TEC: Evidence Based Therapeutics
Therapeutics Education Collaboration
Medication Mythbusters – Home of the Best Science (BS) Medicine Podcast

Episode 5: Swiss Cheese & The Evidence Holes in the Lipid Hypothesis

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

Major coronary events (%)* Death (%) Strokes (%) FROM WHAT CVD TO WHAT CVD (%)
Primary 1-1.5* 8-9 to 7
Diabetes 2 1-1.5 10 to 7
Secondary 4 2 1 20 to 15

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

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

3) Ezetrol data

4) Fibrate data

5) Torcetrapib

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

Episode 4: De-constructing Risk (or Benefit)

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

Major coronary events (%)* Death (%) Strokes (%) FROM WHAT CVD TO WHAT CVD (%)
Primary 1-1.5* 8-9 to 7
Diabetes 2 1-1.5 10 to 7
Secondary 4 2 1 20 to 15

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

Episode 3: The Risky Business of CVD Risk Assessment

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%)

  • Therapeutics Letter #62.
  • Absolute benefit of statins over approx 5 years

    Major coronary events (%)* Death (%) Strokes (%) FROM WHAT CVD TO WHAT CVD (%)
    Primary 1-1.5* 8-9 to 7
    Diabetes 2 1-1.5 10 to 7
    Secondary 4 2 1 20 to 15

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

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