Large prospective trial offers reassurance for long-term PPI use

Aside from a possible increased risk of enteric infections, long-term use of the proton pump inhibitor (PPI) pantoprazole appears safe in patients with stable atherosclerotic vascular disease, according to a prospective trial involving more than 17,000 participants.

In contrast with published observational studies, the present trial found no associations between long-term PPI use and previously reported risks such as pneumonia, fracture, or cerebrovascular events, according to lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Ont., and colleagues.

“To our knowledge, this is the largest PPI trial for any indication and the first prospective randomized trial to evaluate the many long-term safety concerns related to PPI therapy,” the investigators wrote in Gastroenterology. “It is reassuring that there was no evidence for harm for most of these events other than an excess of enteric infections.”

“Given how commonly acid suppressive medications are used, it is important to ensure that this class of drugs is safe,” the investigators wrote. They noted that patients are often alarmed by “sensational headlines” about PPI safety. “There are balancing articles that more carefully discuss the risks and benefits of taking PPI therapy but these receive less media attention,” the investigators added.

The present, prospective trial, COMPASS, involved 17,598 participants from 33 countries with stable peripheral artery disease and cardiovascular disease. “We use the term participants, rather than patients, as not all of those taking part in this research would have been patients throughout the trial but all participated in the randomized controlled trial,” the investigators wrote.

In addition to evaluating the safety of pantoprazole, the study was initially designed to measure the efficacy of pantoprazole for preventing upper gastrointestinal events in participants taking rivaroxaban and/or aspirin, which, in combination, were recently shown to reduce cardiovascular outcomes among patients with stable cardiovascular conditions. As such, participants in the trial were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or 2.5-mg rivaroxaban twice daily combined with 100-mg aspirin once daily. The primary efficacy outcomes for these three groups were stroke, myocardial infarction, and cardiovascular death. This portion of the trial was discontinued early because of evidence that showed the superiority of combination therapy over aspirin alone; however, the pantoprazole component of the trial continued, as planned, for 3 years.

At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. Pantoprazole safety outcomes centered on those previously reported by observational studies, including dementia, chronic kidney disease, gastric atrophy, fracture, cancer, pneumonia, diabetes mellitus, chronic obstructive lung disease, Clostrididoides difficile infection, and other enteric infections. Hospitalization rates for noncardiovascular and cardiovascular events were also reported. Data were gathered via questionnaires, which were conducted every 6 months.

 

Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking an NSAID (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.

Analysis of cardiovascular outcomes revealed no significant differences between placebo and pantoprazole groups. Of all the evaluated safety measures, only enteric infections differed significantly between groups, occurring at a higher rate in the pantoprazole group than in the placebo group (1.4% vs. 1.0%; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). Although C. difficile infection was more common among pantoprazole users, only 13 such events occurred, precluding statistical significance.

According to the investigators, these findings should offer reassurance to PPI prescribers and users; they noted that previous findings from observational studies warrant skepticism. “A significant proportion of patients are prescribed PPI therapy inappropriately, and in these cases, it is reasonable to advocate strategies to discontinue acid suppression. However, when there is a clinical need for PPI therapy, these data suggest that the benefits are likely to outweigh any putative risks.”

In regard to the possible increased risk of enteric infection, the investigators again urged a conservative interpretation, as the increased rate of enteric infection among PPI users was still lower than rates reported by systematic reviews. “The data in the current randomized trial were not adjusted for multiple testing so this result should be interpreted with caution,” the investigators wrote. Although acid suppression may allow for increased ingestion of pathogenic organisms, which could theoretically increase the risk of enteric infection, the investigators stated that the benefits of PPIs likely outweigh their risks.

The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Bayer, Allergan, Takeda, Janssen, and others.

SOURCE: Moayyedi P et al. Gastro. 2019 May 29. doi: 10.1053/j.gastro.2019.05.056.

AGA patient education on GERD can help your patients better understand and manage the disorder. Post this education or your practice website or share you’re your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.

Aside from a possible increased risk of enteric infections, long-term use of the proton pump inhibitor (PPI) pantoprazole appears safe in patients with stable atherosclerotic vascular disease, according to a prospective trial involving more than 17,000 participants.

In contrast with published observational studies, the present trial found no associations between long-term PPI use and previously reported risks such as pneumonia, fracture, or cerebrovascular events, according to lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Ont., and colleagues.

“To our knowledge, this is the largest PPI trial for any indication and the first prospective randomized trial to evaluate the many long-term safety concerns related to PPI therapy,” the investigators wrote in Gastroenterology. “It is reassuring that there was no evidence for harm for most of these events other than an excess of enteric infections.”

“Given how commonly acid suppressive medications are used, it is important to ensure that this class of drugs is safe,” the investigators wrote. They noted that patients are often alarmed by “sensational headlines” about PPI safety. “There are balancing articles that more carefully discuss the risks and benefits of taking PPI therapy but these receive less media attention,” the investigators added.

The present, prospective trial, COMPASS, involved 17,598 participants from 33 countries with stable peripheral artery disease and cardiovascular disease. “We use the term participants, rather than patients, as not all of those taking part in this research would have been patients throughout the trial but all participated in the randomized controlled trial,” the investigators wrote.

In addition to evaluating the safety of pantoprazole, the study was initially designed to measure the efficacy of pantoprazole for preventing upper gastrointestinal events in participants taking rivaroxaban and/or aspirin, which, in combination, were recently shown to reduce cardiovascular outcomes among patients with stable cardiovascular conditions. As such, participants in the trial were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or 2.5-mg rivaroxaban twice daily combined with 100-mg aspirin once daily. The primary efficacy outcomes for these three groups were stroke, myocardial infarction, and cardiovascular death. This portion of the trial was discontinued early because of evidence that showed the superiority of combination therapy over aspirin alone; however, the pantoprazole component of the trial continued, as planned, for 3 years.

At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. Pantoprazole safety outcomes centered on those previously reported by observational studies, including dementia, chronic kidney disease, gastric atrophy, fracture, cancer, pneumonia, diabetes mellitus, chronic obstructive lung disease, Clostrididoides difficile infection, and other enteric infections. Hospitalization rates for noncardiovascular and cardiovascular events were also reported. Data were gathered via questionnaires, which were conducted every 6 months.

 

Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking an NSAID (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.

Analysis of cardiovascular outcomes revealed no significant differences between placebo and pantoprazole groups. Of all the evaluated safety measures, only enteric infections differed significantly between groups, occurring at a higher rate in the pantoprazole group than in the placebo group (1.4% vs. 1.0%; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). Although C. difficile infection was more common among pantoprazole users, only 13 such events occurred, precluding statistical significance.

According to the investigators, these findings should offer reassurance to PPI prescribers and users; they noted that previous findings from observational studies warrant skepticism. “A significant proportion of patients are prescribed PPI therapy inappropriately, and in these cases, it is reasonable to advocate strategies to discontinue acid suppression. However, when there is a clinical need for PPI therapy, these data suggest that the benefits are likely to outweigh any putative risks.”

In regard to the possible increased risk of enteric infection, the investigators again urged a conservative interpretation, as the increased rate of enteric infection among PPI users was still lower than rates reported by systematic reviews. “The data in the current randomized trial were not adjusted for multiple testing so this result should be interpreted with caution,” the investigators wrote. Although acid suppression may allow for increased ingestion of pathogenic organisms, which could theoretically increase the risk of enteric infection, the investigators stated that the benefits of PPIs likely outweigh their risks.

The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Bayer, Allergan, Takeda, Janssen, and others.

SOURCE: Moayyedi P et al. Gastro. 2019 May 29. doi: 10.1053/j.gastro.2019.05.056.

AGA patient education on GERD can help your patients better understand and manage the disorder. Post this education or your practice website or share you’re your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.

Aside from a possible increased risk of enteric infections, long-term use of the proton pump inhibitor (PPI) pantoprazole appears safe in patients with stable atherosclerotic vascular disease, according to a prospective trial involving more than 17,000 participants.

In contrast with published observational studies, the present trial found no associations between long-term PPI use and previously reported risks such as pneumonia, fracture, or cerebrovascular events, according to lead author Paul Moayyedi, MB ChB, PhD, of McMaster University in Hamilton, Ont., and colleagues.

“To our knowledge, this is the largest PPI trial for any indication and the first prospective randomized trial to evaluate the many long-term safety concerns related to PPI therapy,” the investigators wrote in Gastroenterology. “It is reassuring that there was no evidence for harm for most of these events other than an excess of enteric infections.”

“Given how commonly acid suppressive medications are used, it is important to ensure that this class of drugs is safe,” the investigators wrote. They noted that patients are often alarmed by “sensational headlines” about PPI safety. “There are balancing articles that more carefully discuss the risks and benefits of taking PPI therapy but these receive less media attention,” the investigators added.

The present, prospective trial, COMPASS, involved 17,598 participants from 33 countries with stable peripheral artery disease and cardiovascular disease. “We use the term participants, rather than patients, as not all of those taking part in this research would have been patients throughout the trial but all participated in the randomized controlled trial,” the investigators wrote.

In addition to evaluating the safety of pantoprazole, the study was initially designed to measure the efficacy of pantoprazole for preventing upper gastrointestinal events in participants taking rivaroxaban and/or aspirin, which, in combination, were recently shown to reduce cardiovascular outcomes among patients with stable cardiovascular conditions. As such, participants in the trial were randomized to one of three groups: 100-mg aspirin once daily, 5-mg rivaroxaban twice daily, or 2.5-mg rivaroxaban twice daily combined with 100-mg aspirin once daily. The primary efficacy outcomes for these three groups were stroke, myocardial infarction, and cardiovascular death. This portion of the trial was discontinued early because of evidence that showed the superiority of combination therapy over aspirin alone; however, the pantoprazole component of the trial continued, as planned, for 3 years.

At baseline, about two-thirds of participants (64%) were not taking a PPI, requiring randomization to either 40-mg pantoprazole once daily or matching placebo. Pantoprazole safety outcomes centered on those previously reported by observational studies, including dementia, chronic kidney disease, gastric atrophy, fracture, cancer, pneumonia, diabetes mellitus, chronic obstructive lung disease, Clostrididoides difficile infection, and other enteric infections. Hospitalization rates for noncardiovascular and cardiovascular events were also reported. Data were gathered via questionnaires, which were conducted every 6 months.

 

Most patients in the trial (78%) were male, and 23% were current smokers. Smaller proportions of the population were taking an NSAID (5%) and/or had a history of peptic ulcer disease (2.6%). The median follow-up was 3.01 years, ranging from 2.49 to 3.59 years. Permanent discontinuations occurred at approximately equal rates in the pantoprazole (21%) and placebo (22%) group after a median of 11 months (338 days). In both groups, more than 96% of participants who continued treatment took their medications as prescribed at least 80% of the time.

Analysis of cardiovascular outcomes revealed no significant differences between placebo and pantoprazole groups. Of all the evaluated safety measures, only enteric infections differed significantly between groups, occurring at a higher rate in the pantoprazole group than in the placebo group (1.4% vs. 1.0%; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). Although C. difficile infection was more common among pantoprazole users, only 13 such events occurred, precluding statistical significance.

According to the investigators, these findings should offer reassurance to PPI prescribers and users; they noted that previous findings from observational studies warrant skepticism. “A significant proportion of patients are prescribed PPI therapy inappropriately, and in these cases, it is reasonable to advocate strategies to discontinue acid suppression. However, when there is a clinical need for PPI therapy, these data suggest that the benefits are likely to outweigh any putative risks.”

In regard to the possible increased risk of enteric infection, the investigators again urged a conservative interpretation, as the increased rate of enteric infection among PPI users was still lower than rates reported by systematic reviews. “The data in the current randomized trial were not adjusted for multiple testing so this result should be interpreted with caution,” the investigators wrote. Although acid suppression may allow for increased ingestion of pathogenic organisms, which could theoretically increase the risk of enteric infection, the investigators stated that the benefits of PPIs likely outweigh their risks.

The COMPASS trial was funded by Bayer AG. The investigators disclosed additional relationships with Bayer, Allergan, Takeda, Janssen, and others.

SOURCE: Moayyedi P et al. Gastro. 2019 May 29. doi: 10.1053/j.gastro.2019.05.056.

AGA patient education on GERD can help your patients better understand and manage the disorder. Post this education or your practice website or share you’re your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.