Daijiworld Media Network – New Delhi
New Delhi, Aug 28: Statins have remained the cornerstone of cholesterol treatment for decades, helping millions of patients reduce low-density lipoprotein (LDL) cholesterol and lower the risk of heart attacks and strokes. However, a new generation of therapies is changing the way doctors approach patients with severely high cholesterol.
Cardiovascular disease accounts for around 3.2 million deaths in India every year, making up nearly one in four deaths in the country. High LDL cholesterol is among the major modifiable risk factors.
Statins work by reducing the liver's production of cholesterol and helping it remove more LDL from the bloodstream. Depending on the medicine and dosage, they can reduce LDL levels by around 30 to 50 per cent. Their low cost, wide availability and strong evidence in preventing cardiovascular events have made them the standard treatment.
Dr Ashok Seth, chairman of Fortis Escorts Heart Institute, said statins have a long and well-established record of reducing cardiovascular risk. However, newer medicines are becoming important for patients who do not achieve adequate cholesterol control with statins.
One major development has been the targeting of PCSK9, a protein produced in the liver that reduces the number of receptors responsible for removing LDL from the blood. Blocking PCSK9 allows these receptors to remain active for longer, resulting in a significant reduction in cholesterol levels.
Two PCSK9-blocking medicines, evolocumab and alirocumab, are administered as injections every two weeks. When added to statin treatment, they can reduce LDL by another 50 to 60 per cent. Clinical trials have also shown that these medicines can reduce heart attacks and strokes among high-risk patients.
Both drugs are available in India but are considerably more expensive than statins. They are generally reserved for people whose cholesterol remains high despite maximum tolerated statin therapy, those who cannot tolerate statins and patients with familial hypercholesterolaemia, a genetic condition that causes extremely high cholesterol levels.
Another injectable treatment, inclisiran, works by preventing the liver from producing PCSK9. After the initial doses, it is administered twice a year and can reduce LDL by around 50 per cent. However, the clinical trial examining whether it reduces heart attacks and strokes is still underway.
The latest development is enlicitide, the first oral PCSK9 inhibitor, which was approved by the US Food and Drug Administration in July. The once-daily 20 mg tablet is designed to achieve cholesterol reduction comparable to that of injectable PCSK9 medicines.
In its main clinical trial involving 2,904 adults, enlicitide reduced LDL cholesterol by 56 per cent compared with placebo after 24 weeks. Another trial involving patients with a genetic form of severe high cholesterol recorded a reduction of around 59 per cent.
Enlicitide is not yet available in India, although regulatory developments are underway. The Central Drugs Standard Control Organisation approved a Phase 3 clinical trial of the medicine in India on July 20.
Doctors believe the availability of an oral PCSK9 inhibitor could improve acceptance among patients who are reluctant to take expensive cholesterol-lowering injections.
Beyond these medicines, researchers are also exploring gene-editing treatments that could potentially provide long-lasting cholesterol reduction after a single treatment.
VERVE-102, developed by Verve Therapeutics, targets the PCSK9 gene and is designed to permanently reduce its activity in liver cells. Early-stage trials have reported an LDL reduction of around 62 per cent that remained sustained for at least 18 months following a single infusion.
Another experimental treatment, CTX310, uses CRISPR-Cas9 gene-editing technology to target the ANGPTL3 gene. An early trial involving 15 patients reported reductions of 49 per cent in LDL cholesterol and 55 per cent in triglycerides.
However, both gene-editing approaches remain experimental and have so far been studied only in small groups of patients with severe genetic cholesterol disorders. They have not yet been tested widely in people with ordinary high cholesterol.
For patients already taking statins, doctors say there is no reason to abandon the established treatment simply because newer options can lower LDL more aggressively. Statins remain the most extensively proven medicines for reducing heart attacks, strokes and cardiovascular deaths.
The newer therapies are particularly relevant for patients at very high risk, those who cannot tolerate statins or those who fail to reach recommended LDL targets despite treatment.
Dr Upendra Kaul, chairman of Batra Heart Centre, highlighted the case of a severely high-risk 40-year-old patient whose LDL fell from 210 to 30 within six weeks after an injectable PCSK9 treatment was added to statins.
For patients who have already suffered a heart attack or stroke, doctors may aim for extremely low LDL levels, with targets below 50 mg/dL and, in some young high-risk patients, below 35 or even 30 mg/dL.
The emerging treatments therefore represent an important expansion of cholesterol management, but doctors stress that treatment decisions should depend on an individual's cardiovascular risk, LDL levels, response to statins and overall medical condition.