Statins outcome studies

Outcome studies employing the statins have conclusively shown that reduction of LDL translates into reduced clinical cardiovascular events. However, in patients with normal LDL or after LDL levels have been normalized, TG and HDL levels assume an important role in the progression of atherosclerosis. The importance of HDL-cholesterol as an inverse... 

Cardiovascular As was reported in SEDA-32 (p. 817), ILLUMINATE, an outcome study that recruited around 15 000 statin-eligible patients with coronary heart disease or type 2 diabetes mellitus was terminated after a median follow-up of only 550 days, because of a small but significant increase in major cardiovascular events in those taking torcetrapib - - atorvastatin compared with those taking atorvastatin alone (49 versus 35 cardiovascular deaths) [69. This occurred despite a 72% increase in HDL cholesterol and a 25% reduction in LDL cholesterol compared with the statin alone. This was almost certainly correctly attributed to activation of the renin-angiotensin-aldosterone system, resulting in increments in blood pressure and aldosterone and reduced potassium. 

In rodent stroke models, statin pretreatment has been shown to reduce infarct volumes and improve outcomes. Similarly, several clinical studies have shown that prior statin use reduced the severity of acute ischemic stroke and myocardial infarction. Recent studies indicate that beneftt can be achieved even when treatment is initiated after the onset of symptoms. In rodents, atorvastatin and simvastatin have been shown to reduce the growth of ischemic lesions, enhance functional outcome, and induce brain plasticity when administered after stroke onset. A retrospective analysis of the population-based Northern Manhattan Stroke Study (NOMASS) showed that patients using lipid-lowering agents at the time of ischemic stroke have a lower incidence of in-hospital stroke progression and reduced 90-day mortality rates. Retrospective analysis of data of the phase III citicoline trial showed... 

Jonsson N, Asplund K. Does pretreatment with statins improve clinical outcome after stroke A pilot case-referent study. Stroke 2001 32 1112-1115. 

Parra A, Kreiter KT, Williams S, Sciacca R, Mack WJ, Naidech AM, Commichau CS, Fitzsimmons BF, Janjua N, Mayer SA, Connolly Jr. ES, Effect of prior statin use on functional outcome and delayed vasospasm after acute aneurysmal subarachnoid hemorrhage a matched controlled cohort study. Neurosurgery 2005 56 476 84 [discussion 476 84]. 

A number of drugs should be avoided in HF including antiar-rhythmic agents, calcium channel blockers, antipsychotics, antihistamines, corticosteriods, and nonsteroidal anti-inflammatory drugs. Metformin and thiazolidinediones should be used with caution in HF with diabetes. Trials of statins have generally excluded patients with symptomatic HF but two studies with morbidity and mortality outcomes in HF are now under way. 

The results of these studies provided direct proof for the importance of the extent of lipid lowering in order to improve cardiac outcome. In addition, they clearly indicated that, in order to achieve a large reduction in lipid levels and the corresponding cardiovascular event rates, the statins are not equally suitable. The correlation between the degree of lipid lowering and therapeutic benefit, as well as the different effectiveness of the statins to achieve this goal, were corroborated by a meta-analysis of the available clinical data [35]. In 164 short-term studies, the lipid-lowering potency of all statins was shown to correlate more or less linearly... 

Even if the Canadian initiative and its collaborative work with US centres provide scientific evidence on health outcomes, there will still be little research and few assessments of the actual or potential impact of reference pricing (and consequent drug switching) on the appropriateness of the drug treatment which patients receive. The Thomas and Mann study [13] on the prescribing of statins in New Zealand may provide some evidence on the adverse effects of certain uses of products within this drug class. 

It has been an attractive option to use combination therapy of statin and fibrate when HDL remains low but there is no data from RCTs to support this approach. It is ironic that gemfibrozil with the best outcome data should not be used in this context given drug interactions. The results of the FIELD trial with fenofibrate as sole therapy were disappointing [59] however, a combination trial with fenofibrate and statin in type 2 diabetes, the ACCORD study, is in progress. 

In a cohort study of 10 491 patients who took clopidogrel after percutaneous coronary intervention, the co-prescription of CYP3A4-metabolized statins was not associated with an increased risk of adverse outcomes (HR = 1.16 95% Cl = 0.91, 1.47) [175 ]. 

Drug-drug interactions The influence of statins on outcomes of IV thrombolysis in ischaemic stroke is controversial. A case-control study and meta-analysis determined that statin pretreatment may increase the risk of symptomatic intracranial haemorrhage in patients receiving IV rt-PA however, it did not influence the 3-month outcome... 

A study involving clinically stable patients witir relapsing-remitting multiple sclerosis (RRMS), 21 therapy-naive and 14 IFNp with a statin, showed that high-dose statin therapy significantly reduced IFNp fxmction and responses to type I IFNs in RRMS patients. These findings may be an indication of how statins impair the beneficial effects of IFNp and lead to worsened disease outcomes [bl" ]. 

Cancer The concern of statins affecting cancer risk remains inconclusive [56-62]. Several studies for cardiovascular outcomes found no association between statin use and cancer risk [63-66]. 

Gornik I, GaSparovid V, Gubarev Vrdoljak N, Haxiu A, VuceUd B. Prior statin therapy is associated with milder course and better outcome in acute pancreatitis-a cohort study. Pancreatology 2013 13 196-200. 

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