LDL-lowering medications

If LDL = 160-189 mg/dL, continue TLCs and consider LDL-lowering medications in certain high-risk patients. 

Thus, it remains open, when LDL-lowering drugs with a new mode of action will emerge and make their way through the dinic to the market. High medical need and substantial scientific interest are in any case certain. 

Despite its ability as a wide spectrum lipid lowering medication (decreased LDL-c, triglyceride and increased HDL-c) and ability to decrease Lp(a), its widespread uses is limited by the unpleasant flushing. 

Of the cholesterol-lowering medications available to date, statins are currently the first choice for treating patients with hypercholesterolemia. They lower serum LDL cholesterol concentrations by 24-50% (Knopp, 1999) by blocking the synthesis of cholesterol through inhibition of the action of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase in the fiver. 

Perhaps the most hopeful sign of progress is the belated recognition of "paradoxical" reactions to the lipid-lowering diets that have been widely used for decades. For example, researchers at the South-Western Medical Center in Dallas repeatedly find "marked individual variations in response to the diet." In many persons these diets show little benefit, or increase LDL cholesterol, serum triglycerides, or... 

In the 80-mg simvastatin dose group in the Ato Z trial, CRP levels fell from 20,1 to 1,7 at four months and 1,5 at eight months (P < 0.001) (36). Higher-dose simvastatin resulted in lower CRP levels. In PROVE-IT (35), Ato Z (36), and MIRACL trials (37), higher doses of statin medications resulted in lower low-density cholesterol (LDL) and a better outlook. Higher doses of statin also caused greater falls in CRP levels. This suggests a role for inflammation in these ACS patients (37). 

The primary goal of therapy is the control of the hypercholesterolemia and prevention of atherosclerotic cardiovascular disease. Patients with heterozygous FH can usually be successfully treated with medications to lower the LDL cholesterol to acceptable levels (Table 14-2). They are generally responsive to treatment with statins, alone or in combination with other drugs, such as bile acid sequestrants (such as cholestyramine) or cholesterol absorption inhibitors (such as ezetimibe) that act additively to upregulate the expression of the functioning LDL receptor as described in the Biochemical Perspectives section. In a few cases, a more aggressive treatment with LDL apheresis (discussed in this section) may have to be considered in order to reach acceptable LDL cholesterol levels. 

Coincidentally, the medical community was coming to the same conclusion that the lower one s cholesterol the better. I had accepted that idea years before and did everything I could to keep my levels of the bad LDL cholesterol as low as possible and the good HDL cholesterol as high as possible. Why shouldn t I view blood pressure with the same aggressive stance ... 

Perhaps the most successful anti-atherosclerosis medications are the statins. These drugs bind to HMG-CoA reductase and directly inhibit its activity, thereby lowering cholesterol biosynthesis and the pool of hepatic cholesterol. Activation of SREBP in response to this cholesterol depletion promotes increased synthesis of HMG-CoA reductase and the LDL receptor. Of most Importance here is the resulting increased numbers of hepatic LDL receptors, which can mediate increased import of LDL cholesterol from the plasma. Statins also appear to inhibit atherosclerosis by suppressing the inflammation that triggers the process. Although the mechanism of this Inhibition is not well understood, it apparently contributes to the atheroprotec-tive effect of statins. 

Choice of a particular statin will depend on several factors including efficacy, safety, concurrent medication, concurrent medical conditions, RCT evidence of benefit in reducing CVD events, baseline lipids, and, increasingly, cost, given the availability of generics [38]. All statins lower LDL effectively but they do differ in potency, the more potent statins being atorvastatin and rosuvastain... 

A retrospective study of the effects of lovastatin and antihypertensive medication found that when calcium-channel blockers (diltiazem, nifedipine or verapamil) were used in combination with lovastatin there was an additional 3 to 5% lowering in the LDL-cholesterol, which was of marginal significance. Pharmacokinetic studies have shown that oral diltiazem increases the AUC and maximum serum levels of lovastatin by about fourfold. In another study, lovastatin 20 mg and isradipine 5 mg... 

High-density lipoproteins are considered "good cholesterol" and low-density lipoproteins "bad" cholesterol. Some remember the difference by thinking, "H is for health and L is for lethal." HDL levels should be above 40 mg/dL and LDL levels should be below 130 mg/dL for a total cholesterol below 200 mg/dL. Elevated LDL cholesterol is the primary target of cholesterol-lowering therapies (nicotinic acid, bile sequestering, or statin medications). 

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