Monitoring Pulmonary Hypertension to Guide Treatment and Using Sacubitril/Valsartan to Treat Heart Failure Saves Lives

Research results presented at HFSA 2016 support switching from conventional treatment approaches to the new combination treatment.

At the 2016 annual meeting of the Heart Failure Society of America, Milton Packer, MD, Distinguished Scholar in Cardiovascular Science, Baylor University Medical Center at Dallas, provided an update on recent developments in the pharmaceutical treatment of heart failure (HF) with reduced ejection fraction.

He started by critically noting that there is actually very little new when it comes to reduced ejection fraction HF drugs. The main options in widespread use continue to be diuretics, inhibitors of the renin-angiotensin system, inhibitors of the sympathetic nervous system (beta blockers), or aldosterone antagonists. Packer emphasized, “It is amazing that the cornerstone treatment of HF therapy, diuretics, turns out to be one of the least studied. Most importantly, we have no idea how to dose diuretics. If you get 10 different physicians, you are likely to find 10 different diuretic regimens. You might say, ‘Well, what guides that thinking process?’ and the answer is ‘I don’t know!’”

At the most basic level of understanding, Packer said that pulmonary artery hypertension is not just the result of fluid retention, but also fluid redistribution. In the days immediately preceding HF hospitalization, there is actually more often a redistribution of fluids than there is an edematous overt increase in fluid retention (the latter detectable as an increase in weight). Patients equipped with pulmonary artery sensors in randomized trials had a lower risk of heart failure than patients under the care of physicians who did not have access to pulmonary artery sensors.

Consistent with these observations supporting the use of pulmonary artery monitoring to increase therapeutic efficacy, evidence of dramatic decreases in mortality was provided in a separate HFSA 2016 presentation by Michael Shochat, MD, from the Hillel Yaffe Heart Institute in Hadera, Irsrael. These studies used lung-impedance guided treatment. Packer raised the interesting possibility that we need other ways of titrating the use of diuretics, as we still do not have a standard way of doing this.

Finally, Packer also highlighted new ways of inhibiting the renin-angiotensin system (RAS). To date, these approaches have only exerted modest effects on mortality. However, starting with development of the neprilysin inhibitor sacubitril, progress has been made. When patients with heart failure were treated in clinical trials with a combination of sacubitril and the angiotensin receptor blocker valsartan, researchers reported an impressive 20% reduction mortality compared to patients who received enalapril. Essentially, the sacubitril doubled the effects of the RAS blocker. Moreover, patients treated with sacubitril/valsartan reported fewer adverse events than those who received enalapril.

A statistically significant difference was observed within just 30 days of treatment with sacubitril/valsartan. The reduction in death was particularly pronounced in patients who already had an implantable cardioverter defibrillator (ICD). So, the use of ICD does not obviate the use of the combo drug, and actually suggests an urgency to use sacubitril/valsartan in ICD patients, according to Packer.

In the end, Packer pointed out that we have been talking about this for the last 18 months. Other researchers have shown that if you don’t switch patients from an ACE inhibitor or a conventional AR blocker to sacubitril/valsartan, then you will end up with 28,000 unnecessary deaths a year. Calculation yields one unnecessary death every 18 minutes. This brings home the urgency to pay heed to and evangelize these results to support using sacubitril/valsartan instead of conventional ACE inhibitors or AR blockers, he said.

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