Editorials
Preprocedural Dual Antiplatelet Therapy for Percutaneous Coronary Intervention in Japanese Current Practice
2015 Volume 79 Issue 12 Pages 2544-2546
Details
2015 Volume 79 Issue 12 Pages 2544-2546
The introduction of coronary stents for the treatment of coronary artery disease (CAD) brought with it a need for intensive antithrombotic therapy. Standard dual antiplatelet therapy (DAPT) with aspirin and a thienopyridine was based on the results of early clinical trials that indicated better outcomes in patients with this combination therapy compared with the combination of warfarin and aspirin or aspirin alone.1 Vascular injury during percutaneous coronary intervention (PCI) procedures causes endothelial detachment and exposure of the prothrombotic components of atherosclerotic plaque, which may subsequently provoke thrombotic occlusion of deployed stents.2 In vulnerable patients with acute coronary syndrome (ACS), not only local but systemic inflammatory prothrombotic conditions may exist, increasing the risk of ischemic cardiovascular events at non-culprit arterial lesions. Because preexisting large thrombus in a culprit lesion is often seen in ACS patients and is associated with limited success of the PCI, preventing thrombus growth prior to the PCI may be important, especially in ACS patients.
Article p 2598
Antithrombotic pretreatment may be achieved by preprocedural use of DAPT and intravenous heparin. Indeed, reduction of ischemic cardiovascular events by preprocedural DAPT has been demonstrated in PCI patients with chronic CAD, acute ST-segment elevation myocardial infarction (STEMI), and non-ST-segment elevation ACS (NSTE-ACS).3–5 Based on the results of these landmark trials, the guidelines of the American College of Cardiology/American Heart Association, European Society of Cardiology, and Japanese Circulation Society (JCS) recommend pre-PCI DAPT as a class I indication.6–10 However, the evidence for the benefits of pre-PCI DAPT in Japanese patients may be insufficient.
Concerns about bleeding risk are often expressed in regard to intensive antithrombotic therapy in Japanese patients whose ischemic event risk, including stent thrombosis, is thought to be lower than in Caucasian patients.11 Thus, clinically, antithrombotic therapy should be always balanced between reducing the risk of ischemic cardiovascular events and increasing the bleeding risk. Ideally, clinical trials evaluating the efficacy and safety of pre-PCI antithrombotic treatments are warranted, but ethical issues disallow such trials. Thus, we must address alternative evidence from observational studies.
In this issue of the Journal, Ikegami et al12 present their evaluation of the association of preprocedural DAPT and short-term outcomes in consecutive patients undergoing PCI at 12 PCI centers in Japan. The results indicated that non-use of preprocedural DAPT was associated with an increased risk for death, postprocedural shock, heart failure, and postprocedural myocardial infarction. It was not associated with an increased risk for procedure-related bleeding.
In general, we must carefully interpret the data from an observational study because the biases cannot be completely eliminated by statistical methods used for adjustments. We must be particularly careful when the effectiveness of a drug is assessed by observational findings. Indeed, factors that may lead to poorer outcomes (eg, Canadian Cardiovascular Society class 4 and heart failure on admission) were associated with non-use of pre-PCI DAPT. However, the results of the current study that demonstrated possible benefits of preprocedural DAPT are consistent with the guidelines and comfortably fit our consensus.
An unexpected finding was no increase in periprocedural bleeding risk. The authors noted that a low loading dose of clopidogrel and/or advances in PCI procedures (eg, increased use of the transradial approach) might have contributed to this result. Not only the loading dose of clopidogrel but also the time to expression of the antiplatelet effect may alter the risk for periprocedural bleeding events related to pre-PCI DAPT. In a recent trial in Japanese ACS patients that evaluated the antiplatelet effects of clopidogrel and prasugrel using the VerifyNow® P2Y12 assay showed that clopidogrel did not exert significant antiplatelet effects up to 12 h after a 300 mg loading dose.13 Because pre-PCI DAPT was defined as the administration of aspirin and clopidogrel within 24 h before the index PCI procedure,12 many PCI procedures could be performed without the antiplatelet effects of clopidogrel.
Another important issue revealed by the present study was the variability in preprocedural DAPT usage rates among the participating hospitals. Although non-use of DAPT is probably related to worse patient conditions, it might not be responsible for the >30% difference in DAPT use among the participating PCI centers. Thus, preprocedural DAPT has not been sufficiently implemented as a standard therapeutic strategy in current Japanese practice, despite its recommendation in the JCS guidelines. Evaluation of adherence to a standard therapy by an observational study would help improve the quality of our clinical practice.
Many factors influence the optimal loading timing, intensity, and duration of antithrombotic pharmacotherapy (Table). The patients in the study by Ikegami et al represented a wide range of clinical conditions that included chronic CAD, STEMI, and NSTE-ACS treated by first- and second-generation drug-eluting stents (DES). The authors showed consistent results in the STEMI and NSTE-ACS patients.12 Determining whether consistency is also found in older vs. newer, improved DES may be warranted in future studies.
| Factors related to increased or decreased risk | Ischemic risk | Bleeding risk |
|---|---|---|
| Patient factors | ||
| Genetic factor: Asian vs. non-Asian | ↓ | ↑ |
| Older age | ↑ | ↑ |
| Concomitant pathophysiological condition | ||
| Chronic CAD → NSTE-ACS → STEMI | ↑ | → |
| Multivessel disease/polyvascular disease | ↑ | → |
| Heart failure | ↑ | → |
| History of stroke | ↑ | ↑ |
| History of bleeding | → | ↑ |
| Renal dysfunction | ↑ | ↑ |
| Liver cirrhosis | → | ↑ |
| Hypertension | ↑ | ↑ |
| Diabetes mellitus | ↑ | → |
| Antithrombotic therapy | ||
| More intensive antiplatelet therapy | ↓ | ↑ |
| Concomitant anticoagulation therapy | ↓* | ↑ |
| Advancement in stent/scaffold technology† | ↓ | → |
| Factors related to loading timing of antiplatelet therapy | ||
| Modifiable | ||
| Characteristics of antiplatelet drug (time needed to express their effects) | ||
| Unmodifiable/difficult to modify | ||
| Sex, age, prior CABG, severity of angina or concomitant heart failure, possibility of emergency CABG, etc.‡ | ||
*Concomitant anticoagulation therapy may increase the ischemic risk secondary to bleeding events. †Advancement of the new scaffold technology may not be associated with a reduction in the ischemic risk in the acute stage compared with recent coronary stents. However, improvement in each technology always addresses a decrease in ischemic risk. ‡Ikegami Y, et al.12 CABG, coronary artery bypass grafting; CAD, coronary artery disease; NSTE-ACS, non-ST-segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.
Prasugrel became clinically available in Japan after the study period of Ikegami et al had ended. Prasugrel is characterized by its rapid effect and may be useful for emergency PCI. Its use in pre-PCI DAPT may show different effectiveness and/or safety than clopidogrel.14 When an antiplatelet drug with rapid effect is used for pre-PCI DAPT, the timing of the loading dose may become more important. In one study, very early administration of prasugrel (as compared with standard pre-PCI DAPT with the same total dose) resulted in increased TIMI major bleeding events in NSTE-ACS patients.15
Third-generation DES are already available. Also, the next generation of technology, a drug-eluting bioresorbable vascular scaffold, will be used in clinical practice. Because PCI technology and pharmacotherapy are constantly advancing, and it is not possible to customize antithrombotic therapy according to each new agent or stent/scaffold, the updated data from clinical practice must be informative. In this regard, continuous information transmission from well-organized registries is warranted.
Y.F. reports remuneration (eg, lecture fees) from Daiichi Sankyo, Bayer, and Sanofi K.K.
