Findings in heart failure late-breaking research
Researchers presented their findings in Monday’s last Late-Breaking Science session, “Recipes for Success in Heart Failure.” They found that:
- Polypill improves heart failure outcomes compared to usual medications.
- The PCSK9 inhibitor alirocumab improved lipids after heart transplant vs. statin monotherapy, but not arterial plaque volume.
- Fresh produce beats tailored medical meals, usual care after heart failure.
- ·Tirzepatide improves survival vs. dulaglutide in type 2 diabetes with or without heart failure.
Polypill improves heart failure outcomes compared to usual medications
What may be the first trial of a polypill combining multiple guideline-recommended medications for heart failure found that combining multiple formulations in a single capsule improved left ventricular ejection fraction (LVEF) compared to the same medications provided as discrete oral formulations, with up to three absolute percentage points higher LVEF at six months follow-up (39.9% vs. 36.5%).
Polypill use also reduced the risk of heart failure hospitalization and ED visits, improved quality of life and substantially improved medication adherence compared with enhanced usual care with multiple medications.
“The polypill is all about convenience,” said Ambarish Pandey, MD, MSCS, associate professor of cardiology and geriatrics and medical director of the HFpEF Program at the University of Texas Southwestern Medical Center. “Taking just one pill a day reduces the burden of polypharmacy. The polypill also makes initiation and up-titration easier because you can change just one pill instead of adjusting three separate pills. One pill is just a better regimen.”
POLY-HF randomized 212 participants to once-daily over-encapsulated polypill (108 patients) containing metoprolol succinate at either 25/50/100/150 mg, spironolactone 12.5 mg and empagliflozin 10mg or enhanced usual care (104) consisting of the same guideline directed medications as individual pills. Patients continued a separate angiotensin system inhibitor. Over-encapsulation is commonly used in pharmacy to combine multiple medications into a single oral formulation.
The trial population was young, with a median age of 54 years, and recruited primarily from a safety net hospital center. Participants were 54% Black, 33% Hispanic and 20% Spanish-speaking. Participants self-reported a high burden of adverse social determinants of health, with 68% uninsured or dependent on local indigent health programs, 43% reporting food insecurity and 32% reporting housing instability.
The median baseline LVEF was 26% by cardiac MRI, median NT-proBNP 958 pg/mL, a high comorbidity burden and 85% had recent HF hospitalization. Nearly half (48%) were on quadruple guideline-directed medical therapy at any dose, but 73% had moderate-low medication adherence based on self-report via adherence survey.
The primary outcome was LVEF by cardiac MRI at six months. Secondary endpoints included changes in clinical outcomes, quality of life and medication adherence.
In addition to improved LVEF, patients in the polypill group vs. the enhanced usual care group had a 60% fewer HF hospitalizations, emergency visits and deaths. Quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire instrument, improved significantly in the polypill arm vs. usual care by 8.5 points.
Polypill was also associated with improved medication adherence, as assessed by blood-based drug monitoring, 79.3% fully adherent to tested medications in polypill vs. 54.3% in the usual care arm.
Pandey added that odds of adherence were up to fourfold higher in the polypill group vs. usual care.
“This polypill strategy demonstrates that if we make it easier for patients to take medications, we can improve uptake and improve clinical outcomes,” Pandey said. “We have to do a larger study to confirm the clinical improvements, but this should pave the way for bringing polypill as the standard of care. We can use a very simple, very cost-effective pharmacy strategy to improve uptake and outcomes.”
Alirocumab improves lipids after heart transplant, but not arterial plaque volume
A second randomized controlled trial of a PCSK9 inhibitor to reduce the incidence of cardiac allograft vasculopathy found that adding alirocumab to maximum tolerable statin therapy improved lipid profiles one year after transplantation. LDL levels declined to 31.5 mg/dL from a baseline of 72.7 mg/dL for patents on alirocumab + rosuvastatin vs. remaining stable for patients on rosuvastatin alone.
But adding alirocumab to rosuvastatin had no significant effect on the volume of plaque deposited in the left anterior descending (LAD) artery compared to rosuvastatin alone.
William Fearon, MD
A total of 114 heart transplant patients at multiple U.S. centers were started on maximum tolerable dose of rosuvastatin, up to 20 mg/day. Patients were assessed at baseline using intravascular ultrasound, near infrared spectroscopy and coronary physiology, including fractional flow reserve, coronary flow reserve and the index of microcirculatory resistance, and again at 12 months.
Patients were randomized to either alirocumab or placebo following the initial assessment.
The primary endpoints were changes in lipid profiles and plaque volume at 12 months.
Patients in the alirocumab arm showed an absolute reduction in LDL of 41.2 mg/dL (p<0.001) Plaque volume increased numerically in both groups, from 176.3 to 184.5 mm3 in the alirocumab group and 173.7 to 183.1 mm3 in the placebo group, but the difference in change between the groups was not significant.
Fearon noted that patients on statin monotherapy in earlier studies, most often pravastatin and other less potent agents, showed significant increases in plaque volume over time. Statin-only patients in CAVIAR did not show similar increases in plaque volume.
“One reason plaque volume did not increase significantly in the placebo arm is that we were more aggressive with rosuvastatin, up to 20 mg/day or maximum tolerable dose,” Fearon said. “Because patients had such a low baseline LDL and were managed so aggressively, their plaque didn’t increase, which made it hard to show a reduction with alirocumab.”
An ad hoc exploratory analysis of patients who had baseline LDL above the median found that alirocumab did show plaque volume benefit.
CAVIAR was published simultaneously in Circulation.
Fresh produce beats tailored medical meals, usual care after heart failure
A small trial comparing food interventions to usual care following discharge after heart failure treatment found that prescribing food as medicine improves outcomes compared to usual care. The FOOD-HF trial found no statistical difference in rehospitalization or ED visits for heart failure, but patients receiving food supplementation had over two-fold higher odds of achieving clinically meaningful quality of life improvement. The benefit was seen primarily in the fresh produce group.
Ambarish Pandey, MD, MSCS
“A composite win ratio that combined mortality, hospitalization and ED visits, and quality of life was significantly better in favor of food intervention, driven by the higher likelihood of improvement in quality of life, with an adjusted odds ratio of 2.09 compared to usual care.”
The trial randomized 150 acute heart failure patients at both an urban safety net hospital and a university hospital within two weeks of discharge to medically tailored meals, weekly fresh produce boxes or usual care with dietary counseling over 90 days. Patients randomized to food intervention were further randomized to unconditional delivery or delivery tied to completing pharmacy fills and clinic visits.
The study population was 39% female, 42% Black and 33% Hispanic. Participants had a median left ventricular ejection fraction of 35%, and 29% had heart failure with preserved ejection fraction >50%. Most patients (93%) had hypertension, 55% had diabetes and 53% reported a substantial burden of food insecurity. Most reported nutritional insecurity (55%), medium to low medication adherence (69%) and 41% had limited insurance coverage.
The primary endpoint was a composite of hospital heart failure readmission or ED visits. Secondary endpoints included a hierarchical composite outcome (analyzed using win ratio methodology prioritizing all-cause death, heart failure hospitalizations/ED visits and clinically meaningful quality of life improvement (assessed by the Kansas City Cardiomyopathy Questionnaire), change in Kansas City Cardiomyopathy Questionnaire scores, clinic attendance rates and medication adherence.
There were just 32 heart failure readmissions or ED visits, Pandey reported, an artifact of small trial numbers and short duration. Conditional vs. unconditional food delivery had no significant effect on readmissions or ED visits, but food intervention linked to pharmacy and clinic visits was associated with improved quality of life.
“This study showed that in a contemporary hospitalized heart failure population, we can successfully deliver food supplements and food interventions with good fidelity and very good acceptance of fresh produce,” Pandey said. “We saw robust improvement in quality of life, which is highly relevant to patients. FOOD-HF highlights the value of food supplementation in improving health status for patients with heart failure hospitalization. A lot of insurance programs, including Medicare Advantage programs, cover food as medicine, so you can actually prescribe food as medicine as a covered benefit. Grocery prescriptions can be very meaningful to patients.”
Tirzepatide improves survival vs. dulaglutide in type 2 diabetes with or without heart failure
Tirzepatide once weekly reduced all-cause mortality in patients with type 2 diabetes compared to dulaglutide regardless of heart failure history. For individuals with type 2 diabetes and no history of heart failure, those on tirzepatide had fewer deaths and heart failure events vs. those on dulaglutide, 10.5% vs. 12.1%, HR 85 (95% CI: 0.77 to 0.95). Among those with a history of heart failure, the hazard ratio for all-cause mortality or heart failure events was 0.83 (95% CI: 0.70 to 0.99). But there was no difference in hospitalization or urgent visits for heart failure between the two groups. The results were part of a prespecified analysis of the SURPASS-CVOT randomized clinical trial.
Stephen Nicholls, MD
The primary analysis of SURPASS-CVOT showed that tirzepatide is noninferior to dulaglutide in reducing the risk of major cardiovascular events in adults with type 2 diabetes and atherosclerotic cardiovascular disease, HR 0.92 (95% CI: 0.83 to 1.01). The hazard ratio for cardiovascular death and heart failure was 0.91 (95% CI: 0.81 to 1.03) and for all-cause mortality 0.84 (95% CI: 0.75 to 0.94).
A prespecified sub-analysis compared the two agents in the 20.3% of SURPASS-CVOT patients with a history of heart failure and those with no heart failure history. Individuals with a history of heart failure at baseline had more coronary artery disease (77.6% vs. 61.8%) and more prior myocardial infarctions (57.8% vs. 44.5%) than those with no heart failure.
Although the tirzepatide group showed a reduction in risk for all-cause death + heart failure events and for all-cause death (HR 0.80, 95% CI: 0.65 to 0.97) for individuals with a history of heart failure, there was no significant difference for cardiovascular death or heart failure events (HR 0.85, 95% CI: 0.70 to 1.03), cardiovascular death (HR 0.80, 95% CI: 0.63 to 1.02), or hospitalization or urgent visits for heart failure (HR 0.97, 95% CI: 0.73 to 1.27). The results were similar for those with no heart failure history.
“These results are good for patients because it means there are more options,” Nicholls said. “Giving patients choice will improve all the other things that you want, more weight loss, better improvements in glycemic control, more favorable effects on kidney function. We’ve seen benefits in liver disease, sleep apnea and joint disease from GLP-1 agents. These are long-term therapies, and we need people to buy into decision-making on how to treat and how to continue treating in the long term.”
