In what circumstances might it be advantageous to use ticagrelor over clopidogrel along with aspirin for long-term DAPT? Same question for prasugrel.
The long-term treatment of patients with coronary artery disease continues to evolve with new therapeutic strategies as well as the development of decision aid tools. This is particularly important in patients undergoing revascularization for their underlying coronary artery disease. It has been the focus of intense interest since the conclusion and widespread promulgation of the seminal DAPT trial.
Multiple issues need to be considered in addressing the question of whether to add ticagrelor, prasugrel, or clopidogrel to aspirin for long-term DAPT. These issues include among others: 1) the initial presentation of the patient, 2) the specifics about the extent and severity of coronary artery disease, 3) the presence of other comorbidities requiring treatment, particularly atrial fibrillation with the need for oral anticoagulant therapy, 4) the specific technology used for treatment of the coronary artery disease, for example use of a DES versus BMS, 5) the clinical course of the patient after the initial episode of disease up until the time that consideration of long-term therapy is undertaken, 6) patient specific issues including economics, side effects, etc., and 7) attempts at prediction of subsequent cardiovascular events.
Specific concern is focused on the use of long-term DAPT versus aspirin alone. Patient specific individualized treatment duration decisions have been enhanced by the development of risk models such as the DAPT algorithm. This was developed to identify whether an individual patient is more likely to derive benefit or harm from continuing DAPT beyond one year, balancing the risks of cardiac ischemia versus that of bleeding. The DAPT score itself at present does not contain P2Y12 inhibitor-specific data as a variable although the outcome of prasugrel plus aspirin beyond 12 months in patients receiving the Taxus Liberte paclitaxel-eluting stent in the DAPT trial found that prasugrel and aspirin reduced ischemic events of myocardial infarction and stent thrombosis. Compared with aspirin alone, we know from other studies such as PEGASUS-TIMI 54 that in patients with a history of a prior myocardial infarction 1-3 years earlier that the addition of ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke but was associated with an increased risk of major bleeding.
The specific issues then remain related to the disease, the drug, the dose, and the duration, balancing the risk and the benefit ratio. The decision about the initial P2Y12 inhibitor is crucial here – guidelines and practice patterns have been developed. Typically, the more acute patients are treated with either ticagrelor (most commonly) or prasugrel as compared to clopidogrel. There are, however, specific considerations related to the instructions for use for each of these drugs, for example patient age, body weight and history of stroke/TIA have been included in Black Box Warnings for prasugrel. In contrast to these acute patients, in those stented patients with chronic stable angina, clopidogrel is more commonly used. These type of considerations in addition to disease burden and type of stent often dictate the initial DAPT regimen used.
During follow up, clinical considerations include: 1) Recurrent ischemic events, bleeding, or drug specific side effects such as dyspnea. For example, recurrent ischemia in a patient treated with clopidogrel typically results in a change in the specific P2Y12 inhibitor, 2) The duration of DAPT varies depending upon the issues of bleeding, recurrent ischemia, initial presentation, type of stent, and ranges from 3-6 months up to 1 year or even beyond, and 3) At that later point in time, the patient and physician are then faced with making decisions as to whether DAPT is to be continued as previously discussed using some decision aid tool or changed.
Several specific scenarios could be identified.
- If the patient had initially been placed on clopidogrel and now 1 year later or more is doing well without any symptoms, the patient and physician would rarely switch to either ticagrelor or prasugrel.
- On the other hand, the physician may choose based upon the DAPT score to discontinue the P2Y12 inhibitor after full discussion with the patient.
- There may be situations where the side effects would indicate a change in medications being used. For example, if the patient is having significant dyspnea with ticagrelor, the decision might include a change to prasugrel or clopidogrel.
- Economic considerations then play a role because clopidogrel is generic and for many patients there are huge economic issues.
The issue of DAPT following intervention is complex including consideration of secondary prevention endpoints balanced against risks. It must be tailored as part of patient-specific therapy after full discussion with the patient.
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