“Side-effects of Long term PPI 25 years + went Unnoticed, FDA Warns judicious use”
— Dr. Shankar Khobragade
A continuing Medical education programme was conducted to discuss recent alarm by FDA on the rampant use of Proton Pump Inhibitors group of drugs on cardio, renal and neuro functions. Dr.Suhas Kanphade and Dr Mukesh Mishra were the chairpersons for the session.
The first lecture was given by Dr. Vishal Ramteke, MD Medicine, DNB, MNAMS (Nephrology) Consultant Nephrologist and Transplant Physician, on “PPI are they bad for kidneys?.” He said frequently Proton Pump Inhibitors (PPI) and Histamine 2 receptors antagonists are used for Gastro Esophageal Reflux Disease (GERD) and Peptic ulcer patients. The drugs of the second group were first introduced in 1977 (Cimetidine) and first PPI in 1988(Omeprazole). They proved to be star performers with the largest prescribed pharmaceutical drugs worldwide.
1998 Omeprazole was sold worth 8 Billion Dollars. FDA approved the list of PPI include H. Pilori Treatment, GERD/ Erosive Gastritis in children,(all except Pantoprazole) Risk reduction in upper Gastro Intestinal Bleed (Omeprazole). Maintenance of healing of Duodenal and Gastric ulcers (Lanso and Esmoprazole). Reported concerns with PPI were Pneumonia Community and Ventilator Assist Pneumonia, infective diarrhoea, Bone fractures etc.
Many of these studies are observational in nature, residual bias, had no record of over the counter drugs consumption, mechanism of Chronic Kidney disease not specified, disease code used and no access to lab findings are few of the limitations and need further data analysis. However, the FDA (USA) has issued concerns.
The second talk was delivered by Dr. Shankar Khobragade, Consulting Physician and Cardiologist on “PPI –Too much of a Good Thing? Adverse effects associated with the use of PPI”
Explaining what is proton pump Dr. Khobragade said “The integral protein in the parietal cells of stomach, pumps protons in to the stomach, by using ATP the hydrogen ion replaces a nonacidic potassium ion. Proton Pump Inhibitors (PPI) are those group of drugs whose main action is prolonged and long lasting reduction of gastric acid production. Inappropriate PPI prescriptions noted in hospitalized patients were USA (65%) Australia (63%), New Zealand (40%) Italy (68%) Ireland (33%).
A study from Stanford University School for Medicine analyzed the data from 1.8 million patients togeather with 19 million encounters and 35 million diagnoses. It also utilized more than 11 million clinical notes all from US patients of these patients 93,149 patients were diagnosed with heart burn (GERD) and 46% of these took one of the PPIs. In Jan. 19,2017 “PLOS one” study showed use of PPI predicts dearth failure and death in patients with coronary artery disease. PPI seem to increase incidence of cardiovascular events in patients with CAD mainly those using Clopidogrel increased.
Further analysis showed heart burn drugs linked to heart failure and silent kidney damage. Common antacid drugs could raise heart attack risk by 20%. So it is said too much of a good thing is a bad thing, remarked Dr. S.B.Khobragade. Gastric acids are important for breakdown of food and release of micronutrients, studies shown possibilities of interference with absorption of iron, Vit. B12, Calcium and Magnesium. JAMA said over prescribing PPI is reported frequently. PPI increase endothelial ageing. Longer the exposure higher is the risk.
All PPi are same in side effects. People over 75 years using PPI has increased risk of developing dementia than those who are not. PPI also cause anaemia (Japanese CAD patients) As per American Geriatric Society, PPI is responsible for hyperthyroidism, hypomagnesia. It is also linked to osteoporosis-related fractures and hence prudent approach to management of these unless indicated should not be prescribed. Other concerns are increased Pneumonia, Clostridium difficile infection, and other infections. In aspirin teed patients with first-time, myocardial infarction
The treatment with proton pump inhibitors was associated with an increased risk of adverse cardiovascular events. In conclusion, it is noticed that up to 30 to 50% and in some cases 70% acid suppression therapy of PPI may be inappropriate in outpatients and hospital inpatients. PPI is effective in management but carries the risk of several potentially threatening outcomes which were not known earlier.
However, all studies said H2 Receptor blockers have shown no association of Cardiovascular or chronic kidney disease-related events. PPI is associated with several issue, however, all studies that approved issues with PPI have also confirmed no such association with H2As. DAMA, pathways of PPI is class effect increasing the CV risks. These findings make us change the way we look at PPI, suppress the acid, not the heart and kidneys” opined Dr. Shankar Khobragade.
The talks were followed with lively interaction. The CME was supported by unconditional educational grants from J B Chemicals. It was largely attended by Physicians and Postgraduate students.