Statins comparative effectiveness

Erectile dysfunction has been reported in 12% of 339 men treated with fibrate derivatives or statins, compared with 5.6% of similar patients not taking these drugs (62). The mechanism is unknown and should be confirmed in randomized studies. A class effect has been suggested by the case of a 57-year-old man who had impotence after taking lovastatin for 2 weeks and also when he later tried pravastatin (63). 

Koh KK, Son JW, Ahn JY et al, Comparative effects of diet and statin on NO bioactivity and matrix metalloproteinases in hypercholesterolemic patients with coronary artery disease, Arterioscler Thromb Vase Biol 2002 22 e I 9-e23. 

Once has been determined in the absence of inhibitor, can be calculated from equation (47). K, values are used to compare different inhibitors of the same enzyme. The lower the value for K, the more effective the inhibitor. For example, the statin drugs that act as competitive inhibitors of HMG-CoA reductase (Chapter 26) have values several orders of magnimde lower than the AT for the substrate HMG-CoA. 

Compared with monotherapy, combination therapy is relatively unstudied in terms of the effects on CHD event reduction and may reduce patient compliance through increased side effects and increased costs. When used appropriately and with proper precautions, however, they are effective in normalizing lipid abnormalities, particularly in patients who cannot tolerate adequate doses of statin therapy for more severe forms of dyslipidemia. 

As indicated in Table 1, statins, which block cholesterol biosynthesis by inhibition of hepatic HMGCoA reductase, have been used extensively to reduce LDL-C levels. At most therapeutic doses, statins marginally increase HDL levels by 5-10% [3,16]. The HDL elevation observed with statins has been highly variable and not easily extrapolated from the effects on LDL. A recent study (STELLAR) demonstrated increased HDL elevation with the use of rosuvastatin compared to simvastatin, pravastatin or atorvastatin (10% vs. 2-6%) [16,24], Although the mechanism of HDL elevation by statins is not clearly understood, it is proposed that statins enhance hepatic apoA-I synthesis [25] and decrease apoB-containing lipoproteins [26]. A number of clinical trials have demonstrated that statins reduce the risk of major coronary events. However, it is not clear if the statin-induced rise in HDL levels is an independent contributor to the reduced risk of coronary events. The observed small increase in HDL and adverse side effect profile related to liver function abnormalities and muscle toxicity limits the use of statins as monotherapy for HDL elevation [27],... 

Sometimes, the choice of comparator can backfire badly. Zocor Merck s Statin was run by Merck against Pfizer/Warner Lambert s Lipitor in another billion dollar study, and it was proven less effective. Merck made a huge favor to Pfizer that paid dearly but astutely to acquire Lipitor for its cardiovascular franchise. 

It has been suggested that the pharmacokinetics of fluvastatin, including extensive biliary excretion and absence of circulating active metabolites, might be associated with a low incidence of systemic adverse effects compared with other statins. In over 1800 patients treated for an average of 61 weeks, fluvastatin was safe and tolerable (SEDA-19, 408). Pooled data from clinical trials have shown that gastrointestinal symptoms occurred in 14% of fluvastatin recipients compared with 9% taking placebo other complaints occurred... 

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