After an average follow-up of 4.2 years, people in the active intervention arm of STOP-HF had a 5% cumulative incidence of left ventricular dysfunction or heart failure, while those in the control arm had a 9% rate, a 45% relative risk reduction from the active intervention that was statistically significant for the study’s primary endpoint (JAMA. 2013 July 3;310[1]:66-74).
The second study, PONTIAC (NT-proBNP Selected Prevention of Cardiac Events in a Population of Diabetic Patients Without a History of Cardiac Disease), ran in Austria and Germany and involved 300 patients who had type 2 diabetes and were free from cardiac disease at baseline. At baseline, all people considered for the study underwent a screening measure of their blood level of NT-proBNP (a physiologic precursor to BNP) and those with a level above 125 pg/mL were randomized to either a usual-care group or an arm that underwent more intensified up-titration treatment with a renin-angiotensin system antagonist drug and with a beta-blocker. The primary endpoint was the incidence of hospitalization or death due to cardiac disease after 2 years, which was a relative 65% lower in the intensified intervention group, a statistically significant difference (J Am Coll Cardiol. 2013 Oct 8;62[15]:1365-72).
Both studies focused on people with common risk factors seen in primary care practices and used BNP or a BNP-like blood marker to identify people with an elevated risk for developing heart failure or other cardiac disease, and both studies showed that application of a more aggressive risk-factor intervention program resulted in a significant reduction in heart failure or heart failure–related outcomes after 2-4 years. Both studies appeared to offer models for improving risk-factor management by PCPs for people with stage A heart failure, but at the end of 2015 neither model had undergone U.S. testing.
Dr. Tariq Ahmad
“The STOP-HF and PONTIAC studies were proofs of concept for using biomarkers to gain a better sense of cardiac health,” said Dr. Tariq Ahmad, a heart failure physician at Yale University in New Haven, Conn., who is interested in developing biomarkers for guiding heart failure management. “Metrics like blood pressure and heart rate are relatively crude measures of cardiac health. We need to see in a large trial if we can use these more objective measures of cardiac health to decide how to treat patients,” In addition to BNP and NT-proBNP, Dr. Ahmad cited ST2 and galectin-3 as other promising biomarkers in the blood that may better gauge a person’s risk for developing heart failure and the need for intensified risk-factor control. The current inability of PCPs to better risk stratify people who meet the stage A heart failure definition so that those at highest risk could undergo more intensified interventions constitutes a missed opportunity for heart failure prevention, he said.
“The STOP-HF trial is really important and desperately needs replication,” said Dr. Margaret M. Redfield, professor of medicine and a heart failure physician at Mayo Clinic in Rochester, Minn.
She, and her Mayo associates, including Dr. McKie, are planning to launch a research protocol this year to finally test a STOP-HF type of program in a U.S. setting. They are planning to measure NT-proBNP levels in patients with stage A heart failure and then randomize some to an intervention arm with intensified risk reduction treatments.
“The problem with stage A today is, if we apply it according to the ACC and AHA definition, it would include quite a large number of patients, and not all of them – in fact a minority – would go on to develop symptomatic heart failure,” said Dr. McKie. “How you can further risk stratify the stage A population with simple testing is an issue for ongoing research,” he said. “The STOP-HF and PONTIAC strategies need more testing. Both studies were done in Europe, and we haven’t studied this approach in the U.S. Their approach makes sense and is appealing but it needs more testing.”
The economic barrier to intensified stage-A management
Even if a U.S. based study could replicate the STOP-HF results and provide an evidence base for improved prevention of symptomatic heart failure by interventions instituted by PCPs, it’s not clear whether the U.S. health care system as it currently is structured provides a framework that is able to invest in intensified upfront management of risk factors to achieve a reduced incidence of symptomatic heart failure several years later.
“One of the interesting aspects of STOP-HF was its use of a nurse-based intervention. We don’t have the resources for that in our practices right now,” noted Dr. Cunningham, the PCP at Brigham and Women’s Hospital who is medical director of the hospital’s Integrated Care Management Program for medically complex patients. While that program uses nurse care coordinators to pull together the disparate elements of care for heart failure patients and others with more severe, chronic illnesses, the program currently serves only patients with advanced disease, not presymptomatic patients who face a potentially elevated risk for bad outcomes that would happen many years in the future.