Consider The Evidence: Med/Peds Journal Roundup

September 10, 2006

Din-o-mite: Intensive Lipid Lowering in CHD

Filed under: cardiovascular, CHD, lancet — medblog @ 8:33 pm

Lancet 9/9 – In the latest set of reccomendations from the NCEP ATP, the panel reccomended that patients with CHD or risk equivalent have a goal LDL of 100mg/dL, with an option of less than 70mg/dL in high-risk patients. Several prior studies have shown that further reductions in LDL may decrese mortality, but further study is needed.

In the most recent issue of the Lancet, Deedwania et al. publish results of the TNT study on the outcomes of this new goal of intensive lipid lowering. The design was a double blind RCT involving 10,000 patients with over a median of 5 years. To fit the inclusion criteria, subjects had to be aged 35-75 with history of MI, revascularization, or angina with objective evidence of atherosclerotic disease. Subjects were randomized to recieve either 10mg or 80mg of atorvastatin.

Mean LDL levels were 99mg/dL in the low dose, and 72.6mg/dL in the high dose group. The outcome was a statistically significant decrease in risk for major cardiovascular events in the high dose group. With an absolute risk reduction of 3.5% which is 29% relative. The levels obtained were convenient because they closely reflected the new LDL goals. It seems as if this study does show data to support those reccomendations. The question remains as to whether the results can be generalized to CHD risk equivalents such as diabetes, because the study only included clinically evident coronary disease. (more…)


August 23, 2006

Even more uses for ACE-I’s

Filed under: cardiovascular, hypertension, lancet — medblog @ 7:14 am

Lancet 8/19 – Updated guidelines for Abdominal Aortic Aneurysm screening were put out by USPTF last year reccommending ultrasound in men aged 65-75 who have ever smoked, especially due to the mortality and lack of medical treatment options for the disease. Clearly endovascular pathology related to atheroma and smoking are somehow involved. with AAA.
Enter ACE-inhibitors, which seem to be showing evidence of vasoprotective effects through some modulation of the renin-angiotensin system – also thought to be involved somehow with vascular pathology.

Hackam et al. publish a retrospective observational study in the current Lancet, investigating the use of ACE-I’s in patients with AAA. They analyzed records of 15,000 patients hospitalised with a primary diagnosis of abdominal aortic aneurysm in Canada. The researchers found that patients receiving ACE inhibitors before admission were significantly less likely to present with aortic rupture.(Adjusted Odds Ratio: 0.83) They conclude that the beneficial effect of such drugs is independent from their antihypertensive properties, because use of other antihypertensive agents was not associated with a lower risk of AAA. Clearly the study comes with all of the shortcomings of a retrospective study, and although we cannot conclude a causal effect, RCTs are warranted.

August 15, 2006

ACE-Is: ACE in the hole for atherosclerosis

Filed under: Cardiology, cardiovascular, lancet — medblog @ 11:12 pm

Lancet 8/12 – ACE inhibitors initially hit the big time due to two clearly beneficial effects: reduction of ventricular remodeling in heart failure, and renal protection in diabetes with hypertension. These studies also suggested ACE-inhibitors have some overall cardiovascular benefit independent of BP lowering and correction of heart failure. Could ACE inhibitors join statins as a class of drugs with multiple vascular benefits beyond the main mechnism it has traditionally known for??

Effects of ACE-Is were studied in the landmark trials HOPE, EUROPA and most recently PEACE. Dagenais et al.published an article looking at these three trials for statistical evidence of benefit in patients with atherosclerosis. And they found it: overall in the three trials, patients without heart failure on ACE therapy had significant risk reductions in cardivascular mortality, acute MI, and stroke. Each effect had an absolute risk reduction around 1%. Small, but significant.

Statins + ACE-inhibitors = crazy delicious.

May 31, 2006

Add Aggrenox? Here we go again. ESPRIT

Filed under: lancet, stroke — medblog @ 12:42 am

Lancet 5/20 – With the growing number of anti-thrombotic drugs, there seems to be a lack of consensus on exactly what anti-thrombotic regimen is to be used after major ischemic events such as stroke.

This weeks Lancet presents information from the ESPRIT trial – the latest study into the value of dipyridamole for treatment after CVA. The study was an RCT which assigned patients who experienced TIA / stroke within the previous 6 months to aspirin + dipyridamole vs aspirin alone.

In the end, the hazard ratio for major ischemic events was 0.81 in an intention to treat analysis. So the addition of dipyridamole to aspirin after an ischemic CVA lowered the risk of a  subsequent major ischemic event by about 20%. In addition the combination group had less (HR 0.67) bleeding complications. Unfortunately, about three times as many patients in the combo group dropped out, mostly due to headache. The effect was robust enough to be significant in an ITT analysis despite the high dropout rate.

Now if I could just get this whole Clodoprigel thing figured out….

April 3, 2006

Donzepil in severe dementia: Not too little too late

Filed under: alzheimer's disease, lancet — medblog @ 10:57 pm

Lancet 4/1 – Although Donzepil has been shown to slow the inevitable progression of Alzheimer's dementia (AD), its effects are often subtle, even in mild disease. In the severe stages, it may be difficult to ascertain any benefit, and the drug is often discontinued with the thinking that it is no longer effective.

Winblad et al. studied the efficacy of donzepil in a population with severe AD. They found a significant preseveration in multiple measures of disease and impairment severity including MMSE score. The effects were significant in an intent-to-treat analysis despite a nearly 12% greater level of discontinuation among the Donzepil group.

The study shows a clear benefit to starting donzepil despite advanced disease stage. However, the study did not specifically look at the effect of continuing therapy from the mild stage through the severe stage. The study patients had limited or no exposure to cholinergic inhibitors before the trial, and it remains unclear whether the effect would be similar in patients already on long term therapy.

March 14, 2006

Flight Risk: Air Travel and DVT

Filed under: lancet, VTE — medblog @ 5:43 pm

Lancet 3/11 – Shreijer et al present an interesting discovery about the increased risk of venous thrombosis during airplane travel. They wondered whether in addition to immobilization as a risk factor, passengers were also prone to hypercoagualibility during flight.

In the crossover controlled study, 71 subjects were tested during 8 hours in flight, 8 hours seated while watching movies, and during 8 hours of daily activities. Several markers of coagulation including Thrombin-Antithrombin complex (TAT), D-dimer, and prothrombin fragment 1 and 2 were measured before and after the the test conditions.

The researchers found that the levels of TAT, D-dimer, and the combination of the three factors were significantly increased after the flight in comparison to the other situations. They conclude that there are other mechanisms beyond immobilization to account for the 2 to 4 fold increased risk of DVT during flight. Whether this is related to pressure, oxygen content, or something else, will requre further research. (more…)

March 7, 2006

Attack of the clones: Community Aquired MRSA

Filed under: annals of internal medicine, infectious disease, lancet, MRSA — medblog @ 10:00 pm

Community Aquired MRSA and the USA 300 clone are making news in two journals this week… Get used to those stupid yellow gowns 😦
AnnalsIM 3/7 – A study by King et al. in The Annals of Internal Medicine documents the epidemiology of community aquired MRSA in a major hospital system in Atlanta, GA. The study included patients with community aquired skin and soft tissue infections due to Staph aureus. The results show that a majority (63%) of S. aureus isolates were methicillin resistant. 99% of the CA-MRSA samples that were further analyzed were the USA 300 clone.

A second paper, by Graham et al., analyzed the NHANES data on nasal swabs taken in a population sample. They found that, “The prevalence of colonization with S. aureus and with MRSA was 31.6% and 0.84%, respectively, in the noninstitutionalized U.S. population.”

Lancet 3/4 – An article in the Lancet by Diep et al. details the genome of the USA300 clone and the particular elements that lead to its epidemiology and virology. Frankly, much too dense for me to read more than the abstract – but I’m glad somebody else cares… (more…)

February 25, 2006

Crohn’s breakthrough: Have we had it wrong all along?

Filed under: crohns, IBD, immunity, lancet — medblog @ 2:43 pm

Lancet 2/25 – In what is being touted as a landmark study, Marks, et al. show evidence that Crohn’s disease is due to an immune deficiency rather than an autoimmune process. This controversial finding seems to contradict the evidence supporting the use of immunosuppressive therapy that has been the mainstay of treatment for years.

The study involved the biopsy of rectal mucosa from Crohn’s pts, UC pts, and healthy controls. Samples were taken from clinically unaffected tissue. Immune cell and cytokine markers were compared among the pre- and post- biopsy samples. The response was significantly lower in the Crohn’s group.

One of the most telling parts of the study involved (more…)

February 20, 2006

Facilitated PCI a bust yet again

Filed under: Cardiology, lancet, myocardial infarction, PCI — medblog @ 3:22 pm

Lancet 2/20 – There has been some buzz of late about facilitated percutaneous coronary intervention (PCI) – using fibrinolytics before going to the cath lab in order to increase the critical 2-3 hour window of opportunity for reperfusion. An article by the ASSENT4-PCI group in this weeks Lancet adds to the data that such a strategy is not beneficial. (more…)

February 6, 2006

Statins for sepsis???

Filed under: critical care, lancet, sepsis, statins, Uncategorized — medblog @ 11:21 pm

Lancet 2/4 – They slice, they dice, they even make julienne fries…Adding to the list of potential uses of statins is sepsis. In this weeks Lancet, Hackam et al., (as well as an accompanying editorial) investigate the evidence supporting a lower risk of sepsis in those patients on statin treatment. (more…)

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