments are not required, and adverse effect profiles of the drugs do not differ, 184, 271 there is some evidence that lower doses may be effective in these populations and that 176, 177, 187 rapid metabolizers may have a higher rate of failure to eradicate Helicobacter pylori 272 and to heal esophagitis. Subgroup analysis found no effect by race in 1 study of esomeprazole 4 and lansoprazole in healing of erosive esophagitis. A small study (N=80) found no statistically significant difference at 8 weeks in rate of ulcer healing between rabeprazole 10 mg daily and 108 omeprazole 20 mg daily among patients with differing CYP2C19 genotype. The few adverse events were not analyzed by genotype. A trial of omeprazole in Japanese patients with recurrent 273 esophagitis found no difference in efficacy or safety by genotype. Older patients also metabolize proton pump inhibitors more slowly, resulting in significantly higher drug levels and half-lifes. However, accumulation has not been shown, and dose adjustments are not recommended. One reanalysis of data from 2 trials comparing omeprazole with either ranitidine or cimetidine for reflux esophagitis compared effect in patients 274 age 65 or older with those under age 65. In this analysis there was no difference in healing rate or symptom resolution at 4 or 8 weeks, with a slightly higher proportion of older patients both healed and symptom-free. Withdrawals due to adverse event were higher in the older group, 7. Similar data are not available for other proton pump inhibitors. Comorbidity In an uncontrolled, non-randomized open-label study, patients with peptic ulcer and comorbid 275 liver disease were given 6 to 8 weeks of rabeprazole 10 mg to 20 mg. Eleven of 108 patients (10%) reported 21 adverse drug events, resulting in 5 withdrawals (5%) and an additional 5 patients with an adverse event were lost to follow up. Two patients (2%) had adverse events that were rated as serious, 1 had an elevated bilirubin level, and the other had hepatic encephalopathy. Concomitant medications Two good quality observational studies assessed the impact of a potential drug interaction between proton pump inhibitors and clopidogrel following an acute coronary syndrome (ACS). A cohort study of 8205 patients who were discharged after an ACS and were prescribed clopidogrel between October 2003 and January 2006 were examined to Proton pump inhibitors Page 66 of 121 Final Report Update 5 Drug Effectiveness Review Project determine if the rate of death or rehospitalization for ACS was affected by concomitant use of a 276 proton pump inhibitor. Of these patients, 64% were prescribed a proton pump inhibitor. Multivariable analysis found that there was an increased risk of death or rehospitalization for ACS in those patients taking both clopidogrel and a proton pump inhibitor; adjusted odds ratio 1. The analysis controlled for multiple variables, included demographic characteristics, comorbidities, previous cardiac history, and other medications. In patients who had period with and without a proton pump inhibitor, but continued clopidogrel use, the risk of the primary outcome was also increased during the proton pump inhibitor periods; adjusted odds ratio 1. In addition to the primary outcome, secondary outcomes were evaluated. The risk of rehospitalization for ACS was increased (adjusted odds ratio 1. The authors also conducted a nested case-control analysis with these data in an attempt to confirm their findings, resulting in an adjusted odds ratio of 1. Multiple sensitivity analyses were conducted, with no meaningful change to the results. This study was conducted using data from the Veteran’s Affairs hospitals, and no patients were taking esomeprazole. Too few patients were taking pantoprazole or lansoprazole to be able to conduct individual analyses, but omeprazole and rabeprazole resulted in increased adjusted odds ratios for the primary outcome (adjusted odds ratios: 1. Analysis by dose of proton pump inhibitor indicated did not indicate a dose-response relationship.