Search This Blog

Follow by Email

Tuesday, May 16, 2017

Reducing my cardiovascular risks--the ongoing saga

About 5 months ago I embarked on an adventure in healthcare. My healthcare. I decided to take medicine to reduce my cardiovascular risk. I recognize that my cardiovascular risk is pretty low, and when I am much older I may wish for a nice clean cardiac death before I lose my faculties. Having found a plaque in my carotid artery while ultrasounding myself, I decided that perhaps I should enter the ranks of consumers who take drugs to reduce their blood pressure and cholesterol.

Astute readers made various comments, including that perhaps I should first try diet, weight loss, exercise and that I should be aware that someone of my description has a low likelihood of actually benefiting from drug treatment of these things. These were reasonable comments. It turns out that I don't need to lose weight, being at the bottom of the healthy range of body mass index, and that my exercise level is pretty optimal, my diet is as evidence based as I can make it, and although I have a low risk for vascular disease, the ultrasound says I have it anyway.

I made it my mission to find drugs that would lower my risk of stroke and heart attack without sacrificing my health and well being. This has been surprisingly tricky.

No side effects
If I am to take pills for decades on the small chance that they will keep me from having some vile health event, they need to cause me no trouble. That means they can't make me feel bad and they can't cost very much money. They should also be unlikely to kill me.

I started with lisinopril, an inhibitor of the enzyme that converts angiotensin to its active form. It is an old drug and inexpensive. It can kill me by making my tongue swell up unpredictably, but that is very unlikely. In certain circumstances it can cause kidney failure, but it can also prevent kidney failure. It is usually quite effective in reducing blood pressure. My pharmacy charges just over $1 for a 1 month supply. I found that it wanted to get stuck going down my throat (it's not very slippery) and that at a low dose it didn't do much to lower my blood pressure.

Statin drugs reduce cholesterol and reduce vascular disease, though their effects in patients who have not had any cardiovascular events are minimal. Atorvastatin is pretty cheap, less than $10 a month through my pharmacy. It can definitely make my muscles weak and painful, but I haven't noticed that so far. If it does make me weaker, I may never be aware of that, just thinking that I am experiencing normal aging. Since I am hoping to buy vibrant health, that would be a nasty little irony. It almost never kills anyone, other than by causing a slight increase in the incidence of diabetes, which definitely does kill people. My physician told me I had to take it at night, which means that I forget to take it most of the time. The reason that a person should take a statin at night is because it works best during fasting states. But atorvastatin is a long acting statin and can be taken any time of day. Now I will start being more compliant, taking all of my pills at the same time, vaguely with breakfast. After my first month of taking it nearly every day, my cholesterol was lower than it had ever been, well within guidelines. Whether this is a relevant surrogate measure for any sort of health benefit, I'm not sure.

Chlorthalidone or Atenolol/Chlorthalidone
A recent meta-analysis showed that chlorthalidone, an old and less frequently used thiazide diuretic, may be more effective than its sister drug, hydrochlorothiazide (HCTZ), in preventing cardiovascular disease. Other studies have shown that it is more potent, milligram for milligram and more long lasting. Unfortunately it is also more expensive than HCTZ by a factor of more than 10. It is, however, cheap when combined with atenolol, a beta blocker. (Why it is more expensive than its newer relative and less expensive in combination with atenolol is another story that has to do with the dysfunctional economics of drug pricing.)  Thiazide diuretics can lower the potassium level and the sodium levels and by that mechanism can kill people, but this can be monitored and is rare in its most severe forms. Beta blockers have been associated with dangerously low heart rates in some people along with weight gain and depression, but this is not common. I tried the combination. I had to get up and pee more often at night but otherwise it was innocuous. It did not lower my blood pressure very much if at all.

Lisinopril in combination with a thiazide diuretic such as HCTZ or chlorthalidone is much more effective than either drug alone. They make a generic combination pill and it is also very cheap, just about the same price as lisinopril alone. I got a prescription for 90 of these, and after having taken 2 found they controlled my blood pressure very nicely, were easy to swallow and made me itch and burn in my sun-exposed areas of skin. HCTZ is well known to do this. Chlorthalidone can too, since they are similar in structure, but it didn't have that effect on me. Know anyone who needs 88 lisinopril/HCTZ tablets?

No drug manufacturer in the US makes a combination pill of these two, and I'm betting when they do it will be expensive. But I did, after all, try taking lisinopril plus a half of an atenolol/chlorthalidone pill which has caused no side effects other than the annoyance of the lisinopril pill taking its time to navigate my esophagus. Hooray! Maybe. It probably gives me a little tickle in my throat. This is classic for lisinopril and is very subtle indeed for me. I don't cough all the time, but find that as I fall asleep or am otherwise not occupied, I notice the need to cough or have a sip of water to clear the tickle. This is nearly a deal breaker, but I am willing to wait awhile and see if it persists. This combination works well for my blood pressure.

Why not? Aspirin reduces the tendency of platelets to clump and form clots, so it should reduce my risk of strokes. It will also increase my risk of significant bleeding. Aspirin is a non-steroidal anti-inflammatory drug, and even though low doses do not work to quell knee or back pain, they can cause ulcers or heartburn. I had heartburn as a wee medical student but haven't had it for years. As a new aspirin user I have it again. Nothing terrible, but not nothing.

So theoretically I am now on lisinopril, atenolol/chlorthalidone, atorvastatin and aspirin. They pretty cheap, around $10/month for everything. That still is $120 for a year and $1200 for 10 years and likely to go up in price with time. I am a little more miserable than I was on no drugs at all, and I am being bad about both compliance (taking the pills all the time) and followup. My chance of benefiting from these drugs is low. The pills are on probation.

It is important to ask, while contemplating a lifelong commitment to deliberately putting toxic chemicals into my body, if my data is sufficient. My blood pressure runs 140-160/90-94 untreated (though it is quite normal after 20 minutes of meditation.) We know that treating a population of people to bring their blood pressure down below those numbers reduces heart attacks and strokes, but do we know that my blood pressure, in the setting of otherwise good health, is harmful at all to me? I have a carotid plaque: it is not obstructing flow to any extent, but is impressively lumpy and looks like Mt. Fuji on one view. It is calcified, so it has been there awhile. It probably formed before I even had high blood pressure. Did it happen in the physical stress of childbirth? Was it formed in any of the stressful years when bad life events disturbed my otherwise charmed existence? Is it merely a signpost indicating a path not taken, or will it eventually be one of many? In a nutshell, am I just fine the way I am?

So far the experiment with pills has not been a big win. I have definitely gained, however, from the experience of being a patient, though a mighty privileged one. I have learned that side effects are real, even if they aren't on the package insert, and may be in categories like inconvenience, worry and always wondering if I have a side effect. I have learned that effective medication can be pretty inexpensive, but that the dollar cost belies the expense associated with the life disruption that taking pills can have. And that even cheap pills add up over time. I've learned that when effective medication doesn't have the desired effect, it is sometimes because the patient isn't taking the medication, but sometimes because a given pill just doesn't tweak a given person's physiology in a way that works. I've learned that even though I consider myself to be very tolerant and easy going when it comes to physical hardship, if I mentioned all of these concerns to a personal physician I would almost certainly sound like a whiner.

Monday, May 15, 2017

Bystander CPR--some interesting statistics

"Annie, Annie, are you OK?"

Many of us learned to resuscitate a person who has collapsed using Annie, the manikin based on a death mask of a young woman who had drowned in the Seine in Paris in the 19th century. Bystander cardiopulmonary resuscitation (CPR) has become increasingly accepted and expected as the years have passed, and we have even begun to make affordable machines to deliver a life-saving shock (defibrillation) to the heart of a person who has collapsed with an otherwise life threatening heart rhythm disturbance.

We lack, though, much good information about how useful the procedure is in saving lives and bringing people back to meaningful existence.

A recent study completed in Denmark looked at the outcomes of bystander performed CPR and defibrillation. Denmark has been quite aggressive in training and encouraging citizens to perform CPR when a person collapses and is found to have no pulse. They have also been scrupulous about keeping records of what happened in each of these cases. Records spanning 2001-2012 show that having bystander CPR helps a person to survive with their brain intact, more than just waiting for an emergency medical technician to arrive with the ambulance.

What is most interesting, though, is the overall outcome of cardiac arrest. In the period of study, 8.3% of patients on whom resuscitation was attempted survived for 30 days. Of these, 10.3% had brain damage or were admitted to nursing homes. As bystander CPR became more common, the percentage of patients surviving cardiac arrest rose, and was over 12% by 2012. Also, compared to no bystander CPR, those who received bystander CPR were much less likely to end up in a nursing home. The group of survivors with the best outcome were those who were treated by bystanders with an automatic defibrillator; only 2% of those survivors had brain damage. Of the patients who survived for 30 days, 9.7% died in the subsequent year, most often of heart disease.

So, to recap, slightly more than 1 in 10 Danes who collapse and receive cardiopulmonary resuscitation survive over 30 days. Of those who survive, about 1 in 10 will have brain damage sufficient to require nursing home care. Since Danes have healthcare statistics pretty similar to Americans, this study may represent us pretty well. Getting cardiopulmonary resuscitation as soon as possible, in most cases this means by a bystander, probably gets the blood flowing to the brain sooner and helps prevent brain damage in survivors. Having a defibrillator available and using it is even better.

It is a powerful thing, being able to bring someone back from death. If we choose to engage in it, we should stay skilled, start right away after a person collapses, be aware of defibrillators in the places we frequent and plan to use them, and understand our limitations. For those of us who don't want the to receive vigorous resuscitation with a significant risk of failure or brain damage, displaying this preference, possibly with a medical alert bracelet or necklace, may be wise.

Tuesday, May 9, 2017

Don't look hard for thyroid cancer--you will probably find it

Gilbert Welch has written an excellent commentary on the fresh-out-of-the-printer recommendations of the US Preventive Services Task Force (USPSTF) regarding screening for thyroid cancer. Dr. Welch, a professor at Dartmouth University, has spoken out about wasteful and harmful procedures done in the name of prevention. He is a compelling writer, has written several books aimed at people who are not doctors, and has captured the essence of the thyroid cancer screening controversy in this article, published in JAMA today.

Briefly, he applauds the recommendations of the USPSTF which state that there is no evidence that looking for thyroid cancer in people who have no concerning symptoms (symptoms such as a neck lump, difficulty swallowing or hoarseness) helps them. He looks at the population data on thyroid cancer, first evidence out of Finland that suggested that nearly everyone probably has a small thyroid cancer if you look hard enough, and evidence that discovering and treating these tumors does nothing to reduce the rate at which people die of thyroid cancer. Death from thyroid cancer has always been very rare, and thyroid cancers are pretty common.

He also discusses how the USPSTF can continue to develop recommendations which are based on evidence but often go against what is commonly done by physicians. The panel is made up of volunteers who are physicians in primary care and epidemiologists, medical professionals who study how disease occurs and can be controlled in populations. This limits conflicts of interest since none of these professionals stands to gain from promoting or discouraging given procedures. Apparently in November of 2016 legislation was introduced to put specialists and representatives from industry on the USPSTF. It did not pass, and should not be allowed to pass if it is introduced again. Screening for thyroid cancer results in many people being diagnosed with thyroid cancer which would never harm them if left untreated, but will result in hefty medical costs which will go to endocrine specialists, surgeons, pharmaceutical manufacturers and radiation providers. It is vital that task force members not be connected to fields which would gain or lose based on their recommendations..

Those of you who have been following this blog may recall the saga of my very own thyroid nodule. Much like many of my fellow humans who have been overdiagnosed with thyroid cancer, my thyroid nodule was discovered by an overzealous doctor. Actually me. I hadn't had a physical exam in awhile and thought maybe I better check myself out to see if there was anything amiss. I discovered a small lump in the right side of my neck. Being skilled in ultrasound, I headed down the very same garden path trod by the ranks of the overdiagnosed and had a scan (by me) of the nodule. It had characteristics that were benign and ones that were suspicious. I chose to follow it along for a year or more, but was alarmed when I heard that even benign appearing thyroid nodules sometimes harbored thyroid cancer. I was lucky at this point, however, when my thyroid biopsy (which hurt a lot and was very expensive) did not show cancer.

With the present guidelines, I would have spared myself multiple repeated ultrasound scans (all free in my case, because I did them myself) and the fear that persisted over the time that I followed the nodule as well as thousands of dollars and a very sore neck. Had thyroid cancer been discovered, and data suggest that it is probably there somewhere, I would have also had surgery, radiation and regular followup for recurrence, putting me at risk for complications and costing many tens of thousands of dollars, to say nothing of work lost, anxiety, pain and inconvenience. The new recommendations of the USPSTF will likely draw criticism. Those recommendations appear to me to be well considered and right on target.

Do read Dr. Welch's commentary. He is an excellent writer. Also be aware of the great resource we still have in the USPSTF which can say true things that might be unpopular with other powerful interests.

Thursday, May 4, 2017

How reduced regulation by the FDA will save money--except not

There is enthusiasm in politics about reducing regulation to stimulate creativity and economic growth. Maybe. But reduction in oversight of medication and medical devices by the Food and Drug Administration (FDA) will probably lead to a proliferation of expensive potions and gadgets that don't actually help.

This week, the New England Journal of Medicine published an article detailing the near miss associated with an injectable monoclonal antibody for Alzheimer's disease. (Spoiler alert: it doesn't work.)

Authors Chana Sacks, Jerry Avorn and Aaron Kesselheim detail the saga of Solanezumab, a drug that attacks the protein in the brain that is associated with Alzheimer's dementia. A monoclonal antibody is a molecule that binds to a specific target allowing the immune system to clear it from the body. Solanezumab binds to amyloid beta protein which is increased in the brains of patients with Alzheimer's disease. Although it may help clear amyloid protein from patients' brains, it did not help patients' brains to work better. It wasn't clear that the drug was worthless until all of the studies that the FDA required were completed. In fact, before the final, costly and rather time consuming trial, it looked like it might help patients with mild dementia. But it really doesn't help.

Because so many people have mild dementia and are desperate for a way to delay or reverse it, this could have been a very sought after drug. We don't know what it would have cost, but we can guess that it might have been similar to other monoclonal antibody drugs on the market, ranging from $14,000 to nearly $30,000 per year. There are several million people in the US who have mild dementia, so the cost to Medicare, private insurance companies and individual patients would have been in the many billions of dollars each year.

Drugs can be very good at changing blood tests or pathology slides without being good at all at changing patients' health.

I will digress a bit here, on the subject of expensive monoclonal antibody drugs that don't actually do much to help people. Evolocumab (Repatha) was approved by the FDA recently as an injectable drug to reduce cholesterol. This it does incredibly well. Read about it here. It has finally undergone testing to see if it really does any good by reducing cholesterol so dramatically and the results were hailed as a victory. The study enrolled patients with heart disease who were already on medication that had reduced their cholesterol. In this group, evolocumab actually does reduce the incidence of strokes, heart attacks, heart surgery or stents, hospitalizations for unstable angina and cardiovascular death, but only just a little bit. At the cost of over $14,000 per year for the injections, it saves only a few patients receiving the drug from these events at a cost of nearly $1 million per event avoided every year. If you only look at death or death from heart disease, there is no difference between patients who take the injections and ones who do not. Since the initial studies done for approval of this drug only looked at safety and the drug's ability to reduce cholesterol, it wasn't clear until after it was in clinical use that it didn't actually work that well for the outcomes we care about.

There are other drugs in other classes that looked like great ideas and weren't, and they either cost the taxpayer loads of money as we finally figured this out, or died in clinical trials. Drugs that increased the strength of the heart to treat heart failure often fell in this category, and, if they had been adopted in standard clinical practice, there would have been needless deaths in addition to needless costs. There are other drugs that appeared safe and were eventually taken off of the market when monitoring by the FDA showed significant side effects. The FDA monitors and approves (or doesn't) not only drugs, but also medical devices, food, cosmetics, veterinary products and machines which emit radiation. Its budget is $4.7 billion, of which not quite half is paid by the companies it monitors.

We should not ask the FDA to reduce its oversight of medication. What would be more helpful would be to increase funding for their efforts so they can do a better job and even complete an approval process more quickly when it's indicated. Perhaps an FDA with more funding and more teeth, not less, might have been able to be firmer with the makers of evolocumab, requiring it to show more efficacy before it was rolled out to physicians and patients eager to try something new to reduce the risk of heart attacks. The FDA's work on solenazumab, the Alzheimer's cure that wasn't, more than paid their cost to the taxpayer.