The first line of treatment for H. pylori eradication based on various guidelines around the world is the use of a proton pump inhibitor (PPI) and two antimicrobial agents (clarithromycin, amoxicillin or metronidazole). The success rate of H. pylori eradication in previous studies was reported to be about 80–96%, but in recent studies this rate has been reported below 80% 3. Much of this reduction in effect is due to drug resistance to antibiotics and the rate of drug resistance increases over time 3, 14. Therefore, finding alternative therapies is needed to improve the eradication of H. pylori.
As a general rule, the physician should choose a medication regimen for the patient that has a 90% eradication rate 25. According to studies conducted in Iran, one of the first treatment regimens for H. pylori is 4-drug regimen of PPI, bismuth, amoxicillin and metronidazole or clarithromycin 26. However, studies show that over time, the success rate of these drug regimens in eradicating H. pylori has decreased from 90% to about 80% 26 and even in some studies it has decreased to less than 70% 27. Therefore, adding adjuvant medications or changing diet therapy seems to be necessary to eradicate H. pylori.
Therefore, due to the anti-inflammatory and antibacterial effects of statins and the fact that studies have shown that H. pylori increase cytokine production and inflammatory factors 23, statins are one of the drugs that can help eliminate H. pylori. In the present study, due to the severe drug interactions of clarithromycin and atorvastatin (D class interaction) 28, 29 for the standard treatment regimen of a 240mg bismuth subcitrate tablet, a 40mg pantoprazole tablet, a 500mg metronidazole tablet and 2 capsules of 500mg amoxicillin, all of which were used BID for 14 days, and in the intervention group, in addition to receiving a standard diet, patients were also prescribed 40mg of atorvastatin. In the present study, the eradication rate of H. pylori was 80% in the control group and 80.9% in the intervention group, which did not show a statistically significant difference between the two groups (p-value = 0.97), while in the study of Nseir et al, and another study by Shakerian et al, it was found that adding statins to a 4-drug regimen significantly increased the success rate of H. pylori eradication. In a 2012 study by Nseir et al, in the placebo group, the rate of elimination of H. pylori was 72%, and for those receiving simvastatin, in addition to the standard treatment, it was 91%, with a statistically significant difference of p-value of 0.03 3.In the Shakerian study, 110 patients in the control group received a 14-day diet of amoxicillin, clarithromycin, bismuth, and esomeprazole, and 110 patients in the day-to-day intervention group received 40mg of atorvastatin with an antibiotic regimen for 14 days. The test results were tested a month later using H. pylori fecal antigen testing. H. pylori eradication rates in the intervention and control groups were 78.18% and 65.45%, respectively (p-value = 0.025) 30. Comparing the two studies with the present study, it is found that adding statins to the 4-drug regimen containing clarithromycin increases the eradication rate of H. pylori, while in the therapeutic regimen used in the present study, clarithromycin was replaced by metronidazole, and adding statins does not statistically improve H. pylori eradication.
Studies have shown that clarithromycin inhibits CATP3A4 by inhibiting OATP1B1 and OATP1B3 cells in hepatocyte cells, which can lead to complications such as AV block, rhabdomyolysis, acute renal failure, hyperkalemia, and death 31–37. Therefore, the positive effect of statins on regimen containing clarithromycin may be due to the high accumulation of statins, which on the one hand increases the eradication rate of H. pylori eradication, but on the other hand will have dangerous side effects. Therefore, the combination of this class of drugs with clarithromycin in the anti-Helicobacter pylori diet does not appear to be beneficial. On the other hand, it should be noted that the drug regimen used in the study of Shakerian et al, the is not recommended regimen in Iran (study place). However, the success rate of a treatment regimen is related to geographical area, age and sex, and as reported in the results of their study, the intervention and control groups were 78.18% and 65.65%, respectively 30. Which was less than the results of the present study (80.9% and 80%). Therefore, in addition to avoiding the use of statin drugs at the same time as clarithromycin, it is recommended that statins be studied with other preferred regimens in the region.