Considering Ranitidine in Episodic Heartburn Relief-A Practice Perspective

Heartburn is a cardinal symptom of gastroesophageal reflux disease (GERD). (1) It is defined as a sensation of burning discomfort in the chest, upper abdomen, or behind the breastbone and may sometimes spread to the throat. (2)

Heartburn is commonly caused by stomach acid flowing back into the esophagus, and a treatment that reduces stomach acid volume and increases the pH of refluxed material can effectively relieve the symptoms. (3) Heartburn is frequently associated with stomach acid reflux through the lower esophageal sphincter. (2)

Prevalence of Heartburn:

GERD is a major public health and economic burden due to increasing numbers of prevalent cases and incident cases. (4) An Indian survey report has indicated that 3.6% of Indian GERD patients have heartburn daily, and 5.9% report heartburn weekly. (1) Given the similar mechanism between GERD and functional dyspepsia, the prevalence of heartburn is high among dyspepsia patients, approximately 34.6%. (5) A nationwide telephone survey by the American Gastroenterological Association on 1000 adults with GERD reported that 79% of the subjects had night-time heartburn. (6)

The risk factors for GERD/heartburn in the Indian population include age, high body mass index (usually above 30 kg/m2), non-vegetarian diet, tea/coffee intake, tobacco, and alcohol consumption. (7)

Management of Heartburn:

Given the multifactorial etiology, poor dietary habits and lifestyle factors may induce or aggravate GERD symptoms, including heartburn. Identification of triggers for reflux symptoms is the first step in managing heartburn, followed by lifestyle interventions, including dietary modification, weight reduction, head-of-bed elevation, cessation of smoking and frequent alcohol use, avoidance of meals 2–3 h before bedtime, and reduced intake of coffee, chocolate, spices, acidic foods, and high-fat foods. (8)

The empirical treatment for heartburn includes histamine H2 receptor blockers (H2RAs), proton pump inhibitors (PPI), and antacids. The Indian Society of Gastroenterology (ISG) and Association of Physicians of India (API) guidelines for the diagnosis and management of GERD in India suggested using H2RAs. The guideline noted that H2RAs reduce acid secretion by competitively antagonizing the H2 receptors on the parietal cells and also noted the superiority of H2RA agents over placebo in providing GERD symptom relief. (5)

H2RAs such as Ranitidine provide relief of heartburn by inhibiting acid secretion, thereby elevating intragastric pH and reducing the volume of gastric contents and acid available for reflux into the esophagus. (9) Among the selective H2RAs, Ranitidine remains an important drug for treating acid-peptic disorders such as GERD; it reduces baseline gastric and acid secretion generated by histamine. Additionally, Ranitidine is known for its faster healing rates and efficacy in relieving symptoms of acid peptic disorders. (10)

Application of Ranitidine in Heartburn Conditions: Review of Clinical Evidence:

Ranitidine Effective in Indian Patients with GERD with Heartburn: An open-label, prospective, multicenter study analyzed the efficacy and safety of Ranitidine HCl in Indian patients with GERD (N=2446). Patients received Ranitidine HCl 150 mg twice a day (BID) (ARM-A), Ranitidine HCl 300 mg once daily (OD) or twice daily (BID) (ARM-B), and Ranitidine HCl 300 mg once daily (OD) (ARM-C). The Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) score and Heartburn Severity score were used to assess the drug's efficacy. The result noted that 72.82% of ARM-A, 68.49% of ARM-B, and 70.27% of ARM-C patients had 24-hour heartburn-free days. Furthermore, 66.89% of ARM-A, 55.63% of ARM-B, and 52.70% of ARM-C patients had 7 consecutive heartburn-free days. The GSAS scores reduced from 2.02 to 0.23 in ARM-A, 2.01 to 0.24 in ARM-B, and 2.07 to 0.26 in ARM-C patients. This study suggested that Ranitidine is effective in relieving heartburn symptoms in GERD patients. (10)

Ranitidine Effective in Prevention and Reduction of Heartburn and Its Severity: A randomized double-blind study compared the efficacy and safety of Ranitidine in preventing or reducing subsequent heartburn symptoms. The study included 284 patients randomly assigned to receive either double-blind intervention of Ranitidine 75 mg or placebo 30 min before meal for a duration of 4–14 days. The percentage of patients with complete heartburn prevention was 16% for Ranitidine 75 mg and 5% for placebo (P<0.001). The percentage reduction in heartburn severity [Area Under Curve (AUC) in 4.5 h] was 59.6% vs. 28.7% in Ranitidine and placebo groups (P<0.001). The percentage reduction in peak heartburn severity scores was also significantly (P<0.001) higher in the Ranitidine 75 mg group relative to placebo (52.0% vs. 29.8%). The study concluded that Ranitidine effectively prevents or decreases heartburn events. (3)

Ranitidine Effective than Antacids in Treating Heartburn: Another randomized, double-blind, parallel-group study compared the efficacy of Ranitidine to antacids in treating heartburn. The study included 155 patients with frequent antacid-responsive heartburn, randomized to receive Ranitidine 150 mg tablets b.d. or calcium carbonate 750 mg for 12 weeks. The frequency and average severity of heartburn episodes were significantly less (P≤0.015) within 1 day of receiving study medication in subjects treated with Ranitidine compared to subjects treated with antacids, and these differences continued throughout the study period with only sporadic variations. This study suggested that Ranitidine is more effective than antacids in treating heartburn. (9)

Key Points:

• Heartburn is a cardinal symptom of GERD. There is a high prevalence of heartburn among GERD and dyspepsia patients.
• Age, body mass index (BMI), non-vegetarian diet, tea/coffee intake, and tobacco and alcohol consumption are some common risk factors for heartburn in the Indian population.
• The empirical treatment for heartburn includes histamine receptor blockers (H2RAs), proton pump inhibitors (PPIs), and antacids.
• Histamine receptor blockers (H2RAs) such as Ranitidine provide relief of heartburn by inhibiting acid secretion, thereby elevating intragastric pH and reducing the volume of gastric contents and acid available for reflux into the esophagus.
• Indian and international clinical studies have demonstrated the effectiveness of Ranitidine in treating and preventing episodic heartburn and reducing its severity.

References:

1. Bhatia SJ, Makharia GK, Abraham P, et al. Indian consensus on gastroesophageal reflux disease in adults: A position statement of the Indian Society of Gastroenterology. Indian J Gastroenterol. 2019;38(5):411-440. doi:10.1007/s12664-019-00979-y

2. Garg V, Narang P, Taneja R. Antacids revisited: review on contemporary facts and relevance for self-management. J Int Med Res. 2022;50(3):3000605221086457. doi:10.1177/03000605221086457

3. Pappa, K. A., Williams, B. O., Payne, J. E., Buaron, K. S., Mussari, K. L., & Ciociola, A. A. A double-blind, placebo-controlled study of the efficacy and safety of non-prescription ranitidine 75 mg in the prevention of meal-induced heartburn: LOW-DOSE RANITIDINE FOR HEARTBURN PREVENTION. Alimentary Pharmacology & Therapeutics, 13(4), 467–473.

4. Zhang D, Liu S, Li Z, Wang R. Global, regional and national burden of gastroesophageal reflux disease, 1990-2019: update from the GBD 2019 study. Ann Med. 2022;54(1):1372-1384. doi:10.1080/07853890.2022.2074535

5. Bhatia S, Pareek KK, Kumar A, et al. API-ISG Consensus Guidelines for Management of Gastrooesophageal Reflux Disease. J Assoc Physicians India. 2020;68(10):69-80.

6. Shaker R, Castell DO, Schoenfeld PS, Spechler SJ. Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association. Am J Gastroenterol. 2003;98(7):1487-1493. doi:10.1111/j.1572-0241.2003.07531.x

7. Rai S, Kulkarni A, Ghoshal UC. Prevalence and risk factors for gastroesophageal reflux disease in the Indian population: A meta-analysis and meta-regression study. Indian J Gastroenterol. 2021;40(2):209-219. doi:10.1007/s12664-020-01104-0

8. Yuan LZ, Yi P, Wang GS, et al. Lifestyle intervention for gastroesophageal reflux disease: a national multicenter survey of lifestyle factor effects on gastroesophageal reflux disease in China. Therap Adv Gastroenterol. 2019;12:1756284819877788. Published 2019 Sep 25. doi:10.1177/1756284819877788

9. Earnest D, Robinson M, Rodriguez-Stanley S, et al. Managing heartburn at the 'base' of the GERD 'iceberg': effervescent ranitidine 150 mg b.d. provides faster and better heartburn relief than antacids. Aliment Pharmacol Ther. 2000;14(7):911-918. doi:10.1046/j.1365-2036.2000.00785.x

10. Shukla, A., Awasthi, A., Rao, R., Yadav, D., Nolkha, N., Pendlimari, R., Dua, S., Bhatnagar, S., Mote, R., Birla, A., Savai, J., Mehta, K. and Salunke, S. (2023) A Prospective, Multicentric, Post Marketing Surveillance to Evaluate Efficacy & Safety of Ranitidine HCl (150 & 300 mg IR/CR) in Indian Patients with Gastroesophageal Reflux Disease (PROGRADE). Open Journal of Gastroenterology, 13, 237-249. doi: 10.4236/ojgas.2023.137022.