No reason to fear very low LDL

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"There was no apparent safety concern for patients whose resultant LDL on intensive therapy was lower than current guidelines. There was a trend toward improved clinical outcomes in the lowest LDL groups," said Stephen D. Wiviott, M.D., from Brigham and Women's Hospital in Boston, Massachusetts.

The researchers used data from a large trial comparing two cholesterol-lowering statin drugs in patients following acute coronary syndromes, such as unstable angina or heart attacks, the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) study. This new analysis involved 1,825 heart patients who had received high doses (80 milligrams per day) of atorvastatin. More than 90 percent of the patients had LDL (low-density lipoprotein, the so-called "bad" cholesterol) levels below the target level of 100 milligrams per deciliter of blood after four months of therapy. Some patients saw their LDL levels drop below 40 mg/dl.

Dr. Wiviott said that they reviewed this data from PROVE IT because some studies have suggested an association between very low levels of cholesterol and higher rates of death, strokes caused by bleeding, and other health issues. Rather than assessing the safety of statin treatment itself, this analysis looked at the effects of various levels of LDL by comparing the results for patients who were all taking the same high doses of atorvastatin.

"While the main results of the trial demonstrated that intensive statin therapy is superior to moderate statin therapy in patients following acute coronary syndromes, there has been concern among the medical community about treating patients with very high doses of potent statins. This stems largely from the epidemiologic literature which shows that patients with very low cholesterol, not on treatment, have higher mortality," Dr. Wiviott said.

There was no significant difference in safety outcomes among the groups of patients, including rates of death, bleeding strokes, or muscle, liver or retinal abnormalities. What's more, the patients who achieved LDL levels of 60 mg/dl or lower had fewer major cardiac events, including death, heart attack, stroke, recurrent coronary artery blockages or treatment to reopen coronary arteries.

Dr. Wiviott said the results offer reassurance to patients and clinicians using high doses of statins following acute coronary syndromes.

"In order to achieve the greatest benefit following acute coronary syndromes, patients should be treated early with intensive statin therapy. There is no need to reduce the dose in follow-up just because LDL is well below targeted levels," he said.

Dr. Wiviott noted that the PROVE IT trial was not originally designed to answer questions about the safety of very low LDL levels.

"This type of analysis should be considered 'hypothesis generating' and needs to be confirmed in other studies," he said.

John J.P. Kastelein, M.D. from the Academic Medical Center at the University of Amsterdam, Netherlands, who was not connected with this study, but who is helping to lead two large long-term studies of intensive statin therapy, welcomed this first solid information about the safety of low LDL levels.

"What's very important for me is that this trial is the first indication that very low LDL levels are actually safe. Of course, the time frame is modest, but it is the first indication that we can sustain low LDL levels without any cost in terms of extra side effects," Dr. Kastelein said.

American College of Cardiology