Most readers know that I run morning report 2-3 times each week (at 3 different hospitals.) We frequently discuss the rationale for statin therapy. Many students and residents focus on LDL and LDL goals, yet recent data suggest that statins really work in at least 2 ways. Clearly, statins do lower LDL, and thus probably either decrease atherosclerotic plaques or delay their growth. However, statins also decrease the ongoing inflammatory process within the atherosclerotic plaque. This plaque stabilization should decrease cardiac events.
We know that immediate statin treatment improves myocardial infarction outcomes. We believe that this effect stems from a marked decrease in subsequent infarctions.
Recent data are raising questions about our selection criteria for statins. All experts agree that statins have important effectiveness as secondary prevention. Data suggest that all patients with proven atherosclerosis benefit from statins, regardless of their initial LDL. Recent data argue that treating patients with elevated CRP levels might make sense in primary prevention.
This rather long article discusses the data – The Goal of Statin Therapy: LDL? CRP? JUPITER Study
Talking about the Jupiter trial:
Dr. Gotto: What lead to the development of this trial was a post hoc analysis that Dr. Ridker and I and colleagues did on the AFCAPS/TEXCAPS Study.[4] It was a primary prevention trial in people who at that time had what were considered normal lipids except they had a below average HDL. Lovastatin reduced events by 37%. In post hoc analysis, if you had above the median LDL and CRP, you benefited. If you had above the median of either one with the other one below the median, you benefited. The only group that did not benefit were those who had a low LDL and a low CRP — low being below the median — and that group was not tested in this present trial.
The potential synergism of LDL and CRP reduction:
Dr. Willerson: To be complete, also in the New England Journal of Medicine, Steve Nissen and his associates at the Cleveland Clinic did a separate study.[5] They were using ultrasound looking at coronary arteries, looking at reductions in LDL and CRP. They showed exactly the same thing. If you reduced LDL, you got a certain stability of progression of atherosclerosis. If you reduce CRP, you get a certain stability. But if you reduce both, you got an additive stability of coronary atherosclerosis.
So what is my current take? Secondary prevention is not controversial; primary prevention is very controversial. I would divide the primary prevention candidates into overall low risk and moderate to high risk. Those at moderate to high risk represent the real controversy. The CRP data have caught my eye. I suspect that measuring CRP in patients with other factors raising risk might make sense. Fortunately, several excellent statins are generic. If I had CAD risk factors (my only personal risk is my Y chromosome), I would probably take a statin. Of course, I take no medications, enjoy taking no medications, and have a desire to continue taking no medications, so I do not know what I would really do.
Statins are not totally benign, but clearly for secondary prevention the risk benefit ratio is tilted strongly to the benefit side. We still do not have solid answers on primary prevention, but in my mind the data are building towards treating patients with both elevated LDL and CRP.
{ 3 comments… read them below or add one }
Very interesting issue. I recently saw Dr. Ridker speak, and he mentioned that population CRP levels seem to predict population burden of cardiovascular disease. For example, in blood samples obtained from a certain low-risk population decades ago (I think it was the Japanese), you saw CRP levels that were much lower than those in the general US population. But with increasing Westernization of the Japanese lifestyle, CRP levels are starting to rise there, with a concomitant rise in CV risk.
Are statins really some kind of antedote to Western lifestyle? Clearly the “treat to target” evidence on both lipids and CRP is lacking, but the data to support just taking the highest-dose statin you can afford are pretty convincing…and even with rosuvastatin, the myopathy rates in JUPITER were surprisingly low.
Something about sending a spider to catch a fly comes to mind…
Facts Believed To Be Qualities Of All Statin Medications:
Statins are a class of medications specifically prescribed to lower LDL- one of five lipid parameters of a person’s lipid profile, which is alto the name of the blood test to measure these parameters. They are known as statins, as all of these types of medications end with the letters, statin.
There are about 6 available statins to choose for lipid management as needed- with three that are combination drugs that have a statin in these combinations, I believe.
There are other classes of medications for lipid management, such as bile acid sequestrants and nicotinic acid, which is known as niacin. Yet the side effect profile is more unfavorable of these classes of medications compared with the statin class of drugs.
One’s cholesterol level is primarily due to how they produce cholesterol in their liver, which is overall genetically determined. This level is also determined by one’s lifestyle and diet as well. If a person has too much cholesterol in their blood, it can lead to hardening and narrowing of their arteries as well as the formation of coronary plaques in the coronary arteries.
If these plaques break off of the arterial wall, this leads to a myocardial infarction, or heart attack. Statins are believed to stabilize coronary plaques so this does not occur.
To measure one’s cholesterol, a blood test called a lipid profile is obtained from a person after they have fasted for at least 12 hours. The test should also be performed only if the person is free of any acute illness, as this may affect true lipid measures.
If the results prove to be abnormal, lipid altering medicinal therapy may be initiated- according to the discretion of the person’s health care provider. This therapy usually involves a statin medication.
Adverse events associated with the statin class of pharmaceuticals are thought to occur more often than they are reported- with high doses of statins prescribed to patients in particular at times that may not be necessary to control their dyslipidemia based on their lipid profile. Side effects may include muscle pain, or possible damage to the patient’s liver.
However, since this class of statin drugs has existed for use for over 20 years, statins are considered to be overall safe and effective for enhancing the clearance of LDL noted to be elevated in the lipid profiles of patients.
Also, they have proven to reduce cardiovascular mortality with one who is treated with a statin that has dyslipidemia. In addition to lowering LDL by up to about 60 percent- depending on the choice of the statin prescribed for the patient, and how high the LDL cholesterol is in a patient.
This class of drugs also has the ability to raise their HDL lipid parameter as well as lower to their benefit their triglyceride parameter of their lipid profile. Both of these additional effects in addition to lowering the LDL parameter from taking a statin drug is ultimately beneficial for the patient on a statin drug for lipid management.
Statin therapy is also recommended for those patients who have a greater than twenty percent risk of developing cardiovascular disease, or those patients that have clinical evidence of this disease.
Additionally, there appears to be no comparable reduction in cardiovascular morbidity or mortality, as well as a difference in the increase of one’s lifespan, if one is on any particular statin medication for their lipid management over another, others have concluded. So caution should perhaps be considered if one chooses to prescribe a statin for a patient if they are absent of, or have only mild dyslipidemia to a significant degree.
Furthermore, research should be done by the health care provider if they are under the belief that one statin medication provides a greater cardiovascular benefit over another. In other words, the health care provider should be assured that any choice of statin therapy for their patients is considered reasonable and necessary if the LDL in their patients need to be reduced, and the statin selection should be determined by the results that have been shown with a particular statin.
There exist abstract etiologies for health care providers at times to choose to prescribe statin drugs on occasion for reasons not indicated with the medicinal treatment of these statin drugs. Examples include the speculated benefits associated with statins- such as reducing CRP levels, or for Alzheimer’s treatment, or other reasons not directly related to cholesterol management.
Statin therapy for such patients may not be considered appropriate, reasonable, or necessary prophylaxis at this point for any patient who does not have the indications for which statins are approved for to treat patients with dyslipidemia. All other benefits that appear to have favorable effects in such areas not involved with a patient’s cholesterol are suggested at this point due to minimal research in these other variables aside from lipid management.
Other reasons for placing a patient on a statin drug at this time require further research for these disease states and dysfunctions that may exist with a patient aside from dyslipidemia.
Statins as a class of drugs seem to in fact decrease the risk of cardiovascular events significantly, it has been proven. Statins also decrease thrombus formation as well as modulate inflammatory responses (CRP) as additional benefits of the medication.
For those patients with dyslipidemia who are placed on a statin, the effects of that statin on reducing a patient’s LDL level can be measured after about five weeks of therapy on a particular statin drug.
Liver Function blood tests are recommended for those patients on continued statin therapy, and most are chronically taking statins for the rest of their lives to manage their lipid profile in regards to maintaining the suitable LDL level for a particular patient presently. Patients should be made aware of potential additional side effects as well, such as myopathy and muscular dysfunctions that occur on occasion when one is on statin therapy.
Yet some have said that about half of all strokes and heart attacks that do occur are not because of increased cholesterol levels of these patients. So it appears clear that high cholesterol may not be an absolute for cardiovascular events for them to occur.
Others believe that it is oxidized cholesterol that causes vulnerable plaques to form on coronary arterial walls, which is the catalyst for a heart attack, and that there is no medicinal treatment for the formation or stabilization of these plaques to prevent heart attacks or strokes.
Some who support statin medicinal therapy for their clinically appropriate patients claim that these drugs, do, in fact, stabilize these plaques as an added benefit, and therefore are beneficial.
As stated previously, in regards to other uses of statins besides just primarily LDL reduction, there is some evidence to suggest that statins have other benefits besides lowering LDL, but not enough evidence yet.
These other disease states include aside from what has been stated already, such as those patients with neurological disease, as well as statins being beneficial for certain cancer patients. Some have suggested that statins interfere with cancer treatment with bladder cancer patients as well. Yet again, these other roles for statin therapy have only been minimally explored and researched, comparatively speaking.
Because of the limited evidence regarding additional benefits of statin medications, the drug should again be prescribed for those with dyslipidemia only at this time involving elevated LDL levels as detected in the patient’s bloodstream.
Yet overall, the existing cholesterol lowering recommendations or guidelines should possibly be re-evaluated. The cholesterol guidelines that presently exist may be over-exaggerated possibly due to tacit suggestions from the makers of statins to those who create these current lipid lowering guidelines.
This is notable if one chooses to compare these cholesterol guidelines with the other guidelines that have existed in the past. The cholesterol guidelines that exist now are considered by many health care providers and experts to be rather unreasonable and unnecessary, as well as possibly have the potential to be detrimental to a patient’s health.
Yet statins are beneficial medications for those many people that exist with elevated LDL levels that can cause cardiovascular events to occur because of this abnormality. What that ideal LDL level is may have yet to be empirically determined.
Finally, a focus on children and their lifestyles should be amplified so their arteries do not become those of one who is middle-aged, and this may prevent them from being candidates for statin therapy now and in the future, regarding the high cholesterol issue. Treating children with a statin drug for dyslipidemia is controversial presently. Dietary management should be the first consideration in regards to correcting lipid dysfunctions that may exist in patients,
Dan Abshear
Secondary prevention is not controversial; primary prevention is very controversial.
Where exactly do you draw the line defining the difference between the two? What kind of “cardiac event” tips a patient over into secondary vs. primary prevention? Clearly a documented MI counts, but what about ACS? Is asymptomatic non-obstructing coronary disease enough of an “event”?
What about coronary disease discovered at cath, but in a case where the patient didn’t really meet clinical criteria to go to the cath lab in the first place? (atypical chest pain, no risk factors, normal EKG/stress testing/echo, negative enzymes) Yes, these people frequently end up at cath and are found to have non-obstructing disease. I end up putting them on statins, of course, but does that count as accepted secondary prevention or controversial primary prevention?