Patrick Campbell

Patrick Campbell is the assistant managing editor of Endocrinology Network, as well as its sister publications Practical Cardiology and Rheumatology Network. Prior to joining these brands, he led coverage of cardiology and diabetes with HCPLive. Before joining parent company MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA, and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a freelance multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

Few agents in the landscape of medicine have had as dramatic an impact on disease course as statins for prevention of cardiovascular disease. September 1 marked 35 years since approval of lovastatin in 1987 introduced statins to the general population. To say statins have revolutionized the care of dyslipidemia and prevention of atherosclerotic cardiovascular disease since that approval on September 1, 1987, would be an understatement.

In the past 35 years, mountains of data have emerged outlining the efficacy and safety of these agents as LDL-lowering agents, but also for reducing risk of cardiovascular events. In addition to this, unlike many gamechanging agents that are bogarted by steep prices or limited availability, statins are among the most widely prescribed and inexpensive drugs in the US, with insurance coverage and prescription programs reducing costs to under $100 per month for generics.

Given the availability of statins and growing understanding of LDL-C exposure, some have begun to question whether the role of statins should be expanded to include a wider swath of the population. This question of whether the role of statins in primary prevention should be expanded to be more akin to primordial prevention is the subject of this feature: “Rethinking Statins: Time for Primordial Prevention?”.

 queried a half dozen of the leading experts in cardiometabolic health on the topic. This group of experts includes Erin Michos, MD, of Johns Hopkins School of Medicine, Peter Toth, MD, PhD, of the CGH Medical Center, Deepak Bhatt, MD, MPH, of Brigham and Women’s Hospital, Jorge Plutzky, MD, of Brigham and Women’s Hospital, Alison Bailey, MD, of Centennial Heart, and Robert Busch, MD, of Albany Medical Center.

Rethinking Statins: Time for Primordial Prevention?

Well, it would be great to kind of eradicate atherosclerosis, right? I think this is really important that when we think about LDL years or cholesterol years, we are not only thinking of the magnitude of elevation, but the number of years of exposure. Even with mild to moderately elevated cholesterol for a longer duration of time, these individuals have increased risk for earlier onset of atherosclerotic cardiovascular disease compared to their counterparts that have had lifelong low LDL.

I think we wait too long to treat. The ideal LDL in fetuses and infants is around 30 mg/dL. Compare it to the concept of blood pressure management. So, if you have somebody who is 20-30 years of age that comes in with a systolic blood pressure of 160, you're not going to say, 'Oh, your 10-year risk is low. We're not going to treat your blood pressure'. No, we treat their blood pressure. So, I think that some of the problems of using these 10-year risk scores for cholesterol or for making decisions for initiating statins is that young adults do have a low risk in the next 10 years, but I don't want to just prevent a heart attack in the next 10 years, I want to prevent a heart attack over their lifetime for the next 30 or 40 or 50 years.

So, we wait too long to treat because we focus on these 10-year risk scores and younger adults are never eligible. The whole time their arteries are marinating in these atherogenic lipid particles. The classic example of this is familial hypercholesterolemia. These individuals have genetically very high cholesterol from birth and studies have already shown that if you intervene early and you treat with statins, by adolescence, the offspring don't develop the early onset of ASCVD as their parents. You can change the whole trajectory by starting early. So, that's the classic example with FH.

We should be thinking about this for broader populations and getting LDL lower starting earlier. There is certainly an important role for lifestyle and, particularly, for young adults who are at lower risk. Diet and lifestyle is one of the mainstays of therapy, although the LDL makes that liver makes LDL cholesterol and a lot of cholesterol is genetically determined—up to 3/4ths of this is genetically determined, but 20-30% can still be influenced by diet. So, that does matter, especially in younger adults. If we could be trying to have everybody eating a healthier diet and optimizing lifestyle from utero on through childhood and into young adulthood, that'd be really, really important, but I do think we should have increased consideration for starting statins early.

That's actually a fabulous question. For a long time in primary prevention, an LDL-C of less than 130 was considered to be normal. The average patient who presents to the ER with an MI has an LDL of 128. So, how could that LDL of 128 be normal? It's simply ludicrous. Yet, the older guidelines said less than 130 was normal. In fact, for the low-risk patient, less than 160 was considered to be okay.

I'll tell you right now, for the average patient, if their LDL is above 100, they're experiencing atherogenesis from an early age. We know that in familial hypercholesterolemia, children can have fatty streaks in their coronary tree. We also know, based on autopsy studies from Korea and Vietnam, when looking at young men killed at time of war, more than 50% had anatomical evidence of established plaquing in their coronary arteries. Atherogenesis begins in childhood and it progresses throughout our lifetimes. People, on average, have events in their 5th, 6th, or 7th decades depending upon how much LDL they've been exposed to and what other risk factors they may harbor.

In this light, I think we're now looking at LDL exposure almost like cigarette smoking. What dose of LDL-C you have been exposed to and over how much time can very nicely predict how long it's going to take for that patient to develop significant disease and have an event.

Do I favor lowering LDL cholesterol in everybody? Given the fact that coronary disease is a scourge globally and gives rise to more suffering and more deaths than any other disease? Yes. Do I find it ludicrous that we typically wait till people have their first event and then start a statin? I think it's ludicrous, because certainly we have enough data that this disease starts early, progresses through life, and gives rise to human suffering. Does it make sense to reduce the LDL burden, the burden of atherogenic lipoprotein in serum at a much younger age? You better believe it does.

That's a great question. I never overreact to what's going on in social media, because it's typically an echo chamber of people confirming their own beliefs, but I do think statins could and should have a larger role in primary prevention on the basis of LDL cholesterol. That is, I think there are a lot of people walking around with elevated LDL cholesterol, where starting them on a statin earlier in life would probably reduce a substantial number of atherosclerotic events. We already have positive primary prevention data for statins—the JUPITER trial, for example. So, it's not a data-free zone.

There are certainly patients right now that should be getting statins in the primary prevention universe. So, just how low should the LDL be allowed to be before starting a statin? I think that might be a bit controversial. We should normally have LDL at around 30 if we were newborns again. That's sort of the range of LDL that we have seen historically in more rural parts of the world that hadn't been industrialized and urbanized. That was sort of a"normal LDL".

So, most of us in the US are walking around with an abnormal LDL. You could make a theoretical argument just to treat everyone that's got an LDL above that range, but in the absence of actual data supporting statins for primary prevention in the range I'm talking about, I wouldn't just do it. There is, of course, the occasional real side effect that does occur with statins, then there's the more minor side effects, and then there's the nocebo effects where people are really convinced they're having side effects, but if they were on a placebo they would have the same side effects.

So, it makes life tough. I think advocating too strongly for that, where there isn't data, will just sort of fuel the anti-statin folks and then keep statins from being used where they absolutely should be used, including secondary prevention and high-risk primary prevention. So, for now, I'd say to stick where the data are and not go beyond that, but, if one really thinks that type of primordial prevention is the way to go, perhaps then it's not even a statin, but a PCSK9 inhibitor—where it takes adherence out of the question. I'm not advocating for that, by the way, there would need to be data supporting that. If there were data that ultimately support that approach, there you take adherence out of the question, and you get really large reductions in LDL.

I think we really need more research on what to do. Primary prevention is tough. Secondary prevention, I think is a lot easier because, after someone's had an MI, they ought to be on a statin. The only reason not to be are intolerances, perceived intolerances, or side effects, but otherwise they really ought to do it. But, in primary prevention, it gets trickier because the absolute risk reductions are smaller and adherence is really tough. If somebody's feeling great, and they've never had an ischemic event, it can be tough to take a pill a day the rest of your life. So, I think there are a lot of important interesting questions here, but I suspect future research in lower risk primary prevention populations will help define the right thing to do.

Well, there is considerable evidence that patients are getting undertreated for primary prevention of cardiovascular risk. The idea that you're going to wait for a patient to have an event before you start treating them is really outdated and dangerous, because we know that those events can be very complicated. So, certainly, earlier intervention and use of statins prior to an event is important, but it has to be placed in the context of the risk for that individual. We know that risk is present and we know that risk involves many different factors. So, fully considering that can have you intervening earlier in someone who's considerably younger, who, for example, is smoking, hypertensive, has an elevated number, strong family history, or has an elevated LPa are all things that we actively engaging. At the same time, we want to balance that and not treat people unnecessarily and expose them to all the various issues that can come up with drug therapy.

So, I think it's a question of balance—of recognizing the risk, recognizing we have an intervention, and supporting that. Sometimes in the younger patient, when you're starting to think about risk, that also becomes a great opportunity to implement lifestyle and to really focus on that because you might be seeing a patient who is really years away from when they might have a first event. Using that time to get them off cigarettes, a little bit more active, and eating a little bit better, I think is really important. We should not just be relying on drug therapy.

So, we know that your LDL over your lifespan contributes to your burden of atherosclerosis, not just from heart disease, but also from stroke, kidney disease, and all the other sort of chronic illnesses that we deal with in the United States and increasingly around the world. So, I think low LDL over your lifespan is important. How we get there is also important.

I think the first thing we should focus on is lifestyle for everybody. You know, when I meet people who are overweight, not exercising, and eating poorly, I think they can make pretty substantial changes in their lipid profile by changing their lifestyle. So, I like to have that discussion first. Let's change our lifestyle and then let's reassess.

However, I wouldn't want to walk around with an LDL-C of 130 for the remainder of my life, because I know my risk for cardiovascular disease is going to go up. So, I think statin should be offered to patients earlier, but after a patient-centered discussion about the risks, the benefits, and where the data sits today.

We have lots of tools that we never had before, such as CAC scores. We're learning that using those in younger patients than we ever did before, these lower risk cohorts, may give us additional data. So, I think statins should be expanded after having informed discussions. Obviously, there are groups that are at risk, specifically women who are of childbearing age. To me, that one's the trickiest one. I see a lot of women in my practice and we have very extended discussions about using contraceptive and just knowing what the risks are with statins if they were to get pregnant.

So, the risk with a statin is so minimal and the benefit is so great, I personally feel statins should be in the drinking water, unless your woman is going to get pregnant or are pregnant. The harm of a statin is so minimal and the benefit of statin is so great. Practicing in an era before statins in the 1980s, compared to after that, I'm not seeing the number of strokes and heart attacks that we saw before. That's the game changer.

As an endocrinologist treating someone with diabetes, that's the easiest drug to initiate. It's very well tolerated, it's inexpensive, and we can use it to get to their LDL target goal. That's why the American College of Endocrinology says to everyone with diabetes 'Where is your statin?', based on outcome studies in people with diabetes. But I agree with the notion that we could take it before that. A person with prediabetes is a person with diabetes waiting to happen. Why not treat that patient? What about the obese patient who didn't yet get prediabetes, but they're going to have diabetes in the future?

So, I agree. Statins are imperative for primary prevention and I know a lot of our colleagues calculate a Framingham risk and all that other stuff, and maybe wait for a cardiac calcium score to push the patient, but the fatty streaks are already there. It's unusual to have a zero cardiac calcium score. So, I do think statins are one of the key primary prevention drugs that we have.

Editor's note: These transcripts have been edited for length and clarity. 

Articles

Statins and their specific role have been the subject of debate for years. In this feature, 6 leading experts in cardiometabolic health share their perspectives on whether statins should be used in the sense of primordial prevention for ASCVD. 

Results of the ATLAS trial demonstrate use of subcutaneous implantable cardioverter-defibrillator (S-ICD) was associated with a more than 90% reduction in major lead complications compared against transvenous implantable cardioverter-defibrillator (TV-ICD) in ICD-eligible patients

A randomized trial comparing use of S-ICD versus TV-ICD in a cohort of more than 500 ICD-eligible patients with cardiogenetic syndrome or considered to be at high risk for lead-related complications, results of the trial indicate use of the S-ICD, which is implanted under the skin just below the patient’s armpit, was associated with lower odds of the study’s primary outcome of major lead complications at 6 months, with no instances of pneumothorax, lead dislodgement, subclavian venous thrombosis, or significant tricuspid insufficiency occurring among those receiving S-ICD in the trial.

“The S-ICD greatly reduces perioperative, lead-related complications without significantly compromising ICD performance,” says Jeff Healey, a senior scientist at the Population Health Research Institute (PHRI) at McMaster University and Hamilton Health Sciences, 

. “The S-ICD is now an attractive alternative to the TV-ICD, particularly in patients at increased risk for lead-related complications.”

Led by Healey and colleagues at the PHRI, the Boston Scientific-funded Avoid Transvenous Leads in Appropriate Subjects (ATLAS) trial was designed as a multicenter, randomized, open-label, parallel-group trial with the intent of comparing use of a standard, single chamber TV-ICD against S-ICD for risk of preoperative and long-term complications. With this in mind, investigators enrolled patients aged 18-60 years of age with a primary or secondary indication for an ICD and randomized them to either TV-ICD or S-ICD, these patients were then followed for 12-48 months to assess outcome measures.

The primary outcome of interest was a composite of major lead-related preoperative complications at 6 months, which consisted of hemothorax or pneumothorax, cardiac perforation, tamponade, pericardial effusion, or pericarditis, lead dislodgement or loss of pacing/sensing requiring revision, new moderate-severe or severe tricuspid insufficiency, or ipsilateral upper-extremity deep venous thrombosis. The secondary outcome of interest for the trial was a safety composite that included all the primary outcome events and device-related infection requiring surgical revision, significant wound hematoma, myocardial infarction, stroke, and mortality.

Ultimately, 503 patients underwent randomization in the trial, with 251 randomized to S-ICD and 252 randomized to TV-ICD. This cohort had a mean age of 49 (SD, 11.5) years, 74.2% were men, 22.5% had a history of cardiac arrest, 78.5% reported beta-blocker use at baseline, and the mean follow-up time was 2.5 (SD, 1.1) years. Of the 251 in the S-ICD group, 247 underwent implantation. Of the 252 in the TV-ICD group, 246 underwent implantation.

Upon analysis, results indicated the risk of a primary outcome event was significantly reduced with S-ICD compared to TV-ICD (OR, 0.08 [95% CI, 0.00-0.55]; 

.003). Investigators pointed out just a single patient in the S-ICD arm of the trial experienced a patient had cardiac perforation, tamponade, pericardial effusion, or pericarditis, while a total of 12 primary outcome events occurred among patients in the TV-ICD arm. Further analysis indicated there were no statistically significant difference in the rate of secondary outcome events (4.4% vs 5.6%; OR 0.78; 95% CI 0.35-1.75), but Healey pointed out in his presentation that a numerically greater number of these events occurred when assessing any inappropriate shock among patients in the S-ICD arm compared against the TV-ICD arm.

“The S-ICD produces the first demonstration that there is a clear reduction in major lead-related complications of 92%. There is no significant loss in ICD performance; specifically, no reduction in shock efficacy and inappropriate shocks. Although numerically higher, it did not reach statistical significance and will be the subject of additional analyses,” Healey added during his presentation.

This study, “Subcutaneous Versus Transvenous Defibrillators: The Atlas Trial,” was presented at HRS 2022.

Data from the ATLAS trial suggests receiving an S-ICD was associated with a 92% lower risk of major lead-related complications compared to receiving a TV-ICD. 

Subcutaneous ICDs Could Reduce Risk of Lead-Related Complications

A history of infertility could increase a woman’s risk of developing 

 by 16%, according to a new analysis of more than 35,000 postmenopausal women.

Using data from the Women’s Health Initiative, a team from Massachusetts General Hospital assessed risk of heart failure in a cohort of 38,528 postmenopausal women based on history of infertility and found a history of infertility was independently associated with a 16% increase in risk of future heart failure overall and a 27% greater risk of heart failure with preserved ejection fraction (HFpEF).

“We as scientists and doctors are beginning to recognize how important a woman's reproductive history is for their future risk of heart disease. Infertility is one of many cardiovascular risk factors, such as hypertension and high blood pressure, but reproductive history is not routinely considered as part of the cardiovascular risk assessment,” said lead investigator Emily Lau, MD, MPH, cardiologist and director of the Menopause, Hormones and Cardiovascular Clinic at Massachusetts General Hospital, 

 “We cannot change a woman’s history of infertility, but if we know a woman has had a history of infertility, we can be more aggressive about counseling her about other modifiable risk factors including high blood pressure, high cholesterol, smoking, and beyond.”

With support from the National Institutes of Health and the American Heart Association, the current study was conducted by Lau and a team of colleagues at Massachusetts General Hospital with an interest in furthering the knowledge base surrounding risk factors for heart failure among aging women. To do so, investigators designed their study as an analysis of data from the Women’s Health Initiative.

From the prospective study, investigators obtained data related to a cohort of 38,528 postmenopausal women for inclusion in their analyses. This cohort had a mean age of 63±7 years at baseline, 4399 (14%) reported a history of infertility, and, over a median follow-up of 15 years, 2373 developed incident heart failure, including 807 with heart failure with reduced ejection fraction (HFrEF) and 1133 with HFpEF.

For the purpose of analysis, investigators used multivariable cause-specific Cox models to assess associations of infertility with incident overall heart failures and heart failure subtypes. Investigators defined HFrEF as a left ventricular ejection fraction (LVEF) less than 50% and HFpEF as an LVEF of 50% or greater.

In adjusted analysis, results indicated infertility was independently associated with future risk of overall heart failure (HR, 1.16 [95% CI, 1.04-1.30]; 

=.006). When assessing risk according to heart failure subtypes, infertility was associated with an increased risk of future HFpEF (HR, 1.27 [95% CI, 1.09-1.48]; 

=.002), but this increase in risk was not observed for HFrEF (HR, 0.97 [95% CI, 0.80-1.18]).

Investigators pointed out additional analyses were performed to assess if the apparent increase in risk would be mediated by other infertility-related risk factors, such as irregular menses, thyroid disease, and waist circumference, and these analyses indicated these risk factors were associated with infertility, but not associated with incident heart failure risk.

, Ersilia M. DeFilippis, MD, of Brigham and Women’s Hospital, commended both the study’s investigators for their efforts in furthering research and the participants of the Women’s Health Initiative for their contributions to science.

“One of the best ways to honor these research participants is to improve our history taking, early evaluation, and risk assessment of young women of reproductive age, both in clinical practice and as part of clinical trials. This should include an assessment of traditional cardiovascular risk factors but also inquire about age of menarche, difficulty conceiving, number of pregnancies and any adverse pregnancy outcomes, breastfeeding, and timing of menopause,” DeFilippis wrote.

Infertility and Risk of Heart Failure in the Women’s Health Initiative

Journal of the American College of Cardiology.

An analysis of data from more than 35,000 women in the Women's Health Initiative indicates a history of infertility was independently associated with a 16% increase in risk of incident heart failure, with a 27% increase in risk of HFpEF, in postmenopausal women. 

History of Infertility Linked to Increased Risk of Heart Failure in Women

The American Heart Association is hoping to draw attention to an overlooked issue impacting the cardiovascular health of millions worldwide with their latest scientific statement: nonalcoholic fatty liver disease (NAFLD).

With previous data suggesting NAFLD could be affecting 25% of adults worldwide, the AHA’s scientific statement is aimed at increasing awareness around NAFLD as well as facilitate improved diagnosis and early treatment effort to help reduce the impact NAFLD can have on cardiovascular disease risk on a societal level.

“Nonalcoholic fatty liver disease is a common condition that is often hidden or missed in routine medical care. It is important to know about the condition and treat it early because it is a risk factor for chronic liver damage and cardiovascular disease,” said P. Barton Duell, MD, FAHA, chair of the statement writing committee and professor of medicine in the Knight Cardiovascular Institute and Division of Endocrinology, Diabetes and Clinical Nutrition at Oregon Health & Science University, in 

Published on April 14 and citing more than 160 reference documents, the statement composed by Duell and colleagues was prepared by the volunteer writing group on behalf of the American Heart Association’s Council on Atherosclerosis, Thrombosis and Vascular Biology, the Council on Hypertension, the Council on the Kidney in Cardiovascular Disease, the Council on Lifestyle and Cardiometabolic Health, and the Council on Peripheral Vascular Disease. At 18 pages in length, the document dedicates 10 subsections to outlining terminology, risk factors for NAFLD, Pathogenesis of NAFLD, predisposing genetic risk factors, NAFLD and atherosclerotic cardiovascular disease risk, NAFLD in patients undergoing PCI and CABG, hypobetalipoproteinemia and NAFLD, Safety of statins in NAFLD, strategies for screening of NAFLD and NASH, and potential interventions for NAFLD.

A large portion of the statement was dedicated to interventions for NAFLD, both from a pharmacological perspective and also addressing modifiable risk factors. In addition to dietary and lifestyle modification, authors underlined the importance of using proven agents, such as GLP-1 RAs, metformin, and lipid-lowering therapies, among patients with NAFLD or NASH. In addition to providing information on established therapies, the writing committee also offered insight into the potential for experimental agents from contemporary data.

“Part of the good news about managing NAFLD is that healthy eating, regular exercise and weight loss or avoiding weight gain are all valuable interventions to improve health in most of us, regardless of whether we have NAFLD,” said Duell.

In their conclusion, authors provided clinicians with their top take-home messages from the statement, which are summarized in the graphic below.

Summary of the top take-home messages from the AHA's scientific statement on NAFLD's role in cardiovascular disease risk. 

Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association

Arteriosclerosis, Thrombosis, and Vascular Biology.

The latest scientific statement from the American Heart Association is aimed at improving the awareness of NAFLD and its associated cardiovascular risk among clinicians as well as optimizing diagnosis and early treatment strategies for patients with NAFLD. 

AHA Calls Attention to Growing Impact of NAFLD on Cardiovascular Disease Risk

This article was originally published on 

Finerenone (Kerendia) provides a consistent effect for reducing the risk of adverse cardiovascular and kidney events was consistent regardless of whether or not patients had a history of atherosclerotic cardiovascular disease (ASCVD), according to a recent FIDELITY analysis.

With ASCVD placing patients with diabetes at a greater risk of adverse outcomes, results of the respecified analysis provide clinically applicable insight into the magnitude of effect seen with finerenone based on presence of ASCVD among patients with type 2 diabetes and chronic kidney disease.

“In patients with chronic kidney disease associated with type 2 diabetes, cardiovascular complications are among the most frequent causes of death. However, there is limited data on how the risk of cardiovascular events could be reduced in these patients,” said Javed Butler, MD, MPH, MBA, president of the Baylor Scott & White Research Institute and senior vice president for Baylor Scott & White Health, and distinguished professor of medicine at the University of Mississippi, in a 

Combining data from the FIGARO-DKD and FIDELIO-DKD analyses, FIDELITY represents efforts to pool data from both studies to learn more about the effects of finerenone, including the consistency of benefit across different subgroups of patients. At ACC.22, Gerasimos Filippatos, MD, presented data from a FIDELITY analysis assessing impact of baseline ASCVD on cardiorenal outcomes among patients within both trials using finerenone. Primary analyses of FIDELITY indicated use of finerenone reduced risk of a composite cardiovascular outcome, which included cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure, by 14% and risk of chronic kidney disease progression by 23% (HR, 0.77 [95% CI, 0.67-0.88]) when compared against placebo therapy.

Of the more than 13,000 patients enrolled in FIDELIO-DKD and FIGARO-DKD, 5935 had a history of ASCVD and 7091 had no history of ASCVD. When comparing baseline characteristics of these patient subgroups, investigators pointed out patients with ASCVD had a lower eGFR and UACR than those without, but blood pressure and HbA1c were well-controlled in both groups. Investigators also pointed out patients with ASCVD were more likely to be prescribed beta-blockers, statins, and insulin than their counterparts without ASCVD.

Upon analysis, results indicated patients with a history of ASCVD were at a 2-fold increase in risk of a composite cardiovascular outcome that included time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalizations for heart failure compared to those without a history of ASCVD (HR, 2.09 [95% CI, 1.89-2.30]). When assessing the effects of finerenone, use was associated with a 17% (HR, 0.83 [95% CI, 0.74-0.94]) reduction in risk of the composite cardiovascular outcome among those with a history of ASCVD and a 9% (HR, 0.91 [95% CI, 0.78-1.06]) reduction in risk among those without a history of ASCVD when compared against placebo therapy. Analysis of treatment-emergent adverse events indicated the safety profile of finerenone was similar between patients with and without a history of ASCVD.

“In general, overall, the data presented today indicate that finerenone may be used for both primary and secondary cardiovascular disease prevention in these groups of patients with type 2 diabetes and chronic kidney disease as well as protection from worsening kidney disease,” Filippatos said, at the conclusion of his presentation.

This study, “Finerenone and Cardiorenal Outcomes by History of Cardiovascular Disease in Patients with Type 2 Diabetes and Chronic Kidney Disease: Fidelity Analyses,” was presented at ACC.22.

A prespecified analysis of FIDELITY presented at ACC.22 details the effects of finerenone on reducing cardiovascular risk based on whether or not patients had a history of atherosclerotic cardiovascular disease at baseline. 

Finerenone Provides Consistent Benefit for Reducing CV Risk, Regardless of CVD History

Data from a phase 2b trial presented at the 

American College of Cardiology’s 71st Annual Scientific Sessions

 detail the ability of bentracimab to provide immediate and durable reversal of the antiplatelet effects of ticagrelor.

Presented by Deepak Bhatt, MD, MPH, the analysis comes less than a year after results of an interim analysis of the REVERSE-IT trial were presented at AHA 2021 and provides insight into the effects of bentracimab as a reversal agent for ticagrelor in older patients in a double-blind, placebo-controlled trial.

“Compared with placebo, bentracimab significantly restored platelet function as measured by multiple assays by binding and eliminating free ticagrelor and ticagrelor active metabolite,” said Bhatt, who serves as the executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, during his presentation.

A multicenter, open-label, prospective, single-arm trial, REVERSE-IT was designed with the intent of assessing the ability of bentracimab, a monoclonal antibody from PhaseBio, for reversal of the antiplatelet effects of ticagrelor. An interim analysis off the first 140 enrolled patients, results of the interim analysis demonstrated use of bentracimab results in rates of effective hemostasis that were adjudicated as good or excellent in more than 90% of cases, with no drug-related serious adverse events, or allergic or infusion-related reactions.

The phase 2b study was a randomized, double-blind, placebo-controlled trial that randomized patients in a 3:1 ratio to bentracimab or placebo therapy. In this trial, all participants were aged 50-80 years of age and pretreated with ticagrelor and aspirin for 48 prior to receiving bentracimab. The primary outcome of interest for the trial was the inhibition of platelet reality unit (PRU).

In total, the trial enrolled 205 patients, with 154 randomized to bentracimab and 51 randomized to placebo. The overall study population had a mean age of 61.2 (SD, 6.85) years, 50.2% were male, and 80% were White.

Upon analysis, results of the trial suggested bentracimab achieved immediate and sustained reversal of antiplatelet effects among adults aged 50-80 years old who had been pretreated with dual antiplatelet therapy in both VerifyNow PRU and VASP PRI Assay analyses. In his presentation, Bhatt highlighted the effects of bentracimab on the primary endpoint were statistically significant within 4 hours and were consistent across various subgroups, including those defined by sex, age, and race.

In safety analyses, results indicated there were no drug-related serious adverse events or thrombotic events among those in the bentracimab arm. Those most common treatment-related adverse event observed in the trial were headache, ecchymosis, and contusion, but investigators highlighted there were no significant differences observed between bentracimab and placebo for any treatment-emergent adverse events in the trial.

“Based on these data, bentracimab appears to be a very promising option for ticagrelor reversal. Assessments of bentracimab’s clinical effect on patients with bleeding awaits completion of the REVERSE-IT study,” added Bhatt, in the latter portion of his presentation.

This study, “Bentracimab Immediately And Significantly Reverses The Antiplatelet Effects Of Ticagrelor In Older People,” was presented at ACC.22.

Data from a phase 2b trial of bentracimab presented by Deepak Bhatt, MD, MPH, at ACC.22 demonstrates it the ability for reversing antiplatelet effects in an older population.