New research was presented at AHA 2023, the American Heart Association 2023 Annual Scientific Sessions. The features below highlight some of the studies that emerged from the conference.
How Useful Is Anticoagulation in Subclinical Atrial Fibrillation?
When compared with aspirin, apixaban was associated with a reduced risk of stroke or systemic embolism in patients with subclinical atrial fibrillation (AF). However, researchers observed an increased risk for major bleeding in the ARTESIA study.
The randomized, double-blind, active-controlled ARTESIA trial compared the efficacy and safety of the direct anticoagulant agent apixaban with aspirin in patients with subclinical AF and a risk factor for ischemic events. Participants (N=4,012) were randomized to apixaban, either 2.5 mg or 5 mg twice daily, or aspirin 81 mg once daily. The primary endpoint was the rate of stroke or systemic embolism. Jeff Healey, MD, presented the main results.
After a mean 3.5 years of follow-up, “the risk of stroke or systemic embolism was significantly reduced in the apixaban arm as compared with the aspirin arm (HR, 0.63; 95% CI, 0.45–0.88; P=0.007),” said Dr. Healey. However, major bleedings occurred more frequently in the apixaban arm than in the aspirin arm (1.71% per year vs 0.94% per year; HR, 1.80; P<0.001). Thus, these results trigger a discussion of whether there is a positive risk-benefit ratio for the use of anticoagulants in patients with subclinical AF.
Biannual Zilebesiran Linked With Substantial Blood Pressure Reductions
In the phase 2 KARDIA-1 study, a single subcutaneous dose of zilebesiran demonstrated encouraging reductions in systolic blood pressure (BP) in patients with hypertension at 3 and 6 months of follow-up compared with placebo. The investigational agent zilebesiran was further assessed as add-on therapy for patients with hypertension in the phase 2 KARDIA-2 trial. The phase 2 KARDIA-1 study randomized 394 participants with mild-to-moderate hypertension to placebo or one of four dose-levels of the subcutaneously administered RNA-interference therapeutic zilebesiran, ranging from 150 mg once every 6 months to 600 mg once every 6 months. The primary endpoint was the change in 24-hour mean ambulatory systolic BP from baseline to 3 months. George Bakris, MD, presented the findings.
“At 3 months, all zilebesiran groups were associated with significantly larger reductions in 24-hour mean ambulatory systolic BP than placebo,” said Dr. Bakris. In the lowest-dose group, the reduction was -14.1 mmHg compared with placebo (P<0.001), and in the highest-dose group, the reduction was -15.7 mmHg compared with placebo (P<0.001).
These reductions appeared to be maintained at 6 months, with corresponding reductions of -11.1 mmHg for the lowest-dose group and -14.2 for the highest-dose group. “The agent also displayed a favorable safety profile,” said Dr. Bakris. No serious or severe drug-related adverse events were reported. However, the rates of hyperkalaemia and hypotension were somewhat higher in the zilebesiran groups (6% vs 3%; 4% vs 1%). According to Dr. Bakris, these cases were mostly mild or moderate and did not lead to treatment discontinuations. These data support the quarterly or biannual dosing of subcutaneous zilebesiran to reduce the BP of patients with hypertension.
Intensive Blood Pressure Intervention Reduces Risk for Dementia
An intensive blood pressure (BP) intervention outperformed usual care in reducing the risk of dementia in patients with hypertension. “The proven-effective intervention should be scaled up widely to reduce the global burden of dementia,” according to Jiang He, MD, PhD, who presented the main results of the study.
Dr. He and colleagues compared the effectiveness of an intensive BP intervention to usual care on the risk reduction of dementia in patients with hypertension in a cluster-randomized trial. The 33,995 participants with hypertension were randomized to usual care or an intensive intervention. The experimental intervention included doctor-initiated titration of anti- hypertensive drugs, delivering of discounted and free medications to patients, lifestyle interventions, education on BP monitoring, and medication adherence instructions. The primary outcome was all-cause dementia at 48 months.
“In the usual-care arm, the systolic BP had dropped with a mean 7.2 mmHg, and in the experimental arm, this measure was reduced with a mean 29.2 mmHg,” said Dr He. For diastolic BP, the corresponding rates were -6.1 mmHg and -15.4 mmHg. In addition, 67.7% of participants in the intervention arm were normotensive at 48 months, compared with 15.0% in the usual care arm (P<0.001). Not surprisingly, those in the experimental arm were on a higher number of antihypertensive agents (mean. 3.0 vs 1.2; P<0.001). “Importantly, the primary outcome was met, with an annual rate of 1.12% of all-cause dementia in the experimental arm and a rate of 1.31% in the control arm (RR, 0.85; 95% CI, 0.76–0.95; P=0.0035), representing a 15% reduction,” according to Dr. He.
Nicotinamide Riboside May Improve Walking Function in Peripheral Arterial Disease
A phase 2 study assessed the effect of nicotinamide riboside, a B3 vitamin and precursor to nicotinamide adenine dinucleotide (NAD+), on walking function in patients with peripheral arterial disease (PAD; N=90). Enrolled patients were randomized to nicotinamide riboside alone 500 mg twice daily, to nicotinamide riboside plus resveratrol 125 mg once daily, or to placebo. The primary outcome was the change in 6-minute walking distance at 6 months. Mary McDermott, MD, presented the study findings. The 6-minute walking distance increased with 7.00 meters in the monotherapy arm (P=0.078 vs placebo), decreased with 6.93 meters in the combination therapy arm (P=0.376 vs placebo), and was reduced with 10.58 meters in the placebo arm. However, in walk-adherent participants, both experimental arms were associated with improvements in walking distance compared with placebo: >Monotherapy arm: mean difference +35.4 meters (P=0.014) >Combination therapy arm: mean difference +30.2 meters (P=0.028) In walking-adherent patients with PAD, the positive effects of the active arms on walking distance were comparable. “However, due to the limited sample size, there is a need to confirm these findings in larger clinical trials,” concluded Dr. McDermott.
