Concomitant Proton Pump Inhibitors Therapy Research Articles

The Impact of Concomitant Proton Pump Inhibitors Therapy on Clinical Outcome of Cancer Patients Treated With Immune Checkpoint Inhibitors: A Meta-analysis.

In patients with advanced cancer receiving immune checkpoint inhibitors (ICIs) therapy, there are conflict perspectives about the influence of concomitant use of proton pump inhibitors (PPIs). We are aimed at exploring the influence of concomitant PPIs exposure on clinical outcome among cancer patients receiving ICIs treatment. We searched relevant literatures in PubMed, EMBASE, and the Cochrane Library without language restrictions. We extracted the data from selected studies and calculated the pooled hazard ratios (HRs) with 95% CIs through professional software for overall survival and progression-free survival among cancer patients undergoing ICIs therapy exposed to PPIs. Fourteen studies including 6716 advanced cancer patients receiving ICIs treatment were appropriate for analysis judging by pre-set inclusion and exclusion criteria. The result indicated that concomitant PPIs exposure was significantly related to shorter overall survival (HR=1.388; 95% CI: 1.278-1.498, P <0.001) and progression-free survival (HR=1.285; 95% CI: 1.193-1.384, P <0.001) among multiple cancer patients receiving ICIs therapy. Our meta-analysis showed that concomitant PPIs exposure had an adverse impact on clinical outcome among patients receiving ICIs therapy. Clinical oncologists must be cautious of PPIs delivery during ICIs treatment.

Proton pump inhibitors may reduce the efficacy of ribociclib and palbociclib in metastatic breast cancer patients based on an observational study

IntroductionApproximately 20–33% of all cancer patients are treated with acid-reducing agents (ARAs), most commonly proton pump inhibitors (PPIs), to reduce gastroesophageal reflux disease symptoms. Palbociclib and ribociclib are weak bases so their solubility depends on different pH. The solubility of palbociclib dramatically decreases to < 0.5 mg/ml when pH is above 4,5 but ribociclibs’ solubility decreases when pH increases above 6,5. In the current study, we aimed to investigate the effects of concurrent PPIs on palbociclib and ribociclib efficacy in terms of progression-free survival in metastatic breast cancer (mBC) patients.Patients and methodsWe enrolled hormone receptor-positive, HER2-negative mBC patients treated with endocrine treatment (letrozole or fulvestrant) combined palbociclib or ribociclib alone or with PPI accompanying our observational study. During palbociclib/ribociclib therapy, patients should be treated with "concurrent PPIs" defined as all or more than half of treatment with palbociclib/ribociclib, If no PPI was applied, it was defined as ‘no concurrent PPI’, those who used PPI but less than half were excluded from the study. All data was collected from real-life retrospectively.ResultsOur study included 217 patients, 105 of whom received palbociclib and 112 received ribociclib treatment. In the study population CDK inhibitor treatment was added to fulvestrant 102 patients ( 47%), to letrozole 115 patients (53%). In the Palbociclib arm fulvestrant/letrozole ratio was 53.3/46.7%, in the ribociclib arm it was 41.07/58.93%. Of 105 patients who received palbociclib, 65 were on concomitant PPI therapy, 40 were not. Of the 112 patients who received ribociclib, 61 were on concomitant PPI therapy, 51 were not. In the palbociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (13.04 months vs. unreachable, p < 0.001). It was determined that taking PPIs was an independent predictor of shortening PFS (p < 0.001) in the multivariate analysis, In the ribociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (12.64 months vs. unreachable, p = 0.003). It was determined that taking PPIs was single statistically independent predictor of shortening PFS (p = 0.003, univariate analysis).ConclusionsOur study demonstrated that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. If it needs to be used, PPI selection should be made carefully and low-strength PPI or other ARAs (eg H2 antagonists, antacids) should be preferred.

P020 Proton Pump Inhibitor Therapy: Providing "Acid" Outcomes in Patients With Inflammatory Bowel Disease Under Infliximab Treatment.

A recent meta-analysis has suggested that proton pump inhibitor (PPI) therapy is associated with lower clinical remission rates and a higher number of hospitalizations in patients with inflammatory bowel disease (IBD) under infliximab therapy. We aimed to assess if these differences kept their significance when adjusted for other possible confounders. Cohort study of consecutive patients with Crohn's disease (CD) and Ulcerative Colitis (UC) under infliximab therapy. A minimum follow-up of 54 weeks after introduction of infliximab treatment was required. The analyzed outcomes were deep remission at week 54 and the need of IBD-related hospitalization, corticosteroid treatment or abdominal surgery under infliximab treatment. Collected possible confounders were age, gender, smoking habits, perianal disease, extra-intestinal manifestations, familiar history of IBD and concomitant use of immunomodulators. Our final sample included 104 patients, 56 (53.8%) of them females, with a mean age of 38.2±13.1 years. From these, 77 (74.0%) had CD and 27 (26.0%) had UC. PPI therapy was described in 21 (20.2%) of the patients under infliximab treatment. On univariate analysis, PPI users were found to have significantly lower rates of deep remission at week 54 (7.7 vs 28.3%; p = 0.034) and higher IBD-related hospitalization rates (47.6 vs 21.7%; p = 0.034). No differences were found regarding the need of corticosteroid therapy (4.8 vs 10.8%; p = 0.398) or abdominal surgery (33.7 vs 21.7; p = 0.201). When adjusted for the collected confounders by multivariate analysis, while not significantly influencing deep remission at week 54 (OR = 0.16; 95%CI = 0.02-1.63; p = 0.121), concomitant PPI therapy was a significant independent risk factor for IBD-related hospitalization (OR = 3.22; 95%CI = 1.11-9.34; p = 0.04). Despite not conducting to significantly different deep remission rates, concomitant PPI therapy was associated with a three-fold increase in hospitalization rates in IBD patients under infliximab treatment, even when adjusted for classical risk factors for adverse outcomes in IBD. These findings emphasize the importance of restricting PPI treatment to those with a clear clinical indication, especially in this set of patients.

The association between proton pump inhibitors use and clinical outcome of patients receiving immune checkpoint inhibitors therapy

BackgroundThe gut microbiome can mediate the efficacy of immune checkpoint inhibitors (ICI). Meanwhile, proton pump inhibitors (PPI) can modulate the gut microbiome significantly. However, the impact of PPI use on the clinical outcome of ICI therapy remains unclear. MethodsSearches of PubMed, EMBASE, and the Cochrane Library were conducted to retrieve studies exploring the relationship between PPI use and the clinical benefit of patients undergoing ICI therapy through June 2020. The pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to evaluate the influence of PPI use on overall survival (OS) and progression-free survival (PFS). ResultsA total of seven studies were eligible for our final analysis. There was no significant association between PPI use and OS or PFS (PPI users versus non-users: HR for OS: 1.05, 95% CI: 0.79–1.40, P = 0.73; HR for PFS: 0.90, 95% CI: 0.66–1.23, P = 0.51). However, subgroup analyses demonstrated that PPI use was related to a superior PFS of melanoma patients (HR: 0.50, 95% CI: 0.28–0.91, P = 0.02) and an inferior PFS of non-small cell lung cancer (NSCLC) patients (HR: 1.17, 95% CI: 1.05–1.31, P = 0.006). ConclusionsOur present study indicates that PPI use is not significantly associated with OS and PFS of patients undergoing ICI treatment. However, concomitant PPI therapy may have a positive effect on melanoma patients and a negative effect on NSCLC patients. It is advisable for clinical oncologists to evaluate the necessity for PPI use when they treat patients with ICI therapy.

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy.

To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension. PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.

Consequences and Complications of Long Term Use of proton Pump Inhibitors

Proton Pump Inhibitors (PPIs) have become one of the most commonly prescribed category of drugs in both primary as well as tertiary care, commonly for gastric acid-related disorders. It is advised that no more than three 14-day treatment courses with PPIs should be used in one year. The two main indications for the long-term use of PPIs are gastro esophageal reflux disease and concomitant use with the maintenance dose of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). PPIs block the gastric H + ,K + -ATPase, inhibiting gastric acid secretion. If the drug is discontinued, there is a potential risk for rebound hypersecretion, creating a sort of dependency on the drug because the body is acclimated to having acid suppressed. The potential adverse effects relating to PPIs are Hypochlorhydria (11%- 24%) leading to pernicious anaemia and bone fractures(elevated risk after 7 years of continuous PPI therapy) and Hypergastrinemia (20%- 25%). Review of various literatures have shown that long-term PPI use is associated with upto fourfold increase in the risk of fundic gland polyps(upto 36%). Other potential consequences of chronic PPI use are malabsorption of key minerals (calcium and magnesium) in the body, increased risk of infections, cancer (5%-12%), severe drug interactions and birth defects. The most commonly seen infections with chronic PPI use are Enteric Infections and Community Acquired Pneumonia(CAP).A case-controlled study discovered an associated 2.5-fold risk of infection with concomitant PPI therapy. A population-based case-controlled study of7642 CAP cases identified, 11% were chronic PPI users. Another study found that 50% of chronic PPI users are more likely to develop CAP.Elderly, malnourished, immune-compromised, chronically ill, and osteoporotic patients theoretically could be at increased risk from longterm therapy. In conclusion, based on the above evidences, pharmacists are poised to educate patients about the benefits and risks associated with chronic PPI use.

Association between adherence to concomitant proton pump inhibitor therapy in current NSAID users and upper gastrointestinal complications

Proton pump inhibitors (PPIs) play a well-documented role as a gastroprotective agent among NSAID users at an increased risk of peptic ulcer and bleeding. Observational studies have, however, suggested that the clinical efficacy of PPI therapy may be reduced because of poor adherence. To study the association between adherence to concomitant PPI in current NSAID users and the risk of peptic ulcer and bleeding. Case-control study linking nationwide data from the Swedish Patient Registry with the Swedish Drug Prescription Database. The study population included patients admitted for a first-time peptic ulcer or bleeding and who were incident users of NSAID. Each case was matched on age, sex, NSAID duration, and calendar month with five controls. PPI adherence was calculated as the proportion of NSAID days being covered by PPI therapy. Matched and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using conditional logistic regression. A total of 3649 cases were identified. Patients with poor adherence (<20% PPI coverage) had a significantly increased risk of upper gastrointestinal complications (OR=1.88, 95% CI 1.22-2.88) compared with fully adherent patients (≥80% PPI coverage). As a continuous variable, the risk of an event increased with 6% points for every 10% decrease in PPI adherence (OR=1.06, 95% CI 1.03-1.10). The gastroprotective effect of PPI in NSAID users is highly dependent on adherence, with about twice the risk in patients with poor adherence. Efforts to increase adherence should be an integrated part of clinical practice.

Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical implications.

Proton pump inhibitors (PPIs) remain the superior choice worldwide in antisecretory therapy in the evidence-based treatment of upper gastrointestinal disorders including gastroesophageal reflux disease, erosive esophagitis, dyspepsia and peptic ulcer disease. PPI overutilization in ambulatory care settings is often a result of failure to re-evaluate the need for continuation of therapy, or insufficient use of on-demand and step-down therapy. Nonjudicious use of PPIs creates both preventable financial as well as medical concerns. PPIs have been associated with an increased risk of vitamin and mineral deficiencies impacting vitamin B12, vitamin C, calcium, iron and magnesium metabolism. While these risks are considered to be relatively low in the general population, they may be notable in elderly and malnourished patients, as well as those on chronic hemodialysis and concomitant PPI therapy. No current evidence recommends routine screening or supplementation for these potential vitamin and mineral deficiencies in patients on either short- or long-term PPI therapy. Reducing inappropriate prescribing of PPIs can minimize the potential risk of vitamin and mineral deficiencies.

Safety of clopidogrel and proton pump inhibitors in patients undergoing drug-eluting stent implantation

A pharmacodynamic interaction between clopidogrel and proton pump inhibitors (PPIs) has been suggested, leading to reduced clopidogrel-induced platelet inhibitory effects. However, data from clinical studies are conflicting. The aim of this study was to evaluate the safety of long-term clopidogrel and PPI therapy. A total of 1328 consecutive patients (age 63±11 years; 81% male) undergoing drug-eluting stent implantation and 1-year follow-up were included. All patients were treated with a standard aspirin and clopidogrel treatment regimen for 12 months. The concomitant PPI therapy for the same duration was at the discretion of the clinical cardiologist. PPI therapy included lansoprazole (30 mg/day), pantoprazole (20 mg/day), or omeprazole (20 mg/day). At 1-year follow-up, major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), acute coronary syndrome leading to hospitalization and nonfatal stroke, were recorded. All cause death, any stent thrombosis (ST), and bleeding (Thrombolysis in MI major and minor) were also assessed. Lansoprazole, pantoprazole, and omeprazole were administered to 855, 178, and 125 patients, whereas 170 were not prescribed any PPI therapy. Among patients treated with PPIs, those on pantoprazole had more often prior MI, multivessel coronary artery disease, and chronic kidney disease, whereas earlier peptic ulcer was more frequent among patients treated with omeprazole. The incidence of 1-year MACE was not statistically different between patients in the PPI and no-PPI groups (7.5 vs. 5.0%; P=0.26). Similarly, 1-year rates of all cause death, ST, and Thrombolysis in MI major and minor bleedings did not significantly differ. After statistical adjustment for potential confounders, the concomitant use of clopidogrel and PPIs was not associated with the risk of 1-year MACE [odds ratio (OR) 1.54, P=0.38], death (OR: 0.97, P=0.961), and ST (OR: 1.01, P=0.998). No differences across the three PPI types were found. The association of clopidogrel and PPIs after drug-eluting stent implantation, prescribed on clinical judgement, seems safe.

Esophageal Mucosal Injury With Low‐Dose Aspirin and Its Prevention by Rabeprazole

Aspirin is used widely as an antithrombotic drug for the prevention of cardiovascular and cerebrovascular events. Although aspirin increases the risk for gastrointestinal mucosal injury, the effect on esophageal mucosa is unclear. This study investigates whether aspirin induces esophageal mucosal injury and whether a proton-pump inhibitor can prevent such injury in relation to CYP2C19 genotypes. Fifteen healthy Japanese volunteers are dosed for 7 days in a 5-way randomly crossover trial: placebo, aspirin 100 mg, rabeprazole 10 mg, and aspirin 100 mg plus rabeprazole 10 mg either once daily or 4 times per day. All subjects undergo endoscopy and 24-hour intragastric pH monitoring on day 7. With the aspirin regimen, esophageal mucosal disorders occur in 7 patients (46.7%) (5, grade M; 2, grade A). The median 24-hour pH differs significantly among subjects who develop grade M or A gastroesophageal reflux disease and those who do not develop gastroesophageal reflux disease; the median pH in grade A gastroesophageal reflux disease is significantly lower (1.5 [range, 1.1-1.9]) than that in patients without gastroesophageal reflux disease (5.6 [range, 0.8-8.4], P = .04). Rabeprazole significantly inhibits acid secretion irrespective of CYP2C19 genotypes and decreases the incidence of aspirin-related esophageal injury and symptoms according to increasing pH value. Aspirin induces esophageal mucosal injury in an acid-dependent manner. Concomitant proton-pump inhibitor therapy may prevent advanced effects of low-dose aspirin.

Risk of Adverse Clinical Outcomes with Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Percutaneous Coronary Intervention

Purpose: Clopidogrel and proton pump inhibitors (PPIs) are often used together in patients who undergo percutaneous coronary intervention (PCI). Previous studies have suggested that PPIs attenuate the benefits of clopidogrel in patients with acute coronary syndromes possibly due to competitive metabolic effects on CYP2C19. The clinical relevance of this interaction in patients who underwent PCI is unknown. We hypothesized that post PCI patients discharged on clopidogrel will have higher cardiovascular events if concomitant PPI therapy is used. Methods: We reviewed medical records of all the patients discharged on clopidogrel who underwent PCI from January 2003 to August 2004. The primary outcome studied was major adverse cardiovascular event (MACE) which was defined as a composite of death, myocardial infarction and target vessel failure. Results: Of the 315 post-PCI patients who were discharged on clopidogrel, 72 patients were discharged on PPI. During a mean follow-up period of 50 months, patients discharged on concomitant clopidogrel-PPI therapy had a MACE rate of 56% (vs. 38% in the clopidogrel alone group) (p=0.025) (Figure). On multiple logistic regression analysis, patients discharged on concomitant PPI-clopidogrel therapy after their PCI had 95% excess risk of MACE over a follow up period of 4 years. Death rates were not different in the two groups.Figure: Kaplan Meier survival curves comparing major adverse cardiac events (MACE) for patients discharged after percutaneous coronary intervention (PCI) on Clopidogrel plus proton pump inhibitor (PPI) and Clopidogrel alone.Conclusion: Concomitant use of clopidogrel and PPI in post PCI patients is associated with a higher risk of MACE. This suggests that PPIs may attenuate clopidogrel's beneficial antiplatelet effect, which is crucial after PCI. Prospective randomized studies are warranted to provide definitive evidence for this interaction.

Risk of Adverse Clinical Outcomes with Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Percutaneous Coronary Intervention

Recent studies have suggested that proton pump inhibitors (PPIs) attenuate the benefits of clopidogrel. The clinical relevance of this interaction in patients who have undergone percutaneous coronary intervention (PCI) is unknown. We hypothesized that post-PCI patients discharged on clopidogrel will have higher cardiovascular events if concomitant PPI therapy is used. To determine whether post-PCI patients discharged on clopidogrel will have higher cardiovascular events if concomitant PPI therapy is used. We reviewed the medical records of all the patients discharged on clopidogrel who underwent PCI from January 2003 to August 2004. The primary outcome studied was a major adverse cardiovascular event (MACE), which was defined as a composite of death, myocardial infarction, and target vessel failure. Of the 315 post-PCI patients who were discharged on clopidogrel, 72 were discharged on PPI. During a mean follow-up period of 50 months, patients discharged on concomitant clopidogrel-PPI therapy had a MACE rate of 56% (vs. 38% in the clopidogrel alone group) (P = 0.025) and had 95% excess risk of MACE. Concomitant use of clopidogrel and PPI in post-PCI patients is associated with a higher risk of MACE. This suggests that PPIs may attenuate clopidogrel's beneficial antiplatelet effect, which is crucial after PCI. Prospective randomized studies are warranted to provide definitive evidence for this interaction.

Bleeding Peptic Ulcer in the Elderly

Peptic ulcer bleeding is a frequent and dramatic event with both a high mortality rate and a substantial cost for healthcare systems worldwide. It has been found that age is an independent predisposing factor for gastrointestinal bleeding, with the risk increasing significantly in individuals aged>65 years and increasing further in those aged>75 years. Indeed, bleeding incidence and mortality are distinctly higher in elderly patients, especially in those with co-morbidities. NSAID therapy and Helicobacter pylori infection are the most prevalent aetiopathogenetic factors involved in peptic ulcer bleeding. The risk of bleeding seems to be higher for NSAID- than for H. pylori-related ulcers, most likely because the antiplatelet action of NSAIDs impairs the clotting process. NSAID users may be classified as low or high risk, according to the absence or presence of one or more of the following factors associated with an increased risk of bleeding: co-morbidities; corticosteroid or anticoagulant co-therapy; previous dyspepsia, peptic ulcer or ulcer bleeding; and alcohol consumption. Different types of NSAIDs have been associated with different bleeding risk, but no anti-inflammatory drug, including selective cyclo-oxygenase (COX)-2 inhibitors, is completely safe for the stomach. Furthermore, even low-dose aspirin (acetylsalicylic acid) [<325 mg/day] and a standard dose of non-aspirin antiplatelet treatment (clopidogrel or ticlopidine) have been found to cause bleeding and mortality. No clear risk factor favouring H. pylori-related ulcer bleeding has been identified. Peptic ulcer bleeding prevention remains a challenge for the physician, but data are now available on use of a safer and cheaper strategy for both low- and high-risk patients. Unfortunately, despite the fact that several society and national guidelines have been formulated, these are poorly followed in clinical practice. Proton pump inhibitor (PPI) or misoprostol therapy and H. pylori eradication in NSAID-naive patients are the most commonly proposed strategies. Selective COX-2 inhibitor therapy in high-risk patients has also been suggested, but concerns over the possible cardiovascular adverse effects of some of these agents should be taken into account. Moreover, switching to selective COX-2 inhibitors in patients with previous bleeding is not completely risk free, and concomitant PPI therapy is also needed. H. pylori eradication is mandatory in all patients with peptic ulcer, and such an approach has been found to be significantly superior to PPI maintenance therapy. H. pylori eradication is frequently achieved with sequential therapy in elderly patients with peptic ulcer. In conclusion, upper gastrointestinal bleeding is a dramatic event with a high mortality rate, particularly in the elderly. Some effective preventative strategies are now available that should be implemented in clinical practice.

Impact of Adherence to Concomitant Gastroprotective Therapy on Nonsteroidal-Related Gastroduodenal Ulcer Complications

The clinical impact of nonadherence to gastroprotective agents (GPAs) coprescribed with anti-inflammatory therapies has not been evaluated. In a large, commercial, managed-care database, we retrospectively characterized the use of GPAs among patients receiving nonselective nonsteroidal anti-inflammatory drugs (ns-NSAIDs) or cyclooxygenase-2-selective inhibitors (coxibs) and determined the impact of nonadherence on the likelihood of gastroduodenal ulcer complications. Analyses identified the populations of patients with concomitant histamine-2 receptor antagonist or proton pump inhibitor (PPI) therapy and determined adherence with the prescribed therapy with respect to the duration of anti-inflammatory treatment. Multivariate regression analyses modeled the association between adherence with concomitant protective therapy and the likelihood of upper gastrointestinal (GI) complications including peptic ulcer disease, ulcer, and/or upper-GI bleed. Among 144,203 patients newly prescribed anti-inflammatory therapies, 1.8% received concomitant GPA treatment (ns-NSAIDs, 1.4% vs coxibs, 2.6%; P < .0001). The likelihood of GPA use increased with the presence of risk factors: age older than 65 years (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.3-1.5) and prior history of peptic ulcer disease (OR, 2.5; 95% CI, 1.8-3.3), esophagitis/gastroesophageal reflux (OR, 3.8; 95% CI, 3.5-4.1), ulcer/upper-GI bleed (OR, 1.4; 95% CI, 1.2-1.5), or gastritis (OR, 2.5; 95% CI, 2.2-2.8). Of patients receiving concomitant PPI therapy, 68% had adherence rates of 80% or more. A significantly higher risk of upper-GI ulcers/complications was observed in ns-NSAID patients with adherence rates of less than 80% compared with adherence rates of 80% or more (OR, 2.4; 95% CI, 1.0-5.6), but no such relationship was observed among patients who took coxibs. Few patients receive concomitant GPA therapy when prescribed anti-inflammatory treatment, although use increased with the presence of risk factors. Adherence to concomitant therapy is paramount to reducing GI events among ns-NSAID users and educational efforts should be undertaken to promote use of and adherence to GPA therapy among these patients.

Proton Pump Inhibitor Therapy in Atazanavir-Treated Patients

Proton Pump Inhibitor Therapy in Atazanavir-Treated Patients