Consumption of medicines used for gastric acid-related disorders in Australia and South Korea: a cross-country comparison.

PURPOSE: The study's aim was to compare the use of proton pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RAs) and mucoprotective medicines (MPs) used for gastric acid-related disorders (GARD) in Australia and South Korea (Korea) from 2004 to 2017. METHODS: Prescription data for PPIs, H2RAs and MPs for Australian outpatients were extracted from the Australian Statistics on Medicines annual reports, with dose-specific and expenditure data obtained from Medicare. Similar data were obtained from Korean National Health Insurance Service claims data. We analysed the volume and expenditure of medicines use annually using the defined daily dose per 1,000 population per day. We calculated which medicines accounted for 90% of use and estimated the proportions of use for low- and high-dose PPIs. RESULTS: While total utilisation for GARD medicines increased over time in both countries, patterns of use differed. Overall, use was somewhat higher in Australia but increased more rapidly in Korea. PPIs were used more extensively in Australia, while more MPs and H2RAs were used in Korea. Expenditure and use of low-dose PPIs is escalating in Korea. CONCLUSION: There were substantial differences in the use of GARD medicines in Australia and Korea over 14 years. Both countries face similar challenges to promote rational medicines use and contain medical care costs. The discrepant prescribing patterns can be attributed to differences in healthcare systems, pharmaceutical policies and demographics. This study provides a baseline to influence more rational use of these medicines. It provides insight into medicines policies for other countries that face similar challenges.

Gastroprotective drugs in Australia: utilization patterns between 1997 and 2006 in relation to NSAID prescribing.

BACKGROUND: In Australia, the prescribing of proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H(2)RAs) for defined gastrointestinal disorders is approved for subsidy by the universal Australian Pharmaceutical Benefits Scheme. These agents also may be used with NSAIDs, but this prescribing is not approved for subsidy. PPI prescribing increased in Australia between 1997 and 2006, and some authorities are concerned that this increase may be due to prescriptions outside the approved indications. OBJECTIVES: The aims of this study were to quantify gastroprotective drug consumption in Australia between 1997 and 2006 and to investigate the relationship over time between this prescribing and NSAID prescribing. METHODS: Data from concession beneficiaries (seniors and welfare recipients) were included. Data on PPIs, H(2)RAs, NSAIDs, and cyclooxygenase (COX)-2 inhibitors dispensed between 1997 and 2006 were gathered from Medicare Australia and are expressed as defined daily doses (DDDs) per 1000 concession beneficiaries per day (CBPDs). Gastroprotective drugs were defined using the World Health Organization Anatomical Therapeutic Chemical classification of 2006. Drug utilization 90% and expenditures in Australian dollars (AUD $, not normalized to an index year) were calculated. RESULTS: H(2)RA prescribing was stable between 1997 and 2001, at approximately 60 DDDs/1000 CBPDs. Dispensation of H(2)RAs began to decrease in 2001 to 20 DDDs/ 1000 CBPDs in 2006. PPI consumption increased consistently, with a sharp change beginning in 2001 (from about 45 to 140 DDDs/1000 CBPDs between 2001 and 2006). The government expenditure for PPIs per concession beneficiary per year also increased from about AUD $26 in 1997 to almost AUD $74 in 2006, whereas the expenditure for H2RAs decreased from about AUD $24 to about AUD $5. Nonselective NSAID prescribing decreased with the introduction of COX-2 inhibitors in 2000. COX-2 inhibitors increased the overall consumption of total NSAIDs in the first 4 years (2000-2003) after their introduction. CONCLUSIONS: The prescribing of H(2)RAs decreased, whereas the prescribing of PPIs increased, between 1997 and 2006 in this population of concession beneficiaries in Australia. During the same period, nonselective NSAID prescribing decreased while COX-2 inhibitor prescribing increased.

Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding.

OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of proton pump inhibitors (PPIs) in the prevention and treatment of acute upper gastrointestinal (UGI) haemorrhage, as well as to compare this with H2-receptor antagonist (H2RA), Helicobacter pylori eradication (in infected patients) or no therapy, for the prevention of first and/or subsequent bleeds among patients who continue to use non-steroidal anti-inflammatory drugs (NSAIDs). Also to evaluate the clinical effectiveness of PPI therapy, compared with other treatments, for the prevention of subsequent bleeds in patients who had previously experienced peptic ulcer (PU) bleeding. DATA SOURCES: Electronic databases and major conference proceedings were searched up to February 2006. REVIEW METHODS: Data were collected from the systematic reviews addressing each research objective. These were then entered into an economic model to compare the costs and quality-adjusted life-days of alternative management strategies over a 28-day period for patients who have had UGI bleeding. A Markov model with a Monte Carlo simulation used data from the systematic reviews to identify the most cost-effective treatment strategy for the prevention of UGI bleeding (first and subsequent) among NSAID users using an outcome of costs per quality-adjusted life-years (QALYs) over a lifetime from age 50 years. RESULTS: PPI treatment initiated after endoscopic diagnosis of PU bleeding significantly reduced re-bleeding and surgery compared with placebo or H2RA. Although there was no evidence of an overall effect of PPI treatment on all-cause mortality, PPIs significantly reduced mortality in subgroups when studies conducted in Asia were examined in isolation or when the analysis was confined to patients with high-risk endoscopic findings. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduced the proportion of patients with stigmata of recent haemorrhage (SRH) at index endoscopy compared with placebo or H2RA, but there was no evidence that PPI treatment affected clinically important outcomes. Giving oral PPI both before and after endoscopy, with endoscopic haemostatic therapy (EHT) for those with major SRH, is preferred to all others on cost-effectiveness grounds at any threshold over 25,000 pounds per QALY, even if only short-term effects are taken into account, and at any threshold over 200 pounds per life-year gained if long-term effects are included. The risk of NSAID-induced endoscopic gastric and duodenal ulcers was reduced by standard doses of PPI and misoprostol, and double doses of H2RAs. Standard doses of H2RAs reduced the risk of endoscopic duodenal ulcers. PPIs reduced NSAID-induced dyspepsia. PPIs were superior to misoprostol in preventing recurrence of NSAID-induced endoscopic duodenal ulcers, but PPIs were comparable to misoprostol in preventing the recurrence of NSAID-induced endoscopic gastric ulcers. Full-dose misoprostol reduced bleeding, perforation or gastric outlet obstruction due to NSAID-induced ulcers, but misoprostol was poorly tolerated and associated with frequent adverse effects. H. pylori eradication treatment was equally effective with PPI treatment for the primary or secondary prevention of endoscopic ulcers in NSAID users. H. pylori eradication treatment was more effective than placebo for the primary prevention of endoscopic PU and for the prevention of re-bleeding from PU in NSAID users. With regard to primary and secondary prevention of bleeding PU in NSAID users, the two most cost-effective strategies are H. pylori eradication alone, and H. pylori eradication followed by misoprostol (substituted by a PPI, if misoprostol is not tolerated) at an additional 4810 pounds per QALY. In patients who had previously experienced a bleed from a PU, re-bleeding was less frequent after H. pylori eradication therapy than after non-eradication antisecretory therapy, whether or not the latter was combined with long-term maintenance antisecretory therapy. CONCLUSIONS: PPI treatment compared with placebo or H2RA reduces mortality following PU bleeding among patients with high-risk endoscopic findings, and reduces re-bleeding rates and surgical intervention. PPI treatment initiated prior to endoscopy in UGI bleeding significantly reduces the proportion of patients with SRH at index endoscopy but does not reduce mortality, re-bleeding or the need for surgery. The strategy of giving oral PPI before and after endoscopy, with EHT for those with major SRH, is likely to be the most cost-effective. Treatment of H. pylori infection was found to be more effective than antisecretory therapy in preventing recurrent bleeding from PU. H. pylori eradication alone or eradication followed by misoprostol (with switch to PPI, if misoprostol is not tolerated) are the two most cost-effective strategies for preventing bleeding ulcers among H. pylori-infected NSAID users, although the data cannot exclude PPIs also being cost-effective. Further large randomised controlled trials are needed to address areas such as PPI administration prior to endoscopic diagnosis, different doses and administration of PPIs, as well as the primary and secondary prevention of UGI bleeding.

Cost-effectiveness and cost-utility of long-term management strategies for heartburn.

OBJECTIVES: To compare the expected costs and outcomes of seven alternative long-term primary care strategies for the management of patients with moderate-to-severe heartburn over a 1-year period. METHODS: A decision-analytic model was developed to estimate costs and effects (weeks with heartburn symptoms and quality adjusted life years [QALYs]) for each strategy. Meta-analyses were used to synthesize acute treatment and maintenance studies and physician surveys to collect information on patient management. The impact of uncertainty on the base case results was assessed using probabilistic sensitivity analysis. Probability distributions were defined for key model parameters and techniques of Monte Carlo simulation were used to draw values from these distributions. Cost-effectiveness acceptability curves (CEACs) conditional on the monetary value decision makers are willing to pay for a symptom-free day or QALY were created for each strategy. RESULTS: In the base case, no strategy was strictly dominated by any other strategy. However, two strategies (maintenance H2-receptor antagonists H2RA] and step-down proton pump inhibitor PPI]) were dominated through principles of extended dominance. The least costly and least effective strategy was intermittent H2RA, while maintenance PPI was the most costly and most effective. CONCLUSIONS: This analysis showed that the best way of managing patients with heartburn depends on how much society is willing to pay to achieve health improvements. Based on the commonly quoted threshold of US 50,000 dollars per QALY, the optimal primary care strategy for managing patients with moderate-to-severe heartburn symptoms is to treat the symptoms with a PPI followed by maintenance therapy with an H2RA to prevent symptomatic recurrence.

Proton pump inhibitors or histamine-2 receptor antagonists for the prevention of recurrences of erosive reflux esophagitis: a cost-effectiveness analysis.

OBJECTIVES: Erosive esophagitis is a recurring condition for which many patients require preventive therapy. If maintenance therapy must be provided, the most cost-effective treatment strategy should be established. We evaluated the costs and benefits associated with three treatment strategies: 1) maintenance therapy with a proton pump inhibitor (PPI) strategy, 2) maintenance therapy with a high-dose histamine-2 receptor antagonist (H2RA) strategy, and 3) maintenance therapy with a standard-dose H2RA. If patients experience a symptomatic recurrence on the H2RA strategies, they then receive PPI maintenance. METHODS: We used a cost-effectiveness model with a 1-yr time frame; data were obtained from randomized trials of lansoprazole and ranitidine, from case series, and expert opinion. RESULTS: In most situations, the high-dose H2RA strategy is the most costly, yet it is less effective than the PPI strategy. Among the remaining two options, the PPI strategy is more costly and more effective than the standard-dose H2RA strategy, requiring an additional $52-688 per recurrence prevented, depending on drug acquisition costs. The greater the degree to which esophagitis decreases quality of life, the more cost effective is the PPI strategy. For example, with a $50,000 per quality-adjusted life year cost-effectiveness threshold and a market-weighted average of drug costs, the PPI strategy appears cost effective for those patients who report that symptoms of esophagitis cause greater than a 9% decrement in quality of life. CONCLUSIONS: The high-dose H2RA strategy is not preferred in terms of either costs or benefits. The PPI strategy appears cost effective relative to the standard-dose H2RA strategy in the following situations: when patients are significantly bothered by esophagitis and in institutional settings where the difference in drug costs between PPIs and H2RAs is small.