ACS

• Patients with atherosclerotic CV disease, including those who experience an ACS, represent one of the groups in which the benefit of statins clearly outweighs their risk.
• Currently, there are no data to support that eplerenone is superior or preferred to spironolactone unless a patient has experienced gynecomastia, breast pain, or impotence while receiving spironolactone.
• Lipid-Lowering Agents Following MI, statins reduce total mortality, CV mortality, and stroke.
• A meta-analysis of randomized controlled clinical trials in almost 18,000 patients with recent ACS found that statin therapy reduces mortality by 19%, with benefits observed after approximately 4 months of treatment.
• According to the most recent practice guidelines, all patients post ACS should receive moderate to high-intensity statin therapy as well as dietary counseling.
• Results from landmark clinical trials have unequivocally demonstrated the value of statins in secondary prevention following MI.
• The new guidelines emphasize that no data support the routine use of nonstatin lipid-lowering drugs in patients taking statins or in statin-intolerant patients.
• Higher-dose statin therapy, such as atorvastatin 40 to 80 mg daily and rosuvastatin 10 to 20 mg daily, produces a greater reduction in CV events such as MI, ischemic stroke, and revascularization than less intensive statin regimens (such as simvastatin 20–40 mg daily).
• The new guidelines focus on identifying patients most likely to benefit from lipid-lowering agents, mostly statins, and the targeted LDL cholesterol reductions.
• The use of fibrate derivatives, niacin, or fish oil is only considered in select high-risk patients who present a “less-than anticipated therapeutic response” to statins in whom the benefits outweigh the potential risks, and in patients who are completely intolerant to statins.
• The timing of the diagnostic angiography in moderate- to high-risk patients is generally guided by the short-term risk of the patients, with an earlier angiography generally preferred in high-risk individuals.
• Long-term desired outcomes are control of CV risk factors, prevention of additional CV events, including reinfarction, stroke, and HF, and improvement in quality of life.
• A high-risk patient is defined as a GRACE Risk Score more than 140 points.
• The TIMI Risk Score for NSTE-ACS assigns one point for each of the seven medical history and clinical presentation findings below: age 65 years or older, three or more CHD risk factors, known CAD, aspirin use within the past 7 days, two or more episodes of chest discomfort within the past 24 hours, ST-segment depression 0.5 mm or greater, positive biochemical marker for infarction.
• Desired outcomes in a patient with ACS are early restoration of blood flow to the infarct-related artery to prevent infarct expansion or complete occlusion and MI, prevention of death and other MI complications, prevention of coronary artery reocclusion, relief of ischemic chest discomfort, and resolution of ST-segment and T-wave changes on the ECG.
• The ischemia-guided strategy is generally reserved for low-risk individuals.
• Various risk scores are used to assess the prognosis of patients presenting with NSTE-ACS.
• General treatment measures for all STEMI and high- and intermediate-risk NSTE-ACS patients include aspirin, clopidogrel, statins, beta-blockers, ACE inhibitors, and angiotensin receptor blockers.
• Selecting evidence-based therapies described in the guidelines for patients without contraindications results in lower mortality.
• Based on the risk assessment, a management strategy is chosen and patients are either treated using an invasive strategy, which involves coronary angiography, or an ischemia-guided strategy in which patients undergo an invasive evaluation only if they fail medical therapy, have objective evidence of ischemia on non-invasive stress testing, or are later stratified as being at very high risk of CV events based on clinical characteristics.
• Atherosclerotic plaque, platelets, and the coagulation system play a role in an acute coronary syndrome (ACS).
• A systematic review and meta-analysis of randomized and nonrandomized trials in more than 25,000 patients demonstrated a reduction in CV ischemic events with a loading dose of 600 mg compared with 300 mg in patients undergoing PCI.
• Both of the more potent P2Y 12 inhibitors are more efficacious than clopidogrel but are also associated with an increased risk of bleeding.
• Ticagrelor significantly reduced the rate of CV death, MI, stroke, and stent thrombosis compared with clopidogrel.
• A large randomized double-blind study demonstrated that, compared to clopidogrel, the addition of prasugrel to ASA for patients undergoing PCI significantly reduced the risk of CV death or MI by 19% (9.9% vs 12.1%), as well as MI and stent thrombosis, but increased the risk of major bleeding (not ICH) by 32% (2.4% vs 1.8%).
• Patients with diabetes mellitus (DM) or those with STEMI appear to have a greater ischemic benefit with prasugrel and ticagrelor without an increase in major bleeding compared to clopidogrel.
• Patients with a history of prior stroke or transient ischemic attack (TIA) had an increased risk of ICH and net harm from prasugrel; therefore, prior stroke or TIA are contraindications to prasugrel.
• A clopidogrel loading dose of 600 mg is recommended over administration of 300 mg for patients undergoing PCI.
• No large randomized trial has directly compared ticagrelor to prasugrel.
• Although no increase in study-defined major bleeding was noted with ticagrelor, the frequency of non-CABG major bleeding was increased compared with clopidogrel.
• The most recent PCI and STEMI guidelines give no preference for one agent over the other, but the NSTE-ACS guidelines indicate that ticagrelor may be preferred over clopidogrel for patients treated with either an ischemia-guided or early invasive approach, and both ticagrelor and prasugrel may be preferred over clopidogrel post PCI if patients are not at high risk of bleeding.
• Patients 75 years and older as well as those weighing less than 60 kg (132 lb) are at increased risk of bleeding with prasugrel compared with clopidogrel and received no net clinical benefit from prasugrel.
• All patients undergoing PCI should receive ASA therapy indefinitely.
• Several studies have also shown less angina, fewer hospitalizations, and improved quality of life with an invasive strategy.
• DAPT may be beneficial for a longer period of time following PCI with a DES.
• For patients with NSTE-ACS, an initial ischemia-guided strategy is recommended for patients with a low risk score, normal ECGs, and negative troponin tests who are without recurrence of chest discomfort.
• Several clinical trials support an “invasive” interventional strategy with early angiography and PCI or CABG versus an ischemia-guided approach, whereby coronary angiography with revascularization is reserved for patients with symptoms refractory to pharmacotherapy and patients with signs of ischemia on stress testing.
• A longer duration of P2Y 12 inhibitor therapy may be considered for select patients with a low bleeding risk receiving a drug-eluting stent (DES) because the risk of stent thrombosis is greater upon cessation of dual antiplatelet therapy (DAPT).
• This is because although DESs reduce the rate of smooth muscle cell growth causing stent restenosis, they induce a delay in endothelial cell regrowth at the site of the stent that places the patient at higher risk of thrombotic events following PCI.
• Fibrinolytic therapy is not indicated and should not be used in patients with NSTE-ACS because increased mortality has been reported with these agents compared with controls in clinical trials.