FIELD study - Can we reduce the amputations in Diabetic population with Fenofibrate?

Diabetes mellitus is the leading cause of non-traumatic lower-extremity amputations in the developed world. In the USA in 2001, at least one amputation due to diabetes occurred every 2 h, with an annual cost exceeding US$1·6 billion.Despite rigorous management of reversible factors, probably around one in ten patients with diabetes will eventually need at least one amputation. Neither control of glycaemia or blood pressure nor lowering of cholesterol has prevented the risk of amputation, underscoring the importance of assessing the management of other potential risk factors. Any further therapeutic option to prevent the morbidity and mortality associated with amputation would be highly desirable. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, 9795 patients aged 50—75 years with type 2 diabetes were randomly assigned by computer-generated randomisation sequence to receive fenofibrate 200 mg per day (n=4895) or matching placebo (n=4900) for 5 years' duration. Information about non-traumatic amputation—a prespecified tertiary endpoint of the study—was routinely gathered.The risks of first amputation (45 vs 70 events; hazard ratio [HR] 0·64, 95% CI 0·44—0·94; p=0·02) and minor amputation events without known large-vessel disease (18 vs 34 events; 0·53, 0·30—0·94; p=0·027) were lower for patients assigned to fenofibrate than for patients assigned to placebo, with no difference between groups in risk of major amputations (24 vs 26 events; 0·93, 0·53—1·62; p=0·79)

In POPADAD study, it was found that Aspirin is ineffective in Diabetics with Asymptomatic Peripheral Vascular Disease for primary prophylaxis! (BMJ 2008)

Peripheral arterial disease patients have an increased risk of subsequent myocardial infarction and stroke and are six times more likely to die from cardiovascular disease within10 years than patients without peripheral arterial disease. Patients with peripheral arterial disease have a 15 year accrued survival rate of about 22% compared with a survival rate of 78% in patients without such disease. So, there is always a question about beneficial effect and safety in giving Aspirin in the asymptomatic PAD patients to prevent the CV complications!

After this POPADAD study a question was asked as to whether these diabetic patients were at sufficient risk, in terms of peripheral arterial disease, as the cut-off point of an ankle brachial pressure index of 0.99 or less is higher than that used to define peripheral arterial disease in the population (<0.9). A subgroup analysis did not, however, find evidence of a difference in effect of aspirin between those with an index of 0.91-0.99 and those below this level.
Furthermore, one of the current major interventions in the specialty of diabetes mellitus is statin therapy. Calculations by two of the centres (DM and CK) in over 10 000 people with diabetes showed a mean total cholesterol level of 6.0 mmol/l in 1996 decreasing to 4.3 mmol/l in 2007. As aspirin was the first drug to have an evidence base for secondary prevention of cardiovascular disease it is always given to patients in subsequent trials and it might be asked if aspirin does indeed provide additional benefit when statins are used to good effect. The importance of the neutral effect of aspirin on cardiovascular events is that this drug is not without side effects. Aspirin is the most commonly prescribed drug in Scotland, with about 544 438 person years exposure per year in 2002. The number of prescriptions is increasing. The overwhelming majority of this, in the region of Tayside at least, is prescription based, with only about 7% being from over the counter use. Aspirin is one of the top 10 causes of adverse drug events reported to the Commission on Human Medicines. Gastrointestinal bleeding is associated ith general use of non-steroidal anti-inflammatory drugs in over 80%of reported cases, and 87%of that use is associated with aspirin, either alone or with other non-steroidal anti-inflammatory drugs. The risk of a bleeding event increases with age and also continuous exposure.
Although the calculated risk of major bleeding is relatively small, the number of people taking aspirin is relatively large and therefore in population terms aspirin induced bleeding is a major problem. In a meta-analysis the number needed to treat to cause an adverse event has been calculated as 248, and this is relevant to the large and increasing population with diabetes.
In addition, of concern was the fact that there was a tendency to harm in the antioxidant group. Anecdotally, many people with diabetes supplement with antioxidants after major publicity in the lay press of a deficiency in antioxidants in such people. It was also found there was no evidence for this perceived benefit in the studies.

Conclusion: Both Aspirin and Antioxidants are not useful in Diabetics with asymptomatic peripheral vascular disease in preventing the cardiovascular events!

Helicobacter pylori  in smokers with peripheral vascular disease - Shoud we consider quadruple therapy for eradication routinely?

Infection with Helicobacter pylori is a substantial public health problem that affects 20 to 50% of people in industrialised nations and up to 80% in less-developed countries. H pylori is associated with many gastroduodenal disorders, including peptic ulcer disease, gastric carcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. In regions with high incidence of gastric carcinoma, eradication of H pylori is advocated to prevent the development of this disease. Further, patients benefit from eradication after endoscopic resection of early gastric carcinoma because it reduces the risk for metachronous gastric neoplasia.
A previous international study, which assessed the efficacy and safety of 10 days of omeprazole with a single (three-in-one) capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy) for H pylori eradication in patients with peptic ulcer disease or non-ulcer dyspepsia, reported overall eradication rates greater than 90%.

Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori, especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy.

Long term follow up (8 yrs) after Endorepair of Thoracic Aortic dissection.

This gentleman was admitted with acute ischemia in both the lower limbs in middle of the night and in emergency the resident on duty attempted thrombectomy but failed to retreive the thrombus. The next morning further investigations revealed dissection of aorta from the left subclavian origin to abdominal aortic bifurcation. After discussions it was decided to do the endorepair. Endorepair was successfully done and remained intact for the past 8 years. He has developed diabetes in the followup. His blood pressure was controlled with medications and he is advised to monitor blood pressure regularly at home.

Obesity and Venous disease (Varicose veins): Weight management in venous disease (varicose veins) patients is very difficult. It is becoming a common problem in the vascular surgery out patient clinics. Some may still feel that obesity is not a major problem in Indian hospitals. In the venous subset of population attending the vascular clinics this is a significant problem. A recent study by the University of Maryland and the National Council of Applied Economic Research found 22 per cent of Indians living in cities were overweight and 7 per cent were obese. The following is the typical presentation in our clinic. Here is a man weighing 107 Kgs with history of bleeding from the leg veins. He was advised to loose 5 kgs by adjusting diet and life styles along with class II stockings. He came back to the clinic after 4 weeks with a weight of 110Kgs. But he is regular with his stockings and there were no episodes of bleeding from the leg. This is a common problem to see weight gain when you advise them to loose weight. Weight management needs special attention to the details and it would not be sufficient if we simply advice the patients to loose weight. Very few patients (from low socioeconomic group) succeed in loosing the weight with a simple advice in the outpatient clinics. India has 70 million people who have been re-classified as overweight or obese, after a lowering of obesity thresholds. In India the BMI limits have been lowered to 23 for being overweight and 25 for being obese, to reflect the risks to the population. Indians also have lower thresholds for waist circumference measurements.