Here is a quote from Elena Citkowitz, MD, PhD, FACP, the Director of Cholesterol Management Center, at Yale University Medical Center..my emphasis so you guys don't miss my point :bouncing: :
She refers specifically to treating FH:
"Maximum doses of one of the stronger HMG-CoA reductase inhibitors (ie, statins) such as atorvastatin or rosuvastatin and one or more other medications, including bile acid sequestrants or niacin, are required to approach the recommended LDLc goals."
The LDL goal she's talking about approaching isn't 70, its 100, just to bring this around to the thread subject.
Not REACH, not ACHIEVE, not SURPASS....but APPROACH ... LDL 100.
She further emphasizes...
"Even the strongest statins at their maximum doses are almost always inadequate for patients with FH, and one or more additional (ie, nonstatin) cholesterol-lowering medication is necessary"
Regression Growth Evaluation Statin Study (REGRESS)5
Restenosis (re-narrowing) after a type of angioplasty called percutaneous transluminal coronary angioplasty (PTCA) is one limitation of the long-term success of this procedure. In previous studies statins have failed to prevent restenosis. However their lack of success in the past may have been due in part to the fact that the studies did not allow a long enough follow-up time. Also, a better understanding of restenosis has led to a better evaluation of it. The REGRESS study investigated the efficacy of pravastatin in reducing restenosis after PTCA. The study considered 221 patients who had undergone PTCA. Patients were randomly selected to receive pravastatin or placebo. The pravastatin group showed a lower percentage of the artery blocked—based on the ratio of blockage to artery diameter (32% vs 45%). In addition, pravastatin provided a 7% reduction in clinical restenosis over placebo. Pravastatin, therefore, is an effective treatment to prevent restenosis after PTCA.
Effect of aggressive lipid lowering on progression of atherosclerosis after coronary artery bypass graft (CABG)6
This follow-up study investigated the difference between moderate LDL lowering therapy and aggressive LDL therapy on the progression of athersclerosis. Four hundred and two patients were randomly assigned into the two treatment groups (aggressive and moderate). The aggressive group received 75-80 mg of lovastatin daily and the moderate group received 2.5-5 mg of lovastatin. Patients in the aggressive group showed average LDL levels of 92-97 mg/dL (a 40% decrease from baseline) while patients in the moderate group had levels of 131-135 (a 12% decrease). More significantly, patients treated with the aggressive treatment had less atherosclerosis than the moderately treated group. Athersclerosis was measured by minimum lumen diameter or by the average change in maximum arterial stenosis. This study, like the Heart Protection Study and the Reversal study demonstrates that at in patients with CABG there are clear benefits to receiving aggressive LDL lowering therapy with a goal of lowering LDL cholesterol to below 100 mg/dl.
Arterial Biology for the Investigation of the Treatment of Effects of Reducing Cholesterol (ARBITER)7
This study further assessed the question of whether lowering LDL cholesterol to well under 100 mg/dl will have benefits above and beyond lowering levels to 100 mg/dl. This study compared pravastatin and atorvastatin, at different doses, on carotid intima-media thickness (CIMT) which is a measure commonly used as a surrogate for vascular atherosclerosis. One hundred and sixty one patients with known cardiovascular disease were randomly divided into a pravastatin (40mg/d) group (n=82) and an atorvastatin (80 mg/d) group (n=79). After one year the average LDL in the pravastatin group was 110 mg/dL and was 76 mg/dL in the atorvastatin group. The CIMT was stable in the pravastatin group while the atorvastatin group showed a regression in CIMT over 12 months. An aggressive reduction in LDL is an efficient way to induce the regression of atherosclerosis which may in turn lead to fewer coronary events.
Pravastatin in the secondary prevention of cardiovascular events in patients with kidney insufficiency8
Since statins have been overwhelmingly shown to reduce cardiovascular disease in the general population, this study investigated the ability of statins to reduce cardiovascular events in patients with renal insufficiency (when the kidneys lose their ability to remove waste from the body). There were 1711 participants in this study who were identified as having chronic kidney insufficiency by having a creatinine clearance of =75 mL/min. Patients were given either pravastatin or placebo. Pravastatin was associated with a lower occurrence of major coronary events but there was not a difference in total mortality between the two groups. The incidence of side effects was similar in patients receiving pravastatin to those receiving placebo. A significant finding is that patients will see the observed benefits whether or not they have kidney insufficiency and regardless of its severity. Pravastatin is therefore a safe and effective method of secondary prevention for patients who have mild chronic kidney insufficiency.
Fluvastatin and prevention of cardiac events after a successful, first percutaneous coronary intervention9 (LIPS study)
Percutaneous coronary intervention (PCI) is effective for short-term improvement in ischemic symptoms but has less long-term efficacy. Sixty percent of patients are free of a major adverse cardiac event (MACE) 5 years after PCI and only 33% after 10 years. The goal of this study was to assess whether fluvastatin reduces major cardiac events. A total of 1677 patients at 77 centers in Europe, Canada, and Brazil were studied. Eight hundred and forty four patients with unstable angina or silent ischemia after their first PCI were randomly assigned to receive 80 mg/d of fluvastatin and 833 a placebo. After a median follow-up time of 3.9 years 21.4% of the patients in the fluvastatin group had a MACE, compared to 26.7% in the placebo group. Also, there was a longer time before a MACE in the fluvistatin group. This study suggests that patients with average cholesterol levels will benefit from fluvistatin treatment after the first successful PCI. The LIPS study has also shown that patients treated with a stent and fluvistatin show a 28% reduction in MACE.
Atorvastatin versus simvastatin on atherosclerosis progression (ASAP) study10,11
The purpose of the ASAP study was to assess the difference of aggressive versus traditional cholesterol treatment on the progression of atherosclerosis in patients with familial high cholesterol. Three hundred and twenty five patients with a family history of high cholesterol were randomly divided into an aggressive group (atorvastatin) and a traditional treatment group (simvastatin). After two years of treatment, the progression of atherosclerosis was compared between the two groups. In one test, the levels of hs-CRP were lower in patients taking atorvastatin compared to simvastatin. hs-CRP is a good marker of inflammation in atherosclerotic vascular disease. In another test—a measurement of the carotid intima media thickness—the atorvastatin group showed a regression of atherosclerosis, whereas the simvastatin group did not. These results show that aggressive lowering of LDL was accompanied by a regression of atherosclerosis in the carotid artery but conventional LDL lowering by simvastatin did not show any benefit.
The Benefit of Aggressive Lipid Lowering12 (AVERT study)
This study examined 341 patients with stable coronary heart disease (CHD). They were randomly assigned to receive atorvastatin (80 md/d) and conventional treatment or angioplasty followed by usual care. The differences in LDL and subsequent ischemic events were compared between the two groups. The atorvastatin/conventional treatment group showed a 48% decrease in LDL compared to an 18% decrease following angioplasty. The atorvastatin group had fewer ischemic events (13% vs 21%, p=.048) and a longer time before the first ischemic event (p=.027) when compared with the angioplasty group. Therefore aggressive lipid lowering is beneficial in patients with existing CHD.
Aggressive LDL lowering provides the greatest reduction in carotid atherosclerosis13
The purpose of this study was to investigate the effects on atherosclerosis of lowering LDL well below the current recommended level of 100 mg/dL. The investigators used the carotid intima media thickness (CIMT) as an indicator of atherosclerosis progression. The study compared the effects of pravastatin (40 mg/d) and atorvastatin (80mg/d) among 161 patients. The final LDL level was directly correlated with the amount of CIMT regression. Sixty-one percent of subjects with final LDL levels of < 70 mg/dL showed a regression whereas only 29% of those with final LDL of = 114 mg/dL. The amount of atherosclerotic regression is directly related to absolute LDL level. The investigators recommend a lower National Cholesterol Education Program guideline.
The relation between atherosclerotic progression and cholesterol levels14
This study assessed the long-term (average of 18.3 months) progression or regression of atherosclerotic plaque in the left main coronary artery (LMCA) by intravascular ultrasound (IVUS). IVUS studies were performed on the LMCA of 60 patients. LDL and plaque progression were positively correlated (i.e. the more LDL, the more plaque). The researchers calculated that LDL levels below 75 mg/dL would not predict any progression of atheroclerosis (i.e. it would be essentially stopped, but not necessarily regress). Also, there was an negative correlation between HDL and plaque (i.e. more HDL less plaque). Therefore lower LDL (at least below 75 mg/dL) and higher HDL slows or halts progression of atherosclerosis. This study is particularly useful because unlike other similar studies it examined the effects of HDL cholesterol on atherosclerotic plaque.
Give me your reference for study 14...I'd like to read it in full.
[quote]The relation between atherosclerotic progression and cholesterol levels14
This study assessed the long-term (average of 18.3 months) progression or regression of atherosclerotic plaque in the left main coronary artery (LMCA) by intravascular ultrasound (IVUS). IVUS studies were performed on the LMCA of 60 patients. LDL and plaque progression were positively correlated (i.e. the more LDL, the more plaque). The researchers calculated that LDL levels below 75 mg/dL would not predict any progression of atheroclerosis (i.e. it would be essentially stopped, but not necessarily regress). Also, there was an negative correlation between HDL and plaque (i.e. more HDL less plaque). Therefore lower LDL (at least below 75 mg/dL) and higher HDL slows or halts progression of atherosclerosis. This study is particularly useful because unlike other similar studies it examined the effects of HDL cholesterol on atherosclerotic plaque.
A couple comments on the AVERT study.
1. It never quite met the level required for statistical difference between the two methodologies it was studying...not to say that BOTH aren't beneficial but a study should study what a study studies:D:D (one of the FIRST rules of statistics)
2. Mention should be made that the atorvastatin group LOWERED its HDL by 8% and then for some bizarro reason the angioplasty group ALSO lowered its HDL by 11% (that 11% looks fishy to my fish-eye...). I mean WHY would no dietary or drug intervention show such a drop in HDL???? In any case, certainly not a good result of either intervention.
3. Also not mentioned was whether stenting was involved in any of the angioplasties...how many would have been of PRIME interest. Since my best estimate is that the study was begun in 1996 or 1997 maybe 60%(very rough guess) stents were involved????
4. You neglected to mention the very large advantage to the angioplastied group in PAIN REDUCTION
[quote]Angina
At the end of the study, 67 patients in the atorvastatin group (41 percent) had an improvement in the CCS classification of angina symptoms, 78 (48 percent) had no change, and 19 (12 percent) had a deterioration. Of the patients in the angioplasty group, 95 (54 percent) had an improvement in the CCS classification, 70 (40 percent) had no change, and 12 (7 percent) had a deterioration. This difference between treatment groups significantly favored angioplasty (P=0.009 by the Cochran–Mantel–Haenszel test). However, this outcome variable was the only one not reviewed by the end-points committee. ..DUUUH (my comment)...especially since pain is the usual presenting symptom for atherosclerosis.
All said, though interesting, I found the AVERT study to be deeply flawed (and more than a tad prejudiced in Lipitor's favor) but one certainly can't avoid being impressed with an untested implication that perhaps ATORVASTATIN + ANGIOPLASTY + STENT simply HAS to be a pretty good path to be on. (but then I don't want to fall into the same trap and conclude something that wasn't being tested for:D:D)
As far as whether atorvastatin is better than angioplasty, the study really did not reach a (reasonable) conclusion. (Gotta wonder why they did it?)
"As far as whether atorvastatin is better than angioplasty, the study really did not reach a (reasonable) conclusion. (Gotta wonder why they did it?)"
Zip2play, why would anyone favor a surgical solution unless their situation was critical, or it was shown that diet/treatment couldn't or wouldn't show enough efficacy in the individual to halt or reverse Atherosclerosis?
It has been clinically proven that atherosclerosis can be reversed without medication through diet. Statins have also shown a lesser ability to reverse athero on their own without dietary change. A combination therapy may well prove even more efficatious.
Surgery is what you do when diet and medication fail, although if you've had angioplasty you have reason to hope that you've short cutted the reversal process to some extent.
In any case, angioplasy and bypass are only a reprieve if you don't go back further and address the causal issue. So why not address it and cure it, instead of treating it invasively and then addressing the causal issue?
And of course no sane definition of a jury would consist of ONE person...or even a couple.
If that were so, then of course, Linus Pauling who said that VITAMIN C CURES HEART DISEASE right after he cured the cold in the '60's; Atkins cured heart disease with a high fat diet in the early 1970's;...and probably Jydia Pinkham cured it before Carter invented his Liittle Liver Pills: ALL had simple non surgical heart disease "cures" making surgery obsolete.
When I said "sane jury" I think it should be reasonable to assume that I meant a consensus of medical peers who have evaluated the total picture. When and IF it becomes clear that diet and drugs can replace surgery, percutaneous or otherwise, they will.
Do you bleed when they test your cholesterol? Do they staunch your blood? Do you consider it major surgery?
And do you honestly believe that Dean, Elena, or Peter, if faced with a 98% blockage in one of their main coronary arteries would opt for a life of "good living" instead of an overnight angioplasty?"
From an earlier post (rahod):
[quote]Intravascular ultrasound was used to assess atherosclerotic plaque status at pre-treatment baseline and after 18 months on therapy. The group treated with atorvastatin showed a median 0.4% reduction in plaque volume (the total plaque in a given section of an artery) while the pravastatin group had a median 2.7% increase in total plaque volume.
So as an alternative, facing a 98% blockage an agressive 18 month atorvastatin treatment regimen would lower a 98% blockage to ....98% but pravachol would take it UP to about 100% (whew, what a relief- dodged THAT bullet; unless you used atorvastatin...or pravachol).
To consider these as sensible treatment plans for serious reductions of existing dangerous plaques is the height of folly...and NO SANE JURY would consider them, as I implied earlier.
