March 12th, 2013

More Negative Heart Failure Trials: Blogging from ACC.13

Several Cardiology Fellows who are attending ACC.13 in San Francisco this week are blogging for CardioExchange. The Fellows include Tariq AhmadMegan CoylewrightJeremiah DeptaKumar Dharmarajan Payal Kohli, and  Sandeep Mangalmurti. View the previous post here and the next one here.

Some important “late breakers” were presented today, the 3rd and last day of ACC.13. I was particularly looking forward to hearing the results of the RELAX trial. Would sildenafil be useful for the treatment of diastolic heart failure? For a disease that appears to have no treatment, the results of this exciting Heart Failure Network study were highly anticipated by patients and physicians alike.

The results of ASTRONAUT were also presented. This looked at the use of aliskiren (direct renin inhibitor) in systolic heart failure.

However, as with most trials in heart failure, the results were negative.

I wonder why we continue to have such terrible luck with therapeutics in heart failure. Perhaps the disease is far too complex for drugs based on single targets to be successful. Or maybe we are viewing the disease process incorrectly and need a paradigm shift in how we describe heart failure.

Is there even such a thing as diastolic and systolic heart failure? Until the 18th century, diseases were described in terms of evil humors, and patients treated accordingly (by bleeding or purging). As might be expected, the treatments were ineffective. We may continue to be victims of inaccurate classifications.

On a more positive note, I found the results of the STOP-HF trial to be quite intriguing. This study looked at the benefit of natriuretic guided screening and treatment in patients with stage A heart failure. The investigators found very significant decreases in heart failure and cardiovascular events.

I am the fellow on the GUIDE-IT trial that just began enrollment. My mentor at DCRI, Mike Felker, is the PI on this trial. We are looking at the effects of natriuretic peptide guided treatment in patients with advanced heart failure.

As we understand more about the molecular biology of heart failure, we may have more tools like the natriuretic peptides that help us define and treat the disease more effectively.

And therapeutics aimed at more accurate definitions of heart failure might result in more positive trial results.

For more of our ACC.13 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our Coverage Headquarters.

3 Responses to “More Negative Heart Failure Trials: Blogging from ACC.13”

  1. Dan Hackam, BSc, MD, PhD, FRCPC says:

    Dear Tariq,

    Re: STOP-HF

    If the trial “very significantly decreased heart failure and cardiovascular events” simply by getting more patients in the BNP-guided arm onto a higher rate of evidence-based therapies (such as beta blockers, ACE inhibitors, aldosterone antagonists, diuretics, etc), then isn’t this just a proof that these drugs work (which we already know from numerous and diverse trials), and that more such high risk patients in primary care need to be optimally treated with these drugs? At baseline, the patients in STOP-HF had a very, very low frequency of these agents (as indicated in the presentation of baseline data at ESC – I am therefore not surprised that treating patients with asymptomatic LVSD would prevent events – I think we already knew that from SOLVD and other trials. Thanks for your comments and insights!

    Dan Hackam

  2. Tariq Ahmad, MD, MPH says:

    Dr. Hackam, Thank you for your comments!

    I think you are completely correct. We have noted this ‘treatment gap’ in patients with NYHA class II-III low ejection fraction heart failure as well. One of the reasons for this may be that currents methods to evaluate degree of heart failure are not very sensitive or specific. Two patients with an EF of 20% may be worlds apart in their disease state. Having a sensitive molecular marker of disease could potentially help close that gap at all stages of heart failure.

    Dr. Jaunzzi showed this very nicely in the PROTECT trial and the ongoing GUIDE-IT trial will be asking this question on a larger scale.

  3. Dan Hackam, BSc, MD, PhD, FRCPC says:

    Hi Tariq,

    Screening everyone over the age of 40 in a family practice who happens to have diabetes or hypertension with BNP (and followed by echocardiography if BNP>50 pg/mL), coupled with initiation of ACE inhibitor, beta blocker and aldosterone antagonist, would likely be massively expensive (even though cardiovascular hospitalizations were reduced by a little less than half – 2.4% per year vs. 4.5% per year). It would be nice to see cost-effectiveness data before proceeding further with population-wide screening. Also, one could argue on the basis of trials like HOPE and ASCOT that patients with diabetes or hypertension should already be on a statin and ACE inhibitor, and in those with resistant hypertension, the addition of either a beta blocker or aldosterone antagonist is often very useful for further reducing risk. I have never see family physicians order either echo or BNP in asymptomatic 40-year-olds with hypertension or diabetes, and the BNP would have to be paid for out-of-pocket in our province.

    In the past, the USPSTF and AHRQ have tended to recommend against widespread screening maneuvers such as resting ECG, treadmill ECG stress testing, carotid ultrasonography, ABI screening, etc. However, few of these have associated studies such as STOP-HF showing clinical outcome benefit coupled with screening in a real life setting. It would be fantastic to have data on quality of life at follow-up as well as economic benefits.