Important challenge to dogma alert:
You may have heard that high cholesterol leads to heart disease. Most experts accept the important role that cholesterol plays in heart disease: High cholesterol, particularly LDL (the bad kind), favors build up of plaque, which then leads to obstructed arteries and heart attack. Itâ€™s simple. It makes sense. Even I can understand it easily. Cholesterol levels make up part of the AHA’s heart attack risk calculator.
So if true, it follows that targeting LDL levels to lower levels would be good. Right again, this is indeed the current practice.
But now I wonder.
The relationship between LDL and heart disease has grown more confusing. ‘Tricky’ even.
The old thinking holds that lowering LDL levels leads to less severe blockage, and fewer heart attacks and death. The believers point to population data (medical people call such evidence, epidemiological) that associates lower LDL levels to lower heart attack risk. More strongly, almost every trial comparing statin to placebo in high-risk patients confirm that statins–but not any other class of cholesterol drug–reduce heart attacks and death. (These drugs are why I think my defibrillator patients don’t often die of heart disease.)
Thus far this is true: high risk = statin benefit.
The enormity of all this data led guideline writers to set LDL goals for treating cholesterol. Cut-offs were decreed and quality of care gets measured against these goals. Not at goal levels of LDL; your doctor seeks to titrate medicines.
Alas…It turns out that this neat little theory may not be so neat.
The theory that LDL acts as an adequate surrogate for heart disease has been challenged. And thus, so has the idea that targeting to a certain LDL level improves outcomes.
And this is where the fun starts. When doctrinal mantras in medicine get challenged, I get interested. (Honest full disclosure: I freely admit to being drawn to opinion that I find agreeable. As in human nature.)
In a recent letter to the Adult Treatment Panel (ATP) of the NIH, two experts in public health and outcomes research have provocatively suggested that the dogmatic policy of targeting LDL levels be abandoned. In an editorial published in Circulation: CV Quality and Outcomes, Drs Rodney Hayward (University of Michigan) and Harlan Krumholz (Yale) cite three reasons to justify such a major change in thinking about treating heart disease.
- “There is no scientific evidence to support treating to LDL targets.” Clinical trials of cholesterol-lowering medicine used fixed doses without titration. Remember, not all drugs that lower LDL reduce heart attacks. Only statins lower real outcomes, like heart attack, stroke and death. This quote captures the essence of their argument: â€œThe critical component of good clinical decision-making is not the scientific evidence regarding disease pathogenesis (cause) or treatment mechanisms but rather the best empirical predictors of patient risk and factors that reduce risk, the 2 elements that help determine the risks and benefits of a treatment in individual patients.”
- “The safety of treating to LDL targets has never been proven.” They cite three lines of argument here: (1) The untested long-term safety (lifetime risk) of cholesterol-drugs. 2.) That low-risk patients have such low-event rates, even small risks of treatment are comparatively amplified. 3) In other diseases, treating aggressively to surrogate markers can increase death rates. (Think high blood pressure in the elderly and hospitalized diabetics.)
- “Tailored treatment is a simpler safer, more effective and more evidence-based approach.” Basically, the authors make the case for using 10-year heart disease risk as the guide for statin therapy. They cite simulations that use LDL levels often under-treat high-risk patients and over-treat those at lower risk.
In presenting this alternate view, I donâ€™t aim to imply that I have the answers.
Though I do have biases: Treating to arbitrary numbers, blindly applying population statistics to individuals, considering expert consensus as gospel and favoring pills over lifestyle changes are all ideas that give me angst. And in the area of statin therapy, I have come to believe strongly that these drugs work to reduce heart attacks and strokes by many other mechanisms other than lowering cholesterol. Just because we can measure cholesterol levels doesn’t mean that’s the reason they reduce heart attacks and strokes. Could the cholesterol-lowering effect of statins be just a side-effect?
It’s also worth emphasizing that the best way to reduce both cholesterol levels and heart attack risk is exercising every day that you eat and eating better (and less) food. We doctors don’t emphasize this enough.
Though I understand well that not all smart interventions need the support of placebo-controlled-trials (think parachutes.), my years in practice seem to bring more questions than answers. Particularly when doctrine suggests using treatments that have risk.
It’s why I like exercise, diet and good sleep as treatment strategies–low risk.