Key Points: 

• • 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.

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Key Points

• In a Phase 2 randomized trial, baxdrostat, a highly potent and selective aldosterone synthase inhibitor, had dose-related reductions in blood pressurein patients with resistant hypertension compared to placebo, without any serious adverse events.

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Key Points

• Hypertension remains a major public health threat contributing significantly to rates of ischemic heart disease and strokes worldwide despite a wide array of antihypertensives available
• A new antihypertensive agent, firibastat, is a first-in-class prodrug that acts through the inhibition of amiopeptidase A to block the conversion of angiotensin II to angiotensin III resulting in a decrease in blood pressure
• Firibastat failed to demonstrate efficacy to decrease blood pressure in patients with difficult-to-treat/resistant hypertension and was associated with allergic skin reactions.

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Key Points

• Despite the many drug classes available to treat hypertension, the prevalence of resistant hypertension (hypertension requiring at least 3 blood pressure medications of different classes) points to significant pathways not yet explored or addressed by current therapeutics
• Dual endothelin receptor antagonist (ERA), aprocitentan, offers a new pathway to the treatment of hypertension, pertinent to those prone to developing resistant hypertension including Black patients, patients with obesity or obstructive sleep apnea
• Aprocitentan lowered both office and 24-hour ambulatory blood pressures compared to placebo after 4 weeks of treatment, maintaining its effect over 48 weeks. It was, however, associated with fluid retention/edema which was clinically manageable with diuretic therapy.

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Key Points:

• Thiazide type diuretics are first-line medications for hypertension (HTN); while chlorthalidone (CTD) has been shown to lower blood pressure to a greater extent than hydrochlorothiazide (HCTZ), whether this translates into improved cardiovascular outcomes is unknown.
• The DCP trial enrolled Veterans Affairs (VA) patients aged 65 or older currently on HCTZ 25-50mg daily and randomized them to either continue taking HCTZ or to switch to an equivalent dose of CTD.
• There was no difference between the two groups for the primary composite outcome of time to non-cancer death, stroke, myocardial infarction (MI), urgent revascularization, or heart failure hospitalization.
• The DCP used a novel pragmatic “point of care” design in which the primary care providers (PCPs) managed the medications, no study staff were present at study sites, and the outcome data was collected passively through the electronic medical record (EMR) or national databases, thereby mitigating the cost of study execution.

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Key Points:

• Endovascular ultrasound denervation (uRDN) is a potentially useful technique in the management of hypertension; however, its effect in patients with mild to moderate HTN has not been well studied. The RADIANCE II study was a sham-controlled RCT aimed at determining the efficacy and safety of uRDN on patients with mild-moderate HTN.
• uRDN resulted in substantial reductions in daytime ambulatory sBP compared to sham and led to a higher percentage of time spent in therapeutic BP range.
• uRDN was a safe procedure, with no major adverse events at 30 days.

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While renal denervation has been shown to improve blood pressure in patients with moderate hypertension, its effects on resistant hypertension have been more modest. During Sunday’s Late Breaking Clinical Trials session of the American College of Cardiology’s 2021 Scientific Sessions, Dr. Ajay Kirtane of Columbia University, presented the findings of the anticipated RADIANCE-HTN TRIO Trial, seeking to shine a light on the previously nebulous data. Continue reading →

A recent trial by Dr. Salim Yusuf, published in The New England Journal of Medicine, indicated that combination therapy with aspirin plus a polypill (consisting of a statin plus three blood-pressure-lowering drugs) can reduce the incidence of cardiovascular events compared with placebo among participants without established cardiovascular disease, but at moderate cardiovascular risk.

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A recent trial by Dr. Jordana B Cohen, published in The LANCET, indicated that consistent with international society recommendations, patients admitted to the hospital with COVID-19 can safely continue treatment with renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB)) unless there is a distinct medical contraindication to ongoing therapy.

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A recent meta-analysis of clinical trials with more than 100,000 patients has shown that the carotid intima-media thickness (cIMT) progression can be used as a surrogate marker for cardiovascular risk in the clinical trials. The results of this study published in Circulation. According to Dr. Willeit, the assessment of cIMT progression can provide a link for the development and license of new therapies for cardiovascular disease. Continue reading →

Medications acting on the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors and angiotensin receptor blockers, did not increase the likelihood of a positive test for Covid-19 or the severity of the Covid-19. A cohort study of more than 12,500 patients conducted in a large health network in New York City, led by Dr. Reynolds, revealed. The findings of the study were recently published in the New England Journal of Medicine. Continue reading →

A recent study by Dr. Mehra, published in the New England Journal of Medicine, disapproved of the previously concerning idea regarding the potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in the clinical context of Coronavirus disease 2019 (Covid-19). This study also demonstrated that Covid-19 may disproportionately affect individuals with cardiovascular disorders.
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A new study by Dr. Hongwei, published in JAMA Cardiology, demonstrated that blood pressure (BP) trajectories over the life course progress more rapidly in women compared to men, a process that begins as early as the third decade of life. This concept is inconsistent with the previously accepted notion that important vascular disease processes in women occur by 10 to 20 years delay compared to men. These sex-based differences in physiology may establish the cornerstone for future cardiovascular disorders that often present differently in women compared with men.

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A recent study by Brian A. Ference et al. based on a UK Biobank study, published in JAMA, has shown that life-time exposure to decreased low-density lipoprotein cholesterol (LDL-C) levels and low systolic blood pressure (SBP) leads to a decreased lifetime risk of cardiovascular disease. Nonetheless, these findings do not constitute the quantified benefit of treating these risk factors in decreasing the life-time cardiovascular disease risk.

This randomized study included the data from 438, 952 individuals who were the participants of the UK Biobank study with the mean age of 65.2 years (range: 40.4 – 80.0 years) and 54.1% female participants. Participants were divided into a total of 4 groups, and 4 x 4 factorial reasoning was carried out. First participants were divided into 2 groups based on having a genetic LDL-C score being equal to or lower than, or higher than the median value. Second, they were further subdivided into 2 groups based on having their genetic systolic BP score being equal to, or lower than, or higher than the median value. The reference group further included 3 groups with each individual group having a higher LDL-C genetic score than the median, higher SBP scores than the median, and combined LDL-C and SBP genetic scores higher than the median, respectively. Differences in the plasma LDL-C, SBP, and cardiovascular event rates between the groups were compared to evaluate the correlations with the lifetime cardiovascular disease risk. The primary outcome included major coronary events which were characterized as a composite of coronary death, coronary revascularization, or nonfatal myocardial infarction. The key secondary outcomes were major cardiovascular events defined as the occurrence of a major coronary event or ischemic stroke.

When compared with the reference group, participants having LDL-C genetic scores higher than the median had 14.7-mg/dL lower LDL-C levels with an Odds ratio of 0.73 for major coronary events (95%CI: 0.70 – 0.75; P < 0.001). Participants with SBP genetic scores higher than the median had 2.9 mmHg lower SBP with an Odds ratio of 0.82 for major coronary events (95%CI: 0.79 – 0.85; P < 0.001). Finally, the participants in the group with both genetic scores higher than the median had 13.9 mg/dL lower LDL-C, 3.1 mmHg lower SBP, with an Odds ratio of 0.61 for major coronary events (95%CI: 0.59 – 0.64; P < 0.001). In a 4×4 factorial analysis, exposure to increasing genetic risk scores and lower LDL-C levels and SBP was associated with dose-dependent lower risks of major coronary events. In a meta-regression analysis, combined exposure to 38.67 mg/dL lower LDL-C and 10 mmHg lower SBP was associated with an Odds ratio of 0.22 for major coronary events (95%CI: 0.17 – 0.26; P < 0.001), and 0.32 for cardiovascular death (95%CI: 0.25 – 0.40; P < 0.001). These findings concluded the positive correlation of lifelong genetic exposure to lower LDL-C levels and lower SBP with the overall lower cardiovascular disease risk without any regard to the magnitude of benefit achieved after treating these risk factors.

There are several limitations to this study, including the lack of evaluation of risks and benefits of medications associated with lowering the LDL-C and SBP. Second, there is a lack of evidence proving that outcomes associated with naturally occurring lower LDL-C or SBP levels are the same as the outcomes associated with extrinsic drug treatment or other interventions to achieve similar plasma LDL-C or SBP levels. Hence, these study findings fail to quantify the amount of benefit gained from various treatments to lower LDL-C, SBP, or both.

Significant improvement in blood pressure control and related cardiovascular disease (CVD) risk is seen as a result of a potentially effective and pragmatic comprehensive model of care conducted as HOPE 4 trial (Heart Outcomes and Prevention Evaluation-4) presented by Dr. JD Schwalm at the European Society of Cardiology (ESC) Congress 2019 and simultaneously published in The LANCET.

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In an original investigation done by Dr.Wen-Yi Yang and his team, the results of which got published in JAMA, concluded that raised 24-hour and nighttime blood pressure (BP) readings are linked to increased risk of death and composite cardiovascular outcomes significantly. They considered it to be an optimal way of measuring risk but noted the difference was small for the improvement in the model.

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Vascular risk factors such as smoking, hypertension, and diabetes were associated with poor brain health. The study by Cox et al., recently published in the European Heart Journal, revealed.

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In a recent original cohort study done by Alexander C. Flint and his team published in the New England Journal of Medicine, it was concluded that systolic hypertension, as well as diastolic hypertension, independently affects the risk of cardiovascular adverse events irrespective of the cutoffs used for hypertension(≥140/90 mm Hg or ≥130/80 mm Hg).

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According to a nationwide cross-sectional study, protein biomarkers along with specific dietary patterns are linked to the development of cardiovascular disease (CVD). These findings, published in the Journal of the American Heart Association, suggest associations between dietary patterns and protein biomarkers have a role in the pathways related to inflammation, endothelial and immune function, cell adhesion and metabolism. Over the years, the role of diet in the prevention of CVD has been scientifically proven; unhealthy dietary components are important risk factors for the total global burden of this comorbidity. Continue reading →

A systematic analysis by Dr. Ashkan Afshin and the Global Burden of Disease (GBD) 2017 Diet Collaborators published in the Lancet showed that in 2017, 11 million deaths and 255 million disability-adjusted life years (DALYs) were attributable to dietary risk factors. The leading dietary risk factors were a high intake of sodium, low intake of whole grains, and low intake of fruits. The study provides a clear image of the potential impact of a sub-optimal diet on death and disability.

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