MARIKA SBOROS | Doctors stick to statins against cholesterol despite controversy

Few pharmaceutical success stories rival statins for impact, longevity and enduring controversy.

These cholesterol-lowering drugs have dominated cardiovascular medicine for more than three decades. Tens of millions worldwide take one daily to prevent a heart attack or stroke.

Yet controversy persists: are statins life-saving marvels of modern medicine or overprescribed pills for a health problem that diet and a brisk walk around the block could more safely resolve?

As medical controversies go, this one has been unusually rancorous and occasionally theatrical.

From a purely commercial viewpoint, blockbuster statins’ golden age has passed. Patents of original drugs, such as simvastatin and atorvastatin, have expired. These drugs are now generic and inexpensive.

The scientific debate has moved on. It’s no longer mostly over whether the drugs work and safety concerns. It’s more over how they work, who needs them most and whether their blockbuster era is evolving rather than ending.

The conversation has shifted from whether doctors should prescribe statins to how best to combine them with new generation, hi-tech biologics for optimum patient benefit and protection.

South African, US-based and board-certified cardiologist and lipidologist Dennis Goodman is unequivocal about statins’ sustainability.

Goodman is professor of medicine at his alma mater, the University of Cape Town, and professor of medicine and director of integrative medicine at New York University Medical School.

Despite the arrival of newer, medical-breakthrough drugs, he said that statins are “here to stay for the foreseeable future”.

He sees them quite simply as the “mainstay of modern medicine’s lipid-lowering toolbox”.

Lipid is the medical term for fat-like substances (mainly cholesterol, triglycerides and phospholipids) that can’t move around on their own through the bloodstream’s major blood vessels (arteries, veins and capillaries). They need lipoproteins, spherical complexes of fats (lipids) and protein, to carry them.

Think of lipids as cargo and lipoproteins as transport vehicles.

Lipoproteins are either low-density (LDL, less dense with more fat and less protein) or high-density (HDL, more dense with more protein than fat). LDL’s job is to deliver lipids to cells. HDL carries excess lipids away from cells to the liver for excretion.

In healthy bodies, arteries are flexible and elastic. Over time, arterial walls can harden, often driven by high levels of “bad” (LDL) cholesterol, according to the “lipid hypothesis”.

The process begins when cholesterol build-up on arterial walls forms structures called plaques, much like “gunk” or scale build-up inside a plumbing pipe.

As the build-up grows, the artery narrows, making it harder for blood to flow through. If a plaque becomes unstable, it can burst, triggering a blood clot that may block the artery entirely.

Statins work by lowering the amount of circulating cholesterol, said Goodman. The treatment benefit is “roughly proportionate” to how much lowering of cholesterol levels contributing to this “clogging” process has been achieved, he said.

In this way, he said that statins significantly lower the risk of major “cardiovascular events” — the medical profession’s term for heart attack and stroke — and mortality (premature death).

Anti-inflammatory properties

Goodman adds the salient point that statins don’t just lower levels of LDL cholesterol. Research suggests they also have anti-inflammatory properties.

That’s a big plus for the drugs. Inflammation is the body’s natural response to injury. When it becomes chronic (long-lasting), it acts as a silent driver of heart disease, stroke and other health issues.

Newer agents are likely to be used as add-ons in statin-intolerant patients, or when LDL targets are not met, Goodman said.

In the UK, statin supporters include heavyweight researchers such as Oxford University physician-epidemiologist Rory Collins.

Collins has led some of the world’s largest studies of cholesterol-lowering drugs, including the Cholesterol Treatment Trialists’ (CTT) Collaboration. As head of the CTT at Oxford, he was the chief architect of data showing that statins are effective and safe.

He also serves as CEO and principal investigator of the UK Biobank, one of the world’s largest biomedical research databases. Its purpose: to help scientists understand why people develop diseases and how best to treat or prevent these.

Collins has long argued that statins have undeniable benefits for high-risk patients and that his research shows the incidence of serious side-effects to be much lower than critics claim it is.

He has faced significant criticism regarding data transparency and the CTT’s historical funding from the pharmaceutical industry. Supporters counter that industry funding is routine and vital because, without it, many large-scale drug trials would not happen.

The CTT’s research remains the primary evidence base for the “lower is better” paradigm in cholesterol management. It continues to publish influential, large-scale analyses that shape global health guidelines.

In February, its massive meta-analysis in The Lancet, involving more than 120,000 participants, concluded that statins are not the cause of most side effects listed on statin labels, including memory loss, depression and sleep disturbances.

The researchers are calling for a “rapid revision” of patient information leaflets to reflect these findings. They argue again that overstated fears about statin side effects prevent high-risk patients from taking a life-saving treatment.

Their study quickly lit up the stage of scientific controversy with a barrage of criticism from predictable quarters. These range from extremist “statin sceptics” to acknowledged cardiology specialists who call for a more cautious approach.

The researchers are calling for a “rapid revision” of patient information leaflets to reflect these findings. They argue again that overstated fears about statin side effects prevent high-risk patients from taking a life-saving treatment.

US cardiologist Rita Redberg, professor of medicine at the University of California San Francisco, is not even close to being a statin sceptic.

Redberg has never suggested that statins don’t work but has questioned their use for primary prevention. She has argued that research focus should be more on the “actual” number of lives saved, not just the “relative” drop in cholesterol numbers.

She has also challenged the lipid hypothesis by suggesting that the “fixation” on lowering LDL cholesterol is a misguided focus on a surrogate marker that does not necessarily translate to longer life.

In shifting blame from cholesterol to insulin resistance and chronic inflammation, Redberg aligns with “disruptor” statin sceptics in the “low-carb movement”.

These are doctors, scientists and nutritionists who believe that the lipid hypothesis is outdated. They say that lifestyle interventions, specifically those targeting metabolic dysfunction driven by diets high in sugar and refined carbs, are more effective for most people than taking statins lifelong for primary prevention.

Some sceptics , such as seasoned academics, have taken to YouTube. Among those is Harvard-trained physician-scientist and metabolism researcher Dr Nick Norwitz.

Norwitz’s position is more nuanced than that statins “don’t work”. He said statins can lower LDL cholesterol and reduce cardiovascular risk in certain high-risk populations but questions their benefit.

Insulin resistance

Norwitz has highlighted research suggesting statins can reduce levels of GLP-1, a hormone produced in the gut that acts as a crucial messenger for regulating blood sugar, appetite and digestion. This may promote insulin resistance, which could help to explain the association between statin use and increased risk of type-2 diabetes in some patients.

He stressed that lowering a biomarker such as LDL does not automatically mean the intervention is harmless or optimal. The “lower LDL is always better” principle “ignores” the broader biological effects of the drugs used to achieve that reduction.

Of course, it may be easier and comforting to believe that simple dietary changes may keep arteries clear.

The reality is that many people battle or don’t want to change their eating or lifestyle habits for different reasons.

Beyond human preference, there is also biology’s cold reality.

Goodman said that for patients with “co-morbidities”, including diabetes, blood sugar, high blood pressure or the genetic “bad luck” of familial hypertension, lifestyle changes are often insufficient to prevent premature death.

In such cases, Goodman joins heart foundations globally that support statins as foundational, with newer agents for those who need extra help or have specific intolerances.

Contemporary official UK guidelines from the National Institute for Health and Care Excellence (NICE), the American Heart Association (AHA) in the US and South Africa’s Heart & Stroke Foundation explicitly designate statins as first-line therapy for managing cholesterol levels and reducing cardiovascular risk.

They provide clear maps for when to level up in patients at high risk when statins alone do not achieve the required LDL levels or who cannot tolerate statins.

Controversy may continue in health blogs, but in cardiology clinics, the “little pill” wins hands down.

For millions at risk, the most important “lifestyle choice” they make might just be remembering to take it.

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