Late-breaking trials challenge conventional treatments to cardiovascular disease
Trial results presented in Saturday’s Late-Breaking Science session shed light on new approaches to initiating lipid-lowering therapy in secondary prevention, statin discontinuation in older adults for primary prevention, intensive blood pressure control and cardiovascular risk in people with type 2 diabetes and a novel cardiac rehabilitation.
Their results found:
- Starting with statin-ezetimibe combination therapy lowered LDL-C more than starting with a statin alone, but cardiovascular outcomes were similar when therapy was adjusted to reach LDL-C goals in secondary prevention.
- Among older adults with at least two chronic conditions but no known cardiovascular disease, discontinuation of statin therapy is noninferior to continuation with respect to major cardiovascular events or death from any cause at two years.
- Targeting a systolic blood pressure below 120 mmHg did not significantly reduce major cardiovascular events compared with a target below
140 mmHg in adults with type 2 diabetes in Brazil. - Yoga-based cardiac rehabilitation did not reduce mortality, hospitalization or stroke in patients with heart failure.
Starting with a statin alone or with statin-ezetimibe led to similar outcomes when LDL-C goals were actively pursued
In secondary prevention, whether to initiate statin monotherapy or combination therapy is an everyday decision clinicians face. Rather than the initial regimen itself, what matters most is actively adjusting lipid-lowering therapy in a target-directed manner to achieve the LDL-C goal, according to “Statin-Ezetimibe Combination Therapy vs. Statin Monotherapy in Patients With Atherosclerotic Cardiovascular Disease: Prespecified Second Randomization of the Ez-PAVE Trial.”
The primary Ez-PAVE multicenter open-label trial randomized 3,048 adults with ASCVD 1:1 to an intensive LDL-C target of <55 mg/dL or a conventional LDL-C target <70 mg/dL and found that targeting an LDL cholesterol level of <55 mg/dL resulted in a reduced risk of cardiovascular events at three years. A prespecified second randomization simultaneously compared statin-ezetimibe combination therapy (1,525 patients) with statin monotherapy (1,523 patients) as an initial lipid-lowering strategy in both LDL-C target groups.
In the statin-ezetimibe combination and monotherapy groups, the statin dose was determined according to each patient’s baseline LDL-C level and assigned LDL-C target. In the combination therapy group, patients received a fixed-dose combination of rosuvastatin and ezetimibe 10 mg. During follow-up, lipid-lowering therapy was adjusted according to a predefined protocol to achieve the assigned LDL-C target. In the statin monotherapy group, ezetimibe was added during follow-up in 34.3% of patients in the intensive-targeting group and 24.8% of patients in the conventional-targeting group.
The statin-ezetimibe combination therapy produced greater LDL-C lowering than statin monotherapy, and a higher proportion of patients in the combination group reached lower LDL-C levels. However, the rate of the primary outcome, a composite of major cardiovascular events at three years, did not differ significantly between the statin-ezetimibe combination therapy and statin monotherapy groups. The primary outcome occurred in 8.5% of patients in the statin-ezetimibe combination group and 7.9% of patients in the statin monotherapy group.
Byeong-Keuk Kim, MD, PhD
“The findings suggest that when LDL-C targets are actively pursued and therapy is adjusted accordingly, clinical outcomes are similar whether treatment begins with combination therapy or with a statin alone,” said co-investigator Byeong-Keuk Kim, MD, PhD, professor of cardiology at Yonsei University College of Medicine and director of the Cardiovascular Intervention Room at Severance Cardiovascular Hospital in Seoul, South Korea. “When LDL-C levels are monitored and therapy is adjusted to reach the treatment goal, starting with statin monotherapy and adding ezetimibe as needed appears to be a reasonable strategy, with clinical outcomes comparable to those of upfront combination therapy.”
Kim noted that the study’s findings support the goal-directed approach emphasized in the “2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia,” which reintroduced LDL-C goals for patients with ASCVD and recommends adding ezetimibe when maximally tolerated statin therapy doesn’t achieve these goals. The study was published in Circulation following the presentation.
Discontinuation of statin therapy for primary prevention was noninferior to continuation with respect to major cardiovascular events or death from any cause at two years
Physicians are already recommending deprescription, with 80% of general practitioners from 30 countries advising discontinuation of statin therapy in persons at least 80 years of age without cardiovascular disease who have statin-related side effects or frailty. But is it safe? That was the question asked in “Discontinuing Statins in Multimorbid Older Adults Without Cardiovascular Disease: A Randomized Noninferiority Clinical Trial (STREAM).”
The multicenter noninferiority trial conducted in 24 centers in Switzerland, France and the Netherlands, randomly assigned 1,880 adults ≥70 years with at least two comorbidities without cardiovascular disease 1:1 to either discontinue statin use (intervention arm) or continue statin use (control arm). The primary endpoint compared the primary composite endpoint of major cardiovascular events (nonfatal myocardial infarction or nonfatal ischemic stroke) and all-cause death between the control and intervention groups over a follow-up of up to 48 months.
Results showed that among older adults with at least two chronic conditions but no known cardiovascular disease, discontinuation of statin therapy was noninferior to continuation with respect to major cardiovascular events or death from any cause over two years. During the first two years of follow-up, 100 participants (10.7%) in the discontinuation group and 77 (8.2%) in the continuation group had a primary-outcome event. Over the full follow-up period (median, 103 weeks), 119 participants (12.7%) in the discontinuation group and 87 (9.2%) in the continuation group had a primary-outcome event.
Nicolas Rodondi, MD, MAS
“Our findings provide information for shared decision-making about cautious statin discontinuation when statins are used for primary prevention only. Although deprescribing inappropriate drugs in older adults appears to be safe, the results of our trial suggest that additional randomized trials of discontinuation are needed for specific drugs,” said Nicolas Rodondi, MD, MAS, professor of primary care and internal medicine and director of the Institute of Primary Health Care at the University of Bern, Switzerland. Rodondi estimated that one additional major cardiovascular event or death would occur over a period of two years for every 40 persons who discontinued statin therapy, which will require further investigation. In a secondary analysis of investigating patient-centered outcomes, including pain, quality of life, fall risk and muscle weakness, there was no difference between the two groups.
After the presentation, the study was published in the New England Journal of Medicine.
Intensive systolic blood pressure target did not reduce cardiovascular events in type 2 diabetes
Lowering systolic blood pressure (SBP) <120 mmHg did not significantly reduce major cardiovascular events in people with type 2 diabetes compared with targeting SBP <140 mmHg, according to “Intensive Blood Pressure Control for the Prevention of Major Cardiovascular Events in Patients with Type 2 Diabetes, the OPTIMAL-DIABETES Trial.”
The open-label trial enrolled a diverse population of 9,476 men and women ≥50 years with type 2 diabetes, hypertension (mean SBP 130-189mmHg) and high cardiovascular risk at 33 centers across Brazil. Participants were randomized 1:1 to a SBP target <120 mmHg (intensive control group) or <140 mmHg (standard strategy), with active blood pressure adjustments to achieve assigned targets over a median of 48 months.
The primary endpoint, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina or hospitalization for heart failure, occurred in 286 people in the intensive group and 315 in the standard group. During follow-up, mean SBP was 13.7 mmHg lower in the intensive group. The difference in the primary endpoint between groups was not statistically significant (HR 0.90; 95% CI: [0.77, 1.06], p=0.20). Decline in kidney function was more common with intensive treatment. End-stage kidney disease was rare and occurred at similar rates in both groups.
Otavio Berwanger, MD, PhD
“OPTIMAL-DIABETES does not support routinely aiming for systolic blood pressure below 120 mmHg in this population, but that does not mean intensive blood pressure lowering is ineffective in diabetes,” said Otavio Berwanger, MD, PhD, executive director of the George Institute for Global Health and Imperial College London, UK, and chair of the OPTIMAL-DIABETES trial steering committee. “It suggests that any cardiovascular benefit is likely to be smaller than in people without diabetes, and too small for even a large single trial to detect with certainty.”
Berwanger noted that OPTIMAL-DIABETES makes a substantial contribution to the overall evidence and highlights the need for a pooled analysis that combines individual patient data across trials, including ACCORD-BP and BPROAD, to determine whether some groups of people with diabetes benefit more than others from an intensive blood pressure lowering strategy. “Given how common type 2 diabetes is worldwide, even a modest reduction in cardiovascular risk could mean a large public health gain,” he said.
The study was published in the New England Journal of Medicine after the presentation.
Yoga-based cardiac rehabilitation improved quality of life but did not reduce death, hospitalization or stroke in patients with heart failure
Yoga-based cardiac rehabilitation did not reduce the first co-primary outcome, a composite of all-cause mortality, all-cause hospitalization and stroke, but improved quality of life, six-minute walk distance (6MWD) and quality-adjusted utility values in patients with reduced ejection fraction (HFrEF), according to “A Randomized Trial of Yoga-Based Cardiac Rehabilitation in Heart Failure (Yoga-CaRe HF Trial).”
The multicenter controlled trial randomized 3,492 patients in India with heart failure with reduced ejection fraction to receive a yoga-based cardiac rehabilitation program delivered by a single trained yoga instructor (n=1737, intervention group) or enhanced standard care (n=1755, control group). Mean age was 57; 27% were female; almost 50% were in NYHA III.
The co-primary outcomes were time to the first occurrence of a composite of all-cause mortality, all-cause hospitalization and stroke, and quality of life was assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) at three months. Secondary confirmatory outcomes were 6MWD and quality-adjusted utility values based on the European Quality of Life Questionnaire (EQ-5D-5L).
The first co-primary outcome occurred in 364 patients (21.0%) in the intervention group and 401 (22.8%) in the control group (HR=0.90; 95% CI: [0.78, 1.04], p=0.15). The second co-primary outcome, MLHFQ score, improved more with yoga-based rehabilitation (between-group difference in change from baseline -8.06; 95% CI: [-8.87, -7.24], p<0.001); lower scores indicate better quality of life. Similar improvements were observed in the secondary confirmatory outcome, 6MWD (between-group difference in change from baseline 25.5; 95% CI: [20.8, 30.3], p<0.001), and quality-adjusted utility values based on the EQ-5D-5L, with a between-group difference in change from baseline (0.05; 95% CI: [0.03, 0.06], p<0.001).
Overall, although yoga-based rehabilitation did not significantly reduce all-cause mortality, all-cause hospitalization and stroke, it improved quality of life, increased 6MWD and quality-adjusted utility-value at three months, with the difference persisting through 24 months.
Dorairaj Prabhakaran, MD
“Reducing hospitalizations and improving quality of life with heart failure is much needed in countries like India, where an estimated 500,000 to 1.8 million new heart failure cases are diagnosed each year,” said principal investigator Dorairaj Prabhakaran, MD, executive director of the Center for Chronic Disease Control in New Delhi, India. He noted that future research needs to focus on scaling yoga interventions and evaluating their effectiveness across diverse international settings.
