Statins: Advantages And Limitations

Cardiovascular disease develops when fatty substances accumulate in coronary arteries, the blood vessels supplying heart muscle. The deposits (also known as atherosclerotic plaques, or cholesterol plaques) are made up of cholesterol and other fats, calcium and fibrous tissue. The risk of these deposits collapsing or narrowing the arteries to the point of putting one’s life in danger tends to increase with age. That’s why older people tend to be more affected with myocardial infarctions, strokes and even blood vessel problems in their lower limbs – a situation known as peripheral arterial disease. Statins are a type of anti-cholesterol drug, widely used everywhere in the world. In fact, it is estimated that about 25 million people take statins… in the US alone!

Statins and regulatory controversy

Many years after being first introduced as a regular lipid-lowering therapy, statins are under the limelight these days as the object of the most recent medical controversy.  

The new guidance states, however, that more adults without heart disease should consider taking the medications to prevent future health problems, more specifically adults with a 7.5 per cent or higher risk of a heart attack or stroke in the next 10 years. This could result in nearly 13 million more adults being put on statins!

Different medical organizations have proposed varying LDL-cholesterol thresholds and risk assessment metrics to determine statin eligibility. For instance, while some guidelines recommend broader statin use, encompassing those with moderate cardiovascular risk, others emphasize their prescription primarily for high-risk patients.

Furthermore, there's debate regarding the role of statins in primary prevention (for individuals without established cardiovascular disease) versus their well-accepted benefits in secondary prevention (those with known cardiovascular disease). The variability in guidelines can create confusion among clinicians and patients, leading to potential under-prescription or over-prescription. Addressing individual patient risk factors, preferences, and potential side effects is essential. Amidst the debates, the central theme remains: tailoring the approach based on individual risk while ensuring evidence-based care.

New statins guidelines and profit taking

Statins are some of the most profitable drugs ever developed by pharmaceutical industry. Do new regulations simply represent a push to generate even more profits?

Contrary to what one might think at first, these new orientations for treatment are not likely to benefit pharmaceutical companies. We are looking at profound changes in the way doctors treat their patients and it is possible that this will undergo some more public discussion before a final decision is made. Therefore, it will take some time before an effect can be seen on the consumption of statins. Until then, many of the most commonly used brand names will lose their patents causing this guideline to possibly be even bad for the companies.

Let us not forget that increasing the population who is likely to benefit from taking statins also means to increase the population that is at risk for suffering from the side effects of statins. Indeed, concerns about the safety of this class of drugs have been voiced quite loudly and frequently in the past few years.

What are the actual benefits of statins?

Statins are drugs that inhibit an enzyme called 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. This enzyme is responsible for a crucial step in the biosynthesis of cholesterol in our body. The first statin was discovered in the 1970s by a research group in Tokyo. This discovery led to the development of a series of HMG CoA reductase inhibitors, which are nowadays available in the market.

In 1994, a very famous clinical trial called Scandinavian Simvastatin Survival Study (4S) came to the conclusion that statins help in the prevention of cardiovascular events associated with increased blood lipids and atherosclerotic lesions. Among the cardiovascular events whose risk statins effectively reduce are myocardial infarction and stroke. Since these two events, especially coronary heart disease, are of the most common causes of death worldwide, statins became medicines of high interest. It can even be suggested that these are wonder drugs, as they have undoubtedly reshaped the treatment of hypercholesterolemia and associated cardiovascular diseases.

And the potential held by statins is not limited to their lipid lowering action, it seems.

See Also: The Pros And Cons Of Taking Statin Drugs

 Many more allegedly beneficial effects of statins are currently being examined and their clinical relevance is still unclear.

Statins Side Effects And Safety Concerns

It is easy to be wondered by such an apparently exceptionable pharmacological profile. But let’s not forget that the target population for statins is comprised of patients that typically need lifelong therapy to maintain their lipid levels balanced. As such, it is important not to undermine the potential risk of adverse effects from continued statin use. 

In 2001, the first statin, cerivastatin was withdrawn from the market worldwide after the confirmed reports of serious myopathy (a condition in which muscle fiber do not work and patients suffer from muscle weakness) and rhabdomyolysis (a condition in which damaged muscles break down rapidly) have been published. The withdrawal sent a wave of panic among drug manufacturers and clinicians given the fact that statins by that time had already established itself as first-line medicine for reduction of CVD risk.

Evidence from various studies suggests that taking statins can result in many other adverse events. The following list summarizes the most significant ones:

• Liver toxicity: liver toxicity induced by statins appears to be rare, but nonetheless serious, since it can range from asymptomatic elevation of liver enzymes in the blood to hepatitis and even acute liver failure. The mechanisms behind this type of statin-induced toxicity are still elusive.
• Renal toxicity: evidence of renal toxicity is conflicting. Most clinical trials reported statins to protect kidney function and only a few reported the presence of blood or proteins in the urine (which normally indicated problems with the kidneys) of patients treated with statins.
• Diabetes mellitus: a recently published large scale study including 1,235,671 participants observed an 18 % increased risk of type 2 diabetes with statin therapy compared to non-treated subjects. Another study investigated the association between different statins and new-onset diabetes. The study concluded that patients on fluvastatin, lovastatin, and rosuvastatin were at lower risk of new-onset diabetes, whereas patients who took pravastatin were at greater risk.
• Neurologic effects: statins, unlike the vast majority of drugs, possesses chemical properties that allow it to diffuse into the brain with relative ease. Data published by the FDA admitted that statins may cause memory loss, forgetfulness, and confusion span. However, these symptoms are typically reversible within a few weeks after the discontinuation of the drug.

Need for balanced approach

Just like the beneficial effects of statins must be analyzed with a critical eye, the data supporting their potential side effects must be carefully considered and the circumstances under which said data were collected must be taken into account. As a very recent study, published in the European Journal of Preventive Cardiology, points out: “the benefit of statin therapy on death, stroke, and heart attack is quantified against placebo control [i.e. the effects of statins are compared to the effects of taking nothing whatsoever], but side effect information is not. Adverse events listed for statins come from many sources, most unable to differentiate between events caused by the drug and spontaneous events.”

The authors analyzed the results of clinical trials comparing statins and placebo and came to the astonishing conclusion that only a small minority of symptoms reported on statins are genuinely due to the statins. Almost all reported symptoms occurred just as frequently when patients were taking placebo. 

See Also: Statin: Drug for Heart Disease

So, similarly to what happens in other fields of medicine, evidence can be confusing or conflicting. Two things, however, are for certain. First, statins are effective lipid-lowering medications and they most definitely help in preventing the mortality and morbidity arising from cardiovascular complications. In most patients, statins are safe and well tolerated. However, patients and doctors need accurate and unbiased information, collected in clinical trials, regarding the actual relationship between the occurrence of the adverse events and the action of the statin they are taking, so that they can make the right therapeutic decisions. This is actually essential, as statins are now among the most frequently prescribed medications and their use is likely to increase significantly in the near future.