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Saturday, May 24, 2014

Ezetimibe (Zetia): why are we still prescribing what appears to be a useless drug? Update*: new study comes out which is still not very convincing.

A health research company just released a list of the 100 top drugs in America according to sales. 29th on the list, with sales of over 1.8 billion, is the cholesterol lowering drug ezetimibe, brand name Zetia. This drug was released over 10 years ago because it worked really well in combination with statin drugs such as Zocor (simvastatin) to lower LDL cholesterol levels. It was released as a single agent and combined with simvastatin as Vytorin. The only problem was that in 2008 a study of the ezetimibe/simvastatin combination compared to simvastatin alone showed the combination did not improve measurements of arterial wall thickness which correlates with things like heart attacks and strokes. Although cholesterol levels were lower in the combination arm, simvastatin was just as effective in achieving the more meaningful outcome. Ezetimibe appeared to increase cancer risk in another study, evaluating patients with aortic stenosis. A study which compared adding niacin or ezetimibe to statin therapy in patients with coronary heart disease in 2009 showed that, even though ezetimibe was very effective in reducing LDL cholesterol levels, it also increased the thickness of the arterial walls when compared to niacin. Niacin wasn't nearly as good at reducing cholesterol levels as ezetimibe, but there were more cardiovascular deaths in the ezetimibe group.

This drug, whose only claim to fame is that it reduces a number on a chemistry panel, continues to be popular in both the US and Canada. An editorial in the Journal of the American Medical Association (JAMA) in 2014 wondered at the failure of very convincing evidence to make us stop prescribing it. The author concluded that it must be that the manufacturer (Merck) has been very effective at marketing ezetimibe and that patients' and doctors' fixation on reducing the cholesterol numbers has made it attractive in defiance of its lack of efficacy. Statin drugs, which also are not immune to controversy, may reduce the risk of heart attacks by reducing inflammation, not by reducing cholesterol levels per se. Since ezetimibe acts to reduce absorption of cholesterol from the gut, it may have no effect at all on inflammation or vascular health despite lowering cholesterol levels.

There are further studies still in the pipeline which may clarify the situation a bit more. It seems right now, though, that there is enough evidence that this is a bad drug for the Food and Drug Administration to rescind its approval. It would be nice to believe that physicians would take the initiative to change their prescribing habits, removing 1.8 billion dollars from our healthcare bill while reducing our patients' pill burden, but apparently we are not stepping up to the plate.

*Note: The Medical Letter came out December 8, 2014, reporting that a new study, reported at the American Heart Association Scientific Sessions showed that adding ezetimibe to 40 mg of simvastatin did improve outcomes. The study, called IMPROVE-IT looked at a composite of cardiovascular events, including cardiovascular death, stroke or coronary revascularization and found that after 7 years 2742 events had occurred in the 9077 patients receiving simvastatin 40 mg daily alone, and only 2572 events had occurred in the 9067 patients receiving a combination of simvastatin 40 mg with 10 mg ezetimibe. This is a pretty tiny proportion of patients, and a very long study. Using Costco drugstore prices, the combination of ezetimibe and simvastatin (still on patent) costs $644 for 90 days, as compared to generic simvastatin which costs a bit over $13 for 100 pills. This calculates out to about a million dollars per cardiovascular event avoided. As an individual patient, you would have to take this drug for 7 years at a cost of over $18,000 for a 1.7% chance of avoiding a stroke, heart attack or cardiac procedure such as a stent or a bypass operation. I haven't seen the actual study, since it doesn't appear to have been published, but there may be more interesting data there, such as what percentage of patients actually took the drug for 7 years and whether there was any actual difference in death or disability. I also look forward to data on side effects which should be available when the study is published and may be interesting, after such a large and long term trial.

Addendum: The IMPROVE-IT study finally came out in the New England Journal of Medicine. There was a 40% +dropout rate. Deaths from all causes and cardiovascular causes were the same for the ezetimibe/simvastatin vs the simvastatin alone groups. Also, this study compares simvastatin to the combination of simvastatin and ezetimibe, but atorvastatin, which is significantly more potent than simvastatin (also has less drug interactions) is generic and inexpensive. Atorvastatin, which is about $32 for a 90 day supply, compared to nearly $700 for the ezetimibe/simvastatin combination, would very likely result in better outcomes than simvastatin. Since both atorvastatin and simvastatin are off patent, there will probably not be a definitive study comparing the two.

Another addendum: right now (12/14) the FDA is debating the significance of IMPROVE-IT and other data regarding the value of ezetimibe. Apparently there was a request by Merck to claim that adding ezetimibe to statin therapy reduces the risk of cardiovascular disease. It looks like FDA is going to deny that claim, based on the extremely small effect in a very tiny subpopulation. The discussion is here. (that link may be temporary)

Thursday, May 22, 2014

Why does American health care cost so much? The New York Times says it's because we pay administrators too much.

A friend sent me a link to a New York Times article on the ridiculous amount that insurance company executives and hospital administrators make. So the reason that American healthcare is so expensive is not because doctors earn too much, or drug companies charge too much or device manufacturers are making ever more expensive devices with ever expanded indications. Except that it is all of that and more.

Hospital administrators and insurance company executives do make lots of money. They make more than I ever will, unless I do their jobs. But it's also pretty easy to make a comfortable living as a physician working for a hospital or even a nurse practitioner in one of the specialty or acute care areas. By "easy" I mean that it is easy to make money, not that the job is easy. The creation of the Affordable Care Act has set into motion some mechanisms for decreasing costs, but it doesn't come close to dealing with the fundamental dynamic that makes health care expensive. Jobs that are indispensable for the functioning of the strange and overly complex and ridiculously fragmented healthcare industry are paid very well, both because they are difficult jobs which not everyone can or will do, but also because there is very little pressure to reduce the costs or complexity.

We built it this way. Because it has always been financially terrible to get sick or injured we created insurance which made it less financially devastating. We paid a little every month and then, if we needed care, the insurance company would pay our bill. But that changed incentives. Because we had paid an insurance company to cover our costs, it was more financially shrewd to get expensive medical care so as to recoup the cost of the insurance. Insurance companies would recoup their costs by raising rates, which allowed them to become larger and hire more staff. The vast majority of medical costs are paid that way, through a third party, but with our approval as consumers. Medicare, our large government insurance company, acts the same way.

Hospitals receive the bulk of healthcare spending and are more successful when they do more business. Costs like administrators' salaries and new wings and fish tanks and flat screen TV's are handed on to the consumer, with our permission, because our insurance pays for it. Administrators that can keep hospitals financially successful are worth their salaries to the companies that pay them, so they make a lot of money. Hospitals are businesses. If they are successful it is because they spend their money in a way that increases their profits.

Health care has grown unfettered for a very long time as insurance has become more universal and costs have lacked natural controls. Salaries of bigwigs and doctors have grown and more people in the US support their families on healthcare dollars. We have reached a point, though, where it is painful to pay for insurance and so we are looking for ways to lower healthcare costs without the incentives that would be present if we had to pay them by ourselves. Transparency, that is knowing where the money goes, is an important step. Thanks, New York Times, for publishing information about what hospital administrators and insurance executives make, but I don't think that being outraged about it is very useful.

What is this VA scandal about?

I've been hearing about the VA (Veterans Health Administration) scandal recently. A traipse through the high quality media coverage available on the internet has brought me up to date. Apparently in 2012 a physician at the VA in Phoenix began to call attention to the fact that her hospital was providing inadequate care, specifically that her emergency department was overcrowded and dangerous. In the primary care arena, reports that veterans had to wait ridiculously long times for appointments were investigated by the General Accounting Office and a report was released in 2013 that found that documentation of wait times was inconsistent, but that it appeared that veterans had to wait an unacceptable amount of time for appointments. Later in 2013 another doctor from the Phoenix VA reported that wait times were unacceptably long and that patients were dying because they were waiting so long to be seen. Numbers I've read on the internet include 6 weeks to even be called back about making a primary care appointment, 9 months to get an echocardiogram, 6 months to see a cardiologist. Administrators have reported wait times less egregiously long than they really are, with one set of figures for official reporting and another more accurate set that is secret (at least that's what it sounds like.) Investigations into other VA medical centers, including one in Albuquerque, suggest that this is a widespread problem. There has been official outrage and promises to fix the problem.

It has been decades since I worked in a VA hospital, but this all sounds pretty familiar. Long wait times were also a problem when I worked in Group Health, a healthcare cooperative in Washington. The situation was similar: patients in the VA system often have care that is completely free of charge. This is true of indigent veterans, veterans with disabilities that are felt to be service connected and several other categories of eligibility. Even veterans who have to pay something for care have a pretty good deal compared to many private health insurance options. In Group Health, costs for visits and medications were also really low which made people more inclined to wait for care or accept other inconveniences. At Group Health I remember my scheduler telling me that I was "a month out for routine appointments and 2 months out for routine physicals." That meant that patients who wanted to see me for their stuffy nose would no longer have the same stuffy nose, and if they had pneumonia they would either die or avail themselves of some sort of emergency visit. For physicals it wasn't necessarily a big deal except that patients had to schedule their lives around when they needed to be in town to see me. For a physical. I can see scheduling a trip to Europe or an audience with the Dalai Lama that far out, but it did seem kind of wrong to schedule a physical 2 months away. And then, naturally, they would forget, because that's a long time to keep something on your radar.

The reason for the long wait times was that Group Health, like the VA, was a system in which there was a certain amount of money per patient to be served and the administration wanted to spend as little of that money as possible, so as to stay under budget. One way to save money was to hire fewer physicians and ask them to see more patients. As physicians we either needed to see patients more quickly or have longer wait times, which naturally got even longer as time passed. I felt inadequate because I couldn't see patients faster and frustrated when long wait times meant that patients were sicker when I finally saw them, meaning that I really couldn't see them in a short amount of time. When I saw sicker patients I had a tendency to order more tests and referrals, which made the patients cost the system more, which made the budget woes of the company worse, encouraging them to further curtail their staffing. False economies with support staff were also common, when phones went unanswered leading to angry patients who took more time to mollify and then received inappropriate care.

I have treated patients who get their care from the VA and they do tell me that it takes a long time to see their primary care doctor and there is so much turnover that they never really get to know him or her and that there is an even longer wait to be seen be specialty providers. The reason I see VA patients is because they actually do have other options than receiving all of their care through the VA. Many of them have Medicare and some have private insurance. Many VA patients end up in non-VA emergency rooms and are then admitted to non-VA hospitals. The VA pays for the hospitalizations, in those cases, if they don't have the capacity to take the patient in transfer. It is expensive, but allows the VA to maintain their present capacity and staffing. The patients usually tell me they prefer to be cared for in the non-VA hospitals because they feel like they get better treatment. Still, when they can, they return to the VA because it's free, or at least very inexpensive.

One of the articles I perused on VA statistics said that the cardiologists at the VA see far fewer patients per day than private cardiologists. I don't know for sure that it's true, but it sounds familiar. Private specialists usually make more money if they see more patients and so they optimize their efficiency. They often use nurses and physician's assistants to gather much of the history and physical data they need so that they can just pop in and tell the patient the diagnosis and the plan. They have learned to perform the procedures that make up the majority of their income quickly and skillfully, because satisfied patients are loyal and lead to referrals which makes for mutually enjoyable relationships and more money. In the VA the patients are a semi-captive audience and the physicians are on salary which doesn't inspire efficiency. Once a waiting list becomes unmanageably long it ceases to be an effective motivator to see more patients.

Elected officials of all sorts are "mad as hell" about the care that veterans are receiving and are going to fix this problem. It would be nice if they could, but it will take huge commitment to change. The Veterans Health Administration is the second largest department in the US government with a yearly budget of over $150 billion. There is probably enough money in the VA system as it is to adequately staff it, but that will mean that they will have to cut administration costs and totally streamline what is undoubtedly a horribly complex and entrenched bureaucracy. The clinical culture will have to change. There needs to be some sort of incentive to provide really good service, which is difficult in the US where this is usually provided by competition and money. Deciding to be excellent is an important step, but the VA is huge and has considerable inertia. Scandals and overhauls have been part of the way the VA rolls, including immense changes in efficiency about 15 years ago, with ripples that are likely part of what we are noticing now.

I have been a strong proponent for paying for healthcare by the person rather than by the visit or procedure, because that would cause us to care for patients in ways that reduce the cost and intensity of treatment. If sick people truly cost more to treat, preventing them getting sick would be economically advantageous. The VA is essentially prepaid, so why doesn't it work this way, and how could it transform itself into a model of health promotion and sickness prevention? I think there are several dynamics at work. First is that the consumers, the veterans, don't have a say in how their benefits are administered. It is incredibly hard to uncover the budgets of any health system and it would be unthinkable to have the veterans who are actually cared for in the VA take a close look at how their money is being spent. Transparency and meaningful patient input would be powerful. Secondly, large bureaucracies grow and become more complex and less amenable to change with time. Tasks need to be simplified and administrative routines changed. Third, it doesn't appear that there is imaginative leadership in the VA to reinvent a nearly ancient system in a way that preserves what is good and moves boldly in the right direction. Perhaps someone wants to take that on?

To summarize, then, the VA has been quietly suffering in its chronic inadequacy for decades. It serves an important role and has a unique way of operating which could, with the right interventions, be a model for excellent healthcare. The chance that any of this will happen soon, or because our leaders are suddenly mad as hell, is zero.