In episode 67, we address ischemic stroke of arterial origin and go over some core therapies (ASA, dipyridamole, clopidogrel and warfarin).  We also discuss complications of anti-thrombotics and the options for patients with a GI bleed on ASA.  Although Peter attempts to guide us through the maze of evidence, all three of us get lost and have trouble finding our way back. Mike rightly corrects James about one of his comments and James responds in a purely professional manner.

Show Notes

1) ASA post-stroke – low dose

ATTC 2009

Lancet 2009;373:1849–60

2) Clopidogrel versus ASA

CAPRIE

Lancet 1996;348:1329–39

3) ASA and clopidogrel versus clopidogrel

CHARISMA

NEJM 2006;354:1706-17

MATCH

Lancet 2004;364:331–37

4) ASA versus warfarin post-stroke

WARSS

NEJM 2001;345:1444-51

5) Dipyridamole plus ASA

ESPS-2

Thromb Res 1998;92:S1-S6

ESPRIT

Lancet 2006;367:1665-75

peterloewen.com

PRoFESS

NEJM 2008;359:1238-51

7) GI bleeding and ASA

PPI added to ASA versus clopidogrel alone

NEJM 2005; 352:238-44

NEJM 2001;344:967-73

H. pylori eradication plus proton pump inhibitor versus H. pylori eradication alone

NEJM 2002;346:2033-8

Clopidogrel plus a PPI – interaction or not

CMAJ 2009;180:713-8

In episode 66, we embark on a journey of epic proportions; at least relative to our understanding.  With the help of Peter Loewen, we outline the anti-platelet options in secondary prevention of heart disease.  We discuss at length the use ASA and clopidogrel but also touch on additional agents like warfarin, dipyridamole and others.  Where the evidence is clear, we create opacity and where it is gray, we go dark. Both Mike and Peter end up in a quagmire and James offers them help by throwing them a string of one-liners and a bottle of low-dose ASA.

Show Notes

Secondary prevention with antiplatelets

1) ATTC Meta-analysis – aspirin in primary and secondary resistance

Lancet 2009;373:1849–60

2) CURE trial – clopidogrel added to aspirin

NEJM 2001;345:494-502

3) Anti-platelets in patients with a history of vascular disease or other predisposing condition – absolute benefit – 3.6% over 2 years (combined CVD events)

BMJ 2002;324:71-86

4) Low-dose aspirin – absolute benefit – around 3.3% combined CVD events and 1.5% mortality over 3 yrs

Am J Med 2008;121:43-9

5) CHARISMA – Clopidogrel and aspirin vs aspirin

N Engl J Med 2006; 354:1706-17

6) Half of the benefit of clopidogrel occurs in the first month of use Clopidogrel for the treatment of adult patients following acute coronary syndrome

Therapeutics Initiative Review

In episode 65, we start back at it with a discussion of using antiplatelets to decrease the chance of MIs and strokes. In this podcast, we cover the whole primary prevention aspect of these agents and we bring in our good friend and colleague Peter Loewen to help us with the numbers. Mike claims he, as a family doctor, is usually able to make a diagnosis of gender in his patients but refuses to do so in James’ case.

Show Notes

1) Primary Prevention with ASA (women and men)

JAMA 2006;295:306-13

ATTC 2009

Lancet 2009;373:1849–60

2) ASA in Type II diabetics (primary prevention)

POPADAD study

BMJ 2008;337:a1840

JPAD study

JAMA 2008;300:2134-41

PPP study

Diabetes Care 2003;26:3264-72

Canadian Diabetes Guideline (specifically, ASA)

Can J Diabet 2008;32:S102-06

3) Adding Clopidogrel to ASA in primary Prevention

CHARISMA Study (primary prevention sub-group)

NEJM 2006;354:1706-17

4) Peripheral vascular disease

Clopidogrel

CAPRIE

Lancet 1996;348:1329-39

5) Peter Loewen

peterloewen.com

Pharmacotherapy for ischemic stroke prevention

In episode 64, we finish off the listener questions and comments and clarify the murkiness, or murkify the clariness, around a number of cardiovascular issues. By the end of the podcast, both Mike and James are heavier because they eat up all the “sweet” comments made by their listeners.

Show Notes

1) BMJ hypertension meta-analysis

BMJ 2009;338:b1665

2) Atenolol lowers blood pressure but no effect on cardiovascular outcomes

Lancet 2004;364:1684–9

3) First-line drugs for hypertension

Cochrane Review

4) UKPDS spin

BMJ 2000;320:1720-3

5) Effect of intensive control of glucose on cardiovascular outcomes – meta-analysis

Lancet 2009;373:1765–72

6) Felodipine and cardiovascular outcomes

J Hypertens 2005;23:2157-72

In episode 63, we again let the listeners take control as we try to deal with the excellent questions and comments that come our way. We get into a heavy discussion around issues of weight and weight loss. Mike asks James a number of questions that make him squirm and James thanks him because fidgeting is a great way to burn calories.

Show Notes

1) InfoPOEMS

Essential Evidence Plus

2) Association between authors’ published positions and their financial relationships with manufacturers

NEJM 1998; 338: 101-6

3) J or U shape curve for BMI and mortality

Lancet 2009;373:1083-96

4) Orlistat  – the setting effects the results Effect in primary care study

J Int Med 2000; 248: 245-54

Effect in tertiary care study

JAMA 1999;281:235-42

5) Comparison of weight loss diets

N Engl J Med 2009;360:859-873

6) Fidgeting burns calories

Science 2005;307:584-6

In episode 62, the eighth and final podcast in our tome on the treatment of type-2 diabetes, we talk about cholesterol and ASA. Statins have evidence of benefit, around 3-4% absolute risk reductions over 5 years, other drugs for cholesterol have little if any evidence of benefit, and there is evidence of no benefit from taking ASA. We come up with an overall synopsis; increase activity, eat good food, use metformin, then maybe sulfonylureas, thiazides/ACE inhibitors for BP, statins but don’t measure cholesterol, and no ASA. Both James and Mike collapse from exhaustion and leave the final word to Chris their producer.

Show Notes

1) Statin meta-analyses

Lancet 2008;371:117-25

Table of data

Another table of data

2) Fibric acid derivatives FIELD

Lancet 2005;366:1849-61

Fibrate meta-analysis

Arch Intern Med 2005;165:725-30

3) ASA – no benefit in diabetics

JAMA 2008;300:2134-41

BMJ 2008;337:a1840

Diabetes Care 2003;26:3264-72

In the 61st episode, the seventh podcast in our thesis on type-2 diabetes, we get off the topic of glucose and talk about STENO and blood pressure treatments. We decide the bottom line is control of blood pressure with low doses of thiazides and ACE inhibitors with no tolerance for side effects. Mike’s blood pressure goes up with some of James’ suggestions but high doses of reserpine, methyldopa and clonidine calm him down.

Show Notes

1) STENO

N Engl J Med 2008;358:580-91

2) Blood pressure trials UKPDS 38

BMJ 1998;317:703-13

HOT Trial

Lancet 1998;351:1755-62

Do ACEI/ARBs uniquely protect the kidney – No?

Lancet 2005;366:2026-33

ALLHAT

JAMA 2002;288:2981-97

Low doses of ACEI – most of the BP effect is from low doses

Cochrane Library

MICROHOPE

Lancet 2000;355:253-59

In episode 60, the sixth podcast in our saga on type-2 diabetes, we talk about what to do when metformin is not enough and get to the evidence surrounding other blood glucose lowering treatments. We fumble around in a pretty much evidence-free zone. James develops a bad case of hypoglycemia during the podcast because he hasn’t eaten since the start of the diabetes section of these podcasts; Mike comes to his aid by prescribing a low dose of a chocolate bar and eats the rest of it himself.

Show Notes

1) UKPDS (recent results)

NEJM 2008;359:1577-89

Table of results

2) Fluoxetine, orlistat, sibutramine for weight loss in type-2 diabetics

Arch Intern Med 2004;164:1395–404

3) Acarbose for impaired glucose tolerance

JAMA 2003;290:486-94

4) Glitazones meta-analyses

JAMA 2007;298:1180-8

JAMA 2007;298:1189-95

Table of results

5) Risks of an elevated A1c

Link to table

6) Long acting insulin analogues – no advantage

CMAJ 2009;180:385-97

In episode 59, the fifth podcast in our diatribe on type-2 diabetes, we finally get to the evidence surrounding specific treatments. The importance of lifestyle is discussed and then the rest of the time is spent talking about the who, what, why, where, and when’s of metformin. James asks lots of rhetorical questions and Mike tries to answer them in a grandiloquent way.

Show Notes

1) UKPDS (original trial)

Lancet 1998;352:854-65

2) UKPDS (recent results)

NEJM 2008;359:1577-89

3) Metformin’s contraindications should be contraindicated

CMAJ 2005;173:502-4

In episode 58, the fourth in our installment of podcasts on diabetes, we briefly talk about the evidence surrounding intensive glucose lowering (ACCORD, ADVANCE, VADT and UKPDS trials) – podcasts #9 and #38 did this in more detail. At the end of the podcast, Mike identifies many of James’ flaws, but does it with compassion and kindness; at least he says he does.

Show Notes

1) Does tight glycemic control burden patients with complex treatment programs, hypoglycemia, weight gain, and costs and offers uncertain benefits in return?

Ann Int Med 2009;150:803-8

2) ACCORD and ADVANCE studies

Click here for a synopsis of the results

N Engl J Med 2008 358:2545-2559

N Engl J Med 2008 358:2560-2572

Also listen to Episode 9: News Flash: Aggressive Blood Sugar Control Not All Sweet

3) VADT trial N Engl J Med 2009;360:129-39

Also listen to Episode 38: New trials you need to know about

4) Glucose lowering meta-analysis – do the results support the conclusions?

Lancet 2009; 373:1765-72

5) UKPDS data

BMJ 2000;320:1720-3

6)UKPDS – 10 year update (recent results)

NEJM 2008;359:1577-89