Heart health and treatment took centre stage at the world’s largest gathering of heart experts in Madrid at the weekend, where a slew of pioneering research and study findings was released, including details of a new pill to lower blood pressure, and research showing a common blood thinner is more effective in preventing CVD than good old aspirin.
Other – more alarming – studies presented at the European Society of Cardiology suggested that beta-blockers, long used as a first-line treatment after a heart attack, actually don’t benefit most patients and may even contribute to a higher risk of hospitalisation and death in some women but not in men.
Reducing high BP
The revelations that a new drug could help in the battle against hypertension for patients resistant to existing medication will be welcomed, after AstraZeneca announced that in trials, the treatment, baxdrostat, significantly lowered BP in patients whose levels remain dangerously high despite taking several medicines.
The Guardian reports that the findings were published simultaneously in The New England Journal of Medicine.
The results of the BaxHTN study trials – sponsored by AstraZeneca – which involved 796 patients from 214 clinics worldwide, showed that after 12 weeks, patients taking baxdrostat saw their blood pressure fall by about 9-10 mmHg (millimetres of mercury, the unit of measurement of blood pressure) more than placebo – a reduction large enough to cut cardiovascular risk.
About four in 10 patients taking the drug, 1mg (39.4%) or 2mg (40%) once daily in tablet form, reached healthy blood pressure levels, compared with fewer than two in 10 (18.7%) on placebo.
Principal investigator Professor Bryan Williams, chair of medicine at University College London’s Institute of Cardiovascular Science, said: “I’ve never seen blood pressure reductions of this magnitude with a drug. Achieving a nearly 10 mmHg reduction in systolic blood pressure with baxdrostat in the BaxHTN phase 3 trial is exciting, as this level of reduction is linked to substantially lower risk of heart attack, stroke, heart failure and kidney disease.
“I think this could change how we approach difficult to control or hard to control blood pressure. The results suggest this drug could help up to half a billion people globally.”
The breakthrough has taken decades of research.
Blood pressure is strongly influenced by the hormone aldosterone, which helps the kidneys regulate salt and water balance. Producing too much aldosterone causes the body to retain salt and water. This aldosterone dysregulation hikes blood pressure, making it difficult to control.
Tackling aldosterone dysregulation has been a key target of research for years, but until now it has been impossible to achieve. Baxdrostat works by blocking aldosterone production, directly addressing this driver of high BP.
“This drug development is really a triumph of scientific discovery,” Williams told reporters in Madrid.
“Aldosterone is a well-known driver of hypertension, but for decades, scientists have struggled to block its production in a precise way. Baxdrostat is one of the first therapies to do so selectively, showing meaningful BP reductions in uncontrolled or resistant hypertension.”
Largely due to changing diets, the numbers of people with hypertension is now far higher in eastern and lower-income countries. More than half of those affected live in Asia, including 226m people in China and 199m in India.
Better than aspirin
In another discovery – which could transform global health guidelines – scientists announced that clopidogrel, a common blood thinner that is also registered and prescribed in South Africa, does a better job than aspirin at preventing heart attacks and strokes.
The Guardian reports that for decades, millions of people have been taking a daily low-dose aspirin to reduce the risk of a cardiovascular event, but this latest study revealed that clopidogrel is more effective.
The data were simultaneously published in The Lancet.
The international team of medics behind the study, from countries including the US, UK, Australia, Switzerland and Japan, told congress delegates that their comprehensive analysis of nearly 29 000 patients with coronary artery disease (CAD) found that clopidogrel was better than aspirin in preventing serious heart and stroke events, without increasing the risk of major bleeding.
CAD is a leading cause of death and disability, occurring when arteries in the heart become narrowed by a build-up of atheroma, the fatty material within their walls. If a blockage occurs, it can cause a heart attack.
The findings challenge the longstanding recommendation of aspirin as the default treatment for preventing serious CVD events in hundreds of millions of CAD patients.
While aspirin has traditionally been prescribed indefinitely for patients with the condition, evidence supporting its long-term benefits and safety has been limited.
The latest analysis of seven clinical trials found that patients taking clopidogrel had a 14% lower risk of major adverse CVD or cerebrovascular events – including heart attack, stroke or cardiovascular death – compared with those taking aspirin.
Importantly, the rates of major bleeding issues in patients were similar between the two drugs, dispelling concerns that clopidogrel might lead to more bleeding complications.
In The Lancet, the study team wrote: “This synthesis of available evidence indicates that…. long-term clopidogrel monotherapy offers superior protection against major cardiovascular and cerebrovascular events compared with aspirin, without an excess risk of bleeding.
“The superior efficacy was consistent across multiple key subgroups, including individuals with clinical features predictive of poor clopidogrel responsiveness.
“The widespread availability, generic formulation and affordability of clopidogrel further supports its potential for extensive adoption in clinical practice.”
The analysis drew from diverse patient groups, including those who had undergone procedures such as stent placement or experienced acute coronary syndrome, and examined various subgroups to ensure the findings applied broadly.
Notably, even patients who might respond less well to clopidogrel because of genetic or clinical factors still benefited from its use over aspirin.
The scientists said the findings have the potential to influence clinical guidelines worldwide and improve patient outcomes, but further research on the cost-effectiveness of clopidogrel, as well as broader population studies, would be needed to support changes in treatment standards.
Heart attack drug hikes death risk
Meanwhile, the findings that beta-blockers don’t benefit the vast majority of patients and could contribute to more chance of hospitalisation and death in some women – but not in men – could reshape all international clinical guidelines, said other researchers.
“This should also spark a long-needed, sex-specific approach to treatment for cardiovascular disease,” senior study author Dr Valentin Fuster, President of Mount Sinai Fuster Heart Hospital in New York City and general director of the National Centre for Cardiovascular Investigation in Madrid, told CNN.
Women with little heart damage after their heart attacks who were treated with beta-blockers were significantly more likely to have another heart attack or be hospitalised for heart failure – and nearly three times more likely to die – than women not given the drug, found the study, published in the European Heart Journal and presented at the ESC Congress on Saturday.
“This was especially true for women receiving high doses of beta-blockers,” said lead study author Dr Borja Ibáñez, scientific sirector for Madrid’s National Centre for Cardiovascular Investigation.
“The number of women in the clinical trial was the largest ever included in a study testing beta-blockers after myocardial infarction, so this is a significant finding,” said Ibáñez, a cardiologist at Madrid’s Jiménez Díaz Foundation University Hospital.
The findings, however, only applied to women with a left ventricular ejection fraction above 50%, which is considered normal function, the study said.
Ejection fraction measures how well the left side of the heart is pumping oxygenated blood throughout the body. For anyone with a score below 40% after a heart attack, beta-blockers continue to be the standard of care due to their ability to calm heart arrhythmias that may trigger a second event.
Still, the drug can have unpleasant side effects, said Dr Andrew Freeman, director of Cardiovascular Prevention and Wellness at National Jewish Health in Denver.
“The drugs can lead to low blood pressure, low heart rate, erectile dysfunction, fatigue and mood swings,” added Freeman, who was not involved in the research. “Anytime we use these drugs, we always have to balance risk versus benefit.”
Why would women be more susceptible to harm from beta-blockers than men?
“That’s actually not surprising,” Freeman said. “Gender has a lot to do with how people respond to medication. Women usually 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.”
In fact, because early research on the heart focused on men, it took medical science years to discover that heart disease presents differently in women.
Men typically have plaque build-up in their major arteries and experience more traditional signs of a heart attack, like chest pain.
Women are more likely to have plaque in the heart’s smaller blood vessels and can have more unusual symptoms of a heart attack, such as back pain, indigestion and shortness of breath.
The analysis on women was part of a larger clinical trial called REBOOT – Treatment with Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction – which followed 8 505 men and women treated for heart attacks at 109 hospitals in Spain and Italy for nearly four years.
Results of the study were published in The New England Journal of Medicine and also presented at the Congress.
None of the patients in the trial had a left ventricular ejection fraction below 40%, a sign of potential heart failure.
“We found no benefit in using beta-blockers for men or women with preserved heart function after heart attack, despite this being the standard of care for some 40 years,” said Fuster, former editor-in-chief of the Journal of the American College of Cardiology and past president of the American Heart Association and the World Health Federation.
That’s probably due to advances in medication treatment such as the immediate use of stents and blood thinners after patients arrive at the hospital. In fact, most men and women who survive heart attacks today have ejection fractions above 50%, Ibáñez said.
“Yet at this time, some 80% of patients in the US, Europe and Asia are treated with beta-blockers because medical guidelines still recommend them,” he said. “While we often test new drugs, it’s much less common to rigorously question the continued need for older treatments.”
While the study did not find any need to use beta-blockers for people with a left ventricular ejection fraction above 50% after a heart attack, a separate meta-analysis of 1 885 patients published in The Lancet did find benefits for those with scores between 40% and 50%, in which the heart may be mildly damaged.
“This subgroup did benefit from a routine use of beta-blockers,” said Ibáñez, who was also a co-author on this paper. “We found about a 25% reduction in the primary endpoint, which was a composite of new heart attacks, heart failure and all-cause death.”
See more from MedicalBrief archives:
Stopping aspirin when on blood thinners cuts bleeding risk – Michigan study
Beta blockers have positive effect in pulmonary arterial hypertension
Strong results for two BP-lowering drugs in resistant hypertension