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2015 March 31

Third weight-loss progress report

Filed under: Uncategorized — gasstationwithoutpumps @ 20:22
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In 2015 New Year’s resolution , I said that I want to lose 10–15 pounds by June 2015. In Weight-loss progress report and Second weight-loss progress report, I provided a monthly updates.

For March, I continued the same diet and exercise as in January and February, except for March 20–29, when I had Spring “break” (a huge pile of grading, rewriting the book for my applied electronics class, and other administrative and course preparation tasks).  I wasn’t cycling up to campus everyday, so my average exercise dropped to 4.31 miles/day of bicycling. Also, my son, a freshman at UCSB, had his Spring break at the same time, and so came home for the break.  Because he is very thin (as I was at a corresponding age), his mother served a number of comfort foods while he was here, to encourage hearty eating.  So I put on a little weight and am trying to lose it again.

A simple linear extrapolation would have me reaching the upper end of my target range by 2015 Apr 23, but an exponential decay predicts that I won't reach it until June 13.

A simple linear extrapolation would have me reaching the upper end of my target range by 2015 Apr 23, but an exponential decay predicts that I won’t reach it until June 13.

I am at the lowest weight I’ve been since I bought the scale in 2011 and started recording my weight.  Although I was losing 1.24 lbs/week in January and 0.74 lbs/week in February, I only lost 0.52 lbs/week in March.  Because of this progressive slowdown, I fit an exponential decay to my weight loss, as well as the simpler linear fit.  The exponential predicts an eventual minimum weight of 157 lbs with a decay time constant of 89 days. This asymptotic weight is comfortably within my target range—but if the exponential holds up, then it will take me longer than I had originally expected even to get within my target range.

During break I had a checkup with my physician, who thinks my target weight range is fine, but she’d be happy even if I just managed to maintain my current weight. Interestingly, my cholesterol was at the lowest level since I’ve had it measured (starting in 1989), and the desirable HDL was actually up.  Unfortunately, I did not check the cholesterol levels before starting my diet, so I don’t know whether the low levels are due to the diet or to the rather high levels of atorvastatin (60mg/day) that I’ve been taking for the past 2 years.  In any case, I’m cutting back to 40mg of atorvastatin a day, and I will check my cholesterol levels again over the summer.


2012 March 28

Non–HDL cholesterol level and statins

Filed under: Uncategorized — gasstationwithoutpumps @ 18:59
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A meta-analysis was just published in the Journal of the American Medical Association, Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins, March 28, 2012, Boekholdt et al. 307 (12): 1302 — JAMA, that suggests setting statin dosage by the non-HDL cholesterol, rather than LDL, as is more commonly done.

They looked at a number of studies and tried to determine the effect (in terms of increase in cardiovascular “events” per standard deviation change) for three measures: LDL cholesterol, non-HDL cholesterol, and apolipoprotein B.  They found that non-HDL cholesterol was the best predictor of risk (hazard ratio of 1.16 per standard deviation, compared to 1.13 for LDL cholesterol and 1.14 for apolipoprotein B). That means for each standard deviation of increase in non-HDL cholesterol, there is a 16% higher chance of a major cardiovascular event (which includes myocardial infarctions, strokes, and  unstable angina).

I looked at my own LDL and non-HDL levels from my most recent blood tests and saw that I was near the average of the top quartile for both, making my hazard ratio (relative to the bottom quartile) 1.26 based on LDL and 1.42 based on non-HDL.  That means I have about a 42% higher chance of a stroke or heart attack than someone with the same age, gender, body mass index, … whose non-HDL levels were in the bottom quartile.

What I don’t know is whether more aggressive statin therapy is warranted in my case.  How does the increased risk of liver or muscle damage from higher doses of statins compare to decreased risk of heart attack or stroke?  Other than the inherited high cholesterol levels, the only risk factors I have are being male and over 55—I get a fair amount of aerobic exercise, don’t smoke, am not overweight, and don’t have high blood pressure.  According to online cardiac-risk factor calculators, my risk of a heart attack (or death from coronary heart disease) in the next 10 years is 8%–12% (depending on which calculator I use and what it considers).  Small changes in cholesterol (about what is achievable based on my 20 years of statin usage) can move me more solidly into the 8% risk category, but not really reduce the risk lower than that.  If the calculations were based on non-HDL cholesterol, they might assess my risk slightly higher.

2012 March 1

New FDA labels for statins

Filed under: Uncategorized — gasstationwithoutpumps @ 09:07
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In earlier posts, I talked about statin drugs (Simvastatin warning and Health Net screws me on their formulary).  This week, the FDA has made some changes in the labeling for all statins, based on the ongoing monitoring of the millions of patients taking the drugs:

There are 4 parts to the new changes:

  1. Liver Injury Called Rare It turns out that liver damage (the main side effect of statins that I’ve worried about) is rare enough that monitoring liver enzymes is no longer recommended.  The reasoning is that “no data exist to show that routine periodic monitoring of liver biochemistries is effective in identifying the very rare individual who may develop significant liver injury from ongoing statin therapy.”
  2. Reports of Memory Loss This one seems to be a scare message only—there have been anecdotal reports of cognitive loss in patients taking statins, but no controlled studies showing there is even a correlation, much less causation.  With millions of older people taking statins, one would expect reports of cognitive loss.  The question is whether the numbers are higher than among those not taking statins.  The data are not there to determine this, so the warning seems a bit misleading to me.
  3. The Risk of Diabetes There have been studies showing blood sugar increases in people taking statins, resulting in a 9% higher risk of diabetes.  I’m not at high risk of diabetes (I think), so multiplying that risk by 1.09 does not worry me, but I wonder whether doctors will be more likely to order tests for diabetes in their patients who take statins.
  4. The Potential for Muscle Damage The potential for rhabdomyolysis has always been present with statins (about 0.44 cases per 10,000 person years of treatment doi:10.1136/bmj.a2286. PMID 18988647), but is greatly increased when certain other drugs are taken at the same time, because of inhibition of the  metabolic machinery is involved in breaking down the statin.  The FDA is tightening the warnings for lovastatin being prescribed with certain other drugs.  It is not clear to me whether the warnings are restricted to lovastatin because that was the most commonly prescribed statin, and so the rare events were seen most often with it, or because lovastatin is metabolized differently from the other statins, and so the risks are higher, or whether the warnings were already in place for the other statins.  The statins do behave somewhat differently in the body (hence the large differences in effect as a function of dosage), so any of these explanations is plausible.  The FDA explains the interactions:

    Lovastatin is a sensitive in vivo cytochrome P450 3A4 (CYP3A4) substrate. Strong CYP3A4 inhibitors are predicted to significantly increase lovastatin exposure. A literature review indicates that itraconazole, a strong CYP3A4 inhibitor, increases lovastatin exposure up to 20-fold and the drug interaction appears to result in rhabdomyolysis. The effect of itraconazole on lovastatin exposure can therefore be extrapolated to other strong CYP3A4 inhibitors, including ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, human immunodeficiency virus (HIV) protease inhibitors, boceprevir, telaprevir, and nefazodone.

    Note that grapefruit juice is an inhibitor of CYP3A4, which is why statin users are recommended not to eat grapefruit or drink grapefruit juice. According to the Wikipedia article on CYP3A4, atorvastatin, lovastatin, simvastatin, and cerivastatin are all CYP3A4 substrates, but pravastatin and rosuvastatin are not. If this is accurate, then the FDA warnings should probably have been extended to atorvastatin, simvastatin, and cerivastatin as well. Of course, cerivastatin has already been withdrawn from the market because of much higher rates of rhabdomyolysis than the other statins.

I’m switching from rosuvastatin to a higher dose of atorvastatin this week, thanks to Health Net making the copayment for rosuvastatin so high.  The only change that the new FDA labeling should have for me is that I’m unlikely to be getting liver enzyme tests in future—though I’ll still have to get a blood test every 6 months to monitor the cholesterol levels.

2011 December 23

Health Net screws me on their formulary

Filed under: Uncategorized — gasstationwithoutpumps @ 14:08
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In my post Simvastatin warning, I discussed the analysis I did of available statin drugs after my doctor informed me of the FDA warning about high doses of simvastatin.  Based on a careful analysis of the publicly available information about the drugs, I determined that Crestor was the best choice for me, as I needed to raise my HDL as well as needing a large dose of statins to keep my LDL levels down. Vytorin was a second choice, and atorvastatin a distant third (since it does not increase HDL).

Today I got a letter from Health Net telling me that they were moving Crestor from Tier 2 ($20/month copayment) to Tier 3 ($35/month copayment), suggesting that I use lovastatin, pravastatin, or simvastatin (all of which would require doses higher than the FDA recommends).  Health Net’s Director of Pharmacy (Janice Kjell) was completely out of line in suggesting the use of these generics without checking my dosage or LDL and HDL levels. Although I’m sure that there are many patients on Crestor who would do just as well on the generics, and I prefer to use generics when I can, the choice to use Crestor was a carefully considered one based on my body’s responses to the generics. Statin drugs are not exactly equivalent, and it is not always possible to replace one with another.

Her form letter also recommended atorvastatin, since it has just gone off patent and should be available as a generic now. That one would be possible for me (the dose I’d need is not above FDA guidelines), but it would probably make my HDL/LDL ratio worse, based on the available data.  So I’m faced with the decision whether Crestor is enough better than atorvastatin to be worth spending an extra $360 a year on it (generics are only $5 a month, Tier 3 $35/month).  I had already made the decision that it was worth an extra $180 a year, but now they’ve doubled the price difference.

There has been one change in the information available since my decision in October.  In November the SATURN trial was published doing direct comparisons between atorvastatin and rosuvastatin (Crestor).  The dosages were not exactly comparable (the Crestor was at a dose designed for greater LDL reductions), but the Crestor did end up with a better HDL/LDL ratio (0.8 instead of 0.7) and less elevation of liver enzymes (0.7% vs. 2%) [source].  I wish that they had done the study for comparable doses (20mg rosuvastatin vs. 80mg atorvastatin, rather than 40mg vs. 80mg), but when studies are funded by drug companies, they try to stack the deck so that they can report things like “CRESTOR resulted in significantly lower LDL-C levels compared to atorvastatin (62.6 vs. 70.2 mg/dL, p<0.001),” even though this particular difference is just one of dosage. I also wish that they had published in a journal, rather than just at an American Heart Association conference, as UC subscribes to most major medical journals, but I have no access to AHA conferences without paying some huge fee.

It irks me that Health Net informed me of this change to their formulary after the Open Enrollment period is over (a legal form of bait-and-switch), and despite an enormous increase in my health insurance costs this year.  Unfortunately, there are very few options for health insurance at UCSC (some of the plans popular at other UCs are useless here, as we don’t have a UC medical  school nor Kaiser, and there is only two sizable medical groups for HMOs to contract with, and only one plan that contracts with the group we’ve been going to).

I wonder who (if anyone) I can complain to about Health Net changing their formulary just after Open Enrollment.  Perhaps the University needs to require that health insurers list any changes to their formulary before Open Enrollment, and not allow any increase in copayments during the year.

2011 October 11

Simvastatin warning

Filed under: Uncategorized — gasstationwithoutpumps @ 16:37
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Recently my doctor informed me of the FDA warning about high doses of simvastatin. Since I’ve been taking the 80mg dose that the FDA suggests is not advisable any longer, I looked at some of the alternatives.  My brother claims that he controls his cholesterol quite effectively just with diet, but he keeps a very strict vegan diet that I would have difficulty adhering to, so I’m still looking at statin drugs.

The FDA conveniently gives the roughly equivalent dosages of statin drugs on the market:

Relative LDL-lowering Efficacy of Statin and Statin-based Therapies

%↓ LDL-C
40 mg
1 mg
20 mg
20 mg
10 mg
10 mg
80 mg
2 mg
40 or 80 mg
40 mg
20 mg
20 mg
4 mg
80 mg
80 mg
5 mg
10/10 mg
40 mg
40 mg
10 mg
10/20 mg
80 mg
80 mg
20 mg
10/40 mg
40 mg
10/80 mg

Atorva=Atorvastatin; Fluva=Fluvastatin; Pitava=Pitavastatin; Lova=Lovastatin; Prava=Pravastatin; Rosuva=Rosuvastatin; Simva=Simvastatin.

Given that I needed 80mg of simvastatin to keep my LDL below 130, it looks like fluvastatin, pitavastatin, lovastatin, and pravastatin are not suitable.  (In the past I’ve taken lovastatin, pravastatin, and atorvastatin—the use of simvastatin was a combination of needing something stronger and avoiding the higher prices of brand-name drugs.)

Now it looks like my choices are narrowed to 40 mg atorvastatin (Liptor), 10 mg rosuvastatin (Crestor), and 10/20 mg ezetimibe/simvastatin (Vytorin).  All three are covered at the same level by my health insurance ($20/month co-payment).  One advantage to atorvastatin is that it goes off-patent soon, so generics will become available, which would lower my co-payment to $5/month.

Since all three are available in doses that have similar effect on LDL, I decided to look at the effect on HDL as well, since my total/HDL ratio is still a bit too high, even on 80 mg simvastatin.  Initially, the best comparison I could find was an infomercial by the makers of Crestor: Raising HDL Cholesterol: Comparative Data | CRESTOR® (rosuvastatin calcium).  It seems that increasing dosage of atorvastatin decreases HDL, rather than increasing it, so atorvastatin does not look like a good choice for me.  They do not show a comparison with Vytorin, though.

Given the choice between Crestor and Vytorin, it is harder to find data to compare their effects on HDL level at the dosages at which they provide the same effect on LDL. I finally found the FDA website on Vytorin, which is confusingly located on rather than a government website.  It lists the dose response of Vytorin:

Table 7: Response to Vytorin in Patients with Primary Hyperlipidemia (Mean* % Change from Untreated Baseline†)
(Daily Dose)
N Total-C LDL-C Apo B HDL-C TG* Non-HDL-C
For triglycerides, median % change from baseline
Baseline – on no lipid-lowering drug
Vytorin doses pooled (10/10-10/80) significantly reduced total-C, LDL-C, Apo B, TG, and non-HDL-C compared to simvastatin and significantly increased HDL-C compared to placebo.
Pooled data (All Vytorin doses) 609 -38 -53 -42 +7 -24 -49
Pooled data (All simvastatin doses) 622 -28 -39 -32 +7 -21 -36
Ezetimibe 10 mg 149 -13 -19 -15 +5 -11 -18
Placebo 148 -1 -2 0 0 -2 -2
Vytorin by dose
10/10 152 -31 -45 -35 +8 -23 -41
10/20 156 -36 -52 -41 +10 -24 -47
10/40 147 -39 -55 -44 +6 -23 -51
10/80 154 -43 -60 -49 +6 -31 -56
Simvastatin by dose
10 mg 158 -23 -33 -26 +5 -17 -30
20 mg 150 -24 -34 -28 +7 -18 -32
40 mg 156 -29 -41 -33 +8 -21 -38
80 mg 158 -35 -49 -39 +7 -27 -45

Similarly, the official FDA page for Crestor gives dose response

Table 5. Dose-Response in Patients With Hyperlipidemia (Adjusted Mean % Change From Baseline at Week 6)
Dose N Total-C LDL-C Non-HDL-C ApoB TG HDL-C
Placebo 13 -5 -7 -7 -3 -3 3
Crestor 5 mg 17 -33 -45 -44 -38 -35 13
Crestor 10 mg 17 -36 -52 -48 -42 -10 14
Crestor 20 mg 17 -40 -55 -51 -46 -23 8
Crestor 40 mg 18 -46 -63 -60 -54 -28 10

It looks like Crestor increases HDL more than Vytorin for the dose with comparable effect on LDL, so my doctor and I decided to try 10mg Crestor for the next few months.  The number of people in the Crestor table seems astonishingly low—I wonder if there is a better dose-response table somewhere (the official data from AstraZeneca does not seem to have anything more than this).

It is also difficult to estimate the risks of liver damage and muscle damage, though I’m not too worried about those, as I’ve been taking statins for 20 years and seen only modest increases in liver enzymes. I will, of course, continue to have blood tests for the liver enzymes once or twice a year (and within 3 months of any change of prescription).



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