LBS 05: Innovation in prevention
Two-drug polypills, electronic nudges, ZODIAC and pacemakers.
Sunday’s Late-Breaking Science session “Innovation in Prevention and Global Implementation” reported that:
- Two-drug polypill combo reduced blood pressure across India.
- Electronic nudges can improve flu vaccination rates, especially in high-risk CVD populations.
- ZODIAC found no benefit from decision support system to encourage more intensive lipid-lowering therapy after ACS versus standard care.
- Preliminary results confirmed reconditioned pacemakers work as well as new units for the first 90 days post implantation.
Two-drug polypill combo reduced blood pressure across India
Three two-drug fixed dose combination successfully lowered blood pressure in the first randomized polypill clinical trial exclusively in South Asians. The TOPSPIN trial compared fixed-dose combinations of amlodipine/perindopril, perindopril/indapamide and amlodipine/indapamide in nearly 2,000 adults with hypertension in India. All three combinations showed similar efficacy and safety, with >70% of participants achieving <140/90 mmHg and >40% achieving <130/80 mmHg. Fewer than 3% of participants withdrew due to adverse effects.
Dorairaj Prabhakaran, MD, DM, MSc
“South Asians account for one-fourth of the world population, and India, in particular, has an enormous burden of hypertension leading to high stroke and cardiovascular disease risk,” said Dorairaj Prabhakaran, MD, DM, MSc, executive director of the Centre for Chronic Disease Control (CCDC) in New Delhi, India. “Optimal blood pressure management is essential to lower the cardiovascular complications of high blood pressure.”
TOPSPIN randomized 1,981 adults between the ages of 30 and 79, 42%, 18.6% with type 2 diabetes, and 6.2% current smokers across 35 centers across four geographic regions of India, reported Dimple Kondal, PhD, head of Med Stats & Data Management and senior research scientist biostatistics, CCDC in New Delhi, India. Most patients, 55%, were already taking at least one blood pressure-lowering medication.
The primary endpoints were change in ambulatory 24-hour blood pressure over six months and safety of the three polypill combinations.
There were statistically no differences in either blood pressure control with similar rates of adverse events between the three groups, Prabhakaran reported.
“The results of this study can be easily extrapolated to larger populations due to the diversity of the participants enrolled in India and the South Asian diaspora at large,” Prabhakaran said. “More than five million South Asians live in the U.S.; our study has huge relevance for them.”
NUDGE FLU: Electronic nudges can improve flu vaccination rates after MI
Three clinical trials among >2 million individuals found that electronic letters to patients delivered via a governmental electronic mailbox can improve influenza vaccination rates. Although a behavioral science informed electronic nudge improved vaccination rates similarly in those with and without prior myocardial infarction (MI) versus usual care, a letter highlighting the cardiovascular benefits of vaccination was significantly more effective in improving vaccination in individuals who survived myocardial infarction. 
Ankeet S. Bhatt, MD, MBA, ScM
“There has been compelling randomized clinical trial evidence suggesting that influenza vaccination in patients with a history of MI might prevent future cardiovascular events,” said Ankeet S. Bhatt, MD, MBA, ScM, a research scientist at the Kaiser Permanente Division of Research and an adjunct professor of Medicine at Stanford University School of Medicine. “We evaluated the effects of subtle changes, or nudges, informed by behavioral economics, to understand if the way we communicate with patients may affect their all-around preventative care.
Three nationwide pragmatic trials, NUDGE-FLU, NUDGE-FLU-2 and NUDGE-FLU CHRONIC, were conducted across the 2022-23 and 2023-24 influenza seasons in Denmark. Participants were randomized to usual care, usually standardized electronic letter informing patients of vaccine availability, or one of several different behaviorally informed letters. There was a total of 2,146,124 randomizations across the two seasons, of whom 59,458 (2.8%) occurred in patients with a history of acute MI (AMI). The primary endpoint was receipt of influenza vaccination.
Improvement in vaccine uptake was similar in individuals who received any nudge letter versus usual care, 1.81% and 1.32% respectively, regardless of AMI status (Pinteraction=0.09). A nudge letter highlighting cardiovascular benefits of flu vaccination was more effective in those with a history of AMI, 3.91% versus 2.03% for those without AMI history (Pinteraction=0.002). Among patients with prior AMI, the nudge letter highlighting cardiovascular benefits was more effective in those who were not vaccinated in the prior season, 13.7% versus 1.48% (Pinteraction<0.001). Highlighting cardiovascular benefits was particularly effective among younger patients with a more recent MI.
“The cardiovascular focused nudge improved vaccination rates for everyone, but even more so for patients with myocardial infarction, a population which is at high risk and may be likely to have multiple benefits with routine influenza vaccination,” Bhatt said. “Of course, validation in other global health care settings is needed, but this is a very simple, low-cost, highly scalable messaging strategy that should be considered to motivate patients with a history of AMI to receive influenza vaccination.”
NUDGE-FLU was published simultaneously in JAMA Cardiology.
No benefit from clinical decision support system for lipid-lowering therapies after ACS versus usual care
First results from a trial comparing standard of care lipid-lowering therapy (LLT) for patients after acute coronary syndrome (ACS) to a decision support system (DSS) based on individual atherosclerotic cardiovascular disease (ASCVD) risk found no significant benefit to DSS.
Preliminary data from the ZODIAC trial showed a numerical trend in favor of DSS, 70.7% versus 59.7%, but the results were not statistically significant, risk ratio (RR) = 1.15, 95% CI 0.93-1.41.
Kausik K. Ray, MD, MPhil
“It’s sobering to remember that the vast majority of patients that are admitted to hospital with an acute coronary syndrome or a myocardial infarction are lipid-lowering treatment naïve,” said Kausik K. Ray, MD, MPhil, professor of public health at the Imperial College London. “The first-time patients often receive a cholesterol lowering treatment is after event.”
Only one in four patients achieve LDL-C goals on monotherapy within three months of ACS, Ray said. Standard of care for LLT following ACS is a stepwise intensification of LLT, usually based on LDL-C levels, that can take weeks to months to reach LDL-C goal if it ever does.
The investigator-initiated trial developed a DSS based on individual ASCVD risk to implement more intensive LLT earlier and potentially reach lipid goal sooner than standard care.
A total of 1,139 ACS patients were randomized to standard care (n=616) or DSS (n=523) across 42 sites in the U.K., Italy and Spain. The median age of patients was about 62 and 21% were female.
Ray noted that the DSS did not tell clinicians what to do but offered medication options associated with ASCVD risk scenarios. Clinicians were not required to accept the medication options offered.
The primary endpoint was the proportion of patients receiving combination therapy, intensified monotherapy, or escalated combination therapy within 16 weeks of ACS, including escalations after discharge. Other endpoints included the LLT regimen at discharge and the timing of LLT escalation.
ZODIAC showed a shift in prescribing behavior toward more potent combination therapies at discharge in the DSS arm, 51.2% vs. 39.1%, and more participants received their first LLT escalation before discharge in the DSS arm.
“The trends were in the right direction,” Ray said. "The changes that occurred in the group with access to the DSS, the vast majority occurred pre-discharge and in the usual care group those changes were occurring post discharge."
Initial data show reconditioned pacemakers not inferior to new pacemakers at 90 days
Individuals living in low- and middle-income countries have poor access to pacemaker therapy, in part because of cost. Reconditioned pacemakers (R-PM) could offer a lower cost alternative to new pacemakers (N-PM), but there are few direct comparisons of infection and/or malfunction between new and reconditioned devices. Preliminary results from the My Heart Your Heart (MHYH) randomized controlled trial found that R-PM are not inferior to N-PM for the first 90 days after implantation. In a group of nearly 300 patents with class 1 indication for pacemaker implantation and without the financial means to obtain a new device, there were similar rates of infection and lead revision for R-PM and N-PM and no device malfunctions.
Thomas Crawford, MD
“In some high-income countries, as many as 1,000 people per million may receive a pacemaker annually,” said Thomas Crawford, MD, professor of cardiovascular disease at the University of Michigan Medical School. “In low-income countries, it could be three per million or fewer who get pacemakers each year.”
MHYH randomized 298 patients in Sierra Leone, Venezuela, Nigeria, Kenya, Paraguay, Mexico and Mozambique to receive either a R-PM or a N-PM between May 2022 and June 2024. The R-PM devices were refurbished using a U.S. FDA approved protocol. Sites were given R-PM devices and received funding to source N-PMs locally and to obtain leads for both R-PM and N-PM devices.
The primary endpoint was procedure-related infection at 12 months with device malfunction at 12 months as a secondary endpoint. Crawford presented preliminary results 90 days after implantation. The non-inferiority margin was 5%.
Of the 298 patients implanted, 280 (94.3%) had at least one follow-up visit. During the first 90 days, there were five pocket infections that required explantation (3 N-PMs, 2 R-PMs) and one superficial cellulitis that was responsive to antibiotics (1 N-PM). A total of 11 patients required lead revision (5 N-PM, 6 R-PM), and there were no device malfunctions in either group. There were three deaths unrelated to the implantation procedure in the R-PM group. The difference in infection rate between the N-PM and R-PM groups was 2.2%, less than the 5% non-inferiority margin.
“Our study shows pacemaker recycling is green, good for the environment and can save the lives of people in countries who can’t afford a new device, Crawford said. “However, longer-term follow-up will be necessary to confirm the safety and efficacy of reconditioned devices, including whether they continue to work as expected and whether the batteries depreciate at the expected rate.”
