I find it fascinating that we can even make national Benchmarks and PPRNet benchmarks when there is no good way to change this.

A while back, Sue Andrews posted a item on putting all diabetics on statins even with good cholesterol and if this was really “needed” and I didn’t see any responses.

I agree with her on this one.  What is the benefit of taking a diabetic in good control, with good blood pressure and “good” cholesterol and putting them on a medication that can now be obtained at $4/mo but Lipitor is still $100/mo and then added blood work costs?  I have started using the Framingham Risk Assessment tool during my OV to show patients why I want their BP better, etc.  Interesting, the existence of Diabetes doesn’t even play into the “risk” for heart attack in this tool.  

Does anyone know of the NNT (number needed to treat) to prevent one heart attack?  Is this really “good” medicine?  Who made up this recommendation anyway?

Your questions and concerns are incredibly pertinent with the huge evolving epidemic of obesity, metabolic syndrome and diabetes.  This is an area I’ve begun to do talks and continue to work on a proposal to track and measure outcome on various approaches to this issue. A few  “brief” comments:

Traditional Framingham risk assessment is inadequate- of those having events- 1/3 were stratified to high risk, 1/3 intermediate, 1/3 low risk.

Though currently not standard of care- there are several tools to better identify those at high risk that have increasing evidence to support- the older  HS CRP  is not specific to vascular inflammation- the newer Lp-PLA2 or PLAC test is. Carotid intimal thickness U/S (CIMT), EBCT  Ca+ count  (I prefer CIMT), and advanced lipid testing (VAP or maybe even better- the Berkely) are helpful. Over the past several years as I’ve used some of these tools- I am astounded at the number of patients who were found to be at much higher risk then originally thought.

Up to 80 % of cardiac events occur without preliminary warning because of ruptured vulnerable inflamed plaque causing a clot to form and then an event. This huge group was either not identified or was inadequately treated. 20 –30 % may have preliminary sx’s from stenotic lesions- but are the minority.

Re use of statins in DM.  HEART ATTACK PREVENTION STUDY out of   Oxford, England using Zocor 40 mg in diabetics showed about 26 %   reduction in C/V events regardless of initial lipid profile- even if “normal.”   PROVE IT- Lipitor 80 mg (which I wouldn't go to) and Pravachol 40 mg (I think?) showed lower is better- e.g. even fewer events with LDL < 70.

HDL is a separate risk factor, frequently difficult to increase. With work- I can get up to 70 –80 % to tolerate niaspan. I am not afraid to selectively add fenofibrate (Tricor, Antrara). Almost all go on omega 3 fish oil (OTC or Lovasa)- flax seed oil for not only trig, HDL but to try to restore balance with currently excessive omega 6 FA’s in diet ( a separate and fascinating topic I’m learning more about!). Aggressive combination therapy can produce outstanding results-  HATS- showed 90% event reduction using niaspan and colestid. FATS- showed similar results with Niaspan and Zocor. This is from Dr. Greg Brown- head of Lipid Clinic - U of W.

Ways to reduce vascular inflammation- life style changes (stop smoking), diet (avoid trans fats, reduce omega 6 FA's, increase omega 3 FA's). Drugs reducing inflammation per Lp-PLA2 test by about 20%: statins, niacin, omega 3,  Zetia, ACE, ARB. Finofibrate only has slight effect if also on statin.

I don't have specific cost vs benefit ratios- cost to prevent an event readily available- may be buried in some of my "stuff"- but if we can better identify those at very high risk- and martial our time and energy (and Rx's) for them- don't you think that would be a huge (including economic) benefit? Most of these are 50 -60, still working- so it's more then cost of medical care- there is huge family and work place economic impact.

Essentially - the lower the LDL the fewer the events. Optional goal for very high risk is < 70. Some are saying even less. Outcome data may eventually help clarify- but its a moving target. Not so clear is if there is a minimum dose of statin to have a positive effect on endothelial dysfunction or what ever other physiologic effects we may or may not know about. 

HDL goals are absolutely arbitrary, and outcome data may not be as clear to justify. Most agree higher is better, current "guide line"-  50 for women, 40 for men at this point- some are advocating > 60

Just listening to CA's Audio Digest- speaker asserts significant LFT elevations from statins are  infrequent and has never been a serious event or death only from a statin- (even now- powers that be recommend much less LFT testing. (excluding the lopid - baycol disaster). CPK elevations that are significant are exceedingly rare. 

I like the 90 % reductions of risk better then a mere 26%

Now for the off label- when I've followed high risk pts who have or nearly have achieved my aggressive goals-  with serial CIMT's, and more recently Lp-PLA2's- up to 70%  had very significant reductions in intimal media thickness and resolution or reduction in soft plaque. (Maybe restudied 70 -80 pt's past 3 years)  Not all have been at ideal lipid goals. But also a small percent inexplicitly appeared to be worse. More recently I've identified several patients with good BP control (< 130), LDL < 70, HDL > 50- with significantly elevated Lp-PLA2's. What's going on? I strongly suspect lipid and BP goals (reached or not) don't tell the whole story- maybe even more important are the life style changes- especially diet (omega 6/omega 3 ratios), and what drugs we use- not just their effect on lipids and BP- but on vascular inflammation, endothelial dysfunction and who knows what else- that confounds us (or at least me), a very humbling experience. Just was listening to a tape referring to association of vit D deficiency and heart disease!

ASA is protective, but still seeing a relatively huge group rupturing their vulnerable plaque and having an event. The Mayo Heart Study followed pts post MI who had an LpPLA2 test. (I assume they were on current approved therapy including ASA.)  If PLAC > 200- 15% had another event within 4 years, if < 200- event rate was 4 %! I believe there are several currently running outcome studies (Hope 2, etc) that are looking at, among other things- the PLAC test- and with the various regimens being used- should answer the question- If initially high PLAC levels are reduced by therapy and life style changes- will the event rate decrease? There are NO outcome studies to date that confirm this logical assumption.

This link from Bandolier provides an evidenced based assessment and NNT based on calculated 10 year cardiac risk.

http://www.jr2.ox.ac.uk/bandolier/booth/cardiac/statcalc.html

I thought I would weigh in on the NNT question... and look forward to additional discussion.

Re: LDL in pts with diabetes

- DM is considered a CHD risk equivalent - which translates to a >20% 10-year risk per Framingham . The NNT estimates in the Bandolier ref that Ben posted answers this question really well.

http://www.jr2.ox.ac.uk/bandolier/booth/cardiac/statcalc.html

- There are 3 studies that help answer the question of benefit in patients with baseline "good" cholesterol and DM. I'll highlight the patient demographics that are relevant to applying this to your patients:

1. Heart protection study - simva 40 mg vs placebo in 6000 pts over 4 yrs, avg 60 yrs of age Baseline LDL 125 mg/dL 70% current or former smokers 50% with a history of vascular disease 40% with HTN *NNT 21 for composite outcome of major vascular event

2. CARDS - atorva 10 mg vs placebo in 2800 pts over 4 yrs, avg 62 yrs of age Baseline LDL 117 mg/dl 84% with HTN 65% current or former smokers 40% with obesity (BMI >30) 30% with retinopathy *NNT 32 for composite outcome of major vascular event

3. ASPEN - atorva 10 mg vs placebo in 2410 pts over 4 yrs, avg 61 yrs of age Baseline LDL 113 mg/dl 55% with HTN 30% with dyslipidemia 12% current smoker *Outcomes were NOT different btw atorva and placebo groups

The answer here is still based on risk stratification - while there isn't an objective calculator for patients with diabetes, the evidence suggests that high risk patients (HTN, smokers, obesity, any existing DM complication) benefit from LDL lowering with a statin. If your patients look like those in the 3rd study (smaller % w/HTN, few smokers), the benefit is not established. We also lack evidence for patients with DM < 40 yrs of age.