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A Common Drug Used To Treat Heart Attacks May Not Help And Could Have Fatal Consequences For Women, Bombshell New Study Finds
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A type of drug used to help treat heart attacks does not work on the majority of patients and may actually contribute to hospitalization and death for women, new research has found.
Beta-blockers are medicines that are used to lower blood pressure and cause the heart to beat more slowly and with less force. They have been used as first-line treatment after heart attacks for decades, according to CNN.
However, a study published Saturday in the European Heart Journal found that women with little heart damage after suffering heart attacks who were treated with beta-blockers were significantly more likely to have another heart attack or be hospitalized for heart failure further down the line.
These women were also nearly three times more likely to die compared with women not given the drug, the study found. This was especially true for women receiving high doses of beta-blockers, according to lead study author Dr. Borja Ibanez.
Despite this, the same is not true for men, the research found.
Beta blockers, a type of drug used to help treat heart attacks, do not work on the majority of patients and may actually contribute to hospitalization and death for women, new research has found (PA Wire)
Ibanez described the findings as "significant," noting that the total number of women in the clinical trial was the largest ever included in a study testing beta-blockers after a heart attack.
The findings related to women with a left ventricular ejection fraction – the measurement used to determine how well the left side of the heart is pumping oxygenated blood – of above 50 percent. That is the level which is considered normal, according to the study.
For those with a score below 40 percent after a heart attack, beta-blockers will continue to be used due to their ability to calm abnormalities that could trigger a second event.
Dr. Andrew Freeman, director of cardiovascular prevention and wellness at National Jewish Health in Denver, told CNN that women being more susceptible to harm caused by beta-blockers than men was "actually not surprising."
"Gender has a lot to do with how people respond to medication," Freeman told the outlet.
"In many cases, women have smaller hearts. They're more sensitive to blood pressure medications. Some of that may have to do with size, and some may have to do with other factors we have yet to fully understand."
Early research on heart disease was so focused on men that it took years to discover that symptoms presented differently in women, according to CNN. While men suffer from symptoms viewed as traditional, such as chest pain, women can have more unusual warning signs of a heart attack such as back pain and indigestion.
The traditional chest pain associated with heart attacks in seen more in men than women. (Getty/iStock)
The analysis was part of a much bigger clinical trial called REBOOT — Treatment with Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction — which followed more than 8,000 men and women treated for heart attacks at 109 hospitals in Spain and Italy for nearly four years.
None of the patients had left ventricular ejection fraction below 40 percent, and the study, published in The New England Journal of Medicine, found "no benefit in using beta-blockers" in males or females whose hearts were in such a condition, despite it still being the norm.
This, according to CNN, is in part down to advances in treatment.
Merck Provides New Results For VERQUVO® (vericiguat) In Patients With Chronic Heart Failure And Reduced Ejection Fraction
The Phase 3 VICTORIA trial focused exclusively on a population with worsening chronic HFrEF at high risk for cardiovascular mortality and repeated heart failure hospitalizations. In a separate pre-specified pooled analysis across VICTOR and VICTORIA, VERQUVO's benefit was examined in a large and broad cohort. In this pooled analysis of 11,155 HFrEF patients, VERQUVO showed a statistically significant risk reduction across the primary composite endpoint of cardiovascular death or heart failure hospitalization and its components as secondary endpoints, in a broad spectrum of patients with HFrEF. No new safety signals, beyond those reported in the individual trials, emerged in the pooled analysis.
"While the VICTOR trial did not meet its primary endpoint, the separate pooled analysis across both VICTOR and VICTORIA did demonstrate a statistically significant reduction in the primary composite endpoint of heart failure hospitalization and cardiovascular deaths in patients with heart failure and reduced ejection fraction across the disease severity," said Javed Butler, MD, MPH, MBA, President of the Baylor Scott and White Research Institute and Professor of Medicine at University of Mississippi in Jackson, Mississippi.
The positive benefit-risk profile of VERQUVO in its approved indication in patients with HFrEF following a recent heart failure event based on the pivotal Phase 3 VICTORIA trial remains unchanged. In the U.S., VERQUVO is approved for the reduction of risk of cardiovascular death and heart failure hospitalization following a hospitalization for heart failure or need for outpatient intravenous diuretics in adults with symptomatic chronic heart failure and ejection fraction less than 45%.
About VICTOR
VICTOR (VerICiguaT in adults with ChrOnic heart failure and Reduced ejection fraction) (NCT05093933) was a randomized, double-blind, placebo-controlled, multicenter, event-driven Phase 3 study investigating the efficacy and safety of VERQUVO in adult patients with symptomatic chronic heart failure (New York Heart Association [NYHA] class II-IV) and a left ventricular ejection fraction (LVEF) of 40% or less. It enrolled 6,105 patients with chronic heart failure with reduced ejection fraction (HFrEF), who had not had a recent hospitalization for heart failure within 6 months or the need for outpatient intravenous diuretics within 3 months before randomization. Patients receiving contemporary guideline-directed medical therapy (GDMT), including SGLT2-inhibitors and angiotensin receptor-neprilysin inhibitor (ARNI), were randomized to receive either VERQUVO or placebo. VICTOR was the first large event-driven HFrEF trial performed in the contemporary era of quadruple foundational GDMT, in a compensated ambulatory heart failure population. Merck and Bayer AG are co-developers of the VICTOR trial. The study was executed by Merck.
About VICTORIA
VICTORIA (NCT02861534) was a randomized, placebo-controlled, parallel-group, multi-center, double-blind, Phase 3 study of VERQUVO versus placebo when given in combination with available heart failure therapies in patients with worsening chronic heart failure with reduced ejection fraction (HFrEF) following a decompensation event, defined as heart failure hospitalization or receiving an intravenous diuretic for heart failure without hospitalization. The primary endpoint of the study was the composite of time to first occurrence of cardiovascular death or heart failure hospitalization. Secondary endpoints included time to occurrence of cardiovascular death, time to first occurrence of heart failure hospitalization, time to total heart failure hospitalizations (including first and recurrent events), time to the composite of all-cause mortality or heart failure hospitalization, and time to all-cause mortality. The study enrolled 5,050 patients who were randomized to receive either VERQUVO once daily (titrated up to 10 mg) or placebo when given in combination with available heart failure therapies. The study, which was co-sponsored by Merck and Bayer, was conducted in collaboration with the Canadian VIGOUR Centre and the Duke Clinical Research Institute in more than 600 centers in 42 countries.
About VERQUVO (vericiguat)VERQUVO is an oral once daily stimulator of soluble guanylate cyclase (sGC), an important enzyme in the nitric oxide (NO) signaling pathway. When NO binds to sGC, the enzyme catalyzes the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger that plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling. Heart failure is associated with impaired synthesis of NO and decreased activity of sGC, which may contribute to myocardial and vascular dysfunction. By directly stimulating sGC, independently of and synergistically with NO, VERQUVO augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation.
VERQUVO is FDA-approved to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following a hospitalization for HF or need for outpatient IV diuretics, in adults with symptomatic chronic HF and ejection fraction less than 45%.
Selected Safety Information for VERQUVO (vericiguat) tablets (2.5 mg, 5 mg, and 10 mg)
WARNING: EMBRYO-FETAL TOXICITY
Females of reproductive potential: Exclude pregnancy before the start of treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment. Do not administer VERQUVO to a pregnant female because it may cause fetal harm.
VERQUVO is contraindicated in patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators. VERQUVO is contraindicated in pregnancy. Based on data from animal reproduction studies, VERQUVO may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to a fetus. Obtain a pregnancy test before the start of treatment. Advise females of reproductive potential to use effective contraception during treatment with VERQUVO and for at least one month after the final dose.
In a clinical trial, the most commonly observed adverse events with VERQUVO vs placebo, occurring at a frequency greater than or equal to 5%, were hypotension (16% vs 15%) and anemia (10% vs 7%).
Concomitant use of VERQUVO with PDE-5 inhibitors is not recommended because of the potential for hypotension.
There are no data on the presence of VERQUVO in human milk, the effects on the breastfed infant, or effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from VERQUVO, advise women not to breastfeed during treatment with VERQUVO.
About Heart Failure with Reduced Ejection FractionHeart failure with reduced ejection fraction (HFrEF), formerly known as systolic heart failure, is characterized by the compromised ability of the heart to pump blood sufficiently during its contraction phase. In the U.S., approximately 6.2 million adults (20 years of age and older) have heart failure, and approximately 50% of heart failure patients have HFrEF. An observational, cohort analysis of PINNACLE registry data showed that approximately half of patients with worsening chronic HFrEF are rehospitalized within 30 days of a worsening event, and an estimated one in five patients with worsening chronic HFrEF will die within two years.
About the Worldwide Collaboration between Merck and BayerSince October 2014, Bayer and Merck (known as MSD outside the U.S. And Canada) have pursued a worldwide collaboration in the field of sGC modulators. The collaboration brings together two leading companies that have stated their intent to fully evaluate this therapeutic class in areas of unmet medical need. The vericiguat program is being co-developed by Bayer and MSD. MSD has the commercial rights to vericiguat in the U.S. And Bayer has the exclusive commercial rights in the rest of world. The companies share equally the costs of the development of vericiguat.
About MerckAt Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.Merck.Com and connect with us on X (formerly Twitter), LinkedIn and YouTube.
Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USAThis news release of Merck & Co., Inc., Rahway, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's Annual Report on Form 10-K for the year ended December 31, 2024 and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (www.Sec.Gov).
Please see Prescribing Information, including Boxed Warning, for VERQUVO (vericiguat) at https://www.Merck.Com/product/usa/pi_circulars/v/verquvo/verquvo_pi.Pdf and Medication Guide at https://www.Merck.Com/product/usa/pi_circulars/v/verquvo/verquvo_mg.Pdf.
View source version on businesswire.Com: https://www.Businesswire.Com/news/home/20250829814571/en/
Contacts
Media Contacts:Julie Cunningham, (617) 519-6264Elizabeth Sell, (484) 689-9978
Investor Contacts:Peter Dannenbaum, (732) 594-1579Ayn Wisler, (917) 691-6218
Digitoxin Improves Outcomes For Patients With HFrEF On Guideline-directed Medical Therapy
August 29, 2025
2 min read
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Key takeaways:In patients with heart failure with reduced ejection fraction on guideline-directed medical therapy, digitoxin conferred lower rates of death or worsening HF compared with placebo, according to results of the DIGIT-HF trial.
For DIGIT-HF, presented at the European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine, Udo Bavendiek, MD, professor in the department of cardiology and angiology at Hannover Medical School, Germany, and colleagues randomly assigned 1,212 patients with symptomatic HFrEF (mean age, 66 years; 20% women; 65% on implantable cardioverter defibrillators; 25% on cardiac resynchronization therapy) on guideline-directed medical therapy for at least 6 months to digitoxin, a cardiac glycoside, at a starting dose of 0.07 mg once daily, or placebo. HFrEF was defined as NYHA class II to IV and left ventricular ejection fraction 40% or less.
Data were derived from Bavendiek U, et al. Hot line 1. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2025; Madrid (hybrid meeting).
At a median follow-up of 36 months, the primary outcome of all-cause death or first hospitalization for worsening HF occurred in 39.5% of the digitoxin group compared with 44.1% of the placebo group (HR = 0.82; 95% CI, 0.69-0.98; P = .03; absolute risk reduction, 4.6%; number needed to treat to prevent one event = 22), Bavendiek said during the press conference.
"Importantly, we showed this on top of very well-implemented guideline-directed medical therapy," Bavendiek said during the press conference. "Almost all the patients, 95%, had beta-blockers, renin-angiotensin system blockers were far above 90%, and [some patients were taking] mineralocorticoid receptor agonists and SGLT2 inhibitors."
He said the results were somewhat surprising because recruitment was slow, but a positive result was achieved despite having fewer patients than expected.
All-cause death occurred in 27.2% of those in the digitoxin group vs. 29.5% of those in the placebo group (HR = 0.86; 95% CI, 0.69-1.07) and a first hospitalization for worsening HF occurred in 28.1% of the digitoxin group vs. 30.4% of the placebo group (HR = 0.85; 95% CI, 0.69-1.05), according to the researchers.
Among the cohort, 4.7% of the digitoxin group and 2.8% of the placebo group had at least one serious adverse event, the researchers found. Serious cardiac disorders occurred in 3.4% of the digitoxin group and 1.8% of the placebo group. The percentage of patients discontinuing the study drug due to adverse events was 9.1% in the digitoxin group and 10.2% in the placebo group.
"Also important was that the treatment appeared to be safe, as there were a lot of reports in the last year from post hoc analyses and nonrandomized trials claiming cardiac glycosides such as digitoxin are harmful for patients," Bavendiek said during the press conference. "These data support the use of digitoxin in patients with heart failure and reduced ejection fraction, and [the findings can] be implemented in clinical practice because we did not have any special exclusion criteria. Digitoxin seems to be an important option in the treatment of heart failure."
Reference: Perspective Back to Top Digitoxin is eliminated predominantly by the enterohepatic pathway, rather than the kidneys, and thus it is anticipated that patients would have more stable blood levels. Because it is not renally excreted, in the setting of renal dysfunction, digitoxin is not expected to manifest significantly elevated levels in the plasma. It is more lipophilic and has higher levels of protein binding and is more stable. This medication is meeting an unmet need in sicker patient populations, particularly those with stage C to D HF. These patients have advanced symptoms and signs and often have intolerance to or side effects from the standard HF medications. That was the population of this study; most were NYHA class III or IV, and those with NYHA class II were enrolled only if their LVEF was less than 30%. They had to have a high symptom burden. These patients have challenges in achieving comprehensive quadruple therapy because they may be intolerant to some of the medications. They have high rates of mortality unless a ventricular assist device or transplant is offered. For these patients, digitoxin use is an exciting opportunity and digoxin is already being used in major advanced HF centers. For patients with lower symptom burden or severity of HF such as individuals with NYHA Class II symptoms and higher EF ranges, one will need to look at the trajectory. If they respond to quadruple therapy, they may not need a cardiac glycoside like digitoxin or digoxin. The evidence provided by this study, which was carefully formulated but had challenges in recruitment, does show a modest relative risk reduction. The number needed to treat is only 22, which is comparable to other therapies. Digitoxin likely will become part of the armamentarium in patients with advanced HF. But keep in mind, sicker patients require individualized therapies based on their profiles. They may not tolerate medications that cause a precipitous drop in blood pressure such as angiotensin receptor/neprilysin inhibitors. For those individuals, a medication with a stable profile on blood pressure that is linked with improvements in contractile performance, symptoms, as well as overall outcomes would become an important addition. The selection of addition of digitalis may depend on specific patient phenotype hemodynamics and patient characteristics. We need to keep in mind, because it is hepatic-eliminated, we would not be able to utilize it in patients with advanced liver disease. It is also interesting to note that a subgroup analysis showed that it had a similar benefit in women and men, potentially attributable to digitoxin's profile. This is a differentiator from digoxin, as previous research showed female patients, especially those with higher levels of digoxin, did not derive benefit from digoxin, and if anything, there was a signal for harm. While there were recruitment challenges in the DIGIT-HF trial and there are not yet large numbers of patients with long-term follow-up, overall, this was a positive trial and is very promising for the severe HF patient population. Biykem Bozkurt, MD, PhD Senior Dean of FacultyProfessor and W. A. "Tex" and Deborah Moncrief, Jr. Chair of Medicine-CardiologyMary and Gordon Cain Chair of Internal Medicine in the Winters Center for Heart Failure ResearchBaylor College of MedicineEditor-in-Chief, JACC: Heart FailureDisclosures: Bozkurt reports no relevant financial disclosures.
Sources/DisclosuresCollapse Source: Bavendiek U, et al. Hot line 1. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2025; Madrid (hybrid meeting).Disclosures: Bavendiek reports speaking for, advising for, receiving a grant from or receiving travel support from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Braukmann-Wittenberg-Herzstiftung, Bristol Myers Squibb, Eli Lilly, Novartis and Pfizer. Please see the study for all other authors' relevant financial disclosures.
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