Myocardial infarction statins

Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to improve vascular outcomes due to their cholesterol-lowering effects as well as multiple pleiotropic effects. In high-risk populations, statin therapy is known to reduce the risk of vascular events such as myocardial infarction and stroke. A meta-analysis of 10 trials involving 79,494 subjects showed that statin therapy reduced the incidence of stroke by 18%, major coronary events by 27%, and all-cause mortality by 15%. The SPARCL trial recently showed that high-dose HMG-CoA reductase inhibitors prevent recurrent stroke and transient ischemic attacks. ... 

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... 

To control risk factors and prevent major adverse cardiac events, statin therapy should be considered in all patients with ischemic heart disease, particularly in those with elevated low-density lipoprotein cholesterol. In the absence of contraindications, angiotensin-converting enzyme inhibitors should be considered in ischemic heart disease patients who also have diabetes melli-tus, left ventricular dysfunction, history of myocardial infarction, or any combination of these. Angiotensin receptor blockers... 

This is not the only example. Recently, polymorphisms in the G protein p3-subunit gene have been shown to predict response to hydrochlorothiazide (Turner et al., 2001). Psaty et al. identified a subset of patients with a variant of the a-adducin gene that were associated with a lower risk of myocardial infarction and cerebral hemorrhage with diuretic therapy (Psaty et al., 2002). In addition, Genaissance has indicated that it has identified markers that predict the response to the statins, a class of drugs used to lower cholesterol. 

Lipid modifying drugs (statins) have shown secondary cardio-vascular preventive effects (myocardial infarction) in a very large number of patients. Only one study (Shepherd et al. 2002) has been conducted in the elderly and showed similar results. However there was a significant increased cancer risk (25%). 

Stenestrand U. Early statin treatment following acute myocardial infarction and 1-year survival. JAMA 2001 285 430-6. 

Evidence-based pharmacotherapy provides a succinct appreciation of the benefits of a drug, but rarely takes into account the patient s quality of life. Eor instance, intensive statin therapy is recommended because it reduces the incidence of cardiovascular death (odds ratio 0.86), myocardial infarction (odds ratio 0.84), and stroke (odds ratio 0.82) however, the increased risks for any adverse event (odds ratio 1.44), for abnormalities on liver function testing (odds ratio 4.48), for elevations in CK (odds ratio 9.97) and for adverse events requiring discontinuation of therapy (odds ratio 1.28) are less often taken into account by the prescriber. This example emphasises that individualisation is of the utmost importance to keep an acceptable benefit/risk ratio (Clin Ther 2007 29 253-60). The benefits of evidence-based pharmacotherapy may be obtained whenever concordance/compliance of the patient is adequate. However, concordance rate is slightly higher than 30% for chronic conditions, such as hypertension (Curr Hypertens Rep 2007 9 184-9), indicating that the patient has to be educated about the use of drugs, and therapy has to be individualised. 

The results of several large clinical trials using the statin drugs (discussed later) show that the tested drugs decreased the risk of both primary and secondary cardiovascular events. The incidence of myocardial infarction and death from cardiovascular disease was reduced in patients with hypercholesterolemia who never had a... 

Absolute reduction in risk of coronary heart disease death and nonfatal myocardial infarction in landmark large-scale statin trials depends on rates of events in control limbs of the trials. Abbreviations-. CHD, coronary heart disease nfMI, nonfatal myocardial infarction. 

There is evidence that coronary blood flow is improved in patients pretreated with statins after acute infarct PCI (73,74). Celik et al, (74) found that Thrombolysis In Myocardial Infarction (TIMI) frame counts were lower, implying better coronary blood flow, in patients who underwent successful acute infarct PCI and were taking atorvastatin for >6 months compared to patients not taking statins. Iwakura et al. found a lower incidence of coronary no-reflow in patients on chronic statin therapy compared to those not taking statin after successful Ml (9,1 % vs. 34% P = 0.003). Multivariate analysis indicated that statin pretreatment was a protective factor against no-reflow. In this study, the statin-treated patients also had better wall motion, smaller left ventricular dimensions and ejection fraction (73). These studies suggest that statin therapy may help to preserve coronary microvascular function in the setting of acute infarct PCI. 

Fonarow GC, Wright RS, Spencer FA, et al. Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction national registry of myocardial infarction. Use of lipid-lowering medications at discharge in patients with acute myocardial infarction data from the National Registry of Myocardial Infarction 3, AmJ Cardiol 2005 96 61 1-616. 

Briguori C, Colombo A, Airoldi p et al, Statin administration before percutaneous coronary intervention impact on periprocedural myocardial infarction, Eur Heart J 2004 25 1822-1828. 

Iwakura K, Ito H, Kawano S, et al. Chronic pre-treatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction, Eur Heart J 2006 27 534-539. 

Cannon CR Braunwald E, McCabe CH, et al. Pravastatin or Atorvastatin Evaluation and Infection Therapy—Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004 350 1495-1 504. 

As yet there are no completed megatrials with the newer statins. A study that compared atorvastatin versus angioplasty in 341 patients with stable CHD over 18 months was recently reported (Pitt et al., 1999). There were fewer ischemic events in the atorvastatin group, but the difference did not quite reach statistical significance. Furthermore, a previous study had shown a significantly lower incidence of such events in a group treated with conventional medical therapy, because angioplasty can be complicated by myocardial infarction and other acute coronary events (RITA-2 trial participants, 1997). 

Based on clinical trial evidence and cost, generic simvastatin 20 mg or 40 mg daily would seem a reasonable first-line choice. In the largest statin trial to date, the Heart Protection Study (2002), which included people with and without existing coronary heart disease (CHD), simvastatin 40 mg was associated with a significant 27% reduction in major coronary events (CHD death plus non-fatal myocardial infarction), equating to an NNT (number needed to treat) of 32 over 5 years. 

HMG Co-A reductase inhibitors (statins) have been shown to reduce the incidence of fatal and non-fatal myocardial infarction, stroke and mortality (all causes), as well as the need for coronary artery bypass surgery. Since no single drug has been shown to be significantly more effective or less expensive than others in the group, none is included in the model list the choice of drug for use in patients at highest risk should be decided at national level. 

The authors estimated that 5 years of statin treatment will prevent 100 major vascular events in every 1000 patients with previous myocardial infarction, or 70-80 events in patients with other forms of coronary heart disease or diabetes. There was no upper age limit to this benefit, and no lower limit to the level of LDL at which benefit was seen. Heart Protection Study Collaborative Group 2002 MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20536 high-risk individuals. Lancet 360 7-22. 

The reports of observably lower incidence of SAD among the patients prescribed statins (56), the differentiated cholesterol response to statin treatment dependent on the allele present (57), and the surprising response of e4 carriers with CVD to statin in a myocardial infarction survival study (58) emphasize the need for large enrollment studies of these links. An additional link between the ApoE allele and AD comes from the increased CSF cortisol as a function of ApoE genotype (59). The highest levels of cortisol that may contribute to neuronal degeneration were observed in e4/e4 individuals with AD. 

J. Herrmann, A. Lerman, D. Baumgart, L. Volbracht, R. Schulz, C. von Birgelen, M. Haude, G. Heusch and R. Erbel, Pre-procedural statin medication reduces the extent of peri-procedural non-Q-wave myocardial infarction, Circulation 106, 2180-2183 (2002). 

FU, follow-up P, interaction between placebo and statin therapy NR, not reported RR, relative risk Cl, confidence interval 4S, Scandinavian Simvastatin Survival Study REGRESS, Regression Growth Evaluation Statin Study CARE, Cholesterol and Recurrent Events CETP, Cholestery 1 ester transfer protein GP, glycoprotein CV, cardiovascular MI, myocardial infarction. 

As previously discussed in the LDL cholesterol section, lipid-lowering agents primarily in the form of HMG-CoA reductase inhibitors (i.e., statins) have consistently demonstrated the ability to significantly reduce the incidence of death, myocardial infarction, revascularization, and stroke and are an essential component to the treatment of patients with chronic ischemic heart disease (45). 

Cardiovascular disease (CVD) remains the most important cause of morbidity and mortality in people with diabetes [1], This high-risk population is more likely to suffer a fatal event as the first manifestation of myocardial infarction (MI) or stroke, making primary prevention a priority. The pathogenesis of atherosclerosis-related disease is multifactorial but dyslipidaemia is a common and important risk predictor and is open to therapeutic intervention. Pharmacological intervention is supported by major randomised, controlled clinical trials (RCTs) of primary and secondary CVD prevention. RCTs with statin drugs have demonstrated unequivocal benefit in reducing major coronary events and stroke. 

Stenestrand, U., and Wallentin, L. for the Swedish Register of Cardiac Intensive Care (RIKS-HIA) (2001). Early Statin Treatment Following Acute Myocardial Infarction and One-Year Survival, J. Am. Med. Assoc. 285,430-436. 

---