The Economics & Politics of Drugs for Mild Hypertension

Dr. David Cundiff was co-author of the Cochrane systematic review, “Pharmacotherapy for Mild Hypertension.”  The following is an unsolicited guest blog post by Dr. Cundiff.

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The Cochrane Collaboration’s Hypertension Group published a systematic review of drug treatment for mild hypertension in August 2012 showing no evidence that drugs benefit patients while about 11% have side effects severe enough to stop treatment. As coauthor of that review, I will comment on the economics, politics, regulatory intrigue, financial conflicts, and subsequent media coverage involved.

Based on data from the American Heart Association’s Heart Disease and Stroke Update, the total costs for drugs and office visits for approximately 22 million Americans with mild hypertension in 2013 will be about $32.1 billion for blood pressure lowering drugs and doctors’ visits—more than 1% of all healthcare costs. For the next 10 years (2014 – 2023) mild hypertension drug treatment will cost $488 billion. For a frame of reference, the medical component of the federal government sequester has been estimated at about $400 billion over the next 10 years. With the money go healthcare and pharmaceutical industry jobs. An American Hospital Association commissioned study projected that the $10.7 billion healthcare cut to Medicare in 2013 from the federal sequestration will result in 496,000 jobs lost. So you can guess how many jobs industry paid economists might project America will lose if we don’t sanction a half trillion dollars for drugs for mild hypertension over the next 10 years.

With a Cochrane review challenging the evidence basis for this huge revenue stream, hypertension specialists and the medical establishment media reacted promptly. On the day of publication of the Cochrane report, Marlene Busko of Heartwire, an American Heart Association online newsletter (now merged with Medscape Cardiology), quoted Dr. Suzanne Oparil (co-chair of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-8) panel), “I don’t think the paper is particularly important, because it’s looking at a very small number of participants . . . followed for only four to five years . . . [and] because of the very small number of events.”  Not mentioned in the Heartwire article was that Dr. Oparil recused herself from voting on the JNC-8 recommendations because of financial conflicts. Indeed, Duff Wilson of the New York Times dug up evidence that she, “received money or reimbursements from at least eight companies with financial interests in the outcome.” The Heartwire article also quoted Dr. William B. White (University of Connecticut, Farmington), president of the American Society of Hypertension, “I think that the entire conclusion of this analysis is flawed. It really has no clinical importance, [and] it should not be adopted by any practicing physician.” It should be noted that Dr. White has had financial relationships with 15 drug companies that make blood pressure lowering medications, topping the eight of Dr. Oparil.

Cochrane is an elite journal in evidence-based medicine, and the review of drugs for mild hypertension had the highest readership of any Cochrane review in 2012. A BMJ article about our review by Jeanne Lenzer concluded by quoting my co-author, Dr. James Wright:  “The fact that we don’t know hopefully should change practice.” He said that doctors should explain to patients the lack of evidence supporting drug treatment for mild hypertension and engage the patient in choosing whether to continue the pills or not.” I ask, “When it is explained truthfully that way, what patient would say, ‘please give me the drug, anyway?’”

Despite the medical and economic importance, to date no major newspaper (NY Times, Wall Street Journal, Washington Post, LA Times, etc.) has published a story about the controversy surrounding drugs for mild hypertension. It is as though, if big news outlets don’t cover a story, there must not be any controversy. Indeed, three weeks after the drugs for mild hypertension review was published, The Center for Disease Control (CDC) issued a report entitled, “Awareness and Treatment of Uncontrolled Hypertension Among Adults — United States, 2003–2010,” which advocated ramping up the drug treatment for hypertension in general, with no exception for mild hypertension. The following week, the CDC issued a report called, “Million Hearts: Strategies to Reduce the Prevalence of Leading Cardiovascular Disease Risk Factors,” calling for better control of risk factors associated with cardiovascular disease (i.e., more drugs). Again, CDC authors made no mention about the Cochrane drugs for mild hypertension review. I called the lead author of both these CDC reports, Dr. Amy Valderrama, who told me that the CDC was aware of our Cochrane review before the publications of their reports. Replying to my question about their lack of response to our challenge to the evidence-basis of drug treatment for mild hypertension, she said the CDC agreed with our statement in the review that more research on drugs for mild hypertension is needed. She also said that the CDC awaits the new Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-8) guidelines.

Well, the CDC and the rest of us have been waiting for nearly six years for those all-important National Heart, Lung, and Blood Institute (NHLBI) funded JNC-8 hypertension guidelines, dubbed “JNC-late.” Concerning the JNC-8 and other guidelines, the NHLBI website stated, “The NHLBI-sponsored clinical guidelines are developed by voluntary expert panels convened by the NHLBI and are, therefore, not official government positions. However, they may inform policy decisions of other government agencies and other groups.” Criticisms of this process have been blistering.

Possibly to escape criticisms of “government-issued” guidelines, in June 2013, the NHLBI shifted the responsibility of the JNC-8 and other guidelines to disease specific nonprofit organizations. For hypertension guidelines, this means the American Heart Association, the American College of Cardiology, and possibly Dr. William White’s American Society of Hypertension. These groups take drug company and other corporate donations. In explaining this monumental shift, one thing the NHLBI authors said was, “The Institute of Medicine standards emphasize the importance of the intersection of guideline development and systematic reviews: specifically, “Clinical Practice Guideline developers should use systematic reviews that meet standards, [and should interact with] the systematic review team regarding the scope, approach, and output of both processes.” Well, my Cochrane co-authors and I are the only team to have systematically reviewed drugs for mild hypertension, and no one from the JNC-8 panel or the NHLBI has contacted us yet. Why did the Affordable Care Act include about $1 billion for systematic reviews and other evidence based medicine work if powerful special interests could overrule the findings and have government health agencies and a complacent media go along with it.

The updated NHLBI website about status of NHLBI guidelines states that Department of Health and Human Services clearance regarding JNC-8 is “pending” and that partnership development with nonprofits is “ongoing.” Conspicuously changed in the updated NHLBI web page on guidelines status is that there is no longer slated to be a “public comment period” before the implementation of the guidelines. Who knows if the American Heart Association and other medical nonprofits that will issue the guidelines will bother with public comments? Without an open debate about drugs for mild hypertension in the media, there may not be many comments anyway.

The Annals of Internal Medicine did host a debate of sorts about drugs for mild hypertension in their American College of Physicians Journal Club. Reading the debate requires a payment to the Annals of Internal Medicine so few people noticed. Dr. James Brophy of McGill University Health Center attacked our review in an article entitled, “Low-quality evidence fails to show that antihypertensive drugs affect outcomes in mild hypertension.” He criticized our methodology in the review because we came up with only 4 small randomized controlled trials including < 9,000 patients followed up to 5 years. He felt that we should have somehow found more data bearing on the question and that we should have done simulations to project likely health outcomes for longer treatment periods. He suggested that we should have included patients with previous cardiovascular disease in our data analysis and then extrapolated the results to apply to people without previous cardiovascular disease. He faulted us for not doing network meta-analysis with hierarchical modeling. I’m a wonk, and I’m not sure what that means. He concluded,

Who can be opposed to more research? However, given our limited resources, a more encompassing approach to evidence-based medicine (defined as the judicious integration of current best evidence with clinical expertise) seems to be provided by current HBP guidelines that recommend treatment for mild HBP.

By email, I read the opinions of at least a dozen strong proponents of drugs for mild hypertension. None used Dr. Brophy’s arguments. We rebutted his points but, as far as I could tell, hardly anyone paid attention.

The effect of the CDC, the JNC-8, and the rest of the U.S. Department of Health and Human Services failing to publicly address and critique our evidence-based drugs for hypertension report is to impede public discussion of treating mild hypertension with diet and lifestyle changes instead of drugs. In one attempt to launch a debate about drugs for mild hypertension, Dr. Curt Furberg (Principle Investigator of the groundbreaking study, “Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial” (ALLHAT), published in JAMA), Joe Graedon (Peoples’ Pharmacy co-host), and I submitted a commentary to JAMA advocating stopping drugs for mild hypertension until further research shows it will save lives and benefit people. Despite the prominent stature of Dr. Furberg and his widely renowned research in this field, JAMA immediately turned it down without sending it for outside peer review.

Next, out of over 70 emails, I found 13 hypertension experts, one on the JNC-8 panel, who were willing or possibly willing to debate. Most favored drug treatment, some thought the JNC-8 should not make a recommendation one way or another, and 3-4 were against drugs. I approached PLOS Medicine about hosting a debate. After a positive initial response, PLOS declined to host a debate. I empathize with Edward Snowdon’s greatest fear as a whistleblower—that after all the trouble of bringing attention to a huge issue, the status quo would prevail completely unscathed because of the powerful have control of the media message and consequently the public remains ignorant or apathetic.

In the spring of 2013, my Cochrane review co-authors and I were invited by the JAMA systematic review editor to distill our drugs for mild hypertension review into an 800 word synopsis. My coauthors and I were giddy with excitement at the opportunity to publish our largely ignored work in the most prominent medical journal in the world. After several drafts were circulated back and forth with the editor, she told us that the invitation to publish a synopsis was withdrawn by JAMA, saying that the studies we reviewed were old and that they didn’t think these studies were sufficient to address whether drugs worked or not. JAMA’s website says its key objective is, “To promote the science and art of medicine and the betterment of the public health.” I guess the editors think that the public health is served by not publicly debating the value of drugs for mild hypertension.

Dr. Iona Heath’s excellent commentary, “Waste & Harm in the Treatment of Mild Hypertension: overtreatment, industry influence” published in May 2013 in the less influential and more contrarian JAMA Internal Medicine still did not ignite a widespread debate. In covering the story in this Health News Watchdog blog, Gary Schwitzer commented, “I could not find one mainstream news organization that reported on Heath’s article. Why not? Too contrarian? It’s just mild hypertension? We have news organizations that publish stories about journal articles on case series of 1 to 4 patients and make sweeping proclamations based on these.  Then why not this?”

As documented in the Cochrane review, each year, about 2 million mild hypertension patients in the U.S. (about 11% of those given pills) suffer side effects serious enough to discontinue medications. Millions more endure impotence, dizzy spells, light headedness, weakness, falls—sometimes with broken hips—and rare life-threatening drug side effects. For example, angioedema (allergic swelling of face and neck) due to commonly prescribed angiotensin converting enzyme (ACE) inhibitors (lisinopril, benazepril, etc.) leads to at least 14,000 emergency room visits per year by mild hypertension patients (about 1 per 500 patients/year) and an unknown number of deaths.

Behind these mind-numbing numbers are real people—patients, doctors, and taxpayers. A friend of mine who had been taking lisinopril 20 mg/day for mild hypertension was found unresponsive at breakfast in a restaurant one morning. When paramedics arrived, they documented that his systolic blood pressure was 90. They brought him to a hospital where the doctors ran tests but failed to make a diagnosis. I suggested that his faint was due to the lisinopril. After some consideration, his Kaiser Permanente doctors agreed. However, instead of stopping the lisinopril, the primary care doctor reduced the dose from 20 mg/day to 10 mg/day. Even when several subsequent outpatient clinic visits showed blood pressure readings of around 122/70, my friend couldn’t talk the primary care physician out of ordering lisinopril and he wouldn’t authorize a referral to a hypertension specialist. I worried about my friend’s risk of another episode of loss of consciousness.

In addition to my concern for my friend, I sympathized with the primary care doctor. Many primary care doctors, including those at Kaiser Permanente, are rated by how well they keep their patients’ blood pressures in the “normal range.” HMO managers consider 85% or more of hypertensive patients “under control” a worthy target for primary care providers to achieve. If the doctor stopped the lisinopril and my friend’s blood pressure shot up to 145/95, the physician’s hypertension control scorecard might be hurt. Worse yet, if my friend had a stroke, the doctor might worry about a medical malpractice suit based on him not adhering to standard practices. On the other hand, if my friend continued lisinopril and suffered a life-threatening attack of angioedema as a complication or lost consciousness while driving his car, the doctor would not be liable because the JNC-7 guidelines deem drug treatment of mild hypertension “standard care.”

The chief of the Kaiser Permanente hypertension service in my area happened to be a friend of mine who was a medical student when I was a medical resident in training. We have stayed in touch for the subsequent 40 years. It turns out that he is also one of the 17 or so members of the JNC-8 panel. With my lisinopril taking friend’s consent, I asked my hypertension specialist friend to consult on the advisability of drugs in this case. Fortunately, my doctor friend stopped the lisinopril.

My friend’s blood pressure has averaged under 140/90 for the subsequent six months. “AVERAGED” is the operative word, since he undoubtedly has times when his blood pressure climbs into the hypertensive range (> 140/90). My Cochrane reviewer colleague Dr. Francois Gueyffier alerted my colleagues and me to the very significant over diagnosis of hypertension that comes from using the JNC-7 criteria for making the diagnosis. The JNC-7 guidelines call for using the mean of two blood pressure readings on any two consecutive clinic visits. However, blood pressures have a wide variation, so, on some occasions, most people will have mild hypertension. Using a computerized Monte Carlo simulation to see the effect of blood pressure variation, Turner and van Schalkwyk found that, with 18 visits to the doctor, people with average blood pressures < 140/90 would be spuriously identified mild hypertension in 27%-76% of cases. My guess is that my friend’s blood pressure was not in the hypertensive range ON AVERAGE in the first place, since it has not been in the hypertensive range on average since stopping the lisinopril. My Kaiser hypertension expert friend told me that the JNC was not considering changing the criteria for diagnosing mild hypertension. In the UK, the diagnosis of hypertension is routinely confirmed with an automatically inflating cuff electronically recording frequent readings for at least a 24 hour period as an outpatient. This should be the criteria here.

A non drug approach for management of mild hypertension and the associated cardiovascular disease risk is therapeutic lifestyle changes. These include diet, exercise, relaxation therapies, smoking cessation, and alcohol moderation. The DASH diet (“Dietary Approaches to Stop Hypertension”) reduced mean systolic blood pressure by 11.5 mmHg in participants with hypertension as compared to a control diet.  The Mediterranean Diet has been shown to reduce total mortality by 56% and adverse cardiovascular events by 47% in patients at high cardiovascular disease risk. The intensive lifestyle change program of Dr. Dean Ornish for cardiovascular disease patients reduced cardiovascular events in half in 5 years. With a fraction of the half trillion dollars over the next 10 years slated to go to drugs and clinic visits, innovative lifestyle change interventions for patients with mild hypertension could potentially benefit many people and create many productive health enhancement jobs.

For over 30 years, JNC guidelines have endorsed drug treatment for mild hypertension without evidence that drugs benefit patients. Americans have wasted over $500 billion up over that time on drugs for mild hypertension. Patients have suffered hundreds of millions of side effects and an unknown number of deaths from drug side effects. Are we supposed to rely on another NHLBI appointed JNC Panel to conclude that the previous seven panels have been wrong for the past three decades?

It’s not likely at this point.

The upcoming publication of JNC-8 guidelines regarding mild hypertension (i.e., drugs or no drugs) will be a litmus test for evidence-based medicine. Let us hope that medical science in the interests of patients will prevail over the influences of money, special interest control over major media, and medical politics. Imagine: Obamacare would become a half trillion dollars more affordable if we stop wasting money on drugs for mild hypertension.

 

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