Renal Denervation: A Promising Yet Controversial approach to Uncontrolled Hypertension
Teh Centers for Medicare adn medicaid Services (CMS) has recently called for public comment on the potential coverage of renal denervation (RDN) for treating uncontrolled hypertension. This move comes as two RDN systems—the ultrasound-based device from the RADIANCE trials and the Symplicity Spyral system from the SPYRAL trials—have gained FDA approval.Though, despite this regulatory green light, the adoption of these devices has been sluggish, primarily due to funding challenges and lingering questions about their efficacy.
The Promise and Pitfalls of RDN
Table of Contents
- Finerenone Shows Modest Benefits in HFpEF Patients, but Questions Remain
- Finerenone Shows Promising Results in Recent Worsening Heart Failure Patients, but Questions Remain
- Finerenone and the Obesity Paradox: A New Perspective on Heart Failure Treatment
- Finerenone and Kidney Outcomes in Heart Failure Patients: Insights from the FINEARTS-HF Trial
- Finerenone in HFmrEF/HFpEF: Balancing Heart and Kidney Outcomes
- New Insights into Heart Failure Therapies and the Setback for Pulsed Field Ablation
RDN, a minimally invasive procedure, aims to reduce blood pressure by disrupting the nerves in the kidneys that contribute to hypertension.While the concept is promising, recent data from sham-controlled trials has been less than stellar.”Recent sham-controlled data is not only not remarkable (in the range of…),” notes John Mandrola, MD, in the latest episode of the This Week in Cardiology podcast. Proponents of RDN often cite open-label extension studies as evidence of its benefits, but Mandrola counters, “open-label anything is essentially worthless for RDN, see SYMPLICITY HTN 1 and 2 vs the sham-controlled Symplicity 3.”
Long-term efficacy is another concern. Animal models have shown re-innervation, raising doubts about the durability of the procedure. Additionally, while distal ablation is believed to be crucial, there are no reliable measures to confirm triumphant ablation. Patient selection also poses a meaningful challenge,with trials revealing a ample number of non-responders.
Key Challenges and Unanswered Questions
One of the most glaring gaps in the RDN data is the absence of evidence on major adverse cardiac events (MACE). Without this critical details, it’s difficult to assess the true risk-benefit profile of the procedure.
To summarize the current state of RDN:
| Key Aspect | Current Status |
|——————————|———————————————————————————–|
| FDA approval | Two systems approved (RADIANCE and Symplicity Spyral) |
| Adoption Rate | Slow, due to funding issues and efficacy concerns |
| Sham-Controlled Data | Unimpressive, raising doubts about efficacy |
| Long-term Efficacy | Concerns about re-innervation in animal models |
| Patient Selection | Difficult, with many non-responders in trials |
| MACE Data | None available, leaving critical safety questions unanswered |
The Road Ahead
As CMS seeks public input on RDN coverage, the medical community remains divided. While some see it as a breakthrough for patients with resistant hypertension, others remain skeptical due to the lack of robust data. For healthcare professionals seeking deeper insights, the This week in Cardiology podcast offers a comprehensive discussion on this and other pressing topics in cardiology.
What’s clear is that more research is needed to address the unanswered questions surrounding RDN. Until then, its role in managing uncontrolled hypertension remains a topic of debate.
For the latest updates on this and other medical advancements, consider subscribing to the This Week in Cardiology podcast or downloading the Medscape app. Stay informed, stay engaged, and join the conversation shaping the future of healthcare.Renal Denervation: A High-Stakes Debate in Hypertension Treatment
Hypertension (HTN) is a global health crisis, affecting millions and frequently enough requiring lifelong management. Amidst this, renal denervation (RDN), a procedure targeting overactive nerves in the kidneys, has emerged as a potential game-changer. However, its efficacy and cost-effectiveness are under intense scrutiny, with experts like Professor Franz Messerli urging caution. In a recent editorial published in the Journal of the American College of Cardiology (JACC) titled “Renal Denervation: Antihypertensive Therapy or Gizmo Idolatry?”, Messerli highlights the need to balance RDN’s benefits against established, low-cost treatments like amlodipine, a generic antihypertensive drug that can reduce blood pressure (BP) by over 10 mmHg within days.
Messerli’s editorial raises critical questions about RDN’s mechanism of action. If RDN works, it blocks sympathetic activity—a mechanism shared with beta-blockers, which are known to be less effective than other antihypertensive drugs in reducing cardiovascular outcomes. “What’s more, if RDN works, it blocks sympathetic activity, the same mechanism as beta-blockers, which are consistently inferior for reducing outcomes when compared with other anti-HTN drugs,” Messerli writes.
The debate over RDN’s role in hypertension management is further fueled by concerns about its adoption in private fee-for-service healthcare systems. Critics argue that without rigorous oversight, RDN could lead to unneeded costs and potential harm. “Imagine the costs and potential waste and harm if this procedure is let loose in the wild of private fee-for-service healthcare,” warns Messerli.
The Case for Rigorous RDN Trials
A recent controversies paper in the American Journal of Medicine, authored by Filippone and colleagues, outlines the ideal design for an RDN trial. The paper calls for:
- Sham-controlled, double-blind studies to eliminate bias.
- Adherence assessment through blood and urine tests.
- Maximal medical therapy in both arms of the trial.
- Long-duration studies (2 years) maintaining sham-blinding.
- Targeting ambulatory BP rather than office BP.
- Second-generation devices for improved accuracy.
- Assessment of medication requirements, quality of life, structural and functional target organ damage, MACE (major adverse cardiovascular events), and cost-efficacy.
These stringent criteria aim to ensure that RDN’s benefits are not overstated and that its adoption is based on solid evidence.
The Cost Conundrum
The financial implications of RDN cannot be ignored. Hypertension is as common, if not more so, than obesity, and the costs of managing it are already substantial. Messerli’s comparison to GLP-1 receptor agonists, which are expensive but effective for weight management, underscores the need for cost-effective solutions in hypertension care.
CMS’s Cautious Approach
The Centers for Medicare & medicaid Services (CMS) has taken a measured approach to RDN, reflecting the need for more robust evidence before widespread adoption.“I am glad CMS is moving slowly,” messerli notes,emphasizing the importance of avoiding premature enthusiasm for new technologies without sufficient proof of their benefits.
FINEARTS Trial: A New Hope in Hypertension Management
While RDN remains controversial, another breakthrough in hypertension treatment has emerged from the FINEARTS trial, recently published in the New England Journal of Medicine (NEJM). The trial focuses on finerenone, the first non-steroidal mineralocorticoid receptor antagonist (MRA). Unlike traditional MRAs like spironolactone, finerenone offers a novel approach to managing hypertension and related complications.
The FINEARTS trial was a highlight of the European Society of Cardiology (ESC) meeting, showcasing finerenone’s potential to improve outcomes in patients with chronic kidney disease and type 2 diabetes.
Key Takeaways
| Aspect | RDN | Finerenone |
|————————–|————————————————————————-|——————————————————————————–|
| Mechanism | Blocks sympathetic activity in kidneys | non-steroidal MRA |
| Cost | Perhaps high, especially in fee-for-service systems | Likely more cost-effective than RDN |
| Evidence | Requires more rigorous trials | Supported by robust clinical trials like FINEARTS |
| Adoption | CMS moving cautiously | Gaining traction as a novel MRA |
Conclusion
The debate over RDN highlights the challenges of integrating new technologies into healthcare systems. While RDN holds promise,its adoption must be guided by rigorous evidence and cost-effectiveness. Simultaneously occurring, advancements like finerenone offer hope for more effective and affordable hypertension management.As the medical community navigates these developments, the focus must remain on patient outcomes and the responsible use of resources.
What are your thoughts on RDN and finerenone? Share your insights in the comments below or explore more about hypertension treatments and cardiovascular innovations.
Finerenone Shows Modest Benefits in HFpEF Patients, but Questions Remain
A recent study evaluating the efficacy of finerenone in patients with heart failure with preserved ejection fraction (HFpEF) has sparked both optimism and debate.the trial, which included 6,000 patients with class 2-4 HF and an ejection fraction (EF) greater than 40%, demonstrated a modest reduction in worsening heart failure events but left some critical questions unanswered.
Key Findings from the FINEARTS trial
The FINEARTS trial compared finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), to placebo in patients with HFpEF. Over a median follow-up of 32 months, the primary endpoint—comprising total worsening heart failure events (hospitalizations or urgent visits) and cardiovascular (CV) death—occurred in 14.9 per 100 patient-years in the finerenone arm,compared to 17.7 per 100 patient-years in the placebo group.This translated to a 16% reduction in risk, with a hazard ratio (HR) of 0.84 (95% CI: 0.75-0.95).
Though, the reduction was primarily driven by an 18% decrease in heart failure events (HR 0.82; 95% CI: 0.71-0.94), while CV death rates remained statistically unchanged at 8.1 vs. 8.7 per 100 patient-years. Additionally, there was no significant difference in all-cause mortality between the two groups.
Symptom Enhancement and Safety Profile
The study also assessed patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire (KCCQ), which measures symptom burden and quality of life. While finerenone showed a statistically significant improvement in the KCCQ total symptom score,the absolute difference was minimal—just 1.6 points.
on the safety front,adverse events were similar between the two groups,though finerenone was associated with a higher incidence of hyperkalemia (elevated potassium levels). Specifically, 3% of patients in the finerenone arm experienced potassium levels above 6 mmol/L, compared to 1.4% in the placebo group. Importantly, no episodes of hyperkalemia led to death.
Comparisons to Previous Trials
The FINEARTS trial has drawn comparisons to the TOPCAT study, which evaluated spironolactone, another MRA, in HFpEF patients. While TOPCAT was largely negative a subgroup analysis excluding data from Russia and Georgia—where irregularities were noted—showed positive results.Critics argue that FINEARTS essentially replicated the Americas cohort of TOPCAT, raising questions about the novelty of its findings.
Another point of contention is the lack of a direct comparison between finerenone and spironolactone, a widely available and less expensive generic choice. With both drugs showing benefits over placebo, a head-to-head trial would have provided clearer guidance on their relative efficacy and safety.
Broader implications for CKD and CV Risk
Finerenone has previously demonstrated benefits in patients with chronic kidney disease (CKD) and type 2 diabetes, as evidenced by the FIGARO-DKD and FIDELIO-DKD trials. These studies showed that finerenone reduced the risk of kidney disease progression and CV events, solidifying its role in this patient population.However, the modest benefits observed in FINEARTS—200 fewer events in a 6,000-patient trial—highlight the need for further research to identify which subgroups of hfpef patients might derive the most benefit from finerenone.
summary of Key Data
| Parameter | Finerenone | Placebo | Hazard Ratio (95% CI) |
|—————————–|—————-|————-|—————————|
| Primary Endpoint (Events/100 PY) | 14.9 | 17.7 | 0.84 (0.75-0.95) |
| Heart failure Events | Reduced by 18% | – | 0.82 (0.71-0.94) |
| CV Death | 8.1 | 8.7 | Not significant |
| KCCQ Total Symptom Score | +1.6 points | – | Significant |
| Hyperkalemia (K > 6 mmol/L) | 3% | 1.4% | – |
Expert Criticisms and Future Directions
While the FINEARTS trial adds to the growing body of evidence supporting finerenone,experts have raised several criticisms:
- Lack of Novelty: The trial largely mirrored the Americas cohort of TOPCAT,raising questions about its incremental value.
- Missed Opportunity for Comparison: A direct comparison with spironolactone would have provided more actionable insights.
- Modest Clinical Impact: The absolute reduction in events was small, and no difference in CV death was observed.
moving forward, researchers must address these gaps to better define finerenone’s role in HFpEF management. for now, the drug offers a promising, albeit modest, addition to the therapeutic arsenal for this challenging condition.
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For more insights on heart failure management, explore our comprehensive guide on HFpEF treatment strategies.
Finerenone Shows Promising Results in Recent Worsening Heart Failure Patients, but Questions Remain
A new subanalysis published in the Journal of the American College of Cardiology (JACC) highlights the potential benefits of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in patients with a recent worsening heart failure (WHF) event. The study, which builds on findings from a larger trial, suggests that the timing of treatment initiation may influence the drug’s efficacy. However, the authors caution that the results are not definitive and should be interpreted as hypothesis-generating.
A Closer Look at the Subgroup Analysis
The study focused on patients enrolled in the trial at different time intervals following a WHF event: within 7 days, between 7 days and 3 months, and more than 3 months after the event. The results showed a clear trend: patients treated with finerenone within 7 days of a WHF event experienced a 26% reduction in the risk of the primary composite outcome (cardiovascular [CV] death or worsening HF) compared to placebo (relative risk [RR]: 0.74; 95% CI: 0.57-0.95). similarly, those treated between 7 days and 3 months post-event saw a 21% risk reduction (RR: 0.79; 95% CI: 0.64-0.97). in contrast, patients enrolled more than 3 months after a WHF event or without a prior WHF event showed no significant benefit (RR: 0.99; 95% CI: 0.81-1.21).
The absolute risk reduction (ARR) further underscored this trend: 7.8% for the within-7-days group, 4.6% for the 7-days-to-3-months group, and just 0.1% for the more-than-3-months group.The authors noted that this trend across ordinal categories was statistically significant, suggesting a potential enhanced treatment benefit for patients with recent WHF events.
A Signal, but Not a Slam Dunk
Despite these promising findings, the study’s limitations temper the enthusiasm. The P value for the interaction between treatment effect and timing of enrollment was 0.07, which did not reach the threshold for statistical significance. Additionally, the secondary analysis of time-to-first occurrence of CV death or WHF events did not replicate the same pattern of diminishing treatment efficacy over time.As the authors stated in their limitations section:
“Although treatment effects appeared to be greater among those enrolled proximate to a WHF in the primary analysis of total WHF events and CV death, there was no definitive treatment-by-time interaction and secondary analysis of time-to-first occurrence of CV death or WHF event analysis did not suggest the same pattern of diminishing treatment efficacy over time from WHF.”
This cautious interpretation underscores the need for further research to confirm whether finerenone truly offers enhanced benefits for patients with recent WHF events.
Implications for Clinical Practice
The findings, while not conclusive, suggest that finerenone may be especially effective when initiated shortly after a WHF event. This could have significant implications for clinical practice, as timely intervention in heart failure management is critical to improving outcomes. However,clinicians should remain mindful of the study’s limitations and await additional data before making definitive changes to treatment protocols.
Key Takeaways
| Subgroup | Relative Risk (RR) | 95% Confidence Interval (CI) | Absolute Risk Reduction (ARR) |
|—————————-|————————|———————————–|———————————–|
| Within 7 days of WHF | 0.74 | 0.57-0.95 | 7.8% |
| 7 days to 3 months post-WHF| 0.79 | 0.64-0.97 | 4.6% |
| >3 months post-WHF | 0.99 | 0.81-1.21 | 0.1% |
A Commitment to Advancing Cardiovascular Science
This themed issue of JACC reflects the journal’s dedication to advancing cardiovascular science by curating key findings and analyses from transformative trials. As Editor-in-Chief Harlan Krumholz noted in his introduction, the issue provides a comprehensive view of the trial’s implications for clinical care and future research.
while the finerenone subanalysis offers intriguing insights, it also highlights the complexities of interpreting subgroup data. As the authors emphasize, these findings should be viewed as hypothesis-generating rather than definitive. Future studies will be crucial to determining whether finerenone’s potential benefits in recent WHF patients can be confirmed and translated into clinical practice.
For more details, you can access the full study here.
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what are your thoughts on the potential of finerenone in treating recent WHF events? Share your insights in the comments below! be studied in the REDEFINE HF: A Study to Determine the Efficacy and Safety of Finerenone on Morbidity and Mortality Among Hospitalized Heart Failure Patients.
This subanalysis also included a favorable editorial.
Subanalysis Number 2: Effect of Finerenone on the KCCQ in Patients With HFmrEF/HFpEF:
Change from baseline KCCQ in the two group,finerenone vs placebo was a secondary endpoint of the main trial. It was in favor of finerenone but the difference was small at less than 2 points. recall that the scale goes from zero to100.
This paper looked at the effect of finerenone in patients with differing KCCQ baseline scores. First, the baseline KCCQ was quite high at 70.
The authors made three groups or tertiles based on KCCQ: 81. Finerenone reduced the primary endpoint nearly as well in all three categories, 0.82, 0.88 and 0.88 respectively. âHowever, compared with placebo, treatment with finerenone did not reduce mortality (caused by CV or all-causes), and did not improve New York Heart Association functional class across the tertiles of KCCQ.â
So, no heterogeneity based on functional capacity.
They then restated the 1.62 point meen improvement from the main trial. But this paper added something called a âresponder analysisâ to sort out quality of life signals.
This is a complex type of analysis. In fact, the JACC issue included two papers explaining how it works, and its limitations. This is what AI generates when I ask for an explanation.
A responder analysis in a clinical trial measuring KCCQ (Kansas City Cardiomyopathy Questionnaire) is a method used to identify the proportion of patients who achieve a predefined level of improvement in their health status or quality of life (QOL).
this approach involves setting a threshold for what constitutes a meaningful change in the KCCQ score,and then categorizing patients as either “responders” or “non-responders” based on whether they meet or exceed this threshold.
In the context of KCCQ, which measures various aspects of heart failure symptoms and their impact on daily life, a responder analysis typically involves:
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Defining a threshold: Researchers determine what change in KCCQ score represents a clinically meaningful improvement. For example, a change of 5 points or more in the KCCQ Overall Summary Score (OSS) might be considered significant.
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Categorizing patients: After the intervention or treatment period, patients whose KCCQ scores improve by at least the predetermined threshold are classified as “responders,” while those who do not meet this criteria are “non-responders.”
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Comparing groups: The proportion of responders in the treatment group is compared to the proportion in the control or placebo group to assess the effectiveness of the intervention.
Responder analyses can provide clinically relevant information by
Finerenone and the Obesity Paradox: A New Perspective on Heart Failure Treatment
Heart failure remains a leading cause of morbidity and mortality worldwide, with obesity often complicating its management. A recent study published in the New England Journal of Medicine sheds new light on the relationship between obesity, heart failure, and the efficacy of finerenone, a novel therapeutic agent. The findings not only challenge the long-debated “obesity paradox” but also provide fresh insights into how body mass index (BMI) influences treatment outcomes.
The Obesity Paradox: A Myth Debunked
For years, the “obesity paradox” has puzzled researchers and clinicians alike. Observational studies have suggested that patients with higher BMIs—classified as overweight or obese—tend to fare better in heart failure outcomes compared to those with normal or low BMIs. This counterintuitive phenomenon has been attributed to collider bias, a type of selection bias that skews results when analyzing specific subgroups, such as hospitalized patients.
As the study authors explain, “Every single one of these paradox papers is marred by collider bias, a type of selection bias wherein if you only look at say hospitalized patients, the patients with normal BMI tend to have disease worse than obesity and do worse. hence the appearance that obesity is protective or even ‘healthy.'”
This new research, however, dismantles the paradox entirely. By examining the effects of finerenone across different BMI categories, the study reveals that obesity is not a protective factor but rather a variable that influences treatment efficacy.
Finerenone’s Efficacy Across BMI Categories
The study, part of the FINEARTS trial, analyzed data from patients with heart failure and mildly reduced or preserved ejection fraction (HFpEF). Participants were categorized based on BMI:
- Underweight to normal weight
- Overweight
- Obese class 1 (BMI 30-35)
- Obese class 2 (BMI 35-39)
- Obese class 3 (BMI > 40)
The median BMI in the study was 29.2, placing most participants in the overweight or obese range. The primary finding was that “the effect of finerenone on the primary outcome did not vary by baseline BMI.” Specifically, the rate ratios for the primary outcome were:
- Underweight/normal weight: 0.80 (95% CI: 0.62-1.04)
- Overweight: 0.91 (95% CI: 0.72-1.15)
- Obese class 1: 0.92 (95% CI: 0.72-1.19)
- Obese class 2 to 3: 0.67 (95% CI: 0.50-0.89)
Interestingly, when BMI was analyzed as a continuous variable, the beneficial effect of finerenone appeared more pronounced in patients with higher BMIs (Pinteraction = 0.005). This trend was also observed in total worsening heart failure events.
However, when waist-to-hip ratio was used as an alternative measure of obesity, no such trend was detected. This suggests that BMI, rather than fat distribution, may be a more relevant factor in predicting finerenone’s efficacy.
Key Findings at a Glance
| BMI Category | Rate Ratio (95% CI) |
|————————-|————————-|
| Underweight/normal | 0.80 (0.62-1.04) |
| Overweight | 0.91 (0.72-1.15) |
| Obese Class 1 | 0.92 (0.72-1.19) |
| Obese Class 2-3 | 0.67 (0.50-0.89) |
Implications for Clinical Practice
The study’s findings have significant implications for the treatment of heart failure,particularly in patients with obesity. By demonstrating that finerenone’s efficacy is consistent across BMI categories—and potentially enhanced in those with higher BMIs—the research underscores the importance of personalized treatment strategies.
Moreover, the debunking of the obesity paradox highlights the need for rigorous study designs that account for biases like collider bias.as the authors assert, “The paradox is totally 100% fake news,” emphasizing that obesity should not be misconstrued as a protective factor in heart failure.
A Step Forward in Heart Failure Management
This study not only advances our understanding of finerenone’s role in heart failure treatment but also challenges long-standing misconceptions about obesity and cardiovascular health. By integrating these findings into clinical practice, healthcare providers can better tailor therapies to individual patient needs, ultimately improving outcomes for those with heart failure.
For more insights into the latest advancements in heart failure treatment, explore our comprehensive guide on emerging therapies for HFpEF.
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What are your thoughts on the obesity paradox and its implications for heart failure treatment? Share your insights in the comments below or join the conversation on Twitter.
Finerenone and Kidney Outcomes in Heart Failure Patients: Insights from the FINEARTS-HF Trial
The FINEARTS-HF trial, a landmark study investigating the effects of finerenone in patients with heart failure, has sparked renewed interest in its impact on kidney outcomes. While the primary findings were published earlier, a recent subanalysis delves deeper into the drug’s influence on renal health, revealing nuanced insights that warrant closer examination.
Key Findings on kidney Outcomes
The study focused on a composite kidney outcome, which included a sustained decrease in the estimated glomerular filtration rate (eGFR) of ≥50%, a decline in eGFR to <15 mL/min/1.73 m², or the initiation of long-term dialysis or kidney transplantation. The results showed no significant difference between the finerenone and placebo groups, with rates of 2.5% and 1.8%, respectively (HR 1.33; CI 0.94-1.89).However, the subanalysis uncovered several noteworthy details:
- Higher Rates of Bad Kidney Outcomes: finerenone was associated with a 33% higher rate of adverse kidney outcomes, though this difference was not statistically significant.
- eGFR Decline and Kidney Failure: The study examined a >57% decline in eGFR or kidney failure, finding similar rates in both groups. While the finerenone group showed a slightly higher incidence, the difference was not significant.
- eGFR Slope and UACR: Finerenone caused an acute decline in eGFR early in treatment but did not alter the chronic eGFR slope. Notably, the drug significantly reduced the urine albumin-to-creatinine ratio (UACR), an effect that persisted throughout follow-up.
Additional Insights
The treatment effect of finerenone did not vary significantly based on baseline eGFR categories (≥60 vs. 45 mL/min/1.73 m²), albuminuria levels, or a history of diabetes. Though, one striking finding emerged: eGFR decline to <15 mL/min/1.73 m²—a more robust component of the composite outcome—was twice as high in the finerenone group (0.8% vs.0.4%; relative risk: 2.1; 95% CI: 1.1-4.1).
Safety and Adverse Events
Serious adverse events, including serum creatinine elevation >3 mg/dL, were more common in the finerenone group. These findings highlight the need for careful monitoring of kidney function in patients receiving the drug.
Weight and Treatment Efficacy
The study also explored the relationship between body mass index (BMI) and treatment outcomes. Similar to findings in the DANISH and PARADIGM-HF trials, rates of adverse events increased with higher BMI. This suggests that heart failure patients, nonetheless of ejection fraction, should be counseled on weight management.
While the drug demonstrated efficacy across all weight categories, it may be slightly more effective in heavier patients. However, this association was not strong and was not observed with other measures of obesity.
What Does This Mean for Clinicians?
The FINEARTS-HF subanalysis provides a deeper understanding of finerenone’s impact on kidney health, reinforcing its role in reducing UACR while raising questions about its effects on eGFR decline. Clinicians should weigh these findings carefully, particularly when treating patients with advanced kidney disease or those at risk for rapid eGFR decline.
Key Takeaways
| Aspect | Finerenone Group | placebo Group |
|———————————|———————-|——————-|
| Composite Kidney Outcome | 2.5% | 1.8% |
| >57% eGFR Decline or kidney Failure | Slightly Higher | Similar |
| eGFR Slope | Acute Decline Early | No Change |
| UACR Reduction | Significant | Minimal |
| eGFR Decline to <15 mL/min/1.73 m² | 0.8% | 0.4% |
Final Thoughts
The FINEARTS-HF trial continues to shed light on finerenone’s multifaceted effects, offering valuable insights for clinicians managing heart failure patients with comorbid kidney disease. While the drug shows promise in reducing albuminuria, its impact on eGFR decline warrants cautious consideration. As research progresses, these findings will help refine treatment strategies, ensuring better outcomes for patients navigating the complex interplay of heart and kidney health.
For more details on the study, visit the original paper.
Finerenone in HFmrEF/HFpEF: Balancing Heart and Kidney Outcomes
The use of mineralocorticoid receptor antagonists (MRAs) like finerenone in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) has sparked significant debate. While the drug shows promise in improving heart failure outcomes, its effects on kidney function remain a point of concern. A recent subanalysis of the FINEARTS-HF trial, published in the Journal of the American College of Cardiology, sheds light on this complex interplay between heart and kidney outcomes.
The Discordance Between Heart and Kidney Outcomes
Finerenone, a nonsteroidal MRA, has demonstrated favorable heart failure outcomes, including reductions in hospitalizations for heart failure (HF) and cardiovascular (CV) death. However, its impact on kidney function has been less impressive. In the FINEARTS-HF trial, finerenone did not significantly modify kidney composite outcomes, despite leading to early and sustained reductions in albuminuria.
As noted by sanjay Kaul and Swapnil Hiremath in their accompanying editorial, the baseline urine albumin-to-creatinine ratio (UACR) in FINEARTS-HF was very low. This may explain why a 30% reduction in UACR did not translate into significant improvements in glomerular filtration rate (eGFR) decline or slope.
The authors raise critical questions:
“How will the guidelines respond to the discordant effects on heart and kidney outcomes? Are the adverse kidney effects concerning enough to offset the favorable HF outcomes? Given similar efficacy and safety profile among steroidal and nonsteroidal MRAs, will cost and affordability drive the decision to initiate an MRA in HFmrEF/HFpEF?”
Initial Decline in eGFR: A Key Concern
A subanalysis led by Matsumoto and colleagues examined the association between an initial decline in eGFR (≥15%) and subsequent outcomes in patients assigned to finerenone or placebo. The primary outcome was a composite of total HF events and CV death.
Key findings from the study include:
- Among approximately 5,500 patients with eGFR measurements at baseline and 1 month, 18.2% experienced a ≥15% decline in eGFR.
- This decline was nearly twice as common in the finerenone group compared to placebo (OR: 1.95; 95% CI: 1.69-2.24).
- After adjustment, an eGFR decline was associated with a higher risk of the primary outcome in patients assigned to placebo (adjusted rate ratio: 1.50; 95% CI: 1.20-1.89) but not in those assigned to finerenone (adjusted rate ratio: 1.07; 95% CI: 0.84-1.35).
This suggests that while finerenone may cause an initial decline in eGFR, it does not appear to increase the risk of adverse heart failure outcomes.
Safety and Adverse Events
Finerenone was associated with a higher incidence of hyperkalemia and acute kidney injury, particularly in patients with lower baseline eGFR. These adverse effects, while concerning, did not outweigh the drug’s benefits in reducing HF events and CV death.
Table: Key Findings from FINEARTS-HF Subanalysis
| parameter | Finerenone Group | Placebo Group |
|—————————–|———————-|——————-|
| ≥15% eGFR decline at 1 month | 18.2% | ~9.3% |
| Adjusted risk of primary outcome (HF + CV death) | 1.07 (0.84-1.35) | 1.50 (1.20-1.89) |
| Hyperkalemia incidence | Higher | Lower |
| Acute kidney injury | Higher | Lower |
Implications for Clinical Practice
The findings from FINEARTS-HF highlight the need for a balanced approach when considering finerenone for hfmref/HFpEF patients.While the drug offers significant benefits for heart failure outcomes, its potential adverse effects on kidney function cannot be ignored.
clinicians must weigh the trade-offs between improved HF outcomes and the risk of kidney-related adverse events.Additionally, the cost and affordability of finerenone compared to other MRAs may influence treatment decisions, especially in resource-limited settings.
Conclusion
The FINEARTS-HF trial and its subanalyses provide valuable insights into the use of finerenone in HFmrEF/HFpEF. While the drug shows promise in reducing HF events and CV death, its impact on kidney function remains a concern. as guidelines evolve, they must address the discordant effects on heart and kidney outcomes, ensuring that patient care is both effective and safe.
For more details, read the full study here and the accompanying editorial here.
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What are your thoughts on the use of finerenone in HFmrEF/HFpEF? Share your insights in the comments below.
New Insights into Heart Failure Therapies and the Setback for Pulsed Field Ablation
The world of cardiovascular medicine is constantly evolving,with new therapies and technologies promising better outcomes for patients. However, recent developments in heart failure (HF) treatments and a significant setback for Johnson & johnson’s pulsed field ablation (PFA) system highlight both progress and challenges in the field.
Heart Failure Therapies: Balancing Kidney Function and Efficacy
Heart failure therapies, including ACE inhibitors, ARNIs, SGLT2 inhibitors, and MRAs, often come with a trade-off: an initial decline in kidney function. A recent analysis of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, revealed that its efficacy remained consistent across varying levels of estimated glomerular filtration rate (eGFR) changes. According to the study, “the efficacy of finerenone was consistent across the range of change in eGFR from baseline to 1 month (P interaction = 0.50 for percent change in eGFR).”
This finding is significant because it suggests that even patients experiencing an early decline in kidney function may still benefit from finerenone. Safety profiles, including the risk of hyperkalemia, were also similar regardless of eGFR changes. As one expert noted, “As with all HF therapies, ACE, ARNI, SGLT2 inhibitors, and MRA, there may be an initial decline in kidney function.Watch it.Check labs but continue the medicine as it appears to provide similar benefits.”
However, the relationship between heart failure and kidney outcomes remains complex. While some studies suggest discordance between HF and kidney outcomes, others emphasize the importance of timing in treatment efficacy. For instance, a subanalysis on timing suggested that drugs may be more effective in acutely sicker patients, though this has been criticized as potentially marketing-driven.
Spironolactone vs. Finerenone: A Call for Evidence-based Trials
In an ideal evidence-based landscape, a head-to-head trial comparing spironolactone and finerenone would provide clarity on which drug should be the first-line treatment for heart failure. Until such a trial is conducted, many clinicians remain inclined to start with spironolactone. As one commentator put it, “In a proper evidence-based landscape, one not dominated by industry, one dominated by evidence-based clinicians, we would have a spironolactone vs. finerenone trial. Until then, I see no reason not to start with spironolactone first for HF.”
The Setback for Johnson & Johnson’s Pulsed Field Ablation System
In a major blow to Johnson & Johnson, the company had to halt a post-approval regulatory study of its pulsed field ablation (PFA) system for atrial fibrillation (AF) ablation due to four reported strokes. This development is particularly concerning given J&J’s leadership in the ablation field, thanks to its CARTO BioSENSE mapping system and ablation catheters.
PFA, a promising energy source for AF ablation, has been gaining traction due to its speed and reduced risk of esophageal injury compared to traditional radiofrequency ablation. As one clinician shared, “PFA is fast.You likely avoid esophageal injury. efficacy data looks similar.” Though, the stroke signal in J&J’s study—four strokes out of 140 cases—is alarming and has raised questions about the safety of the device.
while the strokes may have specific explanations, the incident underscores the importance of rigorous regulatory studies for new devices. As the same clinician noted, “Things like this reinforce my conservative approach to new tech. The PFA system I use had been in use in Europe for 2 years. In the United States,I waited 6 months. Then I looked at the data.”
This setback also highlights the competitive landscape in the PFA market, where Boston Scientific and Medtronic have already established themselves as leaders without reporting similar safety concerns.
Key Takeaways: Heart Failure Therapies and PFA Setback
| Topic | Key Insights |
|——————————-|———————————————————————————|
| Finerenone efficacy | Consistent across eGFR changes; safe even with early kidney function decline. |
| Spironolactone vs.Finerenone | Lack of head-to-head trials leaves spironolactone as a preferred first-line option. |
| PFA Setback | J&J halts study due to stroke risk; Boston Scientific and Medtronic lead the market. |
The latest developments in heart failure therapies and pulsed field ablation underscore the delicate balance between innovation and safety. While finerenone offers hope for patients with varying kidney function, the need for robust comparative trials remains unmet. Simultaneously occurring, the setback for J&J’s PFA system serves as a reminder of the importance of thorough regulatory scrutiny for new technologies.
As the field continues to evolve,clinicians and researchers must remain vigilant,prioritizing evidence-based practices and patient safety above all else.
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What are your thoughts on the latest developments in heart failure therapies and PFA technology? Share your insights in the comments below.nIs your morning coffee habit saving your life? A recent study published in the European Heart journal (EHJ) has sparked a heated debate in the medical community. The observational study, which analyzed data from 40,000 adults in the NHANES study, found that morning coffee drinkers had a 16% lower rate of death compared to those who sipped their brew throughout the day. But before you start celebrating your caffeine routine, let’s dive deeper into the findings—and the controversy surrounding them.
The Study That’s Brewing Attention
The EHJ study, which has garnered significant media attention, suggests that timing your coffee intake could have life-extending benefits.However, the study’s methodology has raised eyebrows. As the author of a ranting column from nearly eight years ago pointed out, observational studies like this one are often flawed, biased, and, frankly, “ridiculous and embarrassing.”
Despite these criticisms, nutritional research continues to thrive, with studies comparing outcomes based on macronutrient exposure. The EHJ’s involvement in this particular study is surprising, given its reputation as a prestigious journal. ”I hope there is nothing in the food or water there,” the author quipped, hinting at the absurdity of the findings.
the Business of Medical Publishing
One of the key takeaways from this study is the role of attention in medical publishing.The paper’s altmetric score is “off the charts,” highlighting how sensational findings can drive engagement. “medical publishing has a business model,” the author notes. “And it is attention.”
While the EHJ may have scored a media win with this study,the author suggests that future publications should include disclaimers,such as,”this one is red meat for the BBC and ABC and NBC.”
The Flaws in the Findings
The study’s authors acknowledge its limitations. It’s observational,meaning it can’t establish causation.There are baseline differences between the groups, and recall bias is a significant issue. “the second lesson from these studies is that their main value is to show how foolish it is to even attempt such a study,” the author writes.
Key Takeaways
Here’s a quick summary of the study’s findings and the surrounding debate:
| Aspect | Details |
|————————–|—————————————————————————–|
| Study Type | Observational |
| Participants | 40,000 adults from the NHANES study |
| Key Finding | Morning coffee drinkers have a 16% lower rate of death |
| Limitations | Observational nature, baseline differences, recall bias |
| media Impact | High altmetric score, widespread media coverage |
The Bottom Line
While the EHJ study has captured headlines, it’s essential to approach its findings with skepticism. Observational studies like this one frequently enough raise more questions than they answer. As the author aptly puts it, “complaining about these studies is like being mad when it rains.”
So,should you adjust your coffee habits based on this study? Probably not. But it’s a fascinating reminder of how science—and the media—can brew up a storm.
The study you mentioned, published in the European Heart Journal (EHJ), has indeed sparked significant interest adn debate within the medical community. The observational study analyzed data from 40,000 adults in the NHANES study and found that morning coffee drinkers had a 16% lower rate of death compared to those who consumed coffee throughout the day.While this finding is intriguing, it’s important to approach it with caution and consider the broader context.
Key Points from the study:
- Timing Matters: The study suggests that the timing of coffee consumption may play a role in its health benefits. Morning coffee drinkers appeared to have a lower mortality rate compared to those who drank coffee later in the day.
- Observational Nature: It’s crucial to remember that this is an observational study, which means it can identify associations but cannot establish causation. Other factors, such as lifestyle habits, diet, or genetics, could be influencing the results.
- Potential Mechanisms: Coffee contains bioactive compounds like polyphenols and antioxidants, which may contribute to its health benefits. Additionally, caffeine’s effects on metabolism, alertness, and cardiovascular health could play a role.
- Controversy and Limitations: Critics argue that the study’s findings may be influenced by confounding variables. Such as, morning coffee drinkers might have healthier overall lifestyles or better sleep patterns, which could explain the lower mortality rate.
Broader Implications:
- Personalized Recommendations: while the study adds to the growing body of evidence supporting the health benefits of coffee, it’s important to tailor recommendations to individual patients.Factors like caffeine sensitivity, existing health conditions, and medication interactions should be considered.
- Need for Further Research: Randomized controlled trials (RCTs) would provide more robust evidence to confirm these findings and explore the underlying mechanisms.
- Balanced Perspective: Coffee can be part of a healthy lifestyle, but moderation is key. Excessive caffeine intake can lead to adverse effects like insomnia, anxiety, and cardiovascular issues.
Final Thoughts:
The EHJ study highlights an interesting association between morning coffee consumption and reduced mortality, but it’s not a definitive endorsement of coffee as a life-saving habit.As with many aspects of nutrition and health, the key lies in balance and individualized care. For now, enjoy your morning coffee, but don’t rely on it as a magic bullet for longevity.
What are your thoughts on this study? Do you think timing plays a significant role in the health benefits of coffee, or are there other factors at play? Share your insights below!
