Heart and stethoscope
There is an increase in awareness of mobile health devices via social media | Source: Pexels | CC0

When I was a (relatively) young resident training in Internal Medicine, we, the hotshot residents in an elite medical school, used to indulgingly sneer at our attending physicians when they would recommend some passé treatment, like the quaint diuretics (for heaven’s sake!) for hypertension. Haven’t they heard of ACE inhibitors, or calcium channel inhibitors, or at the very least an old-fashioned beta blocker? In fact, today’s hypertensives, especially those who also have metabolic syndrome, are a walking pharmacopea—they take all of the above. Now, I am not arguing here that the other drug groups should not be used in the management of hypertension, especially the ones refractive to diuretics. But a study in the latest Archives of Internal Medicine elicited old images and memories of my old profs, smiling benignly at our quotes, with almost religious reverence, from the latest article published in the New England Journal of Medicine. The study was called “Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial” or ALLHAT. Do they invent those names to fit a catchy acronym?

The new research shows that in people with high blood pressure as part of metabolic syndrome, a cluster of conditions that increases the risk for heart disease, diuretics offer greater protection against cardiovascular disease, including heart failure, and are at least as effective for lowering blood pressure as newer, more expensive medications. The findings run counter to current medical practices that favor ACE-inhibitors, alpha-blockers, and calcium channel blockers for treatment of high blood pressure in those with metabolic syndrome. In addition, the results provide important new evidence supporting the use of diuretics for initial blood pressure-lowering therapy in black patients with metabolic syndrome.

The ALLHAT study was a randomized, double-blind trial involving 42,418 participants, ages 55 and older with high blood pressure (140/90 mm Hg or greater) and at least one other risk factor for heart disease. Of those, 23,077 had metabolic syndrome with diabetes or pre-diabetes (fasting blood glucose of 100 mg/dL or greater) at the time of enrollment. Roughly 35% of the participants were black.

In both black and non-black study participants with metabolic syndrome, the diuretic-based treatment was more protective against heart failure and also against overall cardiovascular disease (coronary heart disease, stroke, heart failure, or peripheral arterial disease combined) when compared with the ACE-inhibitor and alpha-blocker-based treatments. Compared with the calcium channel blocker-based treatment, the diuretic-based treatment was more protective against heart failure.

When compared with those taking diuretics, black participants with metabolic syndrome receiving ACE-inhibitors had poorer blood pressure control and a 24% greater risk of overall cardiovascular disease. This included a 19% greater risk of coronary heart disease, a 37% greater risk of stroke, and a 49% greater risk of heart failure. They also had a 70% greater risk of kidney failure.


Why do we ignore the old standbys?

I don’t think there is a simple answer. Patients always want the latest medicine, equating “latest” with “best”, and “old” with the dark ages of medicine. There is also the relentless promotion foisted on physicians by drug companies.

But academic marketing studies suggest another reason: Diuretics are dirt cheap, and low cost is suggestive of low quality. Raise the price of an item and the assumption is that you are selling something superior. If you are a consultant, I’ll let you in on a little secret. When I left academic life, I started a small consulting business. The response was gratifyingly positive, and soon enough I was running out of room for more clients. Rather than refuse new clients, I decided to use market forces: Simply raise my fees to price myself out of the market.

To my astonishment, that only caused an increase in the number of clients. Why? Simple: If this guy charges so much, he must be good. The individual on the other end of the phone was not putting his own money down, “only” the company’s money. Makes the decision to hire this expensive hotshot a lot easier.

I suspect that one of the reasons it is so easy for a person to expect the newest and the most expensive, and for the physician to oblige, is that neither puts his own money into the game.

I’ll leave the solution to this dilemma to the policy wonks among us.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.


  1. Cardiovascular disease, I surmise, is very concerning to both those patients who have this disease, as well as others, which include their health care providers. Furthermore, this disease is likely a cause of distress as well as confusion for those professionals who seek the best treatment options for such diseases involving one’s circulatory system, such as hypertension. Hypertension in particular is a frequent medical condition that affects around 1 billion people in the world, and around 25 percent of those in the United States alone. Over 90 percent of the time, the etiology for one developing hypertension is not known, nor is the condition symptomatic often. If left untreated, hypertension can be the catalyst or such events as stroke, heart attacks, as well as heart and kidney failure.As a result, there are increasingly many pharmacological options available to delay if not prevent such diseases, and these drugs work in different ways for the same cardiovascular diseases that are acquired often. Many health care providers are understandably unclear as to which treatment option would be most beneficial for their cardiac patient- considering the different classes of medications for cardiovascular disease, and taking into consideration the safety and efficacy of each, which would likely be a difficult task.As I understand with hypertension, it is very important to control elevations in one’s blood pressure to prevent future cardiovascular events caused by prolonged uncontrolled hypertension in such individuals. Such events include an increased risk for strokes, heart attacks, and kidney failure, among other damage that can be caused in the unmanaged hypertensive patient. While hypertension is evaluated according to different stages of severity, most hypertensive patients have initially what is called primary,or essential hypertension, and this usually requires medicinal treatment to control their high blood pressure.One significant reassurance that was provided for health care providers was made available regarding which pharmacological therapy for hypertension should be chosen by them for certain hypertensive patients they may have or acquire. This reassurance was due to the results of the ALLHAT trial. This trial lasted 4 years, and the ALLHAT trial was published in the Journal of the American Medical Association in 2002. Also, the trial was conceptualized and implemented by the National Institute of Health during the 1990s. This trial was the largest study to date addressing, among other variables, those patients who were hypertensive. The study thoroughly analyzed and examined which class of medications would be the most effective for these certain patients who were given a selection from these different classes of medications for their hypertension treatment that were involved in the ALLHAT trial.In addition, the ALLHAT trial included over 40,000 subjects who were over the age of 55 and were evaluated in over 600 clinics during the course of this trial. Nearly half of the patients in this trial had metabolic syndrome, which is a syndrome where one is obese, has dyslipidemia, and glycemic issues as well. While Pfizer financially contributed a small portion to support this trial, ALLHAT was overall funded by the National Institutes of Health at a cost of around 130 million dollars, which again was for the purpose to determine the best medicinal treatment for the patients that were studied in this trial according to the trial’s study plan. This study protocol had not been done in the past, and the comparative effectiveness design strengthened this clinical trial. Because the NIH did in fact develop and fund this study, the ALLHAT trial, as a result, was largely if not completely void of bias and commercial interference compared with those trials that are sponsored by the manufacturers of drugs studied in other trials often. Because of the ideal design and methodology in which this trial was performed, most concur the results of this trial are quite accurate and valid.Once again, the ALLHAT trial provided data that allowed a true comparative analysis of these various classes of drugs for hypertension, which included calcium channel blockers, ACE inhibitors, Alpha Blockers, Beta Blockers, and diuretics. The researchers examined the action of these classes of medications on the subjects who possessed various cardiovascular disease states- with a focus on the ability of each one of these different classes of drugs on the disease of hypertension the patients in the study had during the trial. As the trial was completed with data collected and analyzed after a 4 year period, the ALLHAT trial concluded that one particular class of medications involved in this study proved to be the most advantageous for the subjects as it relates to safety, efficacy and cost for those who require treatment for their cardiovascular disease state, as well as the prevention or the delay of progression of additional cardiovascular disease states studied and examined. Amazingly, this one drug class in this study in fact is nearly as old as the subjects involved in the trial.ALLHAT results specifically and clearly concluded that thiazide diuretics are, overall, the preferred choice of medicinal treatment for initial medicinal therapy with those who are hypertensive patients, as this class of drugs overall proved to be equivalent if not superior in many ways compared with the other classes of drugs in the study. Diuretics offered great protection against cardiovascular disease and controlled hypertensive patients as they needed to be, and proved that diuretics should be the first line drug of choice in such patients. The diuretics also decreased the risk of mild congestive heart failure and stroke, as well, compared with the other classes of drugs in this trial. Thiazide diuretics were in fact superior in these risk factors in this comparative effectiveness protocol, and just as effective as the other classes of drugs it was compared to in this trial with preventing myocardial infarctions. Thiazide diuretics in fact have been studied in such disease states associated with cardiovascular disease for over 40 years and have shown similar results as were shown in this trial.This class of medications, diuretics, have been available in the United States for well over 50 years, and presently costs about 25 dollars a year, instead of a few dollars a day for many if not most branded medications for CV conditions that were examined in the ALLHAT trial. So this finding, of course, concludes that diuretics not only provide equivalent if not superior benefits for cardiovascular disease patients, but also provides cost savings as well as illustrated in this trial. Again, the ALLHAT trial was rare and unique in that it compared diuretics to these other classes of medications directly, which is not done frequently with clinical trials involving branded pharmaceuticals, as they usually do comparative studies with simply placebos most of the time, so their efficacy comes into question as a result. Yet, even though this trial was potentially beneficial for so many who are involved with prescribing medications as initial therapy for their hypertensive patients, the recommendations based on this trial to start a patient on such a diuretic was remarkably not followed entirely if not mostly by those health care providers. There was of course hope and expectation that diuretics would be utilized to a greater degree based on the results of this trial, and the researchers were puzzled that this was not occurring. So much amazement was occurring with these researchers of the ALLHAT trial, they eventuallly implemented what was called an ALLHAT dissemination plan from the years 2003 to 2006 at a cost of close to 4 million dollars. They desired to educate health care providers about the ALLHAT results, and the significance of the findings, the acknowledgement of the benefits of diuretics continue to be unrecognized by health care providers who select other classes of drugs to treat their hypertensive patients, as they still do today. The other classes aside fr
    om diuretics do in fact have benefits with cardiovascular patients, with compelling indications in particular. Yet the etiology for the prescribing habits regarding diuretics and why this class of medications is not chosen as often as they should be is largely unknown after several attempts to convince health care providers otherwise.Others have speculated why this issue with diuretics in the ALLHAT trial never caught the attention to change the prescribing habits of health care providers, overall.For example, and of no great surprise, these results of the ALLHAT study appeared to be of notable concern to those pharmaceutical companies who promote the other classes of medications in the ALLHAT trial that are more expensive than a thiazide diuretic. Reportedly, these companies who market these other classes of drugs increased their promotional spending in order to blunt the potential effects this trial may have on the usage of their cardiovascular medications that again belong to the classes that were involved in the ALLHAT trial soon after the results from this trial were published. Sampling of their branded medications to health care providers increased noticeably as well from those pharmaceutical companies that had branded medications for cardiovascular disease states. Thiazide diuretics, while clearly the apex for the prevention and management of hypertension and other cardiovascular disease states, do not engage in this promotional behavior that appears to be more of a powerful force than evidence-based medicine, as with the case of this diuretic and the benefits of this class of drugs that has been discussed..Furthermore, drugs combining two medications from different classes of medications for hypertension and other cardiovascular disease states are increasingly preferred by many health care providers for understandable reasons presently- depending on the severity of the cardiovascular disease states that may exist, along with the risk of developing these cardiovascular conditions. It has been said that nearly 70 percent of hypertensive patients alone require more than one medication to adequately have their hypertension controlled. It is not unusual, for example, for a branded pharmaceutical company to combine their medication for hypertension with a diuretic for those patients that may have a stage of hypertension that requires simply more than just one drug for reduction of their high blood pressure. On the other hand, some cardiovascular combination medications are absent of a diuretic. Yet diuretics remain the first line choice of treatment based on the results of the ALLHAT trial, regardless, and should be included in any combination drug chosen for the treatment of most cardiovascular disease patients with hypertension that requires more than one drug for control of their high blood pressure, according to others. More convincing is that the JNC-7, a report that concludes which medication is best for the prevention and treatment of high blood pressure as well as other cardiovascular conditions, concurs with the results of the ALLHAT trial, and as a result, the JNC states in their report that diuretics are preferred for first-step hypertension therapy, and acknowledge that this class of medications is presently under-utilized. The Report is rather thorough, and is developed by the American Heart Association. The report is also recognized and respected by health care providers who treat cardiovascular disease.I’m comfortable as a layperson in suggesting that the cardiovascular experts should and in fact be obligated to continue to make others aware of the results of the ALLHAT trial, and should also convince other health care providers that diuretics should be the preferred choice of medicinal therapy for the medical conditions illustrated and treated in the ALLHAT trial. Often, such a diuretic is combined with another medication to reduce hypertension, such as a beta blocker, although some believe according to clinical evidence that beta blockers may increase the incidence of diabetes. In particular, thiazide diuretics are most beneficial for those hypertensive patients that are African American, the elderly, obese patients, those with heart failure, or those with chronic kidney disease, others have concluded. And it should be noted that this type of diuretic depletes potassium from the patient taking this drug, so caution should be utilized regarding this issue, as well as the patient who is prescribed a diuretic should be informed of additional possible side effects associated with a thiazide diuretic, although they are infrequent.Along with the cost savings that could amount to billions of dollars saved annually, diuretic medicinal therapy would ensure both health care provider and patients that they are receiving the proven and ideal treatment which will control their hypertension, and delay the progression and prevent additional cardiovascular events with this particular drug. This is most noticeable in those patients who require medicinal treatment for their hypertension long term, as well as those who are elderly.Unfortunately, it appears what may be one of the most authentic trials conducted has been and continues to be largely disregarded or not recalled by those who treat hypertension- possibly due to the forces of others whose objectives are of a different nature besides the restoration of the health of others as it relates to the diseases addressed in the ALLHAT trial. So again, it appears in this situation that promotion has been a more powerful force than what science has provided. —— Dan Abshear

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