Statins, percutaneous coronary intervention and myocardial infarction

Peri-procedural myocardial infarction occurs in up to 40% of otherwise successful percutaneous coronary intervention (PCI) procedures and such patients have a worse long term prognosis than those who do not have this complication. Statins administered at the time of PCI, particularly before the procedure, have been shown to reduce the risk of myocardial infarction during PCI, but the applicability of this treatment may be limited because of the widespread use of statins in patients with existing coronary artery disease, or in those at risk of developing the disease. The results of a study are reported in this issue of the journal in which a single dose of atorvastatin is given prior to PCI to patients already taking a statin, and shows a significant reduction in the risk of peri-procedural myocardial infarction. It may be that a single supplemental dose of a statin at PCI to all patients could confer clinical benefit. Coronary revascularisation by percutaneous coronary intervention (PCI) is the treatment of choice in contemporary European and US guidelines for treatment of ST elevation myocardial infarction (STEMI), and PCI is used electively for the coronary revascularisation. In up to 40% of otherwise successful elective PCI procedures, there is a rise in the serum concentration of markers of cardiac necrosis(1,2). This rise is sufficiently large in some cases to lead to a diagnosis of peri-procedural myocardial infarction and such patients have a worse long term prognosis than those in whom there is no rise in cardiac troponins or creatine kinase MB fraction(3,4). Myocardial infarction is a thrombus-driven event. A number of pre- and peri-procedural therapeutic options are available to antagonise the pro-thrombotic environment seen in vaso-occlusive disease, and caused as a consequence of vessel trauma and embolisation in the revascularisation process(5). The second major pathological process in coronary artery disease is atherosclerosis, driven by the accumulation of low density lipoprotein (LDL) cholesterol in the arterial wall, which leads to plaque formation. Stable atherosclerotic plaques of sufficient size will lead to perfusion defects and angina, or if the plaque cap becomes unstable to thrombus formation and so to an acute coronary syndrome (ACS). Lowering plasma concentrations of LDL cholesterol with statins has been clearly shown to reduce the risk of all major vascular events, both in primary and secondary prevention, and this benefit is proportional to the extent to which LDL cholesterol is lowered(6). It seems likely that this clinical benefit is related to a lack of progression, or indeed regression, of atherosclerotic plaques, and this being so the benefit would be seen only in medium to long term follow up. The risk of recurrent ischaemic events is highest in patients early after suffering an ACS. In the MIRACL study 7, 3086 patients with a non-STEMI or unstable angina were randomised to receive atorvastatin 80 mg/day or placebo with 96 hours of presentation, and they were then followed for 16 weeks. The relative risk of the composite endpoint of death, non-fatal myocardial infarction and symptomatic coronary ischaemia was 0.84 in those treated with atorvastatin. As would be expected in the atorvastatin group LDL cholesterol fell from an average of 3.2 to 1.9 mmol/L and although the authors did not discuss the reasons, it seems unlikely that this clinical benefit was related to an effect on LDL cholesterol driven atherosclerotic process in such a short time period. Statins inhibit an early rate limiting step in cholesterol biosynthesis, by competitively binding to hydroxy methyl glutaryl CoA reductase. This biochemical pathway is complex and a number of other important metabolites are produced as side branches from the cholesterol pathway. It has been speculated that non-LDL-cholesterol lowering effects of statins, the so called 'pleiotropic' effects 8,9, may also be important in the clinical benefit seen with statin therapy. These effects relate to endothelial function, platelet aggregation, thrombus formation and vascular inflammation. It is possible that it was the effects of statins on such non-LDL factors which could explain the outcome of the MIRACL study.