Wednesday, January 30, 2008

Which Hypertension Medicine is Best?

The Washington Post (and others) reported recently on a study in the recent Annals of Internal Medicine that showed diuretics were just as good as preventing heart attacks or strokes in patients with metabolic syndrome (pre-diabetes condition) than other agents, and was better in preventing heart failure in this group. The authors considered this important because new drugs like calcium channel blockers and ACE inhibitors are often used in these patients because diuretics can increase sugar and elevate cholesterol.

Bottom Line: Though the study did show an advantage to diuretics, it also showed they were more likely to increase sugar levels, possibly leading to diabetes. It is not clear which pressure medicine is best.

More if you are interested: This new study is part of a larger study called ALLHAT that examined patients with and without metabolic syndrome designed to look at the same question: do new more expensive drugs have any benefit than the older, cheaper diuretics? Answer: The diuretics acutally did better!
The current US hypertension guidlines (based on ALLHAT and other studies) recommend diuretics as first line therapy for most patients.

So everyone shoud be on a diuretic, right?????.

First, the US guidelines were published right before another big study, very similar to ALLHAT called ASCOT that found just the opposite, that calcium channel blockers and ACE inhibitors did better than diuretics. In fact, the European guidelines , which are more recent, recommend an ACE inhibitor for patients younger than 55 and a diuretic or calcium channel blocker to patients older than 55.

1. Why the discrepancy in studies and guidelines?
2. Which pressure medication should I take?

Guidelines are based on more than just how good a drug works.
Part of the US recommendations are based on cost. At the time of the studies, diuretics (like hydrochlorothiazide or HCTZ) had been generic for some time. ACE inhibitors (lisinopril) and calcium channel blockers (amlodipine), once blockbuster expensive drugs are now generic. Without looking at ASCOT, and looking at prices at the time, the NIH basically recommended diuretics for all.

Blood pressure control, not choice of drug is probably most important. ASCOT was a more Anglo poputlation, and ACE inhibitors tend to work better on whites. In ASCOT, ACE and calcium channel blockers lowered blood pressure better than diuretics, and had fewer heart attacks and strokes. In ALLHAT, the diuretics did a better job on blood pressure, and also on heart attacks and strokes. The key then is lowering blood pressure.

Diuretics may lead to diabetes. The recent report shows that diuretics did increase sugar more. The authors argue that despite this, there was no worsening of heart attacks and stroke. However, it takes years for people with pre-diabetes to develop substantially increased risk for a heart attacks and stroke. If the trial would have gone longer, you would probably see more diabetes in the diueretic group, and likely more heart atttacks and strokes. An interesting article last year in the Lancet analyzed all the large studies that looked for new onset diabetes. They found that ACE inhibitors were less likely to cause diabetes compared to other drugs, especially diuretics. In fact, diuretics were more likely to cause new diabetes compared to placebo!

Most patients need more than one drug. In both ASCOT and ALLHAT, almost all patients needed more than one drug to control their pressure, and many patients needed three or four. Thus, which is the best drug probably doesn't matter Fortunately, there are multiple combinations of old and new drugs that are now available as a generics: (lisinopril/HCTZ, amlodipine/benazapril, atenolol/chlorthalidone).

Chose the drug that's right for you. Look at side effects and benefits. Take what works to keep your blood pressure under control. Consider taking combination pills if needed.

Diuretics (hydrochorothiazide) - best studied, cheapest. May increase risk of diabetes, can cause frequent urination. Reduces risk of heart failure

ACE inhibitors (lisinopril)- fewest side effects (small chance of chronic cough which stops when drug is discontinued), won't increase risk of diabetes, protects the kidney. May not be as effective in black patients

Calcium channel blockers (amlodipine)- generally tolerated well, but can cause edema (swelling in the legs). May be more effective in black patients.

Beta-blockers- (atenolol, metoprolol) also best studied. Tend to cause more dizziness and tiredness. Excellent for patients with known coronary artery disease, and mandatory after a heart attack.


DHS said...

the problem with ASCOT that I can see is that it is amlodipine PLUS perindopril vs atenolol PLUS a thiazide. if you look at PROGRESS, perindopril + thiazide was better than perindopril alone (not sig better than placebo).

Dr. Matthew Mintz said...

Yes, the problem with many of these large studies is that patients were on multiple agents. The reality is that most patients with high blood pressure require more than one medication to control there blood pressure.

Regarding PROGRESS, (Lancet 2001; 358(9287):1033-1041) you are correct that:

"Among participants treated with the combination of perindopril plus indapamide (in whom blood pressure was lowered by a mean of 12/5 mm Hg), stroke risk was significantly lower than that among participants who received double placebo (figure 5). Among participants treated with perindopril alone (in whom blood pressure was lowered by a mean of 5/3 mm Hg), stroke risk was not discernibly different from that among participants who received single placebo (figure 5)."

However, you can't make the claim that perindopril (ACE) is not a good agent. Patients were not randomized to Perinodpril vs. Perindopril +thiazide. Rather, they were randomized to perindopril vs. placebo and docs could add (when they wanted to) a thiazide diuretic. As above, the combination provided much better blood pressure lowering, which was likely needed to prevent stroke. What if patients (in this study) could have taken thiazide alone, whould that have made a difference? We don't really know.
Taking all the evidence (including PROGRESS)together, it probably doesn't matter which drug you start with, you just need to make sure you are able to get control, and if not, you should add another drug.

Dan said...

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 from 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

Minchi Natural Treatment In Hypertension said...

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Thank you,

Anonymous said...

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hypertension treatment new york said...

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Mary said...

In order for blood pressure medications to be effective, patients must actually take them. Beta blockers directly cause erectile dysfunction and delayed or unachievable ejaculation in men and lowered libido in women and men. The former result from the mechanism of action of beta blockers on hypertension! And prescribing diabetes-causing diuretics to prevent cardiovascular diseases the diabetes in turn can cause is short sighted at best.

Research has shown that in addition to lowering blood pressure, ACE inhibitors greatly reduced sexual side effects compared to diuretics and beta blockers, while ACBs actually improve sexual function and frequency. ACE inhibitors cost $4 / 30 count at Walmart, the same as beta blockers and diuretics. Both of the ACBs shown to improve sexual health can be ordered generic from any Canadian pharmacy for $11 / 100 count.

I recognize that culturally the US is essentially a dystopian theocracy where sexual health is disregarded when it isn't actively maligned, but I wish I could at least trust medical professionals to keep it in mind. Instead of undermining or destroying patients' health in one area while treating another, then blaming them for noncompliance, why not prescribe what truly works for the whole individual?