The rosuvastatin (Crestor) Jupiter study–Watch your wallet

This week we were inundated with reports of a major study with near miraculous results. Just under 18,000 participants in the Jupiter study either received rosuvastatin (Crestor) or placebo. Patients were chosen to participate if they had low LDL cholesterol (under 130 mg/deciliter) and elevated C-reactive protein (above 2 mg/liter). The results, as summarized, in a accompanying editorial :

The trial of nearly 18,000 patients was stopped, with only 1.9 of its proposed 4 years of follow-up concluded, when the data and safety monitoring board noted a significant reduction in the primary end point among participants assigned to receive rosuvastatin (142 primary events, vs. 251 in the placebo group; hazard ratio, 0.56; 95% confidence interval [CI], 0.46 to 0.69). There was a similar reduction in a combination of the more important hard outcomes: myocardial infarction, stroke, or death from cardiovascular causes (83 events in the rosuvastatin group vs. 157 in the placebo group; hazard ratio, 0.53; 95% CI, 0.40 to 0.69).

The study also reported virtually no extra side effects among the study patients. “Total numbers of reported serious adverse events were similar in the rosuvastatin and placebo groups (1352 and 1377, respectively; P=0.60) Nineteen myopathic events were reported (in 10 subjects receiving rosuvastatin and 9 receiving placebo, P=0.82)” There was one case of major muscle lysis problems (rhabdomylysis) in a 90 year old man after the study was completed. Virtually all other toxicity was equivalent between drug and placebo.

Medicynical note: As noted above the finding that there was no difference in side-effects between the drug and placebo is at least a little strange. That the reported side effects occurred much less frequently even than the incidence in the FDA drug insert also is remarkable. It could indicate patient selection or bias from in this drug company sponsored trial. Interestingly 25% of patients were reported not taking the drug at the end of the study. Why? That’s left to the imagination.

From the drug insert:

In clinical studies of 10,275 patients, 3.7% were discontinued due to adverse experiences attributable to rosuvastatin. The most frequent adverse events thought to be related to rosuvastatin were myalgia, constipation, asthenia, abdominal pain, and nausea.”

Uncomplicated myalgia has been reported in rosuvastatin-treated patients (see Creatine kinase (CK) elevations (>10 times upper limit of normal) occurred in 0.2% to 0.4% of patients taking rosuvastatin at doses up to 40 mg in clinical studies. Treatment-related myopathy, defined as muscle aches or muscle weakness in conjunction with increases in CK values >10 times upper limit of normal, was reported in up to 0.1% of patients

The NEJM editorial about the study also noted:

On the other side of the balance, of concern are the significantly higher glycated hemoglobin levels and incidence of diabetes in the rosuvastatin group in JUPITER (3.0%, vs. 2.4% in the placebo group; P=0.01). There are also no data on the long-term safety of lowering LDL cholesterol to the level of 55 mg per deciliter (1.4 mmol per liter), as was attained with rosuvastatin in JUPITER, which is lower than in previously reported trials. Long-term safety is clearly important in considering committing low-risk subjects without clinical disease to 20 years or more of drug treatment.”

An additional concern is cost.

“The proportion of participants with hard cardiac events in JUPITER was reduced from 1.8% (157 of 8901 subjects) in the placebo group to 0.9% (83 of the 8901 subjects) in the rosuvastatin group; thus, 120 participants were treated for 1.9 (Medicynical note: 693 days) years to prevent one event.

At a cost of $3.45/day treating 120 patients for 693 days is a total of almost $300,000 spent to prevent one event. This is far above any reasonable cost/effective intervention. It’s obvious why this information was not included in this drug company sponsored study. It is, however, one of the major concerns we all should have in this time of crisis in health care.

Having patients commit to take a medication for the duration of their lives to prevent serious medical problems is the dream of drug companies. But in order to seriously consider such an intervention, it must be very effective, have low toxicity and be affordable both for the patient and the health care system. Use of rosuvastatin to prevent cardiovascular disease doesn’t fully meet these criteria and as such, the report should be viewed as an interesting approach that merits further study, not wholesale adoption.

In the press I noted comment that other statins that are available as generics may have the same beneficial effect at lower cost. It’s unlikely however, that drug company sponsored studies of these low cost alternatives will ever be done.

Quality of Chronic Care in the U.S. Non system of Healthcare

Health care in the U.S. is slowly crumbling. Everyone (except those who are exceptionally financially secure) is dissatisfied, including patients. This report of an article in Health Affairs sums up the patient’s views:

“Chronically ill Americans are more likely to forgo medical care because of high costs or experience medical errors than patients in other affluent countries”

“Fifty-four percent of Americans surveyed said high costs prevented them at some point from getting recommended medical care, filling prescriptions or seeing a doctor when ill. Seven percent of the Dutch cited cost as a barrier to treatment.”

“In addition, 41 percent of the U.S. patients said they spent more than $1,000 over the past year on out-of-pocket medical costs. That compared to lows of 4 percent in Britain and 5 percent in France.”

“In short, the U.S. patients are telling us about inefficient, unsafe and often wasteful care. The lack of access, combined with poorly coordinated care, is putting these patients at very high health risk and driving up costs of care.”

Those who defend our health care say “we have the best care in the world.” (attribute to Bush, McCain, Limbaugh and their ilk) They simply don’t operate in the real world.

We have an opportunity here, the question is whether we’ll be able to act on it.

Vitamin C and E don’t work either!

It’s enough to make a medicynic’s day. JAMA reports this week that Vitamin C and E are ineffective in preventing cardiovascular disease.

“A total of 14,641 male physicians who were 50 or older at enrollment took either 500 milligrams of vitamin C and a placebo, 400 International Units (IU) of vitamin E and a placebo, both vitamins, or two placebos every other day for an average of eight years.”

“During this time there were 1,245 confirmed major cardiovascular events among the study participants.”

“Neither vitamin, nor the combination of the two, was found to have a significant impact on the risk for heart attack, stroke , or other cardiovascular events.”

A first step to health care for all–reforms that won’t cost a penny

Price competition is fundamental to the capitalist system. In a perfect world, competition leads to the right price for product and results in value to consumers. Such competition however is anathema to health care.

Why?

On one hand we have patent monopolies which allow patent holders to charge whatever they want for a product for a generation.

Second we find it difficult as a society, as health providers and as consumers to place a monetary value on health care, a surrogate for life itself.

Third, the system is full of conflicts of interests. Providers, patients and industry all have agendas. Patients want to live but don’t fully understand the nuances of the decision. Pricing information is hard to find. Industry’s interest is in profits not the best health care decision. Information on health care decisions is complex and guarded. As a result value in medicine is an oxymoron.

I’ve focused on cancer medicines in previous posts in part because pricing is extreme and also because patients with cancer perceive that they face the ultimate dilemma-pay or die. Cancer pharmaceutical pricing is indeed a death tax, a system that redistributes wealth rather than assures quality care at reasonable price.

The question is whether there is, or should be, a quid pro quo for a government granted pharmaceutical patent monopoly. One that will assure reasonable pricing. This article on Financing Drug Research offers some suggestions. Medicynic suggestions won’t cost a penny and are a good start to a new health care system:

1. Require the government and pharmaceutical companies to negotiate prices for patented medications purchased for government programs and beneficiaries. Including Medicaid, Medicare, the Federal Employee program and Tricare this would affect 100 million citizens (1/3 the population of the U.S.) Since we like transparency we should make the negotiated prices public.

2. Enforce the reasonably pricing provisions of Dole-Bayh. Retrieve the taxpayer’s contribution to drug development costs (approximately 20 billion a year to basic medical research) from patent holders and use these proceeds to defray pharmaceutical prices to consumers. This would also require the disclosure of the real development costs of pharmaceuticals.

3. Prohibit direct to consumer (DTC) advertising. In a 30 second ad full disclosure as outlined below is not possible. As a result patients do not fully understand the limits and costs of any given product. Few countries allow such advertising.

4. If we don’t wish to completely prohibit DTC advertising, require full disclosure. This would include mention of the risks of treatment and a summary of proven benefits and competing approaches in clear language that a lay person can understand. The price of the medication, with estimates of monthly and yearly costs as well as a measure of cost effectiveness (cost/unit of additional survival time or other approved measure) must be also be provided to fully inform the consumer.

5. Require clinical studies to include cost data as well as a measure of cost effectiveness (QALY-Quality adjusted life year or other) in the discussion of any phase II, III or IV study reporting positive results.

6. Monitor the FDA approval process to be certain that generics come to market quickly on patent expiration.

7. The Canadian system controls patented drug prices by not allowing marketing unless the drug is priced right. A similar program could be instituted here to decrease our pricing to the level of other industrialized countries.

8. Alternatively, link the length of patents to reasonable pricing. As part of the FDA approval process the proposed price of the new medication would be compared with similar medications already on the market and with the same medication in other countries. The same process that the Canadian patent drug review board uses. If priced a significant amount over the comparator, the patent length would be decreased by some period of time to be determined by the review process–there are many ways such a link could be structured. For unique innovative drugs the cost of development could also be factored into the pricing length of patent equation. Price increases during the duration of the patent would be tied to the rate of inflation. If they exceed that rate the patent length would be proportionally shortened.

Stiglitz on the economy (and healthcare)

Washington Post has an op ed by Joseph Siglitz on the Obama’s economic challenges:

“Obama will also need to deal with some vast inefficiencies in our economy if we are to prevent further erosions in our standard of living. Some U.S. sectors are global leaders, such as our world-beating universities and the high-tech firms that thrive on the ideas hatched in our ivory towers. Others are embarrassing, such as health care, where Americans spend far more than citizens in many other industrialized countries and get underwhelming results. We need a bold approach here, reforming not just the way we provide medicine but also thinking more broadly about health. That means doing more about diseases associated with alcohol, drugs, tobacco and obesity, which have increasingly come to symbolize American over-consumption.”

Medicynic believes our system of healthcare has evolved to not contemplate value when considering treatment alternatives. Inefficiency is integrated into every level of our non system. In research the emphasis is developing patentable advances so as to develop new approaches that a company can monopolize for a generation. Despite laws that mandate reasonable pricing our new advances are priced to assure huge company profits rather than assure patients access. The U.S. private care system spends 30% of health expenditures on administrative overhead compared with 5-10% spent by Medicare. (Canada 17%, UK 12 %, France 10%) Suppliers and providers operate in a cost plus environment without any incentive to be efficient. Pharmaceutical manufacturers spend more on marketing than research and pass the costs along to all of us. They obfuscate mediocrity in order to maximize their bottom line rather than showing interest in patient well being or for for that matter the survivability of our health care system. Hospitals view healthcare in terms of product lines and profit margins rather than benefits to patients. Physicians almost never consider cost/efficacy when recommending interventions. How else to explain the popularity of use of expensive ($100,000 plus/year) interventions that have shown minimal effect on longevity.

As noted by Stiglitz notes we pay more and get less out of our healthcare than most other industrialized countries. Hopefully CHANGE is coming!

Guns Guns Guns– Not an AK47 or Uzi but shocking nevertheless

I don’t know what’s more pathetic, this child killing people or the police reaction.

Having weapons in homes is dangerous enough. But not keeping them secure is rediculous.

But according to reports there are fears that the new administration may limit access to semi-automatic assault rifles (including the AK47, UZI and the AR-15 described below), which apparently every self-respecting sportsman desires. These weapons are appropriate for nothing sporting and one can only conjecture why the pro-life gun lobby would promote and protect this weapon’s sales and distribution?

From Wikipedia:

“AR-15 (for Armalite model 15, often mistaken for Automatic Rifle or Assault Rifle) is the common name for the widely-owned semi-automatic rifle patterned after the fully automatic M16 and M4 carbine assault rifles, which are currently in use by the United States military. AR-15 was the original name for what became the militarily designated M16, the assault rifle first used by the U.S. in the Vietnam War. The name AR-15 is now used almost exclusively to refer to the semi-automatic (commercially available) civilian version(s) of the M16 and M4 assault rifles.”

Nothing like the family AK-47

Article in today’s Times about author Carolyn Chute.

“The Chute home does have an industrial-size copying machine, however, and nearby she keeps her AK-47 rifle, which she likes because it has a gas piston that dampens recoil. “It’s very gentle, very soft,” she said.”

The author is also a member of the 2nd Maine Militia

“The 2nd Maine Militia, or Your Wicked Good Militia, as it’s sometimes known, is progun, against corporate lobbying and campaign contributions, and opposed to tax subsidies for big business. The group has been known to meet in a hired hall, but more often it assembles in the woods behind the Chutes’ home, where the members shoot at cans and other targets, talk about what’s wrong with the world and dine on potluck.”

Ahh life in these United States…….

Election, Money, Religion, Health Care

It’s election morning and all await the results. It says something about us that one party has consistently tried to suppress voting. They’ve disseminated false information about polling times and locales; providing information that was threatening to specific voter blocks; and in general tried to decrease the other party’s vote. This is of course long term republican dogma. In a democracy, a term used loosely by this party, fewer voters are better. Paul Weyrich expressed this 20 years ago and his dogma has been supported by various party hacks, the Supreme Court, and today’s republicans. Not a pretty sight for us both domestically and internationally where we purport to support democratic principals.

Money is a problem. Financial support by industry and lobbys unduely influenced elections for the past 20 years. It was amusing to hear complaints about Obama’s decision to forgo government funding this year because he thought he could raise more funds. Turn-a-round was apparently not viewed with favor.

Our religious beliefs mirror those of the Islamic world with a great majority of people who believe in a god and a relatively large minority of this group who are fanatical about this belief. These radical religionists believe all manner of myths, deny science and use their untaxed monies and influence to force their views on the rest of us. How can one explain the religionists support of proposition 8 in California. This constitutional amendment denies equal rights to gay people. It is an abomination! This is yet another irony in a campaign that has otherwise opened opportunity to previously excluded groups.

This tortured discussion leads to health care for all. We have an opportunity today, if Obama wins, to move towards a national health care system. We are already spending enough money now to assure care for all. However, because of the inefficiency and monetarization of our health care system, profit takes priority over health care. Ir is literally “YOUR MONEY OR YOUR LIFE.” The leading cause of bankruptcy in our country is medical expenses. I hope we don’t miss this opportunity because people are dying because of delays in obtaining care and lack of access to care because of cost. We’ve discussed in previous posting ideas for improvement which we will repeat over the next weeks.

Another Only in America Moment……Boy 12 shot while trick or treating

An exconvict murdered a 12 year old who was out trick or treating. He used an AK47, which appears to be one of the the weapons of choice here in the U.S.  See this for more.   What’s wrong with us?

Stupidism, the other S word

I am having difficulty with the current presidential campaign understanding how our political system reveres the stupid.

It’s simply stupid to believe that Palin is the “best” candidate the republican party could find for Vice President. She’s clueless, and unqualified. Her lack of qualification is manifest in her intellectual achievements (see her academic record, also review McCain’s); lack of national experience and basic knowledge of the world; skepticism regarding science and scientific method; performance in interviews after her selection; and in her loudly stated view that a African American son of a single mother who through the strength of his intellect became a highly respected lawyer and community organizer is one of the “elite.” It’s as if being smart is a problem. She simply makes no sense. Yet she is the best the republican party can do. Her choice and views are prime manifestations of stupidism in this campaign.

The presidential candidate for that party has proposed an elaborate shell game that is his health care policy. It will eliminate health insurance as we know it and move most of us to the expensive individual health insurance market. Many will not be accepted for insurance or charged outrageous premiums because of all things they are sick and need their health insurance. Nothing like a policy that works to eliminate coverage for those who need it most.

In regard to healthcare the question is who is more stupid. Those who propose a flawed bizarre policy or those who will seek temporary personal advantage in such a policy–by not having coverage or by buying cheap policies that don’t provide comprehensive coverage. I say temporary because we all will have illness at some point. When that happens these guys will have inadequate or no coverage and be unable to afford their treatment. At that point they may try and upgrade their health insurance policy and as noted above will be flushed out of the private insurance system. Not understanding the implications of segregating risk in health insurance and voting for a candidate who proposes such a policy is also a manifestation of stupidism.

With the economy tanking, the repubicans sell the notion that up is down and down is up. McCain a long term and recent proponent of deregulation now claims he has always been for regulation of financial markets; Palin wonders how a Democrat can propose cutting the military budget in a time or war, while McCain has stated he knows of waste and mismanagement at the Pentagon and can easily cut their budget. For these people, support of a stupid war is patriotic but paying for it with taxes isn’t. What isn’t stupid about this campaign?

Consider this election a ballot initiative on stupidism.