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

In our fifth installment, we end our discussion of cholesterol outlining some of the remaining evidence gaps. Areas discussed are primary prevention for women, the use of other cholesterol reducing medicines, and the need for follow-up cholesterol testing for patients on statins. We avoid filling the evidence gaps with theory-based assumptions and close by discussing the endless fun in tests, doctors’ visits and taking medicines.

Show Notes

1) Absolute benefit of statins over approx 5 years

* just in males and NO difference in overall serious adverse events

2) Meta-analysis data for mortality benefit with Statins in primary prevention

• TI meta-analysis on statins in women for primary prevention.
• “For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may reduce CHD events, but current evidence is insufficient to determine this conclusively.” JAMA 2004;291:2243-52

3) Ezetrol data

• N Engl J Med 2008 358:1431-43
• N Engl J Med 2008;358:1819-28

4) Fibrate data

• Helsinki Heart StudyNEJM 1987;317:1237-45
• FIELD study – fenofibrate for type 2 diabetics – no reduction in coronary eventsLancet 2005;366:1849-61
• Statistical increases in mortality from causes other than cardiovascular disease- approximately 0.75% increase in non-cardiovascular mortality. Arch Intern Med 2005;165:725-30 Am Heart J 2007;154:943-53
• Lipid Research Clinics TrialJAMA 1984;251:351-64

5) Torcetrapib

• BMJ  2007;334:326

6) Treating to Targets

• Optimal targets “because all of the trials compared fixed-dose regimens of more intensive statin therapy with less intensive statin therapy and because none provided a breakdown of event rates by the level of LDL cholesterol reduction achieved, the available data cannot be used to define optimal target LDL cholesterol levels.”
• No long-term data for adding other cholesterol meds to statins in order to hit targets “It is not enough that short-term trials with LDL cholesterol outcomes have demonstrated that other lipid-lowering agents can further lower LDL cholesterol when given along with statins. Large trials are needed to establish the clinical safety and effectiveness of combination therapy.”
• High vs low dose statins in primary prevention. “the current literature provides limited insight into whether more intensive statin therapy should be used in patients without coronary artery disease but with multiple atherosclerotic risk factors” CMAJ 2008;178(5):576-84

In our fourth installment, we apply the absolute benefit for statin therapy to our patient. We discuss the absolute benefits in context of the individual risk and acknowledge that when translating pooled literature numbers to individual patients an element of mysterious uncertainty always remains (except for James who knows but won’t tell and Mike who doesn’t know but tells us he does).

Show Notes

Definitions

CVD is cardiovascular disease and typically refers to the combination of CHD (coronary heart disease – fatal and non-fatal MIs and sometimes angina) PLUS cerebrovascular disease (fatal and non-fatal strokes – and sometimes TIAs) PLUS (sometimes) other conditions (heart failure, peripheral vascular disease)

Calculating benefit

1. Change the factor and recalculate the chance of CVD
2. Use the relative benefits seen in clinical trials (typically 5 years in duration) and apply them to the chance calculated for your patient
3. Avoid the use of CDV calculators and just use the absolute benefits seen in clinical trials

A synopsis of the relative benefit of drugs

• Statins ? 30%? in CHD (0%? in women)? 5 years
• BP ? 40 %? in strokes and ? 20%? in CHD ? 5 years
• Metformin ? 35%? in CHD and stroke ? 8-10 years

A synopsis of the absolute benefit of drugs

Statins over 5 years in a post MI patient Coronary events ?4% (15% to 11%) Death ?2% (12% to 10%) Strokes ?1% (5% to 4%) Treating a Blood Pressure of 160 /100 mmHg for 5 years CVD ? 1% (4% to 3%)

Absolute benefit of statins over approx 5 years

* just in males and NO difference in overall serious adverse events