Are we on the brink of a cure for heart disease? That was the question being whispered by normally cautious cardiologists at the American Heart Association annual conference in Philadelphia last week.
Over three packed days, a raft of game-changing scientific discoveries have been unveiled by the world’s leading specialists – many of which will have a huge impact on millions of patients around the world.
But most startling was a clutch of pioneering treatments that ‘rewrite’ DNA, in some cases permanently, halting the body’s production of damaging cholesterol and driving down high blood pressure – two major risk factors for heart attacks and stroke.
Initially, due to uncertainties around side effects, which still remain to be seen, these treatments will be reserved for those with the most severe diseases and urgent needs. But if these drugs live up to their promise, the daily tablets – such as statins, blood thinners and beta blockers – taken by millions to reduce their risks of heart disease could become a thing of the past.
Are we on the brink of a cure for heart disease? That was the question being whispered by normally cautious cardiologists at the American Heart Association annual conference
Los Angeles-based cardiologist Professor Karol Watson summed up the mood: ‘I cannot emphasise enough how revolutionary these [therapies] are,’ she said. ‘We are delving into uncharted territory with entirely new therapeutic strategies, new molecules and new mechanisms.
MY BLOOD HAS TO BE ‘CLEANED’ TWICE A MONTH – THIS JAB WOULD CHANGE MY LIFE
In 2017, at the age of 47, John-Paul Corry discovered he had elevated levels of Lp(a) – a type of cholesterol that doubles the risk of a heart attack or stroke.
Five years on, after three stents and a heart bypass, the father-of-three has to make a six-hour round trip twice a month to the nearest hospital that offers apheresis– a dialysis-like procedure where he is hooked up to a machine that ‘cleans’ cholesterol from the blood.
At present, it’s the only way that high Lp(a) can be tackled. But the mental toll, he says, is a burden. ‘Knowing I have high Lp(a) is like being followed around by a sniper.’
A drug treatment that could permanently cure his problem would, he says, be life changing. And finally, according to the announcement last week that a single jab of drug lepodisiran could slash Lp(a) levels, hope could be on the horizon.
Slim, fit and healthy, John-Paul, pictured above with his wife, Jacqui, first went to the doctor with ‘mild discomfort’ in his chest. Tests showed his Lp(a) levels were very high and that one of his heart arteries was 99 per cent blocked.
‘The cardiologist told me I was lucky to be alive,’ recalls John-Paul. ‘Now I do all I can to reduce my risk.
‘I’d jump at the chance of an injection. It would mean I could live wherever I want and go on holiday whenever I want. These are things I can’t do because of having to have apheresis.’
‘This is the stuff we could only have dreamed about until a few years ago, and I never thought I’d see in my lifetime.’
Top cardiology researcher Professor Tim Chico, of the British Heart Foundation, said the findings had prompted ‘a shift in perspective’, adding: ‘Rather than managing cardiovascular events in later life, if given early enough these new approaches offer hope of curing cardiovascular disease.’
It couldn’t come a moment sooner: heart attacks account for 100,000 hospital admissions every year in England, and heart disease causes one in four deaths.
And with medical advances saving many, the number of survivors already tops 7.6 million, or roughly one in seven adults.
Last week The Mail on Sunday reported that twice-yearly jab zilebesiran could reduce blood pressure by ‘switching off’ a key gene. The results seen in the trial could equate to a 20 per cent reduction in the risk of heart attacks and strokes.
We also revealed a second experimental drug, Verve-101, could cut LDL (or ‘bad’) cholesterol levels in half after a single dose. It does this by making a small but crucial change to the DNA in liver cells.
There was more good news – this time for those affected by a little-known type of cholesterol called lipoprotein (a).
Also known as Lp(a), it is thought to be as damaging as the better-known LDL, and one in five adults may have high levels.
It’s only recently that cardiologists have begun to understand the key role it plays in heart disease. Experts say raised Lp(a) is usually down to genetics, rather than lifestyle – and even getting tested for it requires a referral to a specialist.
There is no treatment either, bar a dialysis-type therapy called apheresis, which involves being hooked up to a machine that mechanically cleans cholesterol from the blood.
But this could all be set to change. Lepodisiran, the first drug to reduce Lp(a) – and to almost non-existent levels – was unveiled last week.
Once again, genes are the target. Lepodisiran blocks the production of a key protein needed to make Lp(a) in the liver.
In the 48 volunteers tested, a single jab led to an average 94 per cent drop in Lp(a). In some cases, the lipoprotein was undetectable, likely meaning heart risk was slashed to almost nothing.
Levels have remained stable for a year and counting. Although more research will be needed to see if this translates to fewer heart attacks and strokes, the excitement around these early findings was palpable (see box to the right) – and three other drug treatments for lowering Lp(a) are in the pipeline.
Professor Steven Nissen, who led the lepodisiran trial, said: ‘People haven’t heard of Lp(a) but they need to, because having a high level doubles heart attack and stroke risk, independent of other risk factors such as high LDL. And now we’re going to be able to treat it.’
Kausik Ray, Professor of Cardiology at Imperial College London, said: ‘At the moment, one of the only options for people who discover they have high Lp(a) is apheresis. Not that many hospitals offer it, so patients find themselves in a difficult situation.
‘Findings like these are important. This is an exciting time.’
While these developments are raising hopes, there are a range of other announcements that will undoubtedly have a more immediate effect on patients in the UK today or in the not-too-distant future. Read on to find out more…
Control blood pressure to lower dementia risk
Keeping high blood pressure in check could significantly cut the risk of dementia, according to a major study.
The clinical trial – a first of its kind – followed more than 34,000 Chinese patients with high blood pressure for four years. The average age of volunteers was 64 at the start of the study, and half were offered intensive treatment including regular appointments, medication, diet and lifestyle support from doctors to bring their blood pressure down to healthy levels. The other half received the usual care, managed normally by their family doctors with medication, much like a patient would be in the UK.
The vast majority of those offered the intensive regime achieved their healthy blood pressure goal, and by the end of the four-year period these patients were 15 per cent less likely than the ‘usual care’ group to have developed dementia symptoms or memory issues.
New Orleans-based epidemiologist Professor Jiang He said that in the absence of a cure, finding ways to prevent dementia was ‘a public health priority’. He added: ‘We’ve demonstrated that lowering blood pressure is effective in reducing the risk of dementia in people with high blood pressure.’
Cardiologist Professor Keith Ferdinand, also from New Orleans, said the research provided vital clues about the causes of dementia and a solid strategy to help reduce the risk.
‘We used to accept increasing blood pressure as a part of older age,’ he said. ‘There was also a fear of lowering blood pressure in older patients due to concerns about the risk of medication side effects.
‘We now know from other research that these drugs are safe, so the message is clear: doctors should not accept high blood pressure levels.
‘Of course, we should still be cautious, and not prescribe higher doses for patients suffering side effects, but we should be aiming for tight blood pressure control and lower levels.’
Heart attack damage is curbed by diabetes pill
Giving heart attack survivors a low-cost diabetes pill could aid recovery and prevent more severe illness, according to heart experts.
The drug, dapagliflozin, is already used to treat heart failure – a debilitating and incurable condition that often occurs after a heart attack damages the muscle, stopping it pumping as well as it should.
But in a 4,000-patient trial, cardiologists offered it in the immediate aftermath of a heart attack – before heart failure has set in – to see if it could prevent deterioration.
The results suggest the tablets reduced the risk of a subsequent stroke, heart failure, heart rhythm problems or another heart attack, and boosted patients’ quality of life.
Those on dapagliflozin may also be less likely to develop type 2 diabetes or kidney disease.
They also lost around five per cent of their bodyweight.
Swedish cardiologist Professor Stefan James, who led the study, said: ‘We saw a clear clinical benefit from starting dapagliflozin immediately after a heart attack.’
Dapagliflozin, which costs about £1 per pill, is known as an SGLT2 inhibitor, which helps control the high blood sugar levels in diabetics by reducing the amount of glucose absorbed by their kidneys so that it is excreted in urine.
Heart failure affects roughly one million Britons, and causes extreme breathlessness and fatigue. Previously, one in five would die within a year of diagnosis and just a third survive for more than ten years.
Critics pointed out that heart patients were already given many medications – such as cholesterol-lowering statins, blood pressure treatment and blood thinners – and that another drug would add to the ‘pill burden’.
But Prof James said: ‘Patients like taking dapagliflozin. When the trial finished, participants asked if they could stay on it as it made them feel better.’
Prof Ray added: ‘If the muscle is very damaged after a heart attack, we now know there’s no need to wait to prescribe dapaglifozin.’
Stroke drug that won’t cause internal bleeding
A new blood-thinning jab was hailed as ‘the holy grail’ of stroke treatments, after research showed it was much safer than medication offered on the NHS.
Roughly one-in-five over-80s have heart problems that increase the risk of blood clots, which can block the supply to the brain and trigger a stroke.
They rely on blood thinners, also known as anticoagulants, to reduce the risk of this. But there is a major downside: the drugs can cause internal bleeding.
One blood thinner, warfarin, caused severe bleeding in up to 16 per cent of patients, including fatal brain haemorrhages.
For this reason, over the past two years there has been a drive to switch NHS patients to newer, supposedly safer, blood thinners called direct oral anticoagulants, or DOACs. But earlier this year The Mail on Sunday revealed fears that one of the most commonly prescribed of these, rivaroxaban, was riskier than initially believed.
While the drug, also known as Xarelto, is taken safely by most patients, it has been linked to severe gastrointestinal bleeding – a potentially dangerous condition that can affect anywhere in the digestive system from the mouth to the anus.
But there could soon be another option. In a head-to-head trial, the new injection, abelacimab, caused 81 per cent fewer major bleeding incidents when compared to rivaroxaban.
Lead study author, Boston-based cardiologist Professor Christian Ruff, said the research proved abelacimab to be ‘remarkably safe’, adding: ‘I’ve been in this field a long time and this has been the holy grail – to have a treatment that prevents clots without patients needing to worry about bleeding.’
Abelacimab works in a totally new way, blocking factor XI, a protein involved in the clotting process. However, unlike other blood thinners, it doesn’t affect the activity of the other main blood clotting compound, thrombin.
This means patients can still form normal blood clots in response to injury, but large abnormal clots – such as the ones that form inside the heart – don’t occur.
Prof Chico said the development was ‘incredibly exciting’ adding: ‘We now need studies to show us it reduces the risk of stroke.’