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One of the best tools to help practitioners make the best bedside clinical decisions when managing patients with acute cardiovascular disease.
A comprehensive guidelines implementation toolkit especially for Nurses & Allied Professionals.
Dr. Konstantin A. Krychtiuk
Prof. Walter S. Speidl
In patients who have suffered an AMI, the LDL treatment goal is <70 mg/dL (<1.8 mmol/L) or a 50% reduction in LDL-C if the baseline LDL-C is between 70 and 135 mg/dL (1.8 – 3.5 mmol/L). High-intensity statins such as Atorvastatin 40-80 mg or Rosuvastatin 20-40 mg usually result in a LDL-C reduction of >50%. If target levels cannot be reached with maximally dosed high-intensity statins, ezetimibe should be added; for further reduction of LDL-C levels, refer the patient to a lipid specialist to test for PCSK-9 inhibitors.
Optimal lipid management for patients after an acute myocardial infarction (AMI) is of paramount importance. Prompt initiation of high-intensity statin therapy is strongly recommended for every patient after an AMI – regardless of baseline LDL-cholesterol levels, – within 1-4 days of the index event. The type and dose chosen should achieve LDL-C values of <70mg/dL (<1.8 mmol/L) or a reduction of at least 50% (if LDL-C levels are between 70 and 135 mg/dL (1.8 and 3.5 mmol/L)); see Table 1 .
Health professionals need to be aware that during the acute stage after AMI, LDL-C levels have to be taken cautiously as evidence points to reduced lipid levels after AMI . Therefore, a follow-up visit within 4-6 weeks of the index event is highly recommended to re-evaluate LDL-C levels, which is most effective during a multidisciplinary cardiac rehabilitation program.
For an intended reduction of >50% in LDL-C levels, a dose of 40 or 80 mg of Atorvastatin or 20 mg or 40 mg of Rosuvastatin should be used to achieve this goal and to further reduce risk independently of baseline LDL-cholesterol levels .
If the LDL-target values cannot be reached with the highest available or tolerated statin dose, adding Ezetemibe (10 mg once daily) should be strongly considered as it is associated with improved outcome .
Patients who have suffered an AMI and who have persistently elevated levels of LDL-C despite treatment at the maximum tolerated statin dose combined with Ezetemibe or patients with true statin intolerance, should be referred to a lipidology clinic for screening for treatment with a PCSK-9 inhibitor .
By inhibiting the HMG-CoA-reductase activity in hepatocytes, statins reduce hepatic cholesterol synthesis, leading to lower intracellular cholesterol levels. This in turn, causes LDL-receptor upregulation on the hepatocyte surface, which results in increased uptake thereby further decreases the LDL-C levels in the circulation. The degree of this action is dependent on the dose and type of statin used (see Table 1).
As it is one of the most intensively investigated drugs in cardiovascular medicine, the underlying evidence can only be partially discussed here. The Cholesterol Treatment Trialists (CTT) data including >170,000 participants from 26 randomized controlled trials (RCTs) suggest that a 40 mg/dL reduction in LDL-C results in a 10% reduction of all-cause and a 20% drop of CAD mortality as well as a 23% reduction in major coronary events . These benefits were consistent in all subgroups and even more significant after a longer period of treatment.
In secondary prevention, particularly after an AMI, the beneficial effects of statins are particularly significant involving other (pleiotropic) statin effects including potentially anti-inflammatory or plaque-stabilizing effects .
Muscle symptoms ranging from myalgia without any rise in creatine kinase levels to rhabdomyolysis, are the most commonly described adverse effects and the principal reason for statin discontinuation with potential detrimental effect on the patient. The reported frequency varies considerably, with evidence suggesting a 5% occurrence rate . It is not recommended to routinely check creatine kinase levels after a statin therapy is started. Diagnosis should be based on clinical observation: whether symptoms disappear after discontinuation and re-appear after re-challenge with at least three statin types and various dosages. In secondary prevention especially, it is of utmost importance to secure the diagnosis of statin-associated muscle symptoms (SAMS) with a structured work-up and treat the few truly affected patients on the maximum tolerated statin dose combined with non-statin lipid-lowering therapies to attain the recommended LDL-C targets. Further information can be found in the Consensus Statement of the European Atherosclerosis Society . A systematic review found that the incidence of drug-induced hepatotoxicity in patients taking statins is unknown , but it is recommended to have the liver enzymes (alanine transaminase - ALT) checked every 8–12 weeks after a statin treatment is started or the dose has been increased.
As a cholesterol absorption inhibitor, Ezetemibe inhibits intestinal cholesterol uptake and thereby reduces cholesterol transport to the liver. This causes the LDL-receptor upregulation which in turn, lowers the circulating LDL-C levels. Monotherapy with Ezetemibe results in lower LDL-levels, around 15-22%, while adding statin therapy causes a further 15-20% drop. In IMPROVE-IT, Ezetemibe was added to 40 mg Simvastatin in more than 18,000 patients after ACS, this led to an additional LDL-reduction, which resulted in another slight yet statistically significant reduction in cardiovascular events . These results make Ezetemibe a potential add-on therapy for patients after an AMI in which LDL-C goals cannot be reached despite treatment at the maximum tolerated statin dose or because of the occurrence of adverse effects .
After LDL-uptake, PCSK-9 binds to the now intracellular LDL-receptors causing lysosomal degradation. Inhibiting this protein reduces LDL-receptor degradation, thereby causing an increased LDL-receptor expression on the hepatocyte which decreases the circulating LDL-levels. PCSK-9 inhibitors are injected subcutaneously every other week or every month. The efficacy in reducing LDL-C is very high with reported reductions by 50-70% independently of any background therapy. A first RCT suggests a reduction in cardiovascular events in secondary prevention as an add-on to the background lipid lowering therapy without serious safety signals. Therefore, a PCSK9 inhibitor may be considered for patients who have suffered an AMI with persistent high LDL-C despite treatment at the maximum tolerated statin dose, in combination with ezetimibe, or for patients with confirmed statin intolerance.
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The ESC Prevention of Cardiovascular Disease programme is supported by AMGEN, AstraZeneca, Ferrer, and Sanofi and Regeneron in the form of educational grants.
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