Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn

Spechler, Stuart J.; Hunter, John G.; Jones, Karen; Lee, Robert; Smith, Brian R.; Mashimo, Hiroshi; Sanchez, Vivian M.; Dunbar, Kerry B.; Pham, Thai H.; Murthy, Uma K.; Kim, Tae‐Wan; Jackson, Christian S.; Wallen, Jason; Rosenvinge, Erik C. von; Pearl, Jonathan P.; Laine, Loren; Kim, Anthony W.; Kaz, Andrew M.; Tatum, Roger P.; Gellad, Ziad F.; Lagoo‐Deenadayalan, Sandhya; Rubenstein, Joel H.; Ghaferi, Amir A.; Lo, Wai–Kit; Fernando, Ronald; Chan, Bobby S.; Paski, Shirley; Provenzale, Dawn; Castell, Donald O.; Lieberman, David; Souza, Rhonda F.; Chey, William D.; Warren, Stuart; Davis-Karim, Anne; Melton, Shelby D.; Genta, Robert M.; Serpi, Tracey; Biswas, Kousick; Huang, Grant D.

doi:10.1056/nejmoa1811424

Cited by 179 publications

(174 citation statements)

References 39 publications

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“…Vonoprazan, a P-CAB drug, was approved for application in the treatment of acid-related diseases in Japan on December 26, 2014 (Takeda, 2014). Previously, proton pump inhibitors (PPIs) were considered the first-in-class available drug to treat acid-related diseases, such as gastroesophageal reflux disease and gastroduodenal ulcers (Spechler et al, 2019), and has been widely utilized in the eradication therapy of H. pylori (Crowe, 2019). The unmet clinical needs of PPIs promote new drug development.…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P450-Based Drug-Drug Interactions of Vonoprazan In Vitro and In Vivo

Wang

et al. 2020

Front. Pharmacol.

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Background: Vonoprazan fumarate is a potassium-competitive acid blocker that was developed as a novel acid-suppressing drug for multiple indications. As a potential alternative to proton-pump inhibitors, the determination of the drug-drug interactions is vital for further applications. Probe drug cocktails are a type of rapid, economical, and efficient approach for evaluating cytochrome P450 enzyme activities. Since vonoprazan is metabolized partly by cytochrome P450, cocktails were used to study CYP-based drugdrug interactions. Methods: This study was conducted both in vitro and in vivo. In the in vitro study of rat liver microsomes, ultra-performance liquid chromatography coupled to tandem mass spectrometry was utilized to assess the reversible inhibition of cytochrome P450 by vonoprazan by determining the concentration of probe drugs (phenacetin, bupropion, tolbutamide, dextromethorphan, midazolam, chlorzoxazone). The differences in the levels of probe drugs between the rat groups with or without vonoprazan administration were also tested in the rats. Results: In vitro analysis revealed that the IC 50 values of midazolam, tolbutamide, dextromethorphan, and bupropion in rat microsomes were 22.48, 18.34, 3.62, and 3.68 mM, respectively, while chlorzoxazone and phenacetin displayed no inhibition. In vivo analysis revealed that midazolam, bupropion, dextromethorphan, and tolbutamide showed significant (P < 0.05) differences in distinct pharmacokinetic parameters after vonoprazan administration, while those of chlorzoxazone and phenacetin were not significantly different. Conclusion: The in vitro and in vivo results indicated that vonoprazan can inhibit CYP3A4, CYP2C9, CYP2D6, and CYP2B6, suggesting that the coadministration of vonoprazan with cytochrome P450 substrates should be performed cautiously in clinical settings.

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Section: Discussionmentioning

confidence: 99%

Cytochrome P450-Based Drug-Drug Interactions of Vonoprazan In Vitro and In Vivo

Wang

et al. 2020

Front. Pharmacol.

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“…4,5 Recently, the interest in managing GERD surgically has increased. [6][7][8] A recent randomized-controlled trial showed that laparoscopic Nissen fundoplication was superior to medication in reducing reflux-related heartburn. 6 In the study, treatment success, which was defined as an improvement of 50% or more in the GERD-Health Related Quality of Life score, was achieved in 67% of patients who underwent surgery, while 28% of patients who received active medical therapy including omeprazole and baclofen achieved treatment success.…”

mentioning

confidence: 99%

“…[6][7][8] A recent randomized-controlled trial showed that laparoscopic Nissen fundoplication was superior to medication in reducing reflux-related heartburn. 6 In the study, treatment success, which was defined as an improvement of 50% or more in the GERD-Health Related Quality of Life score, was achieved in 67% of patients who underwent surgery, while 28% of patients who received active medical therapy including omeprazole and baclofen achieved treatment success. 6 In another recent study in an Asian population, laparoscopic Nissen fundoplication was shown to be effective in patients for whom medical treatment was ineffective or who were unable to discontinue medication due to symptom recurrence.…”

mentioning

confidence: 99%

“…6 In the study, treatment success, which was defined as an improvement of 50% or more in the GERD-Health Related Quality of Life score, was achieved in 67% of patients who underwent surgery, while 28% of patients who received active medical therapy including omeprazole and baclofen achieved treatment success. 6 In another recent study in an Asian population, laparoscopic Nissen fundoplication was shown to be effective in patients for whom medical treatment was ineffective or who were unable to discontinue medication due to symptom recurrence. 7 Although medication should be the first-line treatment for patients with GERD and even though a large proportion of patients can be medically managed, anti-reflux surgery may offer an option for selected patients.…”

mentioning

confidence: 99%

“…7 Although medication should be the first-line treatment for patients with GERD and even though a large proportion of patients can be medically managed, anti-reflux surgery may offer an option for selected patients. 6 The efficacy of anti-reflux surgery in the management of GERD patients is well-recognized. However, cost-effectiveness must be a primary consideration before recommending surgical treatment widely in clinical practice.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cost-effective Management of Severe Gastroesophageal Reflux Disease: Toward an Improved Understanding of Anti-reflux Surgery

Park

2020

J Neurogastroenterol Motil

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Review of Gastroesophageal Reflux Disease

Mehta

Staller

Chan

2021

JAMA

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To the Editor In their Review about gastroesophageal reflux disease (GERD), Dr Maret-Ouda and colleagues 1 discussed risk factors and treatment options for GERD, including surgery and advanced endoscopic techniques. However, we believe they overlooked several recommendations that may benefit patients with heartburn.First, by stating that dietary factors "have not been associated with the development of GERD," the authors underemphasized the importance of dietary and lifestyle modification to prevent reflux symptoms. In a recent prospective analysis, we found that up to 40% of weekly GERD symptoms can be prevented through 5 dietary and lifestyle factors: eating a diet rich in whole grains, vegetables, and fruits; maintaining a healthy body weight; not smoking; exercising for 30 minutes per day; and drinking no more than 2 cups of soda, coffee, or tea per day. 2 Importantly, the decreased risk of GERD symptoms associated with this "anti-reflux lifestyle" was observed even among regular users of proton pump inhibitors (PPIs) and histamine 2 receptor antagonists. Additionally, in an earlier prospective analysis, we found that substitution of water for coffee, tea, or soda was associated with a modest reduction in GERD symptoms. 3 Second, the authors did not mention the importance of optimal timing of PPI administration for patients with GERD. A recent randomized clinical trial excluded 10% of patients referred for "PPI-refractory GERD" because they experienced a greater than 50% reduction in GERD symptoms when clearly instructed to take a PPI 30 minutes before breakfast and dinner. 4 Another randomized clinical trial demonstrated that in addition to decreasing heartburn symptoms, use of a PPI 30 minutes before the first meal resulted in cost savings from reduced medical care, estimated at approximately $160 per patient, equaling more than $4 billion per year in the US. 5 Prescribing a pill or doubling a medication dose is likely more convenient and less time-consuming than providing dietary and lifestyle counseling or educating patients about medication timing. However, given concerns about the long-term adverse effects of PPIs and histamine 2 receptor antagonists, and the benefits that an "anti-reflux" lifestyle may have for other chronic conditions, we hope that clinicians-as well as future gastroenterology society guidelines-will encourage dietary and lifestyle modifications and medication optimization prior to escalation of therapy.

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Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn

Cited by 179 publications

References 39 publications

Cytochrome P450-Based Drug-Drug Interactions of Vonoprazan In Vitro and In Vivo

Cytochrome P450-Based Drug-Drug Interactions of Vonoprazan In Vitro and In Vivo

Cost-effective Management of Severe Gastroesophageal Reflux Disease: Toward an Improved Understanding of Anti-reflux Surgery

Review of Gastroesophageal Reflux Disease

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