Common Diabetes Meds May Raise Odds for Amputation

People with type 2 diabetes who are taking common drugs called diuretics may be at a significantly increased risk of losing a foot or leg, according to a new French study.

Researchers found that taking a diuretic raised the odds of having an amputation, or requiring an angioplasty or bypass, by 75 percent or more, compared with those not using the medicines.

Based on the findings, “diuretics should be used cautiously in patients with type 2 diabetes at risk of amputations,” concluded a team led by diabetes specialist Dr. Louis Potier, of Bichat Hospital in Paris.

But one U.S. expert said that restricting the use of diuretics puts diabetic patients “between a rock and a hard place.”

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As Dr. Gerald Bernstein explained, diuretics are used to help “get rid of extra salt and water” in the blood, thereby helping patients control blood sugar and blood pressure.

In turn, that could help ward off a major killer: congestive heart failure.

So, the challenge is to “select the right drugs to prevent worsening of heart failure in order to prevent increased risk for amputations,” said Bernstein, coordinator for the Friedman Diabetes Program at Lenox Hill Hospital in New York City.

As Bernstein explained, “type 2 diabetes is a disease heavily associated with cardiovascular complications, in particular the big arteries from the heart to the rest of the body. When these arteries and the heart are diseased there is abnormal blood flow to all the organs but the lower extremities can be affected most because of how long that artery is.”

When circulation issues to the leg and foot become severe, amputation is often the only option.

How much might particular diabetes medicines affect the odds of needing an amputation?

To help find out, Potier’s team tracked outcomes for nearly 1,500 people with type 2 diabetes. The study specifically focused on amputations, as well as procedures such as angioplasty or the bypassing of blocked or damaged blood vessels. Those procedures are used to improve circulation and prevent leg or foot amputations.

Participants were followed until they had a leg procedure or died. Nearly 700 of the study participants were taking a diuretic drug.

Over a follow-up of about seven years, 13 percent of those taking a diuretic had an amputation or other procedure on their lower leg, compared with just 7 percent of those not taking a diuretic.

Said another way, this meant that taking a diuretic increased the risk of having an amputation or an angioplasty/bypass by 75 percent or more, compared with those not using one.

Most of this increase involved amputations, which nearly doubled for those taking a diuretic.

The results of the study were presented Monday at the meeting of the European Association for the Study of Diabetes, in Berlin.

It’s important to note the study was observational in nature, meaning that while it could point to an association between diuretics and amputation rates, it could not prove cause and effect, and other factors might be at play. Furthermore, research presented at medical meetings is typically considered preliminary until published in a peer-reviewed journal.

According to Bernstein, the take-home message here is not to immediately discontinue the use of diuretics, but to keep in mind that “the patient and physician must be very careful not to overtreat and be very selective” in which drugs are used to fight diabetes.

Diabetes specialist Dr. Robert Courgi agreed. Reviewing the findings, he said that while more study is needed to confirm the results, “if a patient is at risk for amputation then perhaps diuretics should be avoided for other equally effective options.” Courgi is an endocrinologist at Southside Hospital in Bay Shore, N.Y.

Randomized Trial of Preventive Angioplasty in Myocardial Infarction.

Patients with acute ST-segment elevation myocardial infarction (STEMI) are effectively treated with emergency angioplasty, hereafter called percutaneous coronary intervention (PCI), to restore blood flow to the coronary artery that is judged to be causing the myocardial infarction (infarct artery, also known as culprit artery).1-5 These patients may have major stenoses in coronary arteries that were not responsible for the myocardial infarction,6 but the value of performing PCI in such arteries for the prevention of future cardiac events is not known.

Some physicians have taken the view that stenoses in noninfarct arteries may cause serious adverse cardiac events that could be avoided by performing preventive PCI during the initial procedure.7-12Others have suggested that medical therapy with antiplatelet, lipid-lowering, and blood-pressure–lowering drugs is sufficient and that the risks of preventive PCI outweigh the benefits.2-4,13-17

The aim of our single-blind, randomized study, called the Preventive Angioplasty in Acute Myocardial Infarction (PRAMI) trial, was to determine whether performing preventive PCI as part of the procedure to treat the infarct artery would reduce the combined incidence of death from cardiac causes, nonfatal myocardial infarction, or refractory angina.


The results of this trial show that in patients with acute STEMI, the use of preventive PCI to treat noninfarct coronary-artery stenoses immediately after PCI in the infarct artery conferred a substantial advantage over not performing this additional procedure. The combined rate of cardiac death, nonfatal myocardial infarction, or refractory angina was reduced by 65%, an absolute risk reduction of 14 percentage points over 23 months. The effect was similar in magnitude and remained highly significant when the analysis was limited to cardiac death and nonfatal myocardial infarction.

In this trial, all decisions regarding the treatment of patients, other than the random assignments to the two study groups, were left to the discretion of the clinicians involved. The rates of use of drug-eluting stents and medical therapy were similar in the two groups. In the group receiving no preventive PCI, ischemia testing was performed in about one third of patients: 44 tests in asymptomatic patients (usually ≤6 weeks after the myocardial infarction) and 37 tests in patients with chest pain. In the preventive-PCI group, ischemia testing was performed in about one sixth of patients: 8 tests in asymptomatic patients and 31 tests in patients with chest pain. Although such testing was not a prespecified trial outcome, these findings suggest that preventive PCI may lead to less ischemia testing and that when such testing is performed, it tends to be in patients with symptoms.

Although refractory angina is a more subjective outcome than myocardial infarction or cardiac death, it was included as a component of the primary outcome because it is a serious symptomatic condition that warrants prevention. We sought to reduce bias in the assessment of this outcome by requiring that the diagnosis be confirmed with objective evidence of ischemia. The benefit of preventive PCI was also evident when the less subjective outcomes of cardiac death and nonfatal myocardial infarction were considered alone.

We decided against using revascularization as a primary outcome, since subsequent revascularization procedures could be prompted by the identification of stenosis in a noninfarct artery in the group receiving no preventive PCI during the initial procedure. This factor would also tend to underestimate the effect of preventive PCI on primary-outcome events by reducing the treatment difference between the two study groups. However, revascularization was retained as a secondary outcome to record the number of subsequent procedures in each group.

In our study, 13 patients did not receive their assigned treatment. In the group receiving no preventive PCI, 2 patients underwent PCI in a noninfarct artery (1 for unknown reasons and 1 because the operator treated what turned out to be a noninfarct right coronary artery and then had to treat the infarct circumflex artery). In the preventive-PCI group, 11 patients underwent PCI only in the infarct artery because the preventive PCI could not be completed owing to insufficient time (because of competing emergency PCIs) in 3 patients, failure of the noninfarct-artery PCI in 5 patients, and other complications in 3 patients. These deviations from the assigned treatment mean that the intention-to-treat analysis, adopted to ensure comparability of the two study groups, will tend to underestimate the benefit of preventive PCI. However, the results of the as-treated analysis were consistent with those of the intention-to-treat analysis.

In two other randomized trials, investigators have specifically assessed the value of preventive PCI in patients with acute STEMI undergoing PCI in the infarct artery. In one study, 69 patients were randomly assigned (in a 3:1 ratio) to preventive PCI (52 patients) or no preventive PCI (17 patients).20 At 1 year, in the preventive-PCI group, there were nonsignificant reductions in the rates of repeat revascularization (17% and 35%, respectively) and cardiac death or myocardial infarction (4% and 6%, respectively). In the other trial, 214 patients were randomly assigned to one of three groups: no preventive PCI (84 patients), immediate preventive PCI (65 patients), and staged preventive PCI performed during a second procedure about 40 days later (65 patients).7 At 2.5 years, the rate of repeat revascularization was less frequent in the immediate– and staged–preventive PCI groups combined, as compared with the group receiving no preventive PCI (11% and 33%, respectively), and there was a nonsignificant decrease in the rate of cardiac death (5% and 12%, respectively). These studies were limited by a lack of statistical power and a reliance on repeat revascularization as an outcome, which, as indicated above, may be subject to bias. However, the results of these studies are consistent with those of our study.

Current guidelines on the management of STEMI recommend infarct-artery-only PCI in patients with multivessel disease, owing to a lack of evidence with respect to the value of preventive PCI.2-5 This uncertainty has led to variations in practice, with some cardiologists performing immediate preventive PCI in spite of the guidelines, some delaying preventive PCI until recovery from the acute episode, and others limiting the procedure to patients with recurrent symptoms or evidence of ischemia. The results of this trial help resolve the uncertainty by making clear that preventive PCI is a better strategy than restricting a further intervention to those patients with refractory angina or a subsequent myocardial infarction. However, our findings do not address the question of immediate versus delayed (staged) preventive PCI, which would need to be clarified in a separate trial.

Several questions remain. First, are the benefits of preventive PCI applicable to patients with non-STEMI?21 Such patients tend to be difficult to study because, unlike those with STEMI (in whom the infarct artery is invariably identifiable), there is often uncertainty over which artery is the culprit. Second, do the benefits extend to coronary-artery stenoses of less than 50%? There is uncertainty over the level of stenosis at which the risks of PCI outweigh the benefits. Third, would a physiological measure of blood flow, such as fractional flow reserve,22,23 offer an advantage over angiographic visual assessment in guiding preventive PCI? Further research is needed to answer these questions.

In conclusion, in this randomized trial, we found that in patients undergoing emergency infarct-artery PCI for acute STEMI, preventive PCI of stenoses in noninfarct arteries reduced the risk of subsequent adverse cardiovascular events, as compared with PCI limited to the infarct artery.


Source: NEJM




Venous Angioplasty Fails to Help MS Patients in First Randomized Trial .

Percutaneous transluminal venous angioplasty is ineffective in correcting chronic cerebrospinal venous insufficiency in patients with multiple sclerosis, according to the first randomized trial of the procedure, presented at the American Academy of Neurology‘s annual meeting.

Researchers studied venous angioplasty in 10 patients with MS in an open-label safety assessment, after which they randomized 19 patients to either angioplasty or a sham control. Primary outcomes included safety at 1 day and 1 month, venous outflow restoration, and new lesion activity and relapse over 6 months.

The researchers concluded that the procedure is not only ineffective but also may exacerbate MS disease activity in the short-term.

Source: American Academy of Neurology meeting website

First Drug-Eluting Stent Approved to Treat Peripheral Artery Disease.

The FDA has approved the first drug-eluting stent to treat stenosis or occlusion of the superficial femoral artery in patients with peripheral artery disease (PAD).

In clinical trials, the Zilver PTX stent was more effective than — and at least as safe as — percutaneous transluminal angioplasty for treating symptomatic PAD. The most frequent major adverse event was restenosis necessitating additional therapy.

The paclitaxel-coated stent is contraindicated in patients with stenoses that cannot be dilated, patients with certain bleeding disorders, and women who are pregnant, breast-feeding, or planning to become pregnant within 5 years.

Source:FDA news

Incidental detection of late presenting co-arctation of the aorta on chest x-ray: the importance of rib notching.


A 31-year-old obese male presented to the emergency department with symptoms and signs suggestive of a viral upper respiratory tract illness with a background of low exercise tolerance. Rib notching was identified on plain film chest radiography and subsequent CT of the thorax identified a moderately tight 2-mm juxta-ductal co-arctation of the aorta with multiple enlarged chest wall collaterals. The patient underwent a two-stage percutaneous procedure involving stent insertion and angioplasty up to 16 mm with significant improvement in exercise capacity and a modest reduction in blood pressure.


Incidental detection of rib notching on plain film radiography led to a diagnosis of co-arctation of the aorta in a male patient. Subsequent endovascular intervention resulted in improvements in the patient’s exercise capacity and energy levels and prevented the development of disastrous complications such as aortic dissection and cardiac failure.

Estimating the pretest probability of the presence of co-arctation of the aorta is difficult when non-specific symptoms such as lack of energy and low exercise capacity are found on clinical assessment. Radio-femoral delay is the clinical sign classically associated with co-arctation of the aorta, but in the present case the trigger was rib notching found on chest radiography.

This case is important as co-arctation can be missed during postnatal screening or develop late. Clinicians and radiologists therefore need to be aware of rib notching.

Case presentation

A 31-year-old obese male presented to the emergency department with shortness of breath, productive cough, chest pain, nausea and vomiting over a 4-day period. The cough was productive of green sputum. The chest pain was sharp, worst posteriorly and brought on by coughing but not on deep inspiration. His breathlessness did not limit his daily functioning, although a subjective background of lifelong reduced exercise tolerance was noted. Significantly, three family contacts had symptoms of viral upper respiratory tract infection over 2 weeks prior to presentation. There was no recent travel history. There was a chronic history of reduced exercise tolerance, intermittent headaches, leg cramps on exertion and a childhood heart murmur, but none of these were considered significant enough to require further investigation. There was no history of hypertension or diabetes. Family history was positive for ischaemic heart disease in his mother. He was on no regular medications. He was employed as an IT worker with a background in nursing, was married with three young children, was a non-smoker and consumed two to three standard drinks of alcohol per week.

On examination his blood pressure was 150/90 mm Hg, pulse was 90 bpm with a regular rhythm, respiratory rate was 19/min and temperature was 36.9°C. Cardiovascular examination revealed impalpable femoral pulses, a grade 1/6 systolic murmur and soft, non-tender calves. Respiratory examination revealed chest wall tenderness on palpation manoeuvres and right lower zone crepitations on auscultation.

These clinical features were most in keeping with an acute upper respiratory tract infection.


Initial investigations included laboratory tests (cell counts and troponin), a 12-lead ECG and plain film chest radiography. Blood investigations were negative except for an elevated white cell count consistent with an acute infection. The 12-lead ECG revealed T-wave inversions in leads V4–V6, unchanged from a previous ECG.

The chest film revealed rib notching of the under surfaces of mid and upper-thoracic ribs), a cardiothoracic ratio at the upper limit of normal and bilateral peribronchial cuffing in the lower zones consistent with bronchitis. The presence of borderline cardiomegaly and rib notching raised the possibility of aortic co-arctation or chronic anaemia.

Cardiovascular MRI revealed an unrestricted bicuspid aortic valve and left aortic arch with normal branching pattern. There was enlargement of the right brachiocephalic trunk, left subclavian artery and internal mammary arteries with large intercostal vessels collateralising the distal aorta. Mild tubular hypoplasia of the aortic arch was also noted.

Differential diagnosis

The differential diagnosis of rib notching includes vascular and non-vascular causes. Vascular causes are due to enlarged collateral intercostal vessels to the distal aorta, which subject adjacent ribs to greater pressure than usual, resulting in bony erosion. Implicated vessels can be arterial as in aortic co-arctation and Takayasu’s arteritis, venous as in superior vena cava obstruction or arteriovenous as seen in arteriovenous fistulae. Non-vascular causes of rib notching include neurofibromatosis, intercostal neuromas and pseudo-rib notching where irregular cortical thickening may occur in the presence of tuberous sclerosis and hyperparathyroidism. Degrees of rib notching on chest radiography may also be of no clinical significance.

Treatment, outcome and follow-up

Preprocedural imaging consisted of cardiovascular MRI, cardiac CT angiogram and transthoracic echocardiogram. The patient underwent an uncomplicated endovascular aortic stent graft with left brachial artery and right femoral artery puncture with a 4×4 mm balloon angioplasty following an intravenous heparin bolus of 5000 IU. A Cheatham stent was deployed up to 10 mm at the level of the co-arctation and 16 mm distal to the co-arctation site. Six months after this procedure the patient reported improvement in exercise tolerance without chest pain, palpitations or leg cramps. His blood pressure was 135/80 mm Hg, slightly reduced compared with initial presentation (150/90 mm Hg) and femoral pulses were palpable bilaterally. CT angiography of the aorta revealed a patent stent without evidence of displacement or narrowing.

Twelve months after the initial procedure the patient underwent an uncomplicated percutaneous transluminal angioplasty of the thoracic stent up to 18 mm. Nine months after the angioplasty he reported further improvements in exercise capacity with no recurrence of chest pain or leg cramps. His blood pressure was 130/80 mm Hg. Echocardiography revealed normal left ventricular function with residual mild left ventricular hypertrophy. Follow-up management consisted of cardiovascular risk factor optimisation including caloric intake reduction to accompany increases in exercise as well as close monitoring of blood pressure. The patient was well at the time of writing, 32 months after the angioplasty.


Co-arctation of the aorta is the sixth most common congenital heart condition in Australia, with 92 cases recorded in 2003 at a rate of 3.6 per 10 000 live births.1 Diagnosis in adulthood is rare and has been associated with high mortality. Of those surviving past early childhood, historical data indicate 25% die before age 20, 50% by age 32, 75% by age 46 and 90% by 58 years.2 The most common cause of death was congestive heart failure, followed by aortic rupture, bacterial endocarditis and intracranial haemorrhage.2

Survival depends on the development of a collateral blood supply from the subclavian arteries (preco-arctation) to the aorta distal to the co-arctation via anastomoses with the intercostal arteries via three pathways: (1) the scapular pathway, including the transverse scapular and transverse cervical arteries originating from the thyrocervical trunk as well as the subscapular artery arising from the axillary artery; (2) the external thoracic pathway, including thoracic branches from the axillary artery; and (3) the internal mammary arteries3 (figure 4). Collateralisation is evidenced on chest x-ray as rib notching, which has been long associated with co-arctation of the aorta. The first three and last two ribs are typically spared due to their blood supply arising from branches unaffected by the co-arctation.

The sensitivity and specificity of rib notching for co-arctation of the aorta have not been defined. The first parameters concerning the utility of rib notching come from a case series of 43 patients with co-arctation of the aorta diagnosed at autopsy aged 2 years or greater from 1946.6 Some 75% of these 43 subjects had recognisable rib notching, giving a false negative rate of 25%. More recently, signs of a collateral circulation (rib notching and/or a visible internal thoracic artery) were seen in 26/38 patients with co-arctation of the aorta (68%, indicating a false negative rate of 32%)7 in one study, rib notching was seen in 39/61 patients (64%, false negative rate of 36%) in another8 and there is also case report evidence of co-arctation of the aorta without rib notching.9 These reports of false negative results of rib notching demonstrate limits to its sensitivity, but there are also reports that rib notching has limited specificity for co-arctation of the aorta despite a lack of numerical data. Rib notching has been visualised in the presence of other cardiovascular pathologies,3 non-vascular pathology4 and in up to 19% of healthy individuals10 (so-called pseudo rib notching).

There are also no reports on the sensitivity and/or specificity of radio-femoral delay, the classic examination sign associated with co-arctation of the aorta. Assessment for radio-femoral delay requires patients to uncover their groin area which may be a disincentive for clinicians in busy settings; additionally, locating femoral pulses can be difficult particularly in obese patients.11

An anecdotally reported alternative to radio-femoral delay involves comparing upper and lower limb systolic blood pressure,11 seeking a differential of at least 20 mm Hg.9 12,,16 Sensitivity and specificity for co-arctation of the aorta have not been calculated for this technique either, and its specificity is likely to be limited by the rarity of adult co-arctation of the aorta, especially with the comparatively high prevalence of peripheral arterial disease which can alter the ankle–brachial pressure index.17

Other signs which may aid the detection of co-arctation of the aorta include comparison of capillary refill times and temperature between the upper and lower limb extremities.18

Despite the uncertain relative utility of these techniques, it is important to be aware that each can be associated with co-arctation of the aorta and may warrant focused assessment and further investigation.

Learning points

  • ▶ As co-arctation of the aorta can be missed during or develop after screening, clinicians and radiologists need to be aware of rib notching.
  • ▶ Co-arctation of the aorta may present without hypertension and with non-specific symptoms of headache, low exercise capacity and intermittent leg cramps, which may not be considered significant enough for further investigation.
  • ▶ Rib notching may be seen in co-arctation of the aorta due to enlarged collateral intercostal arteries and while not specific, mandates the consideration of co-arctation.
  • ▶ Measurement of differences in lower limb and brachial arterial pressure is a reasonable and simple alternative to femoral pulse palpation but may be confounded by peripheral arterial disease.
  • ▶ Capillary refill and temperature differences between the upper and lower limb extremities may also indicate co-arctation of the aorta.


Dr Jenny Ho (Central City Medical Centre, Perth, Western Australia) is thanked for her support.


  • Competing interests None.
  • Patient consent Obtained.


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Source: BMJ