As Korea enters super-aged society, gastrointestinal protection is now a treatment strategy

“I took medication for my aching joints, and ended up hospitalized with gastrointestinal bleeding.”

A female patient in her late 70s came to the emergency room with severe gastrointestinal bleeding after taking non-steroidal anti-inflammatory drugs (NSAIDs) to treat her degenerative arthritis. This situation is not uncommon in the medical field.

“The risk of gastrointestinal bleeding in elderly patients over 75 years old increases exponentially, and the dosage of drugs that damage the gastrointestinal mucosa, such as NSAIDs, antithrombotic drugs, and anticoagulants, is also increasing with population aging,” said Professor Choi Jeong-min of the Department of Gastroenterology at Inje University Sanggye Paik Hospital.

Professor Choi noted that the prevention and management of gastrointestinal diseases is emerging as a significant medical issue in Korea, which has entered a super-aged society.

NSAIDs relieve pain but damage the stomach

NSAIDs are used almost exclusively to treat conditions common in older adults, including degenerative arthritis, chronic back pain, and rheumatic diseases. The problem is that these drugs inhibit the protective mechanisms of the gastrointestinal mucosa.

“NSAIDs work by inhibiting the enzymes COX-1 and COX-2, which are anti-inflammatory, but COX-1 is also responsible for protecting the gastric mucosa, so inhibiting it can lead to ulcers and bleeding in the GI tract,” Choi said.

Professor Choi warns that the risk of peptic ulcers from taking NSAIDs increases by several to several dozen times with advanced age, history of ulcers, and Helicobacter pylori infection.

"Risk factors for peptic ulcers include taking high doses of NSAIDs, being older than 70 years of age, and having H. pylori infection, which increases the risk of ulcer recurrence by about 13.5 times, especially if you have a history of ulcers in the past. Age alone increases the risk by about 5.6 times, and infection with H. pylori, which affects about 50 percent of people in the United States, increases the risk by about 3.5 times," Choi explained.

In addition to NSAIDs, antithrombotic drugs, such as aspirin and clopidogrel, and anticoagulants, such as warfarin and DOACs (newer anticoagulants), also increase the risk of GI injury. The problem is that as cardiovascular disease increases with aging, so do the combinations of these medications.

“Many patients are taking aspirin and clopidogrel for myocardial infarction prevention, and it's not uncommon to see them using NSAIDs at the same time, so you have a triple and quadruple threat to the GI mucosa,” Choi noted.

Prophylactic PPI combination is no longer optional but 'standard of care'

The most obvious way to reduce GI mucosal damage is to prescribe a combination of proton pump inhibitors (PPIs). Preventive use is strongly recommended, especially in patients with a history of GI disease and in high-risk groups over 60.

“When NSAIDs are used in high doses or for prolonged periods, a PPI should be used in addition. Prophylactic PPI use is the most effective way to reduce gastrointestinal bleeding,” Choi emphasized.

The VENUS-PLUTO study found that esomeprazole (Nexium in trademark name) 20 mg was associated with a significantly lower ulcer rate in high-risk patients compared to placebo, and the combination with a COX-2 selective inhibitor reduced ulceration by about 85 percent.

Combining steroids and NSAIDs, or repeatedly administering high doses in injectable form, can lead to gastric ulcers or bleeding,” Choi said, explaining that these adverse events are not uncommon in clinical practice.

"Many patients admitted to internal medicine for gastrointestinal bleeding have been prescribed NSAIDs by other departments without adequate gastrointestinal protection. Medication adjustments are often reversed after hospitalization," he explained.

“To prevent these problems, NSAIDs should be used at the lowest possible dose and for the shortest possible duration, and if prolonged use is unavoidable, concomitant prescribing of a low-dose PPI is strongly recommended,” Choi noted. “This is a treatment principle emphasized by Korean and foreign guidelines.”

What are the caveats to prescribing NSAIDs?

Professor Choi outlined three principles for prescribing NSAIDs in primary care and other settings: prescribe NSAIDs at the lowest dose and for the shortest duration; always combine them with PPIs in elderly patients and those with a history of ulcers; and replace them with COX-2 selective inhibitors whenever possible.

“NSAIDs should not be ruled out for patients who need analgesia, but gastrointestinal protection should also be considered. For prophylaxis, low doses like esomeprazole 20 mg are effective enough.”

The P-Cab (Potassium-Competitive Acid Blocker) class of drugs, which was first launched in Korea in 2018, has emerged with the promise of strong stomach acid suppression. With its fast onset of action, relatively long duration of action, and ability to be taken without meals, P-Cab was touted as a next-generation treatment to compensate for the limitations of existing PPIs.

However, six years after its introduction, Choi emphasizes that “the era of PPIs is still alive and well.”

“P-Cab is certainly a promising class, but there is still insufficient evidence to replace PPIs for either curative or prophylactic treatment,” Choi pointed out.

In particular, Choi emphasized that for prophylactic purposes, low-dose PPIs are sufficiently effective.

Stronger acid suppression does not necessarily mean a proportional increase in preventive effectiveness, as physiologic stomach acid has a necessary function, and excessive suppression can lead to side effects such as intestinal infections, he explained.

Esomeprazole 20 mg can be safely used in patients with a wide range of chronic diseases and is preferred in primary care settings,” Choi said, adding that it has been proven safe and effective in elderly patients and patients with liver disease.

In addition to efficacy, Dr. Choi also noted that accumulated clinical experience, insurance coverage, and cost are other criteria for drug selection in the medical field.

"PPIs have been used in hundreds of millions of patients worldwide and have a proven track record of safety and effectiveness. P-Cab is certainly a promising series, but PPIs are still the most obvious choice for patients in the clinic right now," Professor Choi concluded.