High-dose Lipitor® fails to stop increase in heart scan score
Drug manufacturers would have us believe that statin agents for cholesterol reduction regress plaque all by themselves. In our experience, it's simply not true. A new study confirms that statins alone won't do it.
Can a high dose of statin drug alone shrink plaque?
This question has been tossed around a fair amount recently. The huge popularity of the statin agents—their relative ease, potency, and profitability—have fueled this debate. There is indeed preliminary evidence that high doses of Lipitor® may obtain a small quantity of plaque regression.1,2 The quantity of regression obtained tends to be a few percent but still better than the alternative—tremendous plaque growth.
However, these observations have been inconsistent. In our experience, it's rare that a statin agent alone controls plaque. Much more commonly, plaque growth may be slowed from its expected 30% or so per year to the range of 18–24% per year—better but hardly worth boasting about.
High-dose vs. low-dose Lipitor®
Adding to this experience is Dr. Alex Schmermund's recently reported results of a study comparing high-dose vs. low-dose Lipitor® on the rate of increase in heart scan scores.3
In this study, 471 participants underwent a heart scan at the start of the study. To qualify, scores needed to be 30 or greater (Agatston scores). Participants were then randomized (randomly selected) to receive either high-dose Lipitor® (80 mg) or low-dose Lipitor® (10 mg) for one year. Starting (mean) heart scan scores in the low-dose group was 457; high-dose, 428.
After one year of drug therapy, heart scans were repeated in all participants in both groups.
Was there any difference between high- vs. low-dose? None whatsoever. The high-dose group experienced a heart scan score increase of 28%, while the low-dose was virtually the same at 26%. Recall that the expected rate of plaque growth (increase in heart scan score) is in the neighborhood of 30% without any treatment.
LDL cholesterol in the high-dose group was 87 mg/dl on treatment; 109 mg/dl in the low-dose group, for a 22 mg difference. While on treatment, both groups had HDL cholesterols of 53–54 mg/dl and triglycerides of around 150 mg/dl.
Dr. Schmermund commented, "My …interpretation is simply that the relationship between lipid-lowering therapy, the total amount of atherosclerosis, and the influence of LDL cholesterol on total atherosclerosis and coronary calcium, as well as the progression of disease, is much more complex than we currently understand."
This is yet another study examining (promoting?) the use of statin drugs, though this time using the endpoint that we believe is the best—heart scan scores. Drug manufacturers, especially Pfizer (maker of Lipitor®), have seemingly limitless resources to perform studies on their drugs. Several prior studies (PROVE-IT, REVERSAL,etc.) have shown that high-dose Lipitor® reduces "events" like heart attack and need for heart procedures substantially and achieves a modest quantity of plaque regression (around 1%) when plaque is studied via intracoronary ultrasound.
Why the negative outcome here? Surely there's a difference in results achieved between two treatments with very different potencies.
We can identify several reasons:
* LDL cholesterol is only one cause of coronary plaque. How about small LDL (an extremely important factor), low HDL, Lp(a), inflammation, etc.? The majority of participants in both groups had numerous uncorrected patterns. If low HDL or small LDL remain uncorrected, then it's no surprise that plaque grew at nearly the rate you'd expect without any treatment.
* Triglyceride-rich lipoproteins were not addressed. Addition of fish oil would have added a profoundly helpful agent that reduces or often eliminates triglyceride-dependent lipoproteins like VLDL, the after-eating IDL, and contributes to getting rid of small LDL.
* Vitamin D metabolism was not examined, nor was vitamin D supplemented. This is a relatively recent lesson we've learned in our plaque-regressing experience. Vitamin D blood levels need to be normal (55–60 ng/ml). Otherwise, many features of the metabolic syndrome like small LDL, higher blood sugar and insulin levels, high blood pressure, and heightened inflammation will persist—and coronary plaque will grow.
* Even in the high-dose group, LDL cholesterol was 87 mg/dl. We aim for 60 mg or less. We go even one step farther: Not only should (calculated) LDL cholesterol be reduced to 60 mg, but the far more precise measures of LDL particle number of apoprotein B should also be reduced to our targets. This provides added assurance that LDL ceases to be a contributor to plaque growth. It's amazing to us how often LDL continues to be a factor when LDL appears low. That's because LDL cholesterol is an exceptionally imprecise measure. It's a lot like having a speedometer on your car that's 30 mph inaccurate—it says 35 mph but you're going 60 mph. Tell that to the State Patrol! Your LDL cholesterol might be 100 mg/dl but might really be 150 mg/dl when more precise measures like LDL particle number or apoprotein B are used. The message: LDL cholesterol is an extremely flawed measure that you simply cannot rely on. Lipoprotein measures added far greater certainty, especially when you're looking at whether you've reached an endpoint in your therapy.
To us, it's no surprise that using Lipitor® alone, whether high-dose or low-dose, failed to more powerfully impact on the heart scan score . That continues to be why we expend a lot of time and effort to broadcast how this can be achieved more effectively. There's a lot more to this story than Lipitor®. Sorry, Pfizer.
1. Cannon CP, Braunwald E, McCabe CH et al. Pravastatin or atorvastatin evaluation and infection therapy:Thrombolysis in Myocardial Infarction-22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495–1504.
2. Nissen SE, Tuzcu EM, Schoenhagen P et al. REVERSAL Investigators. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 2004;291:1071–1080.
3. Schmermund A, Achenbach S, Budde T et al. Effect of intensive versus standard lipid-lowering treatment with atorvastatin on the progression of calcified coronary atherosclerosis over 12 months: a multicenter, randomized, double-blind trial. Circulation 2006;113:427–437.