Digest #53: A Stent Per Plaque Keeps the Heart Attacks Back?

May 24, 2024 | By Nora Taranto

Welcome Back to The Curbsiders Digest!

In this issue, we cover  PREVENTing Vulnerable Plaque Rupture….plus Heart Failure Mortality Backslides, Statins and Diabetes Risk, MDRO decolonization strategies, gene editing for sickle cell disease, and a new treatment for uncomplicated UTIs. Effortlessly absorb important medical news, with our twice monthly newsletter featuring easily digestible analysis of the latest practice-changing articles, and of course…bad puns. 

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Issue 53

05/24/2024

Appetizers (to whet your appetite) 

Palate Cleanser (aka the melon part of the meal) 

The Main Course

A Digestif or two

Appetizers

Brought to you hot off the stove, from a variety of specialties. Delivered in super tasty, bite-sized morsels. 
-Laura Glick MD; Alyssa Mancini MD

• Mortality Backslides?! According to a recent research letter published in JAMA Cardiology, heart failure mortality rates are higher than they were in 1999. Researchers analyzed age-adjusted heart failure mortality rates using publicly available data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research (CDC WONDER) from 1999 to 2021, tracking deaths by ICD-10 classification.  Heart failure deaths declined from 1999-2009, plateaued until 2012, and then increased from 2012 – 2021 more substantially than that earlier decline, resulting in a 103% reversal (i.e. increase) in mortality over this whole time period, with younger individuals experiencing the greatest mortality increase.  The trend in increased mortality started prior to the pandemic.  It is, of course, important to remember the study’s limitations– relying on death certificate data, with possible changes in diagnostic testing and diagnostic coding during this time. (LG)
• Do statins increase diabetes risk? In a meta-analysis published in The Lancet Diabetes & Endocrinology, researchers studied the risk of diabetes by statin exposure, analyzing individual participant data from double-blinded, randomized control trials from the Cholesterol Treatment Trialists (CTT) Collaboration. The analysis included 19 studies and >123,000 participants (Trial breakdown: 16 moderate-intensity statin vs. placebo, 1 low-intensity vs. placebo, 2 high-intensity vs. placebo). There was a statistically significant increase in risk of new-onset diabetes with a high-intensity statin compared with placebo (4.8% vs. 3.5% annually) and a more modest increase with low-to-moderate–intensity statins compared with placebo (1.3% vs. 1.2% annually). Patients with already elevated baseline glycemic indicators were more likely to be diagnosed with diabetes. The authors point out that the overall cardiovascular benefit from statin therapy (especially in high-risk individuals) likely outweighs the risk of new-onset diabetes. (LG)
• Decolonizations to reduce MDR infections–and cut costs? According to a recent article published in JAMA, a regional decolonization intervention may be effective in reducing multi-drug resistant organism (MDRO) infections. In this quality improvement study, residents in long-term care and hospitalized patients on contact precautions across 35 health care facilities in Orange County, California (16 hospitals, 16 nursing homes and 3 long-term acute care hospitals) participated in a regional decolonization collaborative which included routine chlorhexidine bathing and nasal iodophor antisepsis.  There was a significant reduction after implementation of decolonization strategies in MDRO carriage, infections, infection-related hospitalizations, hospitalization-related costs, and deaths among participating facilities, compared to non-participating facilities.  (LG) 
• Gene editing to eliminate vaso-occlusive crises. NEJM just published the results of a phase 3, single-group, open label study of exa-cel (exagamglogene autotemcel), a cell therapy designed to reactivate fetal hemoglobin synthesis via gene editing of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs). The study included 44 patients (aged 12 to 35 years) with sickle cell disease with > two severe vaso-occlusive crises in each of the 2 years before screening. Patients underwent myeloablative conditioning with busulfan prior to exa-cel infusion. Of 30 patients with sufficient follow-up for evaluation (median 19.3 months follow-up), 29 were free from vaso-occlusive crises for at least 12 consecutive months, and all 30 were free from hospitalizations for vaso-occlusive crises for >12 consecutive months. There were no unexpected safety events with this therapy. (AM) 
• A new treatment for uncomplicated urinary tract infections. In a recent FDA News Release, the U.S. FDA approved Pivya (pivmecillinam), a beta-lactam antibacterial tablet, for the treatment of female adults with uncomplicated urinary tract infections caused by (susceptible) Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus. Pivya’s efficacy was evaluated in 3 controlled clinical trials looking at the composite response rate, which included clinical cure and microbiological response, assessed 8-14 days after enrollment.  In one of these trials, comparing Pivya to placebo, 62% of patients achieved the composite response with Pivya compared to 10% with placebo.  In a trial comparing Pivya to another oral antibacterial drug (cephalexin), there was a composite response rate of 72% with Pivya compared to 76% with the comparator drug. The most common side effects of Pivya were nausea and diarrhea. (AM)

Palate Cleanser

The melon part. To get rid of the taste of those pesky apps.  And to fill your brain with some fun facts.

Need a happiness boost? Check out “The Happiness Lab” podcast with Dr. Laurie Santos, a Yale professor who studies the science of happiness and shares evidence-based practical tips to incorporate happiness into our everyday lives. Her recent episode on “Five Tips to be Happier at Work” reviews how happiness and mental health can affect your productivity and performance at work, even your salary and companies’ profits.  She also provides tips on how to improve your wellbeing in the workplace, by: (1) acknowledging and leveraging your negative emotions, (2) protecting your time affluence, (3) motivating yourself through self-compassion, (4) crafting your job into a calling, and (5) seeking belonging at work. Listen to her podcast to learn practical strategies and resources to apply these tips in your own life!

– Jennifer DeSalvo MD

The Main Course

Jennifer DeSalvo MD 

PREVENTing coronary artery plaque rupture and thrombosis

Acute coronary syndrome is typically the result of the rupture of a vulnerable, lipid-rich atherosclerotic plaque in the coronary blood vessels. Unfortunately, leading up to rupture, many of these plaques do not appear severe or flow-limiting (i.e. ischemia inducing) on angiography.  New imaging technology has therefore focused recently on defining vulnerable, high risk plaques – with features such as a necrotic core, and a thin cap over a large, lipid rich plaque suggesting greater plaque vulnerability and an increased risk of major adverse cardiovascular events, even without obstructive or flow-limiting disease (Erlinge 2021).  

Despite an evolving understanding of plaque vulnerability, clinical guidelines currently recommend percutaneous coronary intervention (PCI) only for flow-limiting plaques or in the setting of acute coronary syndrome (ACC/AHA/SCAI guidelines; ESC/EACTS Guidelines), with standard treatment for these vulnerable plaques relying on optimal medical therapy.  But is there a benefit to PCI in stabilizing these vulnerable plaques, preventing future plaque rupture, and therefore reducing future adverse cardiac events?  Given a lack of randomized data in this space, the PREVENT trial, the results of which were just published in The Lancet, evaluated the safety and efficacy of revascularization of non-flow-limiting vulnerable plaques by preventive PCI, compared to optimal medical therapy.

Breaking it down  

PREVENT was an open-label, randomized controlled trial conducted at 15 hospitals in South Korea, Japan, Taiwan, and New Zealand. The trial enrolled 1606 adult patients (median age 65, 73% men, 31% with diabetes, 84% with stable coronary artery disease, 12% with unstable angina, and 4% with a recent myocardial infarction) who had vulnerable plaques.  Vulnerable plaques were defined as non-culprit, non-flow limiting lesions (fractional flow reserve >0.8 via intracoronary imaging) with at least 50% stenosis, plus at least 2 of several intravascular imaging criteria suggesting vulnerability (including a thin cap fibroatheroma, plaque burden > 70%, lipid rich plaque based on spectroscopy criteria, or minimal lumen area < 4 mm2).  Patients were randomly assigned to receive preventive PCI in addition to optimal medical therapy (n=803) or optimal medical therapy alone (n=803) and stratified by diabetes status. Of the patients assigned to PCI, 91% received PCI (9% crossover to medical therapy alone), compared to 99% of patients in the optimal medical therapy arm who received their assigned treatment (with 1% crossover). The primary outcome of a composite of death from cardiac causes, target-vessel myocardial infarction, ischemia-driven target-vessel revascularization, or hospitalization for unstable or progressive angina was assessed in the intention-to-treat population. After two years of follow-up, the primary outcome occurred in three (0.4%) PCI-arm patients and 27 (3.4%) optimal-medical-therapy patients (absolute difference -3 percentage points [95% CI -4.4 to -1.8, p=0.0003), a difference sustained sustained over more extended follow-up, and with reductions in each outcome component.   In subgroup analyses, the most significant differences between the two groups occurred in rates of any revascularization, ischemia-driven revascularization, hospitalization for unstable or progressive angina, and death from any cause/target-vessel myocardial infarction. There was also a lower risk of all-cause death, any myocardial infarction, or repeat revascularization in the PCI group compared to medical therapy alone. Both groups had similar rates of serious clinical or adverse events.

What does it all mean? 

In patients with non-flow-limiting vulnerable coronary artery plaques on imaging, preventive PCI plus optimal medical therapy significantly reduced adverse cardiovascular events compared to treatment with optimal medical therapy alone. These findings support consideration of a broader indication for PCI to include vulnerable plaques. This study was limited by its open label design without a placebo control, low observed event rates of the primary outcome, and unclear generalizability given intracoronary imaging for vulnerable plaque evaluation is not the standard of care globally.  Lastly, it is worth noting that a greater proportion of patients in the PCI arm were receiving dual antiplatelet therapy during the study. Despite these limitations, the PREVENT trial demonstrates that preventive PCI for the management of vulnerable plaques may be another promising modality–especially in the population with stable angina–in addition to optimal medical therapy, to prevent future adverse cardiac events.

Read The PREVENT Trial HERE!

Digestifs

Before you go….
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This week on The Curbsiders:  Learn all the ins and outs of Hepatitis B in Episode #440 with Dr. Arthur Kim. Packed with pearls for the management of chronic HBV, screening for Hepatitis B, and vaccination, this one is an essential.

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The Curbsiders Digest

Issue 53

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Disclosures:
Jennifer DeSalvo,  Alyssa Mancini, Laura Glick,  and Nora Taranto report no disclosures.

Kate Grant reports no disclosures

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