Practice changing recommendations for you - Infective Endocarditis guidelines by AHA 2007

For years we all have religiously followed the pre procedure(most commonly dental) antibiotic prophylaxis as per guidelines published in 1997. Every prescription with Mitral valve prolapse or rheumatic valvular heart disease, so common in India and many other diseases at risk for Infective Endocarditis(IE) had instruction on Antibiotic prophylaxis.
2007 guidelines by same AHA have drastically cut down on the indications for IE, also eliminating the requirement for GI/GU procedures.
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Patients for whom dental prophylaxis is recommended. Only those at highest risk, ie, those with:

• A prosthetic cardiac valve
• A history of infective endocarditis
• Certain forms of congenital heart disease
• Unrepaired cyanotic congenital heart disease, including palliative shunts and conduits
• Completely repaired congenital heart defect with prosthetic material or device during the first 6 months after the procedure
• Repaired congenital heart disease with residual defects at the site or adjacent to the site of prosthetic patch or prosthetic device
• Valvulopathy after cardiac transplantation

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Links to the commentary and original guideline

Commentary in CCJM

PDF - Official Guideline from Circulation

Hit that "Pause" button in Type 2 Diabetes

Ever wondered if one could actually do away with medicines in Type 2 Diabetes or at least some way to "pause" the disease, the following study in The Lancet this week is promising.
UKPDS showed that Type 2 diabetics had 50% loss of Beta cell function at diagnosis and kept deteriorating over time. Researchers were in active search for therapeutic interventions which can prolong beta cell life. Some drugs which have shown benefit in this aspect although in animal studies are the Incretins. Thiazolidenediones are also known to preserve or improve beta cell function. Some studies have shown short term intensive glycemic control can induce remission of type 2 Diabetes for some time.

The following is a study conducted in China in Type 2 Diabetics which was designed to assess the efficacy of short term intensive therapy(Insulin or oral agents) to induce remission of Type 2 Diabetes.

• 436 patients - newly diagnosed Type 2 Diabetics
• FPG level 126-300 mg/dl
• Excluded were those with acute or severe diabetic complications, intercurrent illness, positive GAD antibody
• 3 arms - Multiple dose Insulin(MDI) arm, Continuous subcutaneous insulin(CSII) arm, Oral agents arm( either Gliclazide, Metformin or both)
• Doses titrated to achieve FPG less than 110 and Post meal less than 140
• After achieving above targets Rx was continued for 2 weeks
• After interventions were stopped, patients were instructed to continue diet and physical exercise only and were followed-up with glycaemic monitoring monthly during the initial 3 months and at 3-month intervals thereafter.
• Hyperglycaemia relapse was defined as either fasting plasma glucose of more than 7·0 mmol/L or 2-h postprandial plasma glucose of more than 10·0 mmol/L, which was confirmed 1 week later.
• Remission group - those who maintained glycemic control for 12 months without medication.
• 45% of patients who received insulin treatment (CSII or MDI) and 25% of patients treated with oral hypoglycaemic agents achieved long-lasting remission.

In patients newly diagnosed with type 2 diabetes, any kind of early intensive glycaemic control—either induced by insulin or oral hypoglycaemic agents—could rescue β-cell function and induce longterm glycaemic remission in almost half of patients, most likely through eliminating the effects of acute glucotoxicity and related pathogenesis factors. - Weng et al

Original Article in The Lancet here

"Look Out" - New section on promising drugs in pipeline

This new section is on being uptodate with any new drugs which are in trials and hold a lot of promise.

I shall start with the drug "Pirfenidone". We all have diagnosed patients with Idiopathic Pulmonary Fibrosis. There is not much we can do to treat these patients as of now and its frustrating both for the patient as well the treating physician. No drugs have been show to improve lung function or improve survival eg: Cyclophosphamide, Interferon Gamma etc. Some physicians use Azathioprine/Cyclophosphamide with or without corticosteroids in patients with progressive course.

• Pirfenidone is a novel antifibrotic compound that may inhibit collagen synthesis, down regulate production of multiple cytokines and block fibroblast proliferation and stimulation in response to cytokines.
• A small phase 3 study was presented at ATS 2008 which showed a 70ml mean change in vital capacity and also a significant progression free survival between the drug and placebo.
• Adverse effects included phototoxicity.
• Larger studies are planned and only then shall the verdict be out.

Watch out for updates in this blog.

Remembering landmark trials of the past - UKPDS 33/35/57(1998)

The trial was formulated in the background of the DCCT(1993) done in Type 1 diabetics which showed Intensive treatment results in improved outcomes more so for the microvascular than macrovascular injury. So it was a must that same hypothesis be tested in the Type 2 diabetics, the majority group. So the United Kindgom Prospective Diabetes Study was started to test the hypothesis.

Summary is as follows:

• Patients with newly diagnosed type 2 diabetes and within the normal weight range were randomly assigned to conventional treatment with diet alone (30%), intensive treatment with insulin (30%) or intensive treatment with a sulphonylurea (chlorpropamide or glipizide, 40%).
• In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 270 mg/dL.
• The Intensive arm had a target FPG of less than 108 mg/dL
• Intensive pharmacologic therapy achieved a significantly lower HbA1c (HbA1c = 7%) than the conventional approach (HbA1c=7.9%) over a follow-up period of 10 years.

• Adverse effects: Increased risk of hypoglycemia and significant increase in weight in Intensive arm (Insulin>SU>Conventional) was observed.

The achievement of tight blood glucose control in type 2 Diabetes is feasible and should become the standard of care. -UKPDS

UKPDS Original article in The Lancet

Remembering landmark trials of the past - HOPE(2000)

Heart Outcomes Prevention Evaluation(HOPE) published in 2000 was one of the landmark trials in evaluating the efficacy of Ramipril in preventing death in those with known cardiovascular disease and high risk group with diabetes.

Brief summary is as follows:

• A 2 x 2 factorial design which also evaluated the effect of Vitamin E apart from Ramipril
• 9297 patients were included.
• Patients atleast 55 years old were eligible for the study if they had a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes plus at least one other cardiovascular risk factor (hypertension, elevated total cholesterol levels, low high-density lipoprotein cholesterol levels, cigarette smoking, or documented microalbuminuria).
• All patients received 2.5mg ramipril in the run in phase prior to randomisation to look for no compliance and adverse effects.
• Then within a month the ramipril group received 10mg (after 1 month titration from 2.5 mg then 5mg)
• Primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes.

• Secondary outcomes like new onset diabetes, heart failure, revascularisation and complications of diabetes(Nephropathy and retinopathy) also showed significant improvement.


• The benefits with Ramipril were seen in patients who were already on Aspirin, Beta blockers and Statins.


• The reduction in BP was just 3/2 mm Hg and the benefit derived was far beyond this anti hypertensive effect.


• Vitamin E was no more effective than placebo.

Ramipril is an ACEI up our sleeves.

HOPE - Original article - NEJM link here

Remembering landmark trials of the past - DCCT(1993)

Type 1 Diabetes or Insulin dependent Diabetes accounts for a small proportion of total diabetic population, but has younger age of onset. The younger the age the more are they affected by glycemic control. The Diabetes Control and Complications trial was done in Type 1 Diabetics to assess the effect of glycemic control not only on preventing complications but also on the progression of complications.

Key points:

• 1,441 subjects with type 1 diabetes were enrolled
• 726 subjects within 5 yrs of DM and no complications(primary cohort) - randomised to Intensive and conventional arms(1:1)
• 715 subjects within 15 yrs and had mild retinopathy and microalbuminuria(Secondary cohort) - randomised to Intensive and conventional arms(1:1)
• Intensive Rx arm used CSII(insulin pump) or by MDI injections (three or more injections per day); self monitoring of glucose 3-4 times daily, meticulous attention to diet; and monthly visits to the treating clinic.
• Conventional Rx arm used no more than two daily insulin injections; urine glucose monitoring or SMBG no more than twice-daily; periodic diet review; and clinic visits every 2-3 months.
• Intensive arm had median HbA1C throughout the study of 7.2% vs. 9.1% in the Conventional arm
• Macrovascular events, either cardiac or peripheral vascular, were not significantly reduced. There was a 41% nonsignificant risk reduction in Intensive arm when episodes of cardiac and peripheral vascular events were combined.
  

• The most important adverse event associated with Intensive Rx was a three-fold increase in 'severe' hypoglycaemia (episodes requiring assistance of another person to recover), including a three-fold increased risk of coma or seizures.

Intensive therapy, with the goal of achieving glucose levels as close to the nondiabetic range as possible, should be employed in most patients with type 1 diabetes. - DCCT

DCCT - Original Article In NEJM

Stroke - comprehensive review in The Lancet this week

Stroke is 2 nd leading cause of mortality as per world statistics and also morbidity/disability. The Stroke review in The Lancet this week is one of the most comprehensive articles I have read to date. Recent changes in epidemiology, Classification of Stroke, Medical, Interventional and Surgical management of stroke. Primary and secondary prevention also is highlighted - the aspects all clinicians deal with daily.

VIEW ARTICLE HERE

Must read article for all! Includes all evidence to date!

Diamonds are forever, "Evidence" is forever!

The Medicine we practise today is a fruit of all that research that has been done and is still being done till date.

It is a must that we know how things shaped up.

• Why do we want to control Diabetes so intensively?
• Why Beta blockers initially thought to be harmful in heart failure are an essential on the prescription today?
• and many more questions for which we got the answers.

I will also try to explore these trials in the coming updates. Its time we refresh HOPE, DCCT and UKPDS s of the world!

There is Evidence behind most of what we do in practice, lets know it.