Tag Archives: hypertension

European Medicines Agency Starts Review of Combined Use Of Drugs That Block The Renin-Angiotensin System 1

by • Heart Failure, People, Places & Events, Policy & Ethics, Prevention, Epidemiology & Outcomes • Tags: , , , , ,

The European Medicines Agency said last week that it was initiating a review of the combined use of agents that block the renin-angiotensin system (RAS). The three classes of RAS-blocking drugs (ACE inhibitors, ARBs, and direct renin inhibitors) are used to treat hypertension and congestive heart failure.

The EMA said that the review was being performed to address concerns that combined RAS-blocking drugs could increase the risk for hyperkalemia, hypotension, and kidney failure when compared with a single agent.  A recent meta-analysis of 33 clinical studies published in the British Medical Journal concluded that ”although dual blockade of the renin-angiotensin system may have seemingly beneficial effects on certain surrogate endpoints, it failed to reduce mortality and was associated with an excessive risk of adverse events… The risk to benefit ratio argues against the use of dual therapy.”

Franz Messerli, senior author of the BMJ meta-analysis, applauded the EMA action and said that “as usual the FDA is dragging its feet.”

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Click here to read the full story on Forbes.

 

 

 

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St. Jude Raises The Stakes In Renal Denervation With An Outcomes Study Reply

by • Interventional Cardiology & Surgery, Prevention, Epidemiology & Outcomes • Tags: ,

 

The already hot field of renal denervation for resistant hypertension just got a little hotter. With the announcement of a clinical trial powered to detect improvements in cardiovascular outcomes, St. Jude Medical has raised the stakes.

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“To date, the renal denervation studies that have been conducted only looked at reducing blood pressure in patients with uncontrolled or resistant hypertension,” said Michael Böhm, a principal investigator for the trial, in a St. Jude press release. “What we need to know is if this minimally invasive approach for treating hypertension also correlates to a reduction in major cardiac events such as heart attack, stroke and death, which are the primary risks for patients whose blood pressure is not well controlled.”

 Click here to read the entire post on Forbes.

St Jude EngligHTN Rendal Denervation System

St Jude EngligHTN Rendal Denervation System

 

Study Warns Against Dual Blockade of Renin-Angiotensin System In Heart Failure And Hypertension 1

by • Heart Failure, Policy & Ethics, Prevention, Epidemiology & Outcomes • Tags: , , , ,

The enormous success of ACE inhibitors in hypertension and heart failure spurred hope that adding a second drug to block the renin-angiotensin system would yield improved outcomes. Although definitive evidence supporting dual blockade of the renin-angiotensin system has never been found, more than 200,000 patients in the US currently receive  this therapy. Now a large new meta-analysis suggests that dual blockade results in no improvement in mortality but is associated with an increase in important adverse events.

In a paper published online in BMJ, Harikrishna Makani and colleagues at Columbia University and New York University performed a meta-analysis of more than 68,000 patients who were enrolled in clinical trials comparing dual blockade of the renin-angiotensin system with monotherapy. They found no significant difference between the groups for all cause mortality or cardiovascular mortality, although dual blockade was associated with a signifcant 18% reduction in hospital admission for heart failure:

Click here to read the full article on Forbes.

 

Renal Denervation: Delineating Its Uses, Misuses, and Possibilities Reply

by • Interventional Cardiology & Surgery, Prevention, Epidemiology & Outcomes • Tags: , ,

Over on CardioExchange, Murray Essler, the chief investigator of the  Symplicity HTN-2 trial, answers questions from John Ryan about renal denervation:

Non-pharmacologic antihypertensive measures must remain the starting point for patients with hypertension, but will often not be enough. Renal denervation should be reserved for patients in whom behavior modification combined with adequate and skillful antihypertensive drug prescribing cannot achieve BP reduction to target. There are no clinical trial data to support renal denervation in hypertension outside of this setting. In countries where the “genie is out of the bottle”, and clinical use is authorized, prevention of overuse will be difficult. In some instances government regulations will confine the use of renal denervation to drug-resistant hypertension. Insurer or governmental reimbursement rules should be framed to prevent overuse.

Click here to read the entire CardioExchange interview.

Promising One Year Results For Renal Denervation In Resistant Hypertension Spark Hype Reply

by • Interventional Cardiology & Surgery, People, Places & Events, Policy & Ethics, Prevention, Epidemiology & Outcomes • Tags: , , ,

Denervation of the renal sympathetic nerve may become an important new tool in the fight against resistant hypertension.  Previously, the main results of the Symplicity HTN-2 trial demonstrated that in selected patients renal denervation resulted in a large and highly significant reduction in systolic blood pressure (BP) at six months. Now, longer followup from the trial, published in Circulation, demonstrates that the benefits at 6 months extend to one year, and that control patients who crossed over to renal denervation also experienced large reductions in BP.

For 47 patients with resistant hypertension, the reduction in systolic BP at one year (−28.1 mm Hg) was similar to the reduction at 6 months (31.7 mm Hg). For 35 control patients  who crossed over to renal denervation after six months, mean systolic BP dropped from 190.0±19.6 before the procedure to 166.3±24.7 mm Hg. The authors reported one case of renal artery dissection in the crossover group, which was fixed with renal artery stenting, and one episode of hypotension, which was fixed with a medication adjustment.

The results, according to a clinical perspective accompanying the article, suggest that “radiofrequency ablation of renal nerves can significantly lower blood pressure in patients with systolic blood pressures >160 mm Hg with no loss of treatment effect through 1 year and thus may provide a safe and effective adjunctive therapy for treatment-resistant hypertensive patients.”

Comment: Excitement about renal denervation has been growing in recent years. At least some of the optimism may well be warranted. But, for now, the greatest danger is hype. Here’s the #4 item on the AHA’s list, released just this week, of the top advances of 2012:

“Disconnecting” the kidneys might be the key to treating high blood pressure

What does that mean, “the key to treating high blood pressure?” As an invasive procedure, renal denervation will never be more than a important therapeutic option after lifestyle and polypharmacy have failed. I applaud the AHA for highlighting this important new technology, but I think it should have used more cautious wording.

Get ready for much worse. Gullible or naive reporters and editors have already fallen into the trap. Here’s the headline and opening sentences of a story that appeared earlier today in TheStar.com:

Zapping kidneys with radio waves could cure high blood pressure, study finds

In what’s being described as a potential public health miracle, a new study shows that zapping the kidneys with radio waves can safely and dramatically lower blood pressure.

“It makes one dizzy to think about the next set of benefits that follow,” said Dr. Clyde Yancy, head of cardiology at Chicago’s Northwestern University.

This is almost a textbook example of how science and medicine stories should not be reported. It’s important to activate your BS detector whenever you see words like “cure” and “miracle” in a health story. Renal denervation is not a cure and it’s not a miracle. If things work out, it may represent a welcome and significant advance for some patients with resistant hypertension.

To be fair, the rest of the story contains some great quotes and perspective from Clyde Yancy. But by then the damage has been done. It’s impossible to be rational in the presence of cures and miracles. Of course, any reporter can slip at some point and buy into the hype. We’re not perfect. But it helps if the reporter has some prior knowledge and experience in the field. I’m assuming this reporter had little background in this field, since no experienced health reporter would describe renal denervation as “bathing the kidneys in radio waves.” It’s hard enough for physicians and grizzled journalists to figure this kind of stuff out. This is no spot for learning on the job.

But let’s not blame the reporter. He was probably just doing his job as best he could, on a deadline and with few resources. He should be congratulated for getting a good interview with Clyde Yancy. The larger problem here is the way most media treat health, medicine and science stories. Breakthroughs and cures aren’t everyday events, except in the filler pages of tabloids, and on news broadcasts and websites, where scientific inflation is an everyday occurrence. In this context, scientific reporting becomes, essentially, worthless. If everything is a breakthrough then nothing is a breakthrough.
Click here to read the Medtronic press release…

Hypertension And Smoking Top List Of Global Risk Factors 1

by • Prevention, Epidemiology & Outcomes • Tags: , , , , , ,

Screen Shot 2012-12-13 at 2.57.27 PMWorldwide, hypertension and tobacco smoking are the single largest causes of death and disability, according to findings from the Global Burden of Disease Study 2010 (GBD 2010), the largest ever assessment and analysis of global health and disease. In an unprecedented move, the Lancet devoted an entire issue to the study, including seven separate articles and eight comments.

GBD 2010 was led by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington. In a press release, IHME director Chris Murray said, “For decision-makers, health-sector leaders, researchers, and informed citizens, the global burden of disease approach provides an opportunity to see the big picture, to compare diseases, injuries, and risk factors, and to understand in a given place, time, and age-sex group, what are the most important contributors to health loss.”

Despite significant reductions in the rate of ischemic heart disease and stroke since 1990, overall these retained their position as the #1 and #2 worldwide causes of death. Among men 15-49 years of age, CV disease was the single largest cause of death, accounting for 12.8% of all deaths. For women of the same age CV disease was the third largest cause of death, following HIV/AIDS and other non-communicable diseases, accounting for 10.7% of all deaths.

Ischemic heart disease in 2010 now ranks as the largest single cause of global years of life lost. In 1990 it had ranked fourth, behind lower respiratory infections, diarrhea, and preterm birth complications. Stroke moved from fifth place to third place.

High blood pressure emerged as the single most important risk factor for death and disability, followed by tobacco smoking. In 1990 the top two risk factors were childhood underweight (#8 in 2010) and household pollution (#4 in 2010).

Should Body Weight Influence Choice of Antihypertensive Therapy? 1

by • Heart Failure, Prevention, Epidemiology & Outcomes • Tags: , , , , , ,

The hypertension field has been troubled by repeated observations that normal weight patients have more cardiovascular (CV) events than obese patients. Now a new analysis of a large hypertension trial confirms this finding but also suggests that it may be explained by either an adverse effect of diuretics or a protective effect of calcium-channel blockers in non-obese hypertensives.

Michael Weber and colleagues analyzed data from more than 11,000 patients randomized in the ACCOMPLISH trial to shed light on this problem. In 2008 the main results of the trial showed that the combination of benazepril and amlodipine (calcium channel blocker group, CCB) was superior to the combination of benazepril and hydrochlorothiazide (diuretic group) in reducing CV events in high risk hypertensive patients.

The new analysis, published online in the Lancet, confirmed earlier observations and found significant differences in outcome based on weight. However, the differences in outcome occurred mostly in the diuretic group. In the diuretic group, the rate for the primary endpoint was significantly different between the groups (30.7 events per 1,000 patient-years in normal weight patients, 21.9 in overweight patients, and 18.2 in obese patients, p=0.0034). In the CCB group the rates were not significantly different (18.2, 16.9, and 16.5).

To explain their finding the investigators proposed that “hypertension in obese and lean patients is probably mediated by different forms of underlying pathophysiology.” Obese patients, who are more likely to have increased plasma volume and cardiac output, will be responsive to diuretics, while lean patients are more likely to have involvement of the sympathetic and renin-angiotensin systems. They concluded that “diuretic-based regimens seem to be a reasonable choice in obese patients in whom excess volume provides a rationale for this type of treatment, but thiazides are clearly less protective against cardiovascular events in patients who are lean. An alternative therapeutic regimen that includes a calcium channel blocker such as amlodipine, which works equally well across all BMI categories, provides an advantage with respect to clinical outcomes in patients who are not obese.”

In an accompanying comment, Franz Messerli and Sripal Bangalore write that the effectiveness of hydrochlorothiazide in obese people in ACCOMPLISH “has little if anything to do with obesity per se, but simply reflects the fact that among obese patients there was a preponderance of individuals at risk for heart failure who were prone to respond well to diuretic treatment.” They argue that “amlodipine-based treatment should be used irrespective of body size” for the indication of hypertension. Diuretics, on the other hand, should be used for the prevention of left-ventricular dysfunction.
Click here to read the press release from the Lancet…

Investigator Defends Controversial Transcendental Meditation Paper 3

by • People, Places & Events, Policy & Ethics, Prevention, Epidemiology & Outcomes • Tags: , ,

Editor’s Note: Here is a response by Dr. Robert Schneider to my story last week about his controversial paper on Transcendental Meditation that appeared in Circulation: Cardiovascular Quality & Outcomes. I will respond to Dr. Schneider’s post later this week.

Response from Dr. Robert Schneider

We appreciate the interest in our article published in Circulation: Cardiovascular Outcomes and Quality, November 2012.  However, there are several errors and inaccuracies in the blog. Many of these points were addressed in the Circulation Outcomes publication.  Below are highlights.

Robert Schneider, MD, director of the Institute for Natural Medicine and Prevention and dean of Maharishi College of Perfect Health in Fairfield, Iowa. Courtesy MAPI

1.     This was a prospective, randomized, controlled, single-blinded clinical trial.  This report is the first publication of data from the trial. It was revised in response to extensive peer-review over the past months.  Whatever unpublished version of the manuscript the bloggers had access to previously did not have the benefit of the most current peer review and revision.

2. There were a range of check and balances built into the study to ensure veracity.  For example:

  • data were collected blindly at the clinical site in Milwaukee
  • the trial was monitored by independent data safety and monitoring board
  • end point events were adjudicated by an independent reviewer using standardized criteria
  • results were confirmed by independent data analysis
  • limitations are enumerated and discussed in the publication

3. Regarding the hypothesis testing capacity of the study, according to the Consolidated Standards of Reporting Trials (CONSORT) guidelines,

“Randomised clinical trials (RCTs) are generally considered to produce the most solid evidence for the effectiveness of medical interventions”  (Keech 2007).  The CONSORT guidelines are recommended by the International Committee of Medical Journal Editors (ICMJE). The design, implementation, analysis and reporting of this trial followed CONSORT guidelines.  Thus this clinical trial was an experimental study that tested an hypothesis.  By contrast, observational studies, which this was not, generates hypotheses (http://en.wikipedia.org/wiki/Observational_study).

4.  The total number of primary end point events is within one of an earlier, unpublished version of the manuscript (noted in blog update November 18).  In preparation for the revised manuscript, one additional event was identified.  However, this had no meaningful effect on the results or statistical significance. That is, the main results are essentially unchanged.
Click to continue reading…

Mysterious Disappearing Paper Finally Reappears In Another Journal 33

by • People, Places & Events, Policy & Ethics, Prevention, Epidemiology & Outcomes • Tags: , ,

Robert Schneider, MD, director of the Institute for Natural Medicine and Prevention and dean of Maharishi College of Perfect Health in Fairfield, Iowa. Courtesy MAPI

Updated– Last year, in what may have been an unprecedented action, a paper on the effects of Transcendental Mediation (TM) in African Americans was withdrawn by the editors only 12 minutes before the paper’s scheduled publication in Archives of Internal Medicine. No definitive explanation was ever provided, though the editors and authors said that the action was prompted by last minute questions from reviewers at the NIH, which helped fund the study. (The episode was covered in detail on CardioBrief  (here and here) and on RetractionWatch.)

Now a new version of the paper has been published in Circulation: Cardiovascular Quality & Outcomes. The first author is Robert Schneider, from the Institute for Natural Medicine and Prevention at Maharishi University of Management in Maharishi Vedic City, Iowa. The co-authors are from the same institution and from the department of medicine at the Medical College of Wisconsin in Wisconin. It is clearly the same study of 201 African American patients randomized to TM or health education (HE) and followed for 5.4 years, though some of the numbers have changed in important ways between the earlier and later publications. One change involves the primary endpoint: the new paper in Circ:CVQ&O reports  52 primary endpoint events (the composite of death, MI, or stroke). Of these, 20 events occurred in the TM group and 32 in the HE group. By contrast, in the previous Archives version there were 51 primary endpoint events: 20 in the TM group and 31 in the control group.

In both papers the difference in the primary endpoint did not achieve statistical significance until after the investigators adjusted for baseline differences. The unadjusted hazard ratio (HR) for the new study was 0.64, (confidence interval 0.3701.12, p = 0.12); after adjusting for age, gender, and lipid lowering medications the HR drops, presto-chango, to 0.52 (0.29-0.92, p=0.025) and achieves statistical significance..

Dome shaped building on MUM campus, for the group practice of the TM-Sidhi program and Yogic Flying (Photo credit: Wikipedia)

Here are some other key questions that I have asked AHA, Circulation editors, and other experts to address:

– Was the AHA or the Circulation staff aware at any time that an earlier version of this paper had been scheduled for publication in Archives of Internal Medicine and withdrawn only 12 minutes before the scheduled publication time? Should this information have been disclosed by the study authors when submitting the paper?

– As mentioned above, the original publication in Archives appeared to have been cancelled because of questions raised by NIH reviewers. Have the Circulation: Cardiovascular Quality & Outcomes editors received any assurance that these questions have been addressed in the new paper?

– This trial was started all the way back in 1998 but was not registered on ClinicalTrials.Gov until February 2011 (shortly before the intended Archives publication). Why was it not registered earlier than 2011?

– June 2007 is listed in ClinicalTrials.Gov as the final data collection date for primary outcome measure. Why are the primary endpoint numbers different between the Archives and new version of this paper?

Update, November 13-- Harlan Krumholz, the editor of  Circulation: Cardiovascular Quality & Outcomes, sent the following statement:

“We had no prior knowledge of what transpired with the Archives of Internal Medicine.  The Schneider paper went through rigorous peer review, statistical review and editorial discussions and the authors of the article were responsive to the review process.  As a result, the paper was accepted for publication and we are going ahead as planned.  If you have any further questions, we suggest you contact the researchers directly.”

Update, November 18–  An earlier version of this article contained several mistakes. First, the difference in the number of primary endpoint events between the two papers is much smaller than I had stated. The original paper reported 51 primary endpoint events. The new paper reports 52 endpoint events. I am still unclear about why there should be any difference between the two, since, as mentioned above, June 2007 was the final data collection date for the primary endpoint. I also incorrectly claimed that some  data reported in the original Archives paper were not included in the new paper. In fact, as a reader pointed out in the comments section below, these data were reported in Figure 1. I apologize for this mistake and regret the error. –LH

I asked Sanjay Kaul for his perspective on the paper. Here are his points:
Click to continue reading…

Antihypertensive Use Among Pregnant Women on the Rise Reply

by • Prevention, Epidemiology & Outcomes • Tags: , ,

Growing numbers of pregnant women are taking antihypertensive drugs that may harm themselves or their babies, according to a new study published in Hypertension.

Brian Bateman and colleagues analyzed Medicaid data from more than 1.1 million pregnant women. Overall, 4.4% of the women received antihypertensive medications at some point during their pregnancy. From 2000 to 2007 the use of antihypertensive drugs increased from 3.5% to 4.9%. This increase, according to the authors, is “consistent with the rising rates of chronic hypertension and gestational hypertension… which in turn may reflect rising rates of obesity and advanced maternal age in US parturients.”

Exposure to antihypertensive drugs occurred in 1.9% of women during the first trimester, 1.7% during the second trimester, and 3.2% during the third trimester. ACE inhibitors, which are contraindicated in late pregnancy, were used in 4.9% of women who used antihypertensive medications in the second trimester and 1.1% in the third trimester. The authors said that automatic refills and the ”prescribing physicians’ failure to ask about the possibility of pregnancy are two plausible explanations.”

About half of women who had been taking antihypertensive drugs prior to their pregnancy discontinued drug treatment during the first or second trimester. According to the authors, although antihypertensive therapy for mild-to-moderate hypertension can prevent progression to severe hypertension it is unknown whether it can reduce the risk of pregnancy complications, including placental abruption, fetal demise, superimposed preeclampsia, preterm birth, or maternal morbidity.

“While we know high blood pressure, or hypertension, occurs in about 6 percent to 8 percent of all pregnancies, we know little about how women and their doctors treat the condition,” said Bateman, in an AHA press release.

The authors pointed out that “there is virtually no data on the comparative effectiveness and safety of the different treatment options for hypertension” in pregnant women. “Research investigating the comparative safety and efficacy of antihypertensive therapy in pregnancy is urgently needed to define the optimal approach to therapy.”

Republished with permission from CardioExchange, a NEJM group publication.

Click here to read the AHA press release…

CDC: 35 Million Americans Have Uncontrolled Hypertension 2

by • Prevention, Epidemiology & Outcomes • Tags: , , ,

According to the Centers for Disease Control, new data from the National Health and Nutrition Examination Survey (NHANES) shows:

  • 30.4% of US adults (about 66.9 million people) have hypertension.
  • 53.5% have uncontrolled hypertension (about 35.8 million people).
  • 39.4% with uncontrolled hypertension (about 14.1 million) are unaware that they have hypertension.
  • 89.4% with uncontrolled hypertension have a “usual source of health care and insurance, representing a missed opportunity for hypertension control.”

The CDC authors conclude: “The findings in this report can be used to target populations and refine interventions to improve hypertension control. Improved hypertension control will require an expanded effort from patients, health-care providers, and health-care systems.”

 

 

Studies Probe Effect Of CPAP And Sleep Apnea On Hypertension Reply

by • Prevention, Epidemiology & Outcomes • Tags: , ,

Two studies published in JAMA provide additional but not surprising information about the relationship between obstructive sleep apnea (OSA), hypertension, and the role of continuous positive airway pressure (CPAP).

In the first study, Ferran Barbé and colleagues randomized 725 people with OSA but no daytime sleepiness to either CPAP or no active treatment. Although there were fewer cases of systemic hypertension or cardiovascular events in the CPAP group than in the control group after a median followup of 4 years, this difference did not reach significance.

Incidence of hypertension or cardiovascular events:
Click to continue reading…

A Case of Plagiarism Raises Blood Pressures 1

by • Policy & Ethics • Tags: , ,

Plagiarism: it’s enough to raise your blood pressure.

An article in Korean Circulation Journal appears to plagiarize from a similar article in the Journal of the American College of Cardiology (JACC). In 2009, Franz Messerli, a well-known hypertension expert at St Luke’s Roosevelt Hospital Center in New York, and Gurusher Panjrath, at Johns Hopkins Hospital, published a Viewpoint and Commentary in JACC: The J-Curve Between Blood Pressure and Coronary Artery Disease or Essential Hypertension: Exactly How Essential?  Less than two years later, two Korean physicians, Chang Gyu Park and Ju Young Lee, published an article with striking similarities to the JACC article: The Significance of the J-Curve in Hypertension and Coronary Artery Diseases.

The Korean article includes some content not included in or published after the JACC article, but a large proportion of the article represents obvious plagiarism. The Korean article fails to even cite the JACC article from which it clearly derives so much of its content, language, and organization. However, it should be noted that the Korean article does not resort to word-for-word copying of the original.

Here are some similarities in the heading and text found in just one paragraph in the papers:

Heading from JACC:

Pathophysiologic Consideration: Coronary Flow and BP

Heading from Korean Circulation Journal:

Mechanism of the J-Curve and the Pathophysiologic Approach

First sentence from JACC:

The coronary circulation is unique in that most of coronary blood flow to the left ventricle (LV) occurs in diastole.

First sentence from Korean Circulation Journal:

Most of the coronary circulation occurs during diastole.

Second sentence from JACC:

During systole, the contracting LV myocardium compresses intramyocardial vessels and obstructs its own blood flow.

Second sentence from Korean Circulation Journal:

During systole, the left ventricular (LV) myocardium contracts and compresses the intramyocardial vessels to impede its blood flow.

Last sentence in paragraph from JACC:

When coronary perfusion pressure is lowered to 40 to 50 mm Hg, the so-called pressure at 0 flow, diastolic blood flow in the coronaries ceases.

Last sentence in paragraph from Korean Circulation Journal:

When the coronary perfusion pressure is lowered to 40-50 mmHg, the blood flow due to coronary perfusion pressure theoretically approaches 0 with exclusion of the LV diastolic pressure.

A careful examination of the papers reveals many similar instances of obvious copying. In addition, the Korean authors use many of the same headings, figures, and references used in the JACC paper.

When the Korean paper was brought to his attention, Messerli attempted to contact the Korean authors and editors.  He also informed Tony DeMaria, the editor of JACC, about the situation. CardioBrief has requested comments from DeMaria, Ho Joong Youn,the editor of Korean Circulation Journal, and the two authors of the Korean paper.

Editor’s note: Marilyn Mann, a well-known blogger and medical watchdog, performed the detailed comparison of the two articles on which this post relies. Once again, I am extremely grateful for her assistance.