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

In the third session, we discuss the advantages and disadvantages of three methods to present “benefit”: changes in risk calculators, using relative risk, or the absolute benefit. We review the challenges of absolute vs relative risk (or relative vs absolute truth) and discuss patient expectations in regards to the medical miracle of prevention. The duration of therapy is put in context of the epoch time frames of risk calculators and studies.

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

In our second session we discuss the philosophy of calculating risk and the many factors that influence the application of these numbers. We each calculate risk using our personal preference for risk estimators and discuss the mystery of why these numbers are not the same. “Treating” asymptomatic patients and instituting preventive interventions taken for a life time does not require great haste.

Show Notes

Canadian Cardiovascular Society Risk Calculator

12 points =10% risk in 10 years (of non-fatal MI or coronary death)

Can J Cardiol 2006;22(11):913-27

Our 45 y/o 10-year risk

In this first session we offer a slightly long introduction (but not long enough to reach REM sleep). We present Mr. Guy Lines, a 45 year old male with a number of risks for cardiovascular, who we will consider over the next number of sessions on primary prevention. We lay the rocky groundwork of future podcasts; touching on patient values, the arbitrary nature of guidelines, discussing risks, the asymptomatic ‘sick’ patient, and the art (or enigma) of applying the evidence.

Show Notes

Hippocrates would be proud?

Mr G. Lines is a 45 year old male in for his “periodic” health exam. He describes himself as happy and healthy Aside from reminding him to wear a seatbelt, floss regularly, etc, you find…

1. He is relieved to hear routine rectal exams don’t start until age 50
2. His BP is 146/85 today (you took it twice hoping it would be below 140)
3. His BMI=29 and his WC=98 cm
4. His Lipids: Total Cholesterol = 6.8/265, HDL = 1.0/39, LDL = 4.9/191, Trig = 2/312
5. His Blood Sugar = 6.4/115
6. He is not a smoker