News
A single SC dose of Zilebesiran reduced systolic blood pressure in uncontrolled hypertension: KARDIA-2
Key Points:
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- Zilebesiran is a subcutaneous injectable that targets hepatic angiotensinogen (AGT) synthesis by RNA interference.
- The KARDIA-1 trial showed that subcutaneous zilebesiran is associated with sustained reduction in systolic blood pressure.
- In KARDIA-2, patients with mild to moderate uncontrolled hypertension were randomized to receive one subcutaneous injection of zilebesiran 600 mg versus placebo in addition to one standard-of-care anti-hypertensive therapy.
- The investigators found a statistically significant reduction in average ambulatory systolic blood pressure with the addition of zilebesiran at 3 months and 6 months compared to placebo.
- The most commonly seen adverse events with the use of zilebesiran were hypotension, hyperkalemia and decrease in renal function, all of which were typically transient issues.
BE ACTIVE RCT: Financial incentive and gamification strategies borrowed from behavioral economics increased physical activity among adults at elevated ASCVD risk
Key Points:
- The majority of US adults at elevated risk for ASCVD do not engage in the recommended amount of daily exercise.
- Behavioral economic strategies to incentivize increased physical activity have shown promise in short-term trials.
- The purpose of this randomized controlled trial was to determine the impact of these strategies when applied in combination and followed over a longer period of time.
- Adults at elevated ASCVD risk who were randomized to a 12 month intervention of gamification, financial incentive, or a combination of the two significantly increased their physical activity from baseline compared to a control arm consisting solely of text message alerts, however only the combination arm outperformed the control arm 6 months after the intervention period ended.
STEP-HFpEF DM TRIAL: Semaglutide improves HF-related symptoms and results in greater weight loss among patients with obesity-related HFpEF and type 2 DM
Key Points:
- Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, has previously been shown to reduce body weight and improve HF-related symptoms among individuals with HFpEF and obesity who did not have diabetes. Whether similar benefit occurs among individuals with type 2 diabetes mellitus has been unknown.
- The STEP-HFpEF DM trial enrolled 616 patients with obesity-related HFpEF and type 2 diabetes mellitus and randomized them to once weekly subcutaneous semaglutide or placebo.
- At 1-year follow-up, treatment with semaglutide resulted in a greater improvement in HF-related symptoms as assessed by the KCCQ clinical summary score and greater weight loss as compared to placebo.
Remote Acute Assessment Of Patients With High Cardiovascular Risk Post-Acute Coronary Syndrome (TELE-ACS)
Key Points:
- TELE-ACS evaluates the use of telemedicine strategies to reduce hospital readmission rates in patients with a recent history of acute coronary syndrome
- There was a 76% reduction in hospital readmission in the first six months for patients with a history of ACS who received the telemedicine intervention compared to controls (HR: 0.24, 95% CI: 0.13-0.44, p < 0.00)
- The use of a telemedicine intervention resulted in a 41% reduction in emergency department visits (HR: 0.59, 95% CI HR: 0.40-0.89, p < 0.001)
An “Inclisiran First” Strategy Shows Greater LDL-C Lowering Compared With Usual Care In Patients With ASCVD: The VICTORION-INITIATE Randomized Trial
Key Points:
- Most patients with atherosclerotic cardiovascular disease (ASCVD) do not achieve sufficiently reduced low-density lipoprotein cholesterol (LDL-C) levels despite maximum-tolerated lipid-lowering therapy (LLT) to improve cardiovascular outcomes.
- Twice-yearly inclisiran therapy added to maximum-tolerated statin therapy reduces LDL levels by an additional 50% compared to maximum-tolerated statin therapy alone.
- The investigators randomized 450 participants to either inclisiran 284 mg at day 0, day 90, and day 270 plus usual LLT versus usual LLT alone.
- The “inclisiran-first” strategy resulted in greater reductions in LDL and more patients reaching goal LDL reduction with minimal and comparable adverse effects.
EMPACT-MI: Empagliflozin did not meet primary endpoint but significantly reduced HF hospitalizations
Key Points:
- Incident heart failure remains common among patients who experience acute myocardial infarction despite recent advances in medical therapy and revascularization strategies.
- The EMPACT MI trial randomized 6,522 participants with acute myocardial infarction (STEMI or NSTEMI) at high risk of heart failure to empagliflozin 10mg daily or placebo.
- Over a median follow-up of 17.9 months, the primary endpoint of time to first heart failure hospitalization or all-cause mortality was not significantly reduced with empagliflozin.
Self-monitoring and physician-optimized antihypertensive titration post-partum decreases BP during the first 9 months
Key Points:
- Up to 1 in 10 women experience a hypertensive disorder of pregnancy, which is associated with long-term cardiovascular disease. However there are no established interventions to reduce risk post-partum.
- The POP-HT study examined the impact of a targeted physician-optimized postnatal BP control regimen on long-term BP control and cardiac remodeling.
- Physician-Optimized post-partum BP control resulted in a significant reduction in both systolic and diastolic BP at 9 months, in addition to BP-related postnatal admissions and evidence of adverse cardiac remodeling on both cardiac MRI and echocardiogram.
Novel RNA interference therapeutic Zilebesiran results in dose-dependent sustained BP reduction
Key Points:
- Uncontrolled hypertension is a major public health concern, and this condition is often primarily driven by the renin-angiotensin (RAAS) pathway.
- A new RNA interference therapy, Zilebesiran, was developed to target to most upstream precursor of the RAAS pathway (angiotensinogen). This study was a Phase 2 study examining the safety and efficacy of zilebesiran.
- A single dose of subcutaneous zilebesiran resulted in sustained BP reduction with low rates of adverse events over 6 months.
VERVE-101, a novel DNA-base editing medication, results in dose-dependent reductions in blood PCSK9 and LDL-C
Key Points:
- Despite the advent of PCSK9 inhibitors, the majority of patients with familial hypercholesterolemia do not meet their LDL-C targets with standard therapies.
- VERVE-1 is a novel CRISPR base editing medication which was designed to inactivate hepatic PCKS9 with a single DNA base pair change, thus reducing LDL-C.
- In this study, the highest dose of VERVE-101 treatment resulted in a sustained >55% LDL-C reduction at 180 days. VERVE-101 was generally well tolerated, with mild infusion reactions at high doses and two observed severe adverse CV events which were attributed to underlying severe ASCVD.
A multi-level hypertension program improved hypertension control in Nigeria
Key Points:
- The global burden of hypertension is high and increasing, with high rates of underdiagnosis and undertreatment.
- This study implemented a multi-pronged implementation package of HTN treatment within the capital of Nigeria.
- Results showed significant improvement in BP control and successful uptake of the implementation package, specifically anti-HTN medication prescription.
- The investigators hope to scale up this intervention to all the major geopolitical regions within Nigeria.
IMPACTS: A multifaceted implementation significantly improved BP control among low-income patients
Key Points
- This cluster-randomized trial found that a multifaceted implementation strategy to target an SBP <120 among low-income patients cared for at FQHCs lead to a significant reduction in mean blood pressure and a significant increase in the proportion of patients who achieved an SBP <120 compared to usual care.
- This strategy could be applied widely to other practices caring for low-income patients experiencing health disparities.
SPEECH: Novel speech analysis technology may be useful for early recognition of worsening heart failure events
Key Points
- Novel speech processing technology has the potential to detect heart failure exacerbations before they happen, and may be better than the conventional weight monitoring approach.
- Additional studies are needed to explore the generalizability, practicality, efficacy, and effectiveness of the HearO model.
SUPER-LIPID: Non-visit based automated orders sent to central pharmacy increased appropriate statin prescriptions
Key Points
- In two simultaneous pragmatic trials, an asynchronous, non-visit based, automated order for statins placed to a centralized pharmacy significantly increased both overall statin and appropriate dose statin prescriptions, while an interruptive visit based EHR notification strategy had an overall smaller effect.
Recaticimab Effective as Add-On Therapy in Non-Familial Hypercholesterolaemia and Mixed Hyperlipidemia: REMAIN-2 Trial
Key Points
- Recaticimab effectiveness demonstrated dosage-dependent response indicating versatility in treatment options.
- Sustained reduction in LDL-C levels throughout the 48-week study period as well as favorable outcomes observed in additional lipid variables.
Dual Cardioversion More Effective than Single in Obese Patients with AF
Key Points:
- The prevalence of obesity, and AF is increasing substantially and are inextricably linked.
- Patients with obesity show less response to single-DCCV due to chest wall impedance
- This trial compared dual-DCCV to single-DCCV among patients with BMI ≥ 35 in ability to attain sinus rhythm in a patient refractory to initial DCCV
- Dual-DCCV showed significantly lower rates of failure compared to single-DCCV, suggesting its utility for AF refractory to DCCV in obese patients
AI -ECG Results in Faster and More Accurate Identification of STEMI
Key Points:
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- The use of an artificial intelligence electrocardiogram (AI-ECG) support tool in the evaluation of patient ECGs was associated with a reduction in the door to coronary angiography time (43.3 minutes vs. 52.3 minutes) in patients who presented with an ECG concerning for ST-elevation myocardial infarction (STEMI).
- The AI-ECG support tool has a high positive predictive value of 88.0 (81.8-94.1) and high negative predictive value of 99.9 (99.9-100.0).
- AI technology helped to reduce the treatment waiting time for patients with STEMI from about 52 minutes to 43 minutes.
Abelacimab, a novel Factor XI/XIa Inhibitor, reduced bleeding vs Rivaroxaban in AF
Key Points:
- Previous studies have investigated the use of direct oral anticoagulants (DOACs) instead of warfarin for reduction of stroke risk in AF, but the risk of clinically significant bleeding remains.
- Abelacimab is a novel Factor XI inhibitor that may be useful in reducing thromboembolic events while also being less likely to cause major bleeding.
- Patients were assigned to rivaroxaban 20 mg/ day or two different doses of abelacimab, 150mg SC monthly and 90mg SC monthly. The primary endpoint was major or clinically relevant non-major bleeding.
- The trial was stopped premature due to significant reduction in bleeding with 74% reduction in major bleeding and 93% reduction in GI bleeding on abelacimab 150mg SC versus rivaroxaban.
Coronary Inflammation on CCTA as Predictor of Cardiac Events: the ORFAN Study
Key Points:
- Out of all patients who undergo a CCTA, the highest number of cardiac events occurs in patients without obstructive CAD.
- In patients with non-obstructive CAD on CCTA, the use of a novel AI tool to quantify coronary inflammation results in accurate predictions of patients’ ten-year risk of cardiac mortality and MACE.
- In this study, patients with non-obstructive CAD on CCTA who have an inflammation score that is above the 75th percentile have an ~ 20 times higher risk of dying from a cardiac event over the next ten years.
- The AI risk model used in this study results in the reclassification of the risk profile of ~ 40% of patients and was found to lead to changes in clinical management in roughly half the patients.
ESPIRIT: Intensive blood pressure control lowers MACE vs Standard Treatment
Key Points
- This randomized trial of 11255 patients in China with established CVD or at least 2 CVD risk factors but without a significantly reduced ejection fraction or advanced kidney disease (mean age ~65 years, 100% Asian, baseline SBP 147, 39% with diabetes, 27 % with stroke) found that a blood pressure target of <120 led to a 12% reduction in major vascular events, 39% reduction in cardiovascular mortality, and 21% reduction in all-cause mortality compared to a blood pressure target of <140.
- This was the first major randomized trial to show benefit of aggressive blood pressure in those with prior stroke, diabetes, or Asian ancestry.
REPRIEVE Substudy: Pitavastatin reduces non-calcified coronary plaque in people with HIV
Key Points
- The REPRIEVE trial recently demonstrated that pitavastatin reduced major adverse cardiovascular events by 35% among individuals with HIV at low-moderate risk predicted risk for cardiovascular disease. However, little is known regarding the mechanism of benefit.
- The mechanistic sub-study of REPRIEVE enrolled 804 participants from the overall trial from 31 U.S. sites and randomized them to daily pitavastatin at a dose of 4mg or placebo.
- At 2 years follow-up, pitavastatin reduced non-calcified plaque volume by 7% relative to placebo and reduced the risk of plaque progression by 33%.
