A new meta-analysis shows that statin drugs are effective at preventing cardiovascular events and death, especially in patients with a baseline LDL cholesterol >100.
This article originally premiered on Science Based Medicine.
The widespread use of statin drugs remains a little controversial despite the fact that the science is fairly clear. Statin drugs work by lowering bad cholesterol (low-density lipoprotein, or LDL) in the blood. Higher LDL cholesterol is associated with increased deposition of fat on arterial walls, leading to an increased risk of heart attacks, strokes, and death.
We have, therefore, a fairly solid mechanism of action for what should be an effective preventive treatment. We also have good clinical evidence showing that statin drugs actually work – they reduce vascular events and all-cause mortality.
There remain, however, a couple minority opinions that are progressively marginalized by the evidence. There are statin and cholesterol “skeptics” (really deniers, at this point) who think the cholesterol theory of vascular disease is wrong. There are also those who believe that statin drugs work, but not by lowering cholesterol. Rather they work through an anti-inflammatory effect. This view has also been contradicted by evidence.
A new meta-analysis published in JAMA supports the current consensus on statin treatment and adds some details and further weight to the evidence. The study, “Association Between Baseline LDL-C Level and Total and Cardiovascular Mortality After LDL-C Lowering,” as the name implies, focused mainly on the relationship between baseline LDL levels and the effectiveness of statin treatment. Here are the key findings:
In this meta-analysis of 34 randomized clinical trials that included 270 288 participants, more intensive LDL-C–lowering therapy was associated with a progressive reduction in total mortality with higher baseline LDL-C levels (rate ratio, 0.91 for each 40-mg/dL increase in baseline level); however, this relationship was not present with baseline LDL-C levels less than 100 mg/dL. There was a similar relationship for cardiovascular mortality.
This is a meta-analysis, with all the strengths and weaknesses that implies. The primary strength is the amount of data – 270,288 participants. The overall quality of the evidence was also high. Of course, a meta-analysis is only as good as the studies it includes. Combining data from different studies also introduces new potential biases, such as study selection bias, or potential confounding factors in how data is adjusted so that it can be combined. But these are general concerns. I don’t see anything in this study that raises any flags.
The results demonstrate a feature of a legitimate treatment that we like to see – a dose response effect. In this case we have a double dose-response effect. Higher doses of statins were more effective than lower doses of statins. Also, statins were more effective in patients with LDL >100 than in patients with LDL <100, and the dose response effect was only statistically significant in those with LDL >100.
These results also support the LDL hypothesis, the notion that it is the LDL cholesterol itself that raises the risk of vascular disease. So all the ducks appear to be in a row. Statin drugs lower LDL cholesterol, high LDL is associated with heart disease, statin treatment lowers heart disease, stroke, and mortality, and there is a nice dose-response curve.
At this point the effectiveness of statin drugs, and the cholesterol hypothesis, are not in serious question (although fringe critics remain).
The Remaining Controversy
Medicine, however, is a complex business. There is often a bottomless pit of more and more refined clinical questions we can ask. The remaining question have to do with – who gets treated with a statin when, and how does it fit into an overall plan to minimize the risk of vascular disease.
This article is part of our Professor’s Perspective series—a place for experts to share their views and opinions on current events.
However, just because a drug is profitable, that does not mean it is not a good idea. In this case independent scientific study has clearly established that statins are safe and effective. Anti-pharmaceutical conspiracy theories are just poisoning the debate at this point. Generally they are counterproductive, tainting legitimate watchdog criticism with pseudoscientific conspiracy mongering and scaring people away from effective treatments.
The legitimate debate focuses now on where to draw the line – who gets treated.
Of course, the first-line treatment for high cholesterol should be diet and exercise. No one doubts this. Maintaining a lean body mass, regular exercise, and not smoking are the most effective ways to prevent heart disease for most people.
Unfortunately, lifestyle interventions are not very effective. This is not because they don’t work, it’s because it is very difficult to remain compliant over the long term. Obviously we should still make a huge effort to optimize lifestyle factors. But it is not reasonable to argue that we should do this instead of medication treatment.
The best approach is to institute both lifestyle interventions and medication treatment in appropriate patients. Then, if they are successful at lowering their cholesterol with diet and exercise you can always decrease or stop the drugs later. In the meantime, the patient is getting effective prevention. Otherwise you are missing an opportunity to prevent disease while waiting for something that is probably not going to happen for most patients.
Finally we need to consider who gets treated. This is really the only remaining controversy, because there is no clear correct answer. There are some populations who clearly benefit from and need statin treatment. These include secondary prevention – treatment after a vascular event has already occurred. Also in patients with inherited high cholesterol. Diet alone will absolutely not work in this population. They need medication management.
This brings us to primary prevention, preventive treatment in the general population who have not had a vascular event. Do we put it in the proverbial drinking water? Do we give it to everyone over 50? Where do we draw the line?
At this point the recommendation is to make individual decisions (not give them to everyone) based on overall risk. The higher the risk, the higher the benefit of preventive treatment. This is where the current study is most useful. It supports the routine use of statins for primary prevention in patients with an LDL >100.
There are also formal guidelines, based on expert reviews of the evidence. The current recommendations are:
- Use statins in “Adults aged 40 to 75 years with no history of CVD, 1 or more CVD risk factors, and a calculated 10-year CVD event risk of 10% or greater.”
- May use low to moderate dose statins in “Adults aged 40 to 75 years with no history of CVD, 1 or more CVD risk factors, and a calculated 10-year CVD event risk of 7.5% to 10%.”
- And cannot recommend routine treatment in “Adults 76 years and older with no history of CVD.”
This is a common approach – stratify treatment by baseline risk. The higher the risk, the more aggressive the treatment.
The current meta-analysis supports the consensus that statins are effective and should be used in appropriate patients for prevention of cardiovascular disease. Statins clearly save lives. It is important for this clear message to get out to the public, because many people who should be on statins are not. This message needs to cut through all the noise and false controversy over statins that is common online.
Bottom line – if you are 40 or over see your primary care doctor and address the issue of all treatments for cardiovascular disease prevention, including statins. Don’t be scared off from a potentially life-saving preventive treatment because of false controversies.