In episode 15 a guest assists us in addressing the evidence suggesting anti-depressants are not as effective as believed. We review some biases in the anti-depressant research including publication bias (how good studies are published more than bad studies). We discuss how the benefits of anti-depressants over placebo increase as the severity of depression worsens. James prompts us to explain the effectiveness of the medications; although we dodge, some vague commitments do manage to escape.

Show Notes

1) Selective publication of selective serotonin reuptake inhibitors data

BMJ 2003;326:1171-73

2) Another select report on the selective publication of selective serotonin reuptake inhibitors

NEJM 2008; 358: 252

3) Antidepressants have a clinically important effect above placebo only in patients with severe depression

PLOS 2008:5(2):0260-8

4) Fluoxetine – evidence for benefit in children – others maybe not?

Lancet 2004;363:1341-5

5) In children, with antidepressants, the magnitude of benefit is unlikely sufficient to justify the harms

http://www.bmj.com/cgi/content/full/328/7444/879

In episode 14 we attempt to answer some of the mail received from listeners. We talk about using the evidence to promote shared decision-making. We review calculating risk, the limitations of risk calculators and presenting the data in the positive (chance of not having an event). We address heart disease as the leading cause of mortality (despite advancement in treatment) and emerging discussions of statin use in children (age ?8). We unwrap these enigmas to create more confusion.

Show Notes

1) Some references showing high cholesterol in patients over age 75-80 is not necessarily associated with increased mortality or sometimes not even increased cardiovascular disease.

Ann Epidemiol 2004;14:705–21

JAMA 1994;272:1335-40

Ann Int Med 1997;126:753-60

J Am Geriatr Soc 2004;52:1639-47

Arch Int Med 2003;163:1549-54

J Am Geriatr Soc 2005;53:2159-64

J Am Geriatr Soc 2005;53:219-26

2) Treatment of hypertension in patients 80 years of age or older reduces the chance of a cardiovascular event by 3% over 2 years

NEJM 2008;358:1887-98

In our 13th episode, we discuss smoking cessation. We present the impressive benefits in hard outcomes when people stop smoking. We then go through the list of interventions, from brief advice to the pharmaceutical options of nicotine replacement, two anti-depressants (Buproprion or Nortiriptyline) and the newest agent, Varenicline. Dosing, cessation rates and adverse events are reviewed (for medications, not cigarettes: that dose is zero).

Show Notes

1) Intensive smoking cessation intervention reduces mortality in high-risk smokers with cardiovascular disease

Chest 2007; 131: 446–52.

2) Listening empathetically and asking if they are ready to quit smoking

Silagy C, Ketteridge S. The effectiveness of physician advice to aid smoking cessation. Cochrane Database of Systematic Reviews 1998. Issue 2

3) Bupropion at a dose of 150 mg daily works as well as 300 mg daily

New Engl J Med 1997; 337:1195-202

4) Nortriptyline and bupropion for smoking cessation

Antidepressants for smoking cessation. Cochrane Database of Systematic Reviews 2007, Issue 1

5) Varenicline for smoking cessation

Nicotine receptor partial agonists for smoking cessation. Cochrane Database of Systematic Reviews 2008. Issue 3

In our 12th episode, we divide and conquer the remaining points around hypertension. In section A, we talk about monitoring blood pressure: frequency, reliability and home monitoring are all discussed. In section B, we talk about the potential side-effects of different hypertension therapies and the need to monitor for biochemical-metabolic effects. In the end, Mike is hyper and James is tense but both need therapy.

Show Notes

1) Effect of home blood pressure monitoring on blood pressure

BMJ 2004;329:145

2) Hypokalemia and metabolic effects of thiazides are dose related

BMJ 1990;300:975

3) Cardioselective beta-blockers in mild-moderate asthma and COPD Cardioselective beta-blockers in asthma

Ann Intern Med. 2002;137:715-725

Cardioselective beta-blockers in COPD

Cochrane library

Other resources

• Beta-Blockers in Asthma (Ann-Intern-Med, 2003)
• Beta-Blockers in COPD (cochrane, 2005)
• Meta-analysis of home BP monitoring (BMJ, 2004)

In our 11th episode, we discuss the laundry list of the remaining hypertensive medications and their evidence. The issue of blood pressure as a surrogate marker is discussed and we encourage clinicians to focus on hypertensive agents that effect patient oriented outcomes. While the evidence is reasonable for Ca+ Blocker, we put Beta-blockers low down (and Atenolol off) the list with Alpha-blockers and a few others.We have few laughs along the way, primarily at our lack of humor.

Show Notes

1) Atenolol no better than placebo and other drugs are better than atenolol in reducing cardiovascular outcomes in patents with high blood pressure

Lancet 2004;364:1684–9

2) Beta-blockers do appear to increase the chance of developing diabetes

Am J Cardiol 2007;100:1254–62

3) A debate on using or not using betablockers for high blood pressure

Can Fam Physician 2007;53:614-7

4) ALLHAT – the problem with alpha-blockers

JAMA 2000;283:1967-75

5) Data for felodipine and cardiovascular events in patients with high blood pressure

Lancet 1998;351:1755-62

6) Use of low-dose spironolactone in “resistant” hypertension

Amer J Hyper 2003;16:925–30

7) Effect of spironolactone on albuminuria

Diabetes Care 2005;28:2106–12

In our tenth episode, we discuss our second choice of hyperåtensive medication agent, the ACE inhibitor. We review dosing and renal protection (briefly) before agreeing our choice is based mostly on once a day adminstration and costs. We look at substituting with ARBs but not combining with ARBs (with possible exception of co-morbid CHF). Throughout the podcast, James disagrees with Mike on a variety of issues, more on principle than fact.

Show Notes

1) A meta-analysis of ACE inhibitors/ARBs versus other antihypertensive drugs on renal outcomes – in diabetics, no difference in end-stage renal disease or doubling of creatinine – albuminuria was reduced but remember this is a surrogate endpoint

Lancet 2005;366:2026-33

2) Telmisartan produced the same outcome as ramipril in diabetics – the combination did not add benefit but increased adverse events

N Engl J Med 2008;358:1547-59

3) Combining ACEs and ARBs in heart failure did produce a benefit

Lancet. 2003;362:767-71

In our ninth episode, we interrupt our regularly scheduled podcast to talk about the recently released ACCORD and ADVANCE trials which focus on intensive glucose control (reduction) in diabetes. We discuss the patient-oriented outcomes and harms, ranging from mortality to hypoglycemia, as well as the potential benefits such as preventing microalbuminuria. Evidence regarding patient blood sugar monitoring is reviewed while reminding listeners how much fun monitoring is for our patients.

Show Notes

1) A synopsis of what was reported in the ACCORD and ADVANCE studies.

Download PDF

N Engl J Med 2008 358:2545-2559

N Engl J Med 2008 358:2560-2572

2) Studies of monitoring blood sugar in type 2 diabetics showing no benefit and increased depression scores

BMJ. 2007 Jul 21;335(7611):105-6

BMJ. 2008 May 24;336(7654):1174-7

In our eighth installment, we discuss the initiation of hypertensive drug therapy. In recommending thiazide diuretics, we outline the evidence (e.g. ALLHAT trial) showing equivalence and the significantly lower yearly cost. We debate (politely this time) dosing and attempt to dispel the smokescreen of thiazide metabolic issues (e.g. blood glucose). The usual banter ensues around the challenges of monitoring therapeutic effect and the pseudo-logic of initiating combination drugs.

Show Notes

1) ALLHAT – no difference in CVD outcomes between thiazides, ACEI or CCBs in hypertensive patients treated for 4.9 years

2) Additional benefits of ACEIs/ARBs on renal outcomes in diabetic patients is unproven

Lancet 2005;366:2026-33

3) No evidence of superiority of CCBs or ACEs over thiazides for hypertenison in type 2 diabetics

Arch Intern Med 2005;165:1401-9

In our seventh installment, we discuss the options for blood pressure reduction before adding medications. We first talk about medicines, drug use and dietary factors that may increase blood pressure. We review the approach and potential benefits of varying lifestyle interventions like Exercise (e.g. pedometers), Diet (e.g. DASH) and Salt Reduction. The ever elusive balance between nagging and encouragement is debated (James and Mike pick sides).

Show Notes

1) Using a Pedometer

• Ask the patient to wear the pedometer for one week
• Have them calculate their “steps/day”
• Next add 1000 steps to the day average and that will be their daily goal for each day next week.
• They repeat this every week.
• Once at 10,000 steps/day. They can stay stable (and come to see you to brag about their success)

NOTE: This is only one way. There are many and you should feel free to use any safe approach to help you patients increase their activity.

2) Approximately 35% of patients who reduced their salt intake either

had no change in blood pressure (20%)

or an increase in blood pressure (15%)

Hypertension 2003;42:459-67

In our sixth installment, we begin to discuss hypertension. We review the principles of making the diagnosis of hypertension and confounders in the office. Although the identification of an elevated blood pressure for a certain patient may be new, the hypertension itself is likely not and rarely an emergency. The risks of hypertension are put in context of global cardiovascular risk while we wax poetically around evolving hypertension guidelines.

Show Notes

1) Our 45 y/o 10-year risk

2) Treating a Blood Pressure of 160 /100 mmHg for 5 years –

CVD ? 1% (4% to 3%)

• TI Letter # 62.
• Episode 2: Evidence does not equal decision-making

3) Diagnosis of high blood pressure

• CMAJ 2005,173: 480-83