side effect risks and heart dz future RE: Lipid question

[Guest guest]

I'm looking forward to Don's thoughts of the studies.Regarding risks, I

personally don't care (relatively) about the risks of side effects if the condition

being treated is potentially horrible. Basically, I try to advise treatments when I

believe " the potential benefits outweigh the potential risks. "

Massive MI/stroke is horrible, so I want to go " all in " and take on any

risks I might lessen. But I discuss potential risks and then keep an eye out for

them with proper follow up and testing.From what I've been hearing the

last 5 years or so, heart and vascular disease seems to be focusing on the

inflammatory process of the endothelial lining more and more. The statins may

be lowering the cholesterol numbers but their benefit may be greater than expected

as a lucky turn of events because they may also have other effects that lower the

inflammation of the endothelium.There's a chance our treatments for heart and

vascular disease will be changing in the next 5-10 yrs. We can measure

and change some things, like cholesterol panels, blood glucose, A1c, but we have not

caught up with Mother Nature yet and there are other issues going on in the body

that we can not yet measure and respond to adequately. Consider how many heart

attack patients have good blood pressure and chol numbers -- it's surprising, and

thus we must not begin to believe that the tests we follow give us all the story. We

should test and respond as best we can, but let's not fool ourselves that those give

us the full picture. Testing and treating heart disease is like

looking at the silouette of the Mona . You can see that it's the Mona

because we've seen it before, but, really, the details of her smile, eyes, hands and

clothes would not be apparent. Our testing of cholesterol, blood pressure,

A1c, etc, gives us the silouette of our patients' health problems so we can

" help lessen the risks. " But, really, we are not yet seeing the subtle

details of the illness and pathologies.... yet!TimOn Sat, November 15, 2008 8:25 am EST, Brady, MD

wrote:

Don,

Some questions I have been strugglingwith:

1) What do you make of the Vytorin study

which showed the addition ofzetia to the zocor did not decrease mobidity or

mortality even though itdecreased LDL 30%?

2) What about the study on fish oil (I

believe it was Lovaza but don’tknow) which showed something like a 20%

reduction in mortality but only a 2%reduction in total

cholesterol?

Thesestudies together make me question my belief that it’s all about gettingthe LDL down (i.e. something else is going on).

Also, ina patient with all these issues, when do you worry that that adding 3-4 drugsactually does more harm than good (polypharmacy vs. risk reduction)? I’veoften wondered if there any evidence that adding a second, third or fourth drugcontinues to decrease risk as much as the first one or if it is more a law ofdiminishing marginal returns. By the way, this is a question I pose to myselfwhenever I get a patient back from a cardiologist after the patient has had aheart attack and they are on 6 new meds and feel terrible. If my memory servesme correctly, the number 1 risk for subsequent heart attack is depression,

whichI believe many times is due to the traditional post-MI

polypharmacy.

PerhapsI am way off base but I would love your thoughts because I am thoroughlyconfused. Thanks!

RE: Lipid

question

A few comments on

the patient withchronic kidney disease and lipid issues.

The first would be

what his lipid goalsare. Since he has already had a heart attack and stroke,

his LDL goal isat least

The second issue is

that of the risk ofmyopathy, which is quite a bit greater in patients with

renal disease,especially when combination therapy is used. This is not to say

thatcombination therapy cannot be used, but it should be done very

cautiously.

The patient has CKD

stage 3, so his GFRis 30 – 59. This means that if you were to use

fenofibrate, hismaximum dose would be 48 mg a day. When his GFR drops to

below 20,fibrates are basically contraindicated. Since he needs significant

LDLreduction, fenofibrate would be preferable to gemfibrozil, since there is

nosignificant LDL reduction with gemfibrozil (though both fibrates will

lowernon-HDL cholesterol by lowering the Trigs and raising the HDL).

One has to be

careful with statins inpatients with renal failure, too. I, personally would

be concerned abouta simvastatin dose as high as 80 mg in this patient.

Although rosuvastatin ismore potent than atorvastatin, there are significant

renal dosing restrictionswith rosuvastatin. So, I would put him on

atorvastatin, which has norequired adjustment for renal failure.

Fish Oil is

absolutely a winner in apatient like this. No problems with renal dosing,

significant reduction oftriglycerides, and significant reduction of non-HDL

Cholesterol, even thoughthe LDL may go up a little. 4 grams of Lovaza or 8

grams of OTC Fish Oil.

Niacin is also a

winner, since it willbring down the Trigs, LDL, and will increase the HDL, but

I would be cautiousabout dosing, and remember that niacin can raise the uric

acid 30% or more,increasing the risk of gout in this patient who already

probably has elevateduric acid.

Bile Acid

Sequestrants are not a problemin renal failure, and will give up to 15%

additional reduction in LDL.

My suggestions

would be, in this order:

1. Lifestyle modifications, with a low fat, low

carb diet, butwithout high protein (and let me know if you can figure out how

to dothat!) Weight loss will help if he is not at IBW, and exercise will,

too.

2. Adding Fish Oil (due to lack of

risk)

3. Switching to atorvastatin (and if he is

tolerating 80 ofsimvastatin, he would probably tolerate 80 of

atorvastatin).

4. Adding fenofibrate at 48 mg a

day

5. Adding either a BAS or low dose niacin, or

both

dts

From:

[mailto: ]

On Behalf Of hulaterriSent: Thursday, November

13, 20082:20 PMTo:

Subject:

Lipid question

Aloha all,Looking for ideas or opinions as to

what to do next regarding apatient's lipids. His cardiologist is not returning

my calls and Ithink he is not following his lipids. The guys nephrologist is

turningover the problem to be manage by his PCP.52 year old male

with history of MI, brainstem CVA, Hypertensivenephrosclerosis (CKD Stage 3)

and Klinefelter's syndrome. He's onsimvastatin 80 mg qd, zetia 10

mg qd. Cholesterol is 207,triglyceride 320, HDL 42, LDL 101, glucose 109

creatnine 1.9 and LFTSare normal. I'm thinking I need to drive down his LDL

more andprobably improve his triglycerides. Suggestions?Mahalo

(thank you),Theresa

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