5 Steps to prevent Heart Disease

Sunday, March 27, 2016

Americans don't care about absolute risk, they want to know how to live to 100

My compliments to Doctor  Axel F Sigurdsson for a great blog.

Allow me to continue with Dr Braunwald’s American point of view.
Americans want and expect to live till 100 years of age in good health.
That’s the lottery and statins are the insurance to get there.
I am impressed by Dr Sigurdsson’s ability with math.  I have no such ability.
My I ask him to calculate the absolute risk from age 65 to 100
1-to prevent death and
2-to prevent stroke and
3-to prevent MI.

As to side effects, MD’s need to see the patient every 4 months and monitor for that.  
As to residual risk, if goals of LDLp or apoB, not LDLc are met I believe residual risk will be less.
In the end it is the decision of the patient.
Somehow we sell the 85 year old the bypass surgery, yet atorvastatin 20 mg with niacin 1,000 mg a day from age 60 is not worth it?
Americans got the message about smoking.
Americans got the message about carbs and IR before Endocrine society.
Americans got the message about statins and the results have been remarkable.

How to get Docs and patients to take statins earlier and longer

How to sell drugs like insurance or a lottery? link

'Dr Ethan Weiss (University of California San Francisco) told heartwire that rather than a lottery analogy, he likens the results to buying insurance.
"It's not talking to patients about a win, it's talking to them about a loss," said Weiss, who was not involved with this research. "For fire insurance, I'd be subsidizing the very rare events that could happen. I may not have a fire and never know if I would have had a fire. But if I do have a fire, at least I'm protected," he explained.

"These are the types of conversations we're good at having when it comes to implantable cardioverter defibrillators―that they're basically insurance policies. Rather than a win, like with a lottery, it's more about preventing risk."

"In addition, a greater lifespan increase was found in those who started a primary prevention intervention at an early vs later age."

"Instead, potential lifespan gain decreased as the age at initiation increased.
For example, initiation at 50 years produced a gain that was almost two- to three-times that of someone who initiated treatment at 80 years."

Thursday, March 24, 2016

Lifetime risk is why statins should be used earlier and longer

JAMA, Maarten J. G. Leening, MD, March 2016

Some quotes from the above article:

"Despite expanding primary prevention efforts, the majority of individuals will develop cardiovascular disease (CVD) during their lifetime.1,2
The discordance between short-term (10-year) and long-term (30-year to lifetime) cardiovascular risk is well established and is now reflected in the most recent clinical practice guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) on lipid-lowering treatment for primary prevention of atherosclerotic CVD (ASCVD).3,4

Specifically, these guidelines recommend that lifetime risk estimation can be used as a communication strategy for adults younger than 60 years who are free of ASCVD and not candidates for lipid-lowering therapy.

Although a high lifetime ASCVD risk has not been recommended as a class I indication for lipid-lowering treatment, the acknowledgment of lifetime risk in the guidelines indicates a more comprehensive awareness of the importance of prevention of ASCVD over a life span.
Risk estimation remains an imperfect science."

45-year-old nonsmoking white man with a systolic blood pressure of 138 mm Hg, no diabetes, normal HDL-C, and an LDL-C level of 150 mg/dL (3.9 mmol/L; corresponding to a total cholesterol level of 220 mg/dL [5.7 mmol/L]) would have a similar 10-year risk of hard ASCVD events of 3.6%, but current guidelines would not recommend lipid-lowering therapy for this patient.3

However, using the Framingham Heart Study 30-year risk calculator, these individuals have identical 30-year risks of hard ASCVD events, approximately 24%.5
Given the clinical trial evidence of a similar relative benefit of lipid-lowering therapy across a broad range of LDL-C in the short term, it would be reasonable that lipid-lowering therapy should be considered in both cases, and the second patient should be treated because of the presence of a “lifetime risk equivalent.”

The most recent iteration of the ACC/AHA prevention guidelines adds stroke to hard CHD events to form a composite ASCVD outcome of the 10-year risk calculators.4
This is a major step forward, as this better reflects the overall burden of CVD in women and African Americans, among whom the stroke-to-CHD ratio is known to be greater.2

However, limiting predicted ASCVD risk to end points of hard CHD and stroke does not reflect the entire risk of developing ASCVD over a lifetime.
Most first manifestations of ASCVD are not hard end points with fatal or incapacitating consequences and include
1- angina,
2-transient ischemic attacks, or
3-intermittent claudication.2

"These “soft” end points should be incorporated in global ASCVD risk prediction algorithms as they represent a greater portion of the events in women and, particularly, younger individuals.2"

"Experiencing an ASCVD event and its consequences during life may be of greater importance to patients than their mode of death when balancing the risks and benefits of preventive measures."

Monday, March 21, 2016

Response to Doctors on the take from Big Pharma

Full text and my response to Dollars for Docs 
by Ornstein

Below is a short version of my comments to Ornstein's article. 

My comments in purple. 

"Doctors who got money from drug and device makers—even just a meal– prescribed a higher percentage of brand-name drugs overall than doctors who didn’t, our analysis showed."

This type of data is very important.  As in twitter:

To be sure, our analysis didn't show causation (it wasn't intended to) and more research needs to be done. 17/x

As a retired Internist who practiced in a golden age of Medical discovery, it would have been very difficult for me to learn how to use all the new medications if not for the help of the drug company education process.  The Pharmaceutical companies would bring Professors to Topeka to answer our questions about the new drugs.  The sales reps themselves, when they came to the office often had very helpful information that they picked up from other offices about using the new drugs.  This may shock the media but allow me to quote the definition of evidence based medicine:

Definition of Evidence Based Medicine by David Sackett:

“integrating individual clinical expertise with the best external evidence”.

"Indeed, doctors who received industry payments were two to three times as likely to prescribe brand-name drugs at exceptionally high rates as others in their specialty.
Doctors who received more than $5,000 from companies in 2014 typically had the highest brand-name prescribing percentages."
This is the group that must be looked at.  More importantly, Professors who give talks at National meetings should not only disclose their conflicts but also how much money they have received from those conflicts. 
 Expert witnesses at malpractice trials should also disclose their payments.
I suspect the greater than $5,000 group are those that give talks to Doctors? 
 They deserve it. I also gave talks though I never made that much.  
I was talking for Lipitor once with one Doctor and the Sales rep asked me in front of the client what statin I used.  I said I use Crestor personally.  He swallowed hard and I said, you asked. 
 I never got another speaking arrangement with Lipitor.
In fact I prescribed mostly Crestor because at the time I thought it was the strongest and safest statin.  Crestor never hired me for speaking. 
 My Crestor sale reps were so happy with my numbers they couldn’t help themselves by buying me a bottle of scotch at Christmas privately.
Now that Lipitor is generic it is my first choice among statins.

"Among internists who received no payments, for example, the average brand-name prescribing rate was about 20 percent, compared to about 30 percent for those who received more than $5,000."

Times are changing.  There are so many excellent generic drugs now.
I am type 2 diabetic. I take the following very cheap generic brands:
4-Lovaza now is generic.
However my Obamacare type Platinum plan pre-approved these expensive drugs:
5-Invokana (extremely expensive but I got off Insulin and lost 20 lbs with it)
6-Victoza (also expensive but covered under DM while the higher dose Saxenda for weight lose is not)
Finally the shame that Obesity drugs are not covered
7-Qsymia (lost another 28 pounds with this drug since June.)

How did I learn about Qsymia? Not from the drug companies.  
I took the Obesity boards in Dec 2016.
The 4 new diet medications for lifelong treatment of the Chronic disease of Obesity is so exciting that I am going back into part-time private practice to treat Obesity.  I was not influenced by any free dinners.  
I was influenced by the new science.  I believe that is true for the majority of physicians.

"And those who do probably have greater skepticism about the value of brand-name medications. Conversely, doctors have to work to cultivate deep ties with companies—those worth more than $5,000 a year — and such doctors probably have a greater receptiveness to brand-name drugs, he said."
“You have the people who are going out of their way to avoid this and you’ve got people who are, I’ll say, pretty committed and engaged to creating relationships with pharma,” Baron said. “If you are out there advocating for something, you are more likely to believe in it yourself and not to disbelieve it.”

In 2009 I wrote a book which advised a combination of generic simvastatin and over the counter Endur-acin(wax-matrix niacin).  (I said Slo-niacin could be substituted for Endur-acin but I had less experience with it.) I had no financial conflicts with any of these drugs. 
 I advised them because the total cost for the year was  $100 and in combination at low doses was unlikely to have any side effects.  
If the goal of non-HDL-c less than 80 to 100 was not reached, one half tablet of Zetia could be added each day.  
Once Lipitor became generic I switched the recommendation to Atorvastatin because it is stronger and safer than Simvastatin.  
Obviously the Media did not jump on my Tubby Theory from Topeka

Why not?  Nobody was going to make money on it.

I proposed finding out if patients had early atheroma with inexpensive tests not covered by medical insurance,  CAC and CIMT. 
 If they had disease, take cheap medicine early in low dose for safety in combination. 

Since I wrote this advice, Braunwald, Sniderman, Robinson & Stone guidelines suggest the future of reducing residual risk in cardiovascular disease is to treat earlier and longer with medications.  
The Media only listens to academics, who get research money from Big Pharma?  Can we follow their money and advertising? I am not saying there is a causation.  Publishers with contacts with the media tend to get all the media coverage they want for books on non-scientific ways to lose weight and lower cholesterol? Why is that?  Something to do with advertising? Not that there is a causation.
"Dr. Felix Tarm, of Wichita, Kansas, likewise prescribed more than twice the rate of brand-name drugs than internal medicine doctors nationally. Tarm, who is in his 70s, said he’s on the verge of retiring and doesn’t draw a salary from his medical practice, instead subsidizing it with the money he receives from drug companies. He said he doesn’t own a pharmacy, a laboratory or an X-ray machine, all ways in which other doctors increase their incomes.
“I generally prescribe on the basis of what I think is the best drug,” said Tarm, who received $11,700 in payments in 2014. “If the doctor is susceptible to being bought out by a pharmaceutical company, he can just as easily be bought out by other factors.”
I have heard Dr. Tarm speak a couple of times.  He is unbiased and is a great lecturer.  He earns his money. I have learned a great deal from him.  He performs a service to other physicians they can get nowhere else.  His experience is invaluable.

Full disclosure:  To my surprise I am also on the take! 

I looked myself up at https://openpaymentsdata.cms.gov/

However, I am retired so it may not yet affect my prescribing habits. It may affect my blog?

I have no idea what these bribes are. I finished an Obesity course on April 26, 2016. 

On 6-18-16 I was at home.  I guess I need to dispute these charges?  How do I do that?

Saturday, March 19, 2016

New advice on not taking Niacin at night

From chapter 26 in

  Dyslipidemias Pathophysiology, Evaluation and Management Editors: Garg, Abhimanyu (Ed.)

I think it's clear that Niacin is still indicated for high LDLc and also should not be given at night based on the information below. 

In Tubby Theory from Topeka I advise low dose over the counter niacin in the form of Endur-acin 500 mg tablets.

I did this to improve compliance in my patients.  It was very difficult to get patients to take high dose
brand drug Niaspan due to flushing side effects.

Niaspan was also very expensive.

Endur-acin is a wax matrix preparation with very little flushing and very little side effects at the low dose of 1.000 mg.

Some experts say 1.000 mg is homepathic but in my experience with 200 patients this is not true.
Also when I studied for the NLA boards in 2008 I was taught in the following:

 Also the COMPELL trial is often ignored

Other references: 

1- Management of residual risk after statin therapy
Christina Reith  and Jane Armitage
Atherosclerosis 245 (2016) 161- 170

Curr Atheroscler Rep. 2016 Feb;18(2):11. doi: 10.1007/s11883-016-0563-8.

Niacin Alternatives for Dyslipidemia: Fool's Gold or Gold Mine? Part I: Alternative Niacin Regimens.

Dunbar RL1,2,3,4,5, Goel H6.

If Used At All, How Should Niacin Be Used?

If niacin is to be used to prevent MI, we find it harder to support the exploratory regimen based around the ER alternative.

Instead, the overall evidence supports a return to the established cardioprotective regimen, namely 1 g thrice daily with meals.

Practically, we find it surprisingly easy to switch patients from the ER alternative 2 g nightly to IR-niacin 1 g thrice daily, probably because they have substantial tolerance to NASTy symptoms by the time they accommodate 2 g of the ER alternative.

For patients intolerant, averse, or non-responsive to statins, this regimen remains evidence-based monotherapy to prevent MI, whereas under-dosing the ER alternative before the overnight fast provides little such assurance.

Whether niacin per se would benefit statin-responsive patients remains unanswered, since the established cardioprotective regimen has never been tested against a statin background.
For that matter, when introduced the statins were never subjected to the same standard of being formally tested against a niacin background to determine incremental benefit.
Thus, formal testing of incremental effects of new lipid drugs remains in its infancy, with much work to be done.
We submit the exploratory ER regimen (≤2 g/day) has thus far failed to impress because it strays so far from the established regimen, but not because of the delayed-release formulation itself.

Since the niacin pro-drug pentaerythrityl tetranicotinate also delays niacin release, niacin release rates may well prove immaterial.

Accordingly, were the established cardioprotective regimen tested against a statin background, we predict even the ER alternative dosed 1 g thrice daily with meals would prevent CHD among subjects with suboptimal lipids, much as the longer-acting pentaerythrityl tetranicotinate did.

That said, we suspect a more efficacious approach would be to combine the established cardioprotective regimen with the lipid-targeting strategy.

Thus, subjects randomized to niacin would receive the established cardioprotective regimen as a condition of enrollment, but would then titrate upwards if they were short of study-determined non-HDL-C and HDL-C goals, capped at the highest tolerated approved dose (i.e., up to 2 g thrice daily).

Niacin Alternatives for Dyslipidemia: Fool's Gold or Gold Mine? Part II: Novel Niacin Mimetics.

Goel H1, Dunbar RL2,3,4,5,6.
Two cardiovascular outcome trials established niacin 3 g daily prevents hard cardiac events. However, as detailed in part I of this series, an extended-release (ER) alternative at only 2 g nightly demonstrated no comparable benefits in two outcome trials, implying the alternative is not equivalent to the established cardioprotective regimen. Since statins leave a significant maximal HDL-C raising took well beyond 3 months
4- Safety Profile of Extended-release Niacin in the AIM-HIG trial NEJM 2014 371 288-290 July 17, 2014 

In the Tubby Theory from Topeka I advise 1,000 mg of niacin (Endur-acin or Slo-niacin a day)

In these studies:

 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily.

AIM-HIGH trial 
We randomly assigned eligible patients to receive extended-release niacin, 1500 to 2000 mg per day, or matching placebo. 
All patients received simvastatin, 40 to 80 mg per day, plus ezetimibe, 10 mg per day, if needed, to maintain an LDL cholesterol level of 40 to 80 mg per deciliter (1.03 to 2.07 mmol per liter). 

Finally back to Dr. John R Guyton Chapter 26. 

Update on Multiplier Effect: treating LDLc earlier and longer

Thursday, March 17, 2016

What is Evidence Based Medicine

Definition of Evidence Based Medicine by David Sackett: 

 “integrating individual clinical expertise with the best external evidence”.

I still maintain that my approach to find patients with subclinical CVD by CAC & CIMT and then Rx them to a LDLp less than 750 to 1,000 with low dose combination Rx of statin and Endur-acin or Slo-niacin is the safest, cheapest and best way to reach LDLp goal. 
IMPROVE-It with Zetia showed it is all about getting the LDLc as low as possible without side effects. 1,000 mg of Niacin has never been shown to have significant side effects and with a statin has a very good LDLc lowering effect. See Compell trial. 

Periodically I try to update the evidence on using Niacin to lower LDLc in combination with statin at low doses.  Last time was on Nov 23, 2015

 The above paragraph is from Management of Residual Risk after Statin Therapy. Christina Reith, Jane Armitane Atherosclerosis 245 (2016) p 161-170

"Nicotinic acid is the oldest lipid-lowering treatment having been known to affect cholesterol in humans since 1950's." 

  1. Parish S, Tomson J, Wallendszus K, et al. Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients. N Engl J Med. 2014;371(3):203–12. doi:10.​1056/​NEJMoa1300955. The HPS2-THRIVE trial highlighting the lack of significant benefit in statin responders (LDL < 58 mg/dl on statin therapy) but a significant reduction, in acute cardiovascular events, in partial responders with an LDL >77 mg/dl on statin therapy. The unexpectedly high incidence of adverse effects with niacin-laropiprant can at least partially be ascribed to laropiprant.PubMedCrossRef

Wednesday, March 16, 2016

Contrave- Diet medication

In June I plan to go back into practice to treat obesity with diet medications.  There was news today about Contrave.

These news articles should start with this news flash: 

 Obesity is chronic disease and must be treated 4 life w medicine

 The four new diet medications   are all indicated for long term treatment
 Two of these drugs are a combination of 2 drugs that has increased their efficacy.
 Contrave has 2 drugs and Qsymia has 2 drugs.

I myself realized I was on 5 diet medications. 

 Components of Contrave are Naltrexone 8mg and Bupropion 90mg 

These drugs have been on the market independently for many years.

Together they reduce food intake by acting on adrenergic and dopaminergic receptors in hypothalamus.

1-Naltrexone is an opioid antagonist. 
 "Concerns for liver toxicity initially arose from a study of non-addicted obese patients receiving 300 mg of naltrexone.[10] Subsequent studies have suggested limited toxicity in other patient populations." Wiki

2-Wellbutrin (Bupropion) is an anti-depressant that was used to help people stop smoking.
The dosing information when treating for depression is:
"A maximum of 450 mg per day, given in divided doses of not more than 150 mg each, may be considered for patients who show no clinical improvement after several weeks of treatment at 300 mg per day. Administer the 100‑mg tablet 4 times daily to not exceed the limit of 150 mg in a single dose."
Wellbutrin link  for bupropion 75mg per tablet

Slowly increase dose: (to prevent nausea)

First week: one tab each AM

Second week: one AM one PM

Third week:  2 AM one PM

Fourth week:  2AM 2 PM

Thus when taking Contrave for weight loss  the maximum dose of :

1-naltrexone is 4 x 8 mg= 32 mg

2-bupropion is 4 x 90 mg = 360 mg.

I am surprised that Contrave exceeds bupropion's advice on maximum single dose of bupropion.

Contrave must have new data?  It is probably because Contrave has an extended release formula of bupropion.