Clinical Briefs in Primary Care

Continuing Warfarin for Pacemaker/ICD Implantation is Safer Than Bridging

Source: Birnie DH, et al. N Engl J Med 2013;368:2084-2093.

The decision process to determine the optimal scheduling of antithrombotic therapy in the perioperative period is complex. The most recent AT9 CHEST guidelines suggest discontinuation of warfarin 5 days prior to pacemaker/implantable cardioverter-defibrillator (PCM-ICD) implantation, complemented with heparin bridging. This method is somewhat unwieldy, expensive, and has not been confirmed by a large, randomized trial as optimizing risk reduction. During transition from warfarin to heparin, an interval of increased risk for thromboembolism occurs in some, and the use of heparin has also been shown to frequently be associated with device-pocket hematoma.

In the Bridge or Continue Coumadin for Device Surgery Randomized Controlled trial, 681 PCM-ICD patients were randomized to continued warfarin or heparin bridging. Patient selection criteria also included high baseline annual thromboembolism risk (≥ 5%). The primary outcome of the trial was incidence of significant device-pocket hematoma (DPH), which can result in prolongation of hospitalization, need to stop anticoagulation, or additional surgery.

There was a dramatic difference in risk for the DPH primary endpoint between subjects continued on warfarin uninterrupted (3.5%) and subjects randomized to heparin bridging (16%). Risk reduction through continuation of warfarin was not associated with any increased incidence of major surgical adversities compared with bridging. Continuation of warfarin, uninterrupted, was associated with more than 80% reduction in risk of DPH compared to bridging, while not compromising other measures of safety.

Bariatric Surgery Impact on Cholesterol Metabolism

Source: Benetti A, et al. Diabetes Care 2013;36:1443-1447.

Bariatric surgery techniques are often described as restrictive (e.g., gastric banding) or diversionary (e.g., biliointestinal bypass). While diversionary surgery (DIV) is associated with greater weight loss and more rapid metabolic changes than restrictive surgery (RES), the greater simplicity and reversibility of the latter are pertinent in selecting which intervention is preferred.

Although the impact of bariatric surgery on diabetes has been much publicized, the impact of bariatric surgery on cholesterol is less well recognized. To date, most of the favorable impact on cholesterol has been attributed to weight loss. Over the long term, DIV is associated with greater weight loss than RES. However, since DIV and RES are associated with similar overall weight loss during the first postoperative 6 months, one could compare cholesterol metabolism of the two types of surgery independent of weight loss.

Benetti et al compared cholesterol metabolism in DIV with RES (n = 20). They found that with DIV, reduced cholesterol absorption produced a decrease in LDL and non-HDL, associated with enhanced catabolic LDL receptor activity in the liver.

Because metabolic changes in both groups in reference to glucose, insulin, insulin resistance, and weight loss were similar, the authors suggest that these favorable cholesterol metabolic changes are induced specifically with DIV, and because weight loss over the specified interval was essentially equivalent, the changes in lipids are not fully explained by weight loss.

The Do-it-Yourself Diabetes Diagnosis Kit

Source: Bethel MA, et al. Diabetes Care 2013;36:1483-1488.

In the last decade, the threshold for diagnosis of diabetes has expanded to lower levels of fasting glucose, inclusion of reference laboratory A1c, and refinement of the definitions of prediabetes. Use of the oral glucose tolerance test (OGTT) appears to be less and less necessary, considering the relative convenience of other diagnostic tests. Could a self-administered OGTT change the balance and be a positive addition to the diagnostic portfolio?

Bethel et al report on a self-administered OGTT home use kit (SmartGRA) used by 30 diabetic and non-diabetic subjects. The kit includes instructions to guide the user through the process of timed capillary glucose measurement as well as a wireless data recorder for glucose levels, the results of which are not visible to the user (glucose measurements are wirelessly transmitted to the clinic for evaluation).

Was self OGTT accurate? In a word, yes. Comparison of OGTT reports generated by SmartGRA vs office-based testing found comparable reproducibility of results. Although the results of home OGTT tended to overestimate glucose levels compared to the reference laboratory, this emerged as a problem with device calibration, which should be able to be remediated. Overall, subjects found the device easy to use.

As a proof-of-concept trial, these results lend credence to the idea that OGTT — generally conceded to be sufficiently unwieldy so that other diagnostic tests are preferred — might merit reconsideration if a well-calibrated, similarly patient-friendly device comes to market.

Low Creatinine Excretion Associated with Mortality in Type 2 Diabetes

Source: Sinkeler SJ, et al. Diabetes Care 2013;36:1489-1494.

Creatinine excretion (cer), as measured by the 24-hour urinary excretion of creatinine, has recently been noted to be associated with increased mortality, both in persons with underlying renal disease and the general population. CER reflects overall lean muscle mass, so that declines in CER may simply reflect deconditioning, loss of muscle mass, cachexia, malnutrition, etc., each of which may have a negative impact on mortality.

Sinkeler et al report on data accrued from two previously completed trials of angiotensin receptor blockers in diabetic nephropathy: Reduction of Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan trial and the Irbesartan Diabetic Nephropathy trial. Twenty-four hour urinary CER was measured at baseline for the majority (n = 2360) of participants. Since mortality data from both trials are available, the relationship between CER and mortality can be evaluated.

Across the population studied, each halving decrement of CER was associated with a doubling of mortality risk. Since the primary association of CER is with muscle mass, the authors pose the interesting question of whether efforts expended to improve muscle mass, such as enhanced exercise and nutrition, might favorably effect mortality in this population.

Diabetes and Cognitive Function

Source: Spauwen PJJ, et al. Diabetes Care 2013;36:1554-1561.

The relationship between vascular disease and type 2 diabetes is consistent: Risk for microvascular events (retinopathy, neuropathy, and nephropathy) and macrovascular events (stroke and MI) is increased compared to non-diabetics. Additionally, when diabetics suffer macrovascular events, the consequences are typically more severe than similar events in non-diabetics.

The etiology of cognitive impairment is often multifactorial, including vascular insufficiency. Diabetics have a higher prevalence of cognitive impairment than non-diabetics, but the rate of cognitive decline in diabetics has not been studied.

The Maastricht Aging Study is comprised of 10,396 adults residing in the province of Limburg, the Netherlands. A sample from this population (n = 1290) underwent extensive neuropsychological testing at baseline, 6 years, and 12 years. At baseline, approximately 5% of the population had type 2 diabetes, with an incidence of an additional 5% over subsequent 6-year intervals.

When compared with controls, diabetics had a significant rate of cognitive decline over 6 and 12 years. Even when adjusted for variables that are more commonly comorbid in diabetics (hypertension, dyslipidemia, obesity), the acceleration in cognitive decline was greater in diabetics. As might be intuitive, diabetics with baseline cognitive impairment progressed at a more rapid rate than those without. Whether any specific intervention among diabetics (e.g., better control of glucose, lipids, blood pressure) might ameliorate the exaggerated rate of cognitive decline remains to be determined.

Benefits of Screening for Lung Cancer with Low-Dose CT

Source: The National Lung Screening Trial Research Team. N Engl J Med 2013;368:1980-1991.

Lung cancer (lca) is responsible for more deaths than any other cancer worldwide. The burgeoning growth of smoking in developing countries suggests that this dismaying fact is unlikely to diminish in the foreseeable future. Clinical trials of screening for LCA through chest x-ray (CXR) did not show improved outcomes, likely because of its relatively poor discriminative ability in early disease.

The National Lung Screening Trial enrolled smokers and ex-smokers with at least a 30 pack-year history. Participants were randomized to an annual low-dose CT × 3 (n = 26,714) or standard chest x-ray (n = 26,035).

A positive radiographic finding on at least screening was seen in three times as many CT screenees as chest x-ray (27.3% vs 9.2%). LCA was diagnosed in 1.1% of the CT group vs 0.7% in the CXR group.

Screening for LCA was found to reduce LCA-related mortality by 20% and all-cause mortality by 7%.

Most of the abnormalities detected by low-dose CT screening were benign, so that the positive-predictive value for a positive CT was only 3.8% (i.e., about 4% of study subjects with any positive suspicious finding on CT turned out to have LCA). Reassuringly, repeatedly negative low-dose CT had a negative predictive value of 99.9% (i.e., essentially no one who had negative sequential CT screening was diagnosed with LCA during the screening and follow-up period).