Cardiovascular diseases (CVD) are still the leading cause of death worldwide: in 2015 they were responsible for 40% of all deaths. In the last few decades survival rates after CVD have increased and cardiovascular mortality has decreased. However, individuals with established CVD have a high risk of a recurrent event. The currently recommended pharmacological intervention in secondary prevention is a combination of antithrombotic therapy, statins and, in some cases, antihypertensive agents, independent of age and gender. Statins have proven to reduce the risk of recurrent CVD and of cardiovascular and total mortality in secondary prevention. Statins were launched on the marked after some huge clinical studies proved that they were able to exert significant prevention on major cardiovascular accidents (heart attack and stroke). The efficacy of statin treatment in preventing cardiovascular deaths has been documented in a few large multicenter trials, like the YUPITER study, the Cholesterol and Recurrent Events Trial and the West of Scotland Coronary Prevention Study [WOSCOPS].
For millions of people who take statins to prevent the onset of cardiovascular disease, the potential harms of the cholesterol-lowering medication may outweigh the benefits. So concludes a recent modeling study from the University of Zurich in Switzerland that questions whether statins are significantly over-prescribed. The research, which features in the Annals of Internal Medicine, concerns the use of statins for the “primary prevention” of cardiovascular disease in people with no history of the disease. A primary prevention measure is one that intervenes to prevent a condition before it can impact health. Vaccinations, for example, are primary prevention measures. Statins are some of the most prescribed classes of drugs worldwide. They work by blocking an enzyme called HMG-CoA reductase that helps the liver to make cholesterol. Most medical guidelines recommend the use of statins for people with no history of symptoms when their expected risk of developing cardiovascular disease over the next 10 years is 7.5–10%. Such a 10-year risk threshold places around 3 out of every 10 adults worldwide as eligible for treatment.
However, the authors note that whether and how guideline developers weighed harms against benefits is often unclear. In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) updated the recommendations that guide doctors in the treatment of cholesterol and use of statins. One reason for the update was the argument that high blood cholesterol is one of the most prevalent of alterable cardiovascular risk factors. Another argument was that there is evidence that treating cholesterol reduces numbers of people who develop cardiovascular diseases and who die of them. The update caused controversy. This was mainly because it lowered the thresholds that doctors should use to help them decide whether to prescribe statins for primary cardiovascular disease prevention. This recommended that doctors should consider adults with no history of heart problems as eligible for primary prevention if their risk of developing cardiovascular disease in the next 10 years is 7.5% or higher. Also, the revision expanded the target of prevention to include not just coronary heart disease, but also atherosclerosis, stroke, and peripheral arterial disease. Experts predicted at the time that full implementation of the guidelines would identify around 13 million people in the United States as “newly eligible for consideration” for treatment with statins.
The University of Zurich researchers used a computer model to assess the 10-year risk for cardiovascular disease at which statins provide at least a 60% probability of net benefit. They adjusted the results to take out any effects from “competing risk” of death that was not due to cardiovascular disease, as well as baseline risk, frequencies of and preferences for statin benefits and harms. The harms that they included in their calculations were adverse events, such as myopathy (muscle weakness), liver dysfunction, and onset of diabetes. The results showed that the 10-year cardiovascular risk thresholds at which benefits of statin use exceed the harms are consistently higher than those recommended in the guidelines. For instance, in the case of men aged 70–75 years with no history of symptoms, the harms of taking statins were greater than the benefits until the risk of developing cardiovascular disease over 10 years was over 21%. For women aged 70–75 years, the 10-year risk required for benefit to outweigh harms was 22%. For those aged 40–44, the benefits outweighed harms at 14% 10-year cardiovascular risk for men and 17% for women.
Atorvastatin and rosuvastatin provided net benefit at lower 10-year risks than simvastatin and pravastatin,” note the authors. This because, in addition to inhibit the enzyme HMGCoAR, these two molecules have additional mechanisms of action, the most relevant for cardiologists being the anti-inflammatory effect on vessels and the stabilization of ateromasic plaques. Is there not to forget, nonetheless, that a good primary and secondary prevention may be achieved with a proper (in some cases) stringent change in lifestyle. In France, for example, statins are not so widely prescribed for cardiovascular prevention, unless severe risk factors as single or in combination are demonstrated. Doctors, despite the utility of statins, should enhance a more intense prevention program focusing the disciplined correction of diet habits, especially outside the main meals. And remember that main cholesterol is built from glucose (sugar) metabolism and not entirely from foods which, among which few are really enriched with cholesterol.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Richman I, Ross JS. Annals Intern Med. 2018 Dec 4.
Miname MH et al. JACC Cardiovasc Imag 2018 Nov 8.
Lloyd-Jones DM et al. J Am Coll Cardiol. 2018 Nov 3.
Djulbegovic B et al. J Eval Clin Pract. 2017; 23(2):241.
Minder CM et al. Curr Opin Cardiol. 2013; 28(5):554-60.