Statins, Primary Prevention, Risk, and Treatment Efficacy
Recent discussions about statin treatment shine a light on the most pressing healthcare issue for our country and primary care. Too often the care or absence of care is not based on the best evidence resulting in death, disability, complications, and runaway costs. The most appropriate care requires careful attention to risks vs benefits. Great damage to population health can result where decisions are not based on evidence and data. Where these exist, decisions based on anecdote and opinion damage health and kill patients.
Statin treatment is a great example of the problem. Statins are highly effective medications that directly impact the core issues in vascular disease. They reduce inflammation, unstable cholesterol plaque, oxidative particle formation, and the cellular growth that makes the artery thicker and stiffer. In high-risk diabetic patients, statins reduced risk of a cardiovascular event by 55%. Current discussions about statins have confused people. High-risk patients who should be on a statin are not taking them and as a result many of them die or have severe complications. Only about 50% of patients take their prescribed statin treatment.
The number needed to treat (NNT) is a great way to look at who needs statin treatment or other therapies aimed at cardiovascular risk. Here is an explanation of what that means. It is a critical concept when considering risk vs benefit:
“There is a way of understanding how much modern medicine has to offer individual patients. It is a simple statistical concept called the “Number-Needed-to-Treat”, or for short the ‘NNT’. The NNT offers a measurement of the impact of a medicine or therapy by estimating the number of patients that need to be treated in order to have an impact on one person. The concept is statistical, but intuitive, for we know that not everyone is helped by a medicine or intervention — some benefit, some are harmed, and some are unaffected. The NNT tells us how many of each.”
Treatment in individuals without evidence of vascular disease is called primary prevention of atherosclerotic events and it is the most controversial use of statin drugs. Most physicians use statins in these patients based on a risk calculation. There are five different risk calculators. In the primary prevention of atherosclerotic events, based on risk calculation, 18-21 patients must be treated with a statin for 10 years to prevent an event. That seems like a lot, but keep in mind, once you have an event your life is changed forever in many cases. There is no going back to full health and many of these events occur without warning.
Patients in the Steno-2 trial were at much higher risk. They were type 2 diabetics with small amounts of protein in the urine. (microalbuminuria). Even so, 75% of them were still primary prevention patients. Only 25% had a history of a prior cardiovascular event. The average age at study entry was 55 and by 68 half the usual care patients were dead. The number needed to treat for 7.8 years to prevent one atherosclerotic event was 5.0 when compared with usual care. The absolute risk reduction was 20%. The investigators considered it unethical to continue the comparison patients in usual care, and so everyone was on the same intensive treatment for the next 5 years. The difference between initial aggressive management group and usual care continued to grow, and by 13 years, the NNT to prevent a major cardiovascular event was 3.
There were other major benefits as well:
Remember, Steno 2 did not compare aggressive care with no care. It compared aggressive care with usual care. This is the only diabetic study with 21 years of follow-up. The aggressively treated patients lived 8 years longer and at lower annual cost even though all the most impactful medications were brand name and very expensive during the 7.8 years of intervention. Today those medications are generic. The financial benefit would be much greater.
These benefits are by no means assured even with aggressive treatment. The ACCORD and VADT trials also provided high-risk patients with aggressive multifactorial treatment of blood pressure, lipids, and glucose to aggressive targets. That is the same general design as Steno-2, but there was no benefit on major cardiovascular events. In fact, more patients died in the intensive glucose management group of ACCORD. VADT and ACCORD investigators could use any medication approved to lower the risk factor. Obese Steno-2 patients all received metformin, lisinopril, and atorvastatin with an aspirin. That is the difference.
Treating patients with established vascular disease provides even more benefits using a very similar approach with the same risk factor targets and most of the same specific medications to achieve optimal medical therapy for patients with a history of heart attack or threatened heart attack. The NNT for 4.5 years was 4 to save $21,900 annually and reduce absolute mortality by 27%.
This is a very complicated topic. One third of us die of cardiovascular disease. It begins in our teens. The risk is much higher in complicated diabetes and patients with established vascular disease. What is the proper point to intervene? Patients upstream cost very little, but treatment slows progression downstream.
Mild hypertension in the uncomplicated patient becomes more severe hypertension in a patient with multiple chronic conditions. High glucose levels worsen over time. High-risk diabetics with early optimal therapy continued to do much better even after usual care patients went on the same treatment. Treating prediabetics with simple lifestyle instruction and metformin slows their progression to diabetes, more expensive medications, and complications. Progression from primary prevention in the patient with no known vascular disease to secondary prevention with known vascular disease is common. Hypertension, diabetes, and lipid abnormalities are all related at the level of molecular biology. Multiple risk factors are much more dangerous and synergistic. The higher the risk, the more benefit we see from global risk management.
Clinical trials are never going to give us the whole picture. Most of them are looking at very isolated questions with highly select groups of patients for short periods of time. What matters is what happens out in the real world. What matters is comparing usual care with a collection of best practice interventions for patients with multiple related chronic conditions. When we have big data on large numbers of patients treated with optimal medical therapy, we will have a better idea of the risks and benefits compared with large numbers of patients on usual care. Individuals who have influence over policy and benefits must understand these basic facts to be effective.
Dr. Bestermann is Founder/CEO of Epigenex, a cardiometabolic care management organization, which won the 2019 Health Value Award for Program Provider – Specialty Cardiometabolic. Epigenix’s web-based, patient-centric health information exchange tools have been validated by Validation Institute for Program Impact – Savings.