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Tuesday, September 15, 2015

Assessing The Systolic. Would Big Data CER help?

You're likely to have heard the breathless news.

"Preliminary findings of large-scale study supported by the National Institutes of Health (NIH) recommends physicians not wait—and take a more aggressive approach—in treating high blood pressure in certain patient populations. The Systolic Blood Pressure Intervention Trial (SPRINT) finds swifter treatment for hypertension in adults 50 years and older lowered risk of heart attack, heart failure and stroke by almost a third and the risk for death by almost a quarter. The NIH said on Friday they stopped the trial earlier than planned in order to release the notable findings..."
Landmark NIH study shows intensive blood pressure management may save lives
Embargoed for Release: September 11, 2015, 10:30 AM EDT 
Lower blood pressure target greatly reduces cardiovascular complications and deaths in older adults

More intensive management of high blood pressure, below a commonly recommended blood pressure target, significantly reduces rates of cardiovascular disease, and lowers risk of death in a group of adults 50 years and older with high blood pressure. This is according to the initial results of a landmark clinical trial sponsored by the National Institutes of Health called the Systolic Blood Pressure Intervention Trial (SPRINT). The intervention in this trial, which carefully adjusts the amount or type of blood pressure medication to achieve a target systolic pressure of 120 millimeters of mercury (mm Hg), reduced rates of cardiovascular events, such as heart attack and heart failure, as well as stroke, by almost a third and the risk of death by almost a quarter, as compared to the target systolic pressure of 140 mm Hg.

“This study provides potentially lifesaving information that will be useful to health care providers as they consider the best treatment options for some of their patients, particularly those over the age of 50,” said Gary H. Gibbons, M.D., director of the National Heart, Lung, and Blood Institute (NHLBI), the primary sponsor of SPRINT. “We are delighted to have achieved this important milestone in the study in advance of the expected closure date for the SPRINT trial and look forward to quickly communicating the results to help inform patient care and the future development of evidence-based clinical guidelines.”

High blood pressure, or hypertension, is a leading risk factor for heart disease, stroke, kidney failure, and other health problems. An estimated 1 in 3 people in the United States has high blood pressure.

The SPRINT study evaluates the benefits of maintaining a new target for systolic blood pressure, the top number in a blood pressure reading, among a group of patients 50 years and older at increased risk for heart disease or who have kidney disease. A systolic pressure of 120 mm Hg, maintained by this more intensive blood pressure intervention, could ultimately help save lives among adults age 50 and older who have a combination of high blood pressure and at least one additional risk factor for heart disease, the investigators say.

The SPRINT study, which began in the fall of 2009, includes more than 9,300 participants age 50 and older, recruited from about 100 medical centers and clinical practices throughout the United States and Puerto Rico. It is the largest study of its kind to date to examine how maintaining systolic blood pressure at a lower than currently recommended level will impact cardiovascular and kidney diseases. NIH stopped the blood pressure intervention earlier than originally planned in order to quickly disseminate the significant preliminary results.

The study population was diverse and included women, racial/ethnic minorities, and the elderly.  The investigators point out that the SPRINT study did not include patients with diabetes, prior stroke, or polycystic kidney disease, as other research included those populations.

When SPRINT was designed, the well-established clinical guidelines recommended a systolic blood pressure of less than 140 mm Hg for healthy adults and 130 mm Hg for adults with kidney disease or diabetes. Investigators designed SPRINT to determine the potential benefits of achieving systolic blood pressure of less than 120 mm Hg for hypertensive adults 50 years and older who are at risk for developing heart disease or kidney disease.

Between 2010 and 2013, the SPRINT investigators randomly divided the study participants into two groups that differed according to targeted levels of blood pressure control. The standard group received blood pressure medications to achieve a target of less than 140 mm Hg. They received an average of two different blood pressure medications. The intensive treatment group received medications to achieve a target of less than 120 mm Hg and received an average of three medications.

“Our results provide important evidence that treating blood pressure to a lower goal in older or high-risk patients can be beneficial and yield better health results overall,” said Lawrence Fine, M.D., chief, Clinical Applications and Prevention Branch at NHLBI. “But patients should talk to their doctor to determine whether this lower goal is best for their individual care.”

The study is also examining kidney disease, cognitive function, and dementia among the patients; however, those results are still under analysis and are not yet available as additional information will be collected over the next year.  The primary results of the trial will be published within the next few months.

In addition to primary sponsorship by the NHLBI, SPRINT is co-sponsored by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the National Institute on Aging.
“Our results provide important evidence that treating blood pressure to a lower goal in older or high-risk patients can be beneficial and yield better health results overall.”

What's not to love?

Newsweek continues:
"The study’s focus on medications, rather than lifestyle, may raise some concerns since patients can experience some serious side effects from long-term use of many of these drugs. There are dozens of drugs prescribed for high blood pressure that work in many different ways. Since high blood pressure often goes hand-in-hand with other health conditions, a physician typically selects a drug that will lower blood pressure but also help a patient manage another health problem such as chest pain (angina) or diabetes. Even still, all physicians treating patients with high blood pressure recommend lifestyle changes such as eating a healthy diet, staying active and reducing stress.

The researchers will release more detailed findings of the SPRINT study in 2017. The study, the largest to date on systolic blood pressure, involved more than 9,300 patients aged 50 and older, who were recruited from 100 medical centers and clinics in the U.S. and Puerto Rico. The patient population was racially diverse and included men, women and the elderly. In order to achieve baseline data for the general population, patients with existing chronic conditions, such as diabetes, kidney disease and history of stroke, were excluded from the study. The study is also examined the rates of kidney disease, cognitive decline and dementia among patients enrolled..." 
I monitor my BP at home, usually several times a day. Been on both a statin and low-dose Lisinopril for a number of years. I was a 140/90'ish guy for quite some time. Both of my parents had chronic cardiovascular dx's, so, I'm one of those typical "at-risk pts" via my bloodline. My average BP at home in recent years, though, is snugly down in the 120/80 range.

The other day I had to jump into a Quest facility for a "Wellness Screen" required by my wife's company for our health insurance rates, something I have to do every year. (I particularly love having to attest annually in a separate affadavit that I am a lifelong non-smoker. Like I'm gonna now take it up at age 69.)

My BP was up. I'm sure I'm gonna hear about it in the "Wellness" vendor's scolding report (probably written by a computer).

"Y'know, dudes, maybe, just maybe it had something to do with the fact that I'd just come from my daily prostate cancer radiation tx, for which I'd had to consume a quart of water and hold it for quite a while, and I'd not yet eaten (this was about 11:30 a.m.), and, was on my way to another clinical appointment at noon. Maybe, just maybe your point-estimator is worthless, unscientific."

Ahhh... whatever.

My current read.

I give a lot of presentations every year traveling to many countries. Everywhere I have seen the same kind of system shaped like a pyramid. The base features health insurers, governments, and pharmaceutical companies depending on the country. In the middle of the pyramid are medical professionals bearing almost all the responsibility. These stakeholders sometimes mention patients in the smallest segment at the top of the pyramid. This system has been dramatically changing for years to move the patient to the center and break the pyramid down. The patient will soon be able to measure any health parameter about themselves at home; tell what exactly they eat; record blood pressure, ECG, and other basic data almost constantly.

Bertalan Meskó (2014-08-27). The Guide to the Future of Medicine: Technology AND The Human Touch (Kindle Locations 146-151). Dr. Bertalan Mesk√≥ (Webicina Kft.). Kindle Edition. 
More on this breathtaking book shortly. Underachiever Bertalan Meskó, MD, PhD is all of 30 years old, a physician with a doctorate in clinical genomics. Check him out here at ScienceRoll.com.


So, for now, back to the SPRINT study question. Focused on meds, no data on mitigating or exacerbating lifestyle factors (all of the socioeconomic "upstream" stuff actually). For one thing, I wanted to know which meds and their NNT's ("Number Needed to Treat"), their stratifed relative effectiveness, and types and prevalence of side-effects.

The thought occurs: perhaps had we actual, data-standardized interoperable EHRs, we might be able to get a decent "big data" CER (Comparative Effectiveness Research) look at this high-prevalence question (perhaps even triangulated with "omics data"?). Yes, I know that we'd be trading one set of methodological problems for another (mostly "noise" vs "generalizability" along with the "Large N Std Error of Mean" spurious statistical significance issue), but that's an inescapable reality of "research" in general.

The other thought I had when I first heard of this "landmark study" was, "oh, great, you can just hear Big Pharma extolling the prophylactic virtues of starting all kids out on Lisinopril et al. (That very idea got floated with respect to statins not too many years ago.)

apropos, Steve Brill is on another tear:

On May 20, about 100 stock analysts gathered in the ballroom of the Hyatt Regency Hotel in New Brunswick, New Jersey, to hear good news from top executives at Johnson & Johnson: The company had 10 new drugs in the pipeline that might achieve more than a billion dollars in annual sales.

For 129 years, New Brunswick has served as the headquarters of J&J, America’s seventh most valuable public company. With consumer products from Band-Aids to baby powder, Neutrogena to Rogaine, Listerine to Visine, Aveeno to Tylenol and Sudafed to Splenda, Johnson & Johnson is the biggest and, according to multiple surveys, most admired corporation in the world’s most prosperous industry—healthcare.

But the real money—about 80 percent of its revenue and 91 percent of its profit—comes not from those consumer favorites, but from Johnson & Johnson’s high-margin medical devices: artificial hips and knees, heart stents, surgical tools and monitoring devices; and from still higher-margin prescription drugs targeting Crohn’s disease (Remicade), cancer (Zytiga, Velcade), schizophrenia (Risperdal), diabetes (Invokana), psoriasis (Stelara), migraines (Topamax), heart disease (Xarelto) and attention deficit disorder (Concerta).


Ads for many of these products dominate our television screens and magazine pages. Each drug relies on its own elaborate marketing plan and carefully pitched promotional materials, used by hundreds of salespeople whose incomes turn on how much product they can push to the thousands of doctors who write prescriptions. All command increasing portions of our health insurance premiums and our own wallets, as well as our hopes and anxiety when we or our loved ones fall ill.

What follows is the backstage story of how an iconic company marketed a blockbuster drug that raised those hopes and fed on that anxiety. It is a story that in its depiction of strategies, tactics and mindset should make us wonder about the prescription drugs that are so much a part of our lives...
See my July 28th review of Mr. Brill's book "America's Bitter Pill." (Scroll down.)

See also "Trial Evidence Indicates J&J Hid Risperdal Study Results From FDA."
...The FDA approved Risperdal to treat autism spectrum disorders in children in 2006, three years after the Journal of Clinical Psychiatry published the now controversial study.

The drug’s current label includes a warning about the risk of gynecomastia in boys, but J&J allegedly promoted it illegally before receiving FDA approval.

In 2013, J&J settled a lawsuit brought by the U.S. Department of Justice for $2.2 billion for illegally promoting Risperdal from 1999 to 2005. The drug’s side effects were not well established in the medical community at the time.

Many antipsychotics are associated with increased prolactin levels, but a 2012 study found half of all boys taking Risperdal developed gynecomastia compared to one fifth of boys taking other drugs.

Now, the 2003 study’s authors want a fresh take on the data analysis...
UPDATE

Day two of what will be a lengthy series.


Extremely well-done.

apropos of drugs...
We’re Getting Close to a Real-Life Smart Drug
A new TV series wonders what life would be like with access to drugs that make normal people superhuman.


The new CBS series Limitless, based on the 2011 blockbuster of the same name starring Bradley Cooper, will premiere on Sept. 22. The story revolves around a mysterious brain-enhancing drug called “NZT,” which when taken as a pill produces instant superhuman mental abilities, like access to memories from every event in one’s life and above genius-level intelligence.

Sounds pretty far out, right?

As implausible as the plot might seem, it actually isn’t pure science fiction. In fact, the use of pharmaceuticals for brain enhancement has become quite a hot area of research in the scientific community, and a recent systematic review published in the journal European Neuropsychopharmacology has found that a drug prescribed for narcolepsy—named Modafinil—can significantly boost a number of mental skills. However, unlike the fictional drug NZT, the study found no harmful side effects or addictive tendencies with short-term Modafinil use.

This places Modafinil in a category with a number of other synthetic compounds commonly known as “cognitive enhancers”, or more provocatively, “smart drugs.”...

I will have more to say about this ASAP in the context of my current and recent reads, e.g., "The Guide to the Future of Medicine," "Humans are Underrated," "Humans Need Not Apply," "Machines of Loving Grace," and "Rise of the Robots," "Mindless," "The Glass Cage," etc.

THURSDAY UPDATE: MORE STEVE BRILL

Chapter 3 of "America's most admired lawbreaker."

 ___

More to come...

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