December 2018 Issue
ISSN 2689-291X
ISSN 2689-291X
Topic Review
The Art of Switching P2Y12 Inhibitors:
How to Mitigate Platelet Reactivation
Introduction
While aspirin remains the gold standard in antiplatelet therapy, adding a second antiplatelet agent, a P2Y12 inhibitor, to augment the antiplatelet effect of aspirin in highly thrombotic conditions such as acute coronary syndromes or post intervention, or to replace aspirin when the latter is not tolerated, is increasingly common [1]. The currently approved P2Y12 inhibitors include clopidogrel, ticagrelor, and prasugrel in the oral form, while cangrelor is in an intravenous form. These agents have different properties, with variable degrees of platelet inhibition, bleeding risk, other side effects and cost [2].
Switching between P2Y12 inhibitors is increasingly reported, with little science to guide this practice [3]. This prompted a recent white paper publication on the subject to guide clinicians on how to safely switch between these agents while mitigating the serious potential risk of platelet reactivation and subsequent thrombosis [4]. Much of the recommendation were based on the pharmacokinetic and pharmacodynamic properties of these agents, as little clinical data exist to guide this practice. In this review, we summarize the recommendations in table 1, in an attempt to simplify the recommendations. However, the decision to switch, and the method of switching may depend on many patient variables, calling for a tailored patient-specific approach.
Reasons to Switch
Several reasons prompt clinicians to switch between oral P2Y12 inhibitors, including allergy, side effects, risk of bleeding, need for other anticoagulants, potential drug-drug interactions and cost [5]. Table 2 summarizes some of those reasons. The clinician should always weigh the risks versus the benefits before switching between these agents to avoid the potential risk of heightened versus lessened antiplatelet effects.
Cangrelor is an approved intravenous P2Y12 inhibitor with well demonstrated anti-ischemic properties in patients undergoing PCI, without a significant increase in major bleeding risk [6]. The timing to switch from cangrelor to oral P2Y12 inhibitors is also critical to avoid the potential transient reactivation of platelets [7, 8].
Step Up or Step Down
The following effects on platelet inhibition of switching between P2Y12 inhibitors have been reported.
Conclusion
Dual antiplatelet therapy has become the standard of care in many thromboembolic conditions and following coronary interventions. This strategy has greatly improved patient outcomes with regards to reduction of subsequent ischemic events. It has, however, introduced a set of challenges involving the tolerability of this treatment, the side effects of the medications, the increased bleeding risk and the cost. The need to switch from one P2Y12 inhibitor to another is a challenge in itself, and an art that should be tailored to patient-specific factors, as large scientific outcomes data are lacking.
References
Tables
While aspirin remains the gold standard in antiplatelet therapy, adding a second antiplatelet agent, a P2Y12 inhibitor, to augment the antiplatelet effect of aspirin in highly thrombotic conditions such as acute coronary syndromes or post intervention, or to replace aspirin when the latter is not tolerated, is increasingly common [1]. The currently approved P2Y12 inhibitors include clopidogrel, ticagrelor, and prasugrel in the oral form, while cangrelor is in an intravenous form. These agents have different properties, with variable degrees of platelet inhibition, bleeding risk, other side effects and cost [2].
Switching between P2Y12 inhibitors is increasingly reported, with little science to guide this practice [3]. This prompted a recent white paper publication on the subject to guide clinicians on how to safely switch between these agents while mitigating the serious potential risk of platelet reactivation and subsequent thrombosis [4]. Much of the recommendation were based on the pharmacokinetic and pharmacodynamic properties of these agents, as little clinical data exist to guide this practice. In this review, we summarize the recommendations in table 1, in an attempt to simplify the recommendations. However, the decision to switch, and the method of switching may depend on many patient variables, calling for a tailored patient-specific approach.
Reasons to Switch
Several reasons prompt clinicians to switch between oral P2Y12 inhibitors, including allergy, side effects, risk of bleeding, need for other anticoagulants, potential drug-drug interactions and cost [5]. Table 2 summarizes some of those reasons. The clinician should always weigh the risks versus the benefits before switching between these agents to avoid the potential risk of heightened versus lessened antiplatelet effects.
Cangrelor is an approved intravenous P2Y12 inhibitor with well demonstrated anti-ischemic properties in patients undergoing PCI, without a significant increase in major bleeding risk [6]. The timing to switch from cangrelor to oral P2Y12 inhibitors is also critical to avoid the potential transient reactivation of platelets [7, 8].
Step Up or Step Down
The following effects on platelet inhibition of switching between P2Y12 inhibitors have been reported.
- Switching from clopidogrel to prasugrel or ticagrelor increases platelet inhibition [9].
- Switching from ticagrelor to clopidogrel decreases platelet inhibition [10].
- Switching from prasugrel to ticagrelor and from ticagrelor to prasugrel, ticagrelor appears to cause increased inhibition of platelets [11].
- Despite the absence of large outcome data, smaller registries have not shown major safety issues related to switching P2Y12 inhibitors [3].
- Further clinical studies addressing the actual risk of bleeding or thrombosis related to switching P2Y12 inhibitors are needed.
Conclusion
Dual antiplatelet therapy has become the standard of care in many thromboembolic conditions and following coronary interventions. This strategy has greatly improved patient outcomes with regards to reduction of subsequent ischemic events. It has, however, introduced a set of challenges involving the tolerability of this treatment, the side effects of the medications, the increased bleeding risk and the cost. The need to switch from one P2Y12 inhibitor to another is a challenge in itself, and an art that should be tailored to patient-specific factors, as large scientific outcomes data are lacking.
References
- Degrauwe S, Pilgrim T, Aminian A, et al. Dual antiplatelet therapy for secondary prevention of coronary artery disease. Open Heart. 2017 Oct 15;4(2):e000651.
- Baralis G, Rossini R, Musumeci G. Antiplatelet therapy in STEMI undergoing primary PCI: when, which one and how long. Minerva Cardioangiol. 2018 Aug;66(4):422-428.
- Rollini F, Franchi F, Angiolillo DJ. Switching P2Y12 Receptor Inhibiting Therapies. Interv Cardiol Clin. 2017 Jan;6(1):67-89.
- Angiolillo DJ, Rollini F, Storey RF, et al. International Expert Consensus on Switching Platelet P2Y12 Receptor-Inhibiting Therapies. Circulation. 2017 Nov 14;136(20):1955-1975.
- Bagai A, Chua D, Cohen EA, Saw et al. Pharmacodynamic and clinical implications of switching between P2Y12 receptor antagonists: considerations for practice. Crit Pathw Cardiol. 2014 Dec;13(4):156-8.
- Abnousi F, Sundaram V, Yong CM, et al. Cangrelor reduces the risk of ischemic complications in patients with single-vessel and multi-vessel disease undergoing percutaneous coronary intervention: Insights from the CHAMPION PHOENIX trial. Am Heart J. 2017 Jun;188:147-155.
- Schneider DJ, Agarwal Z, Seecheran N, et al. Pharmacodynamic effects during the transition between cangrelor and ticagrelor. JACC Cardiovasc Interv. 2014 Apr;7(4):435-42.
- Schneider DJ, Seecheran N, Raza SS, et al. Pharmacodynamic effects during the transition between cangrelor and prasugrel. Coron Artery Dis. 2015 Jan;26(1):42-8.
- Payne CD, Li YG, Brandt JT, et al. Switching directly to prasugrel from clopidogrel results in greater inhibition of platelet aggregation in aspirin-treated subjects. Platelets. 2008;19(4): 275-81.
- Gurbel PA, Bliden KP, Butler K, et al. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation. 2010;121(10): 1188-99.
- Alexopoulos D, Galati A, Xanthopoulou I, et al. Ticagrelor versus prasugrel in acute coronary syndrome patients with high on-clopidogrel platelet reactivity following percutaneous coronary intervention. J Am Coll Cardiol. 2012;60(3):193-9.
Tables
Authors:
Sarina Sachdev, M.D.
Cardiology Fellow
University of South Alabama
Mobile, AL
Bassam Omar, M.D., PhD.
Professor of Cardiology
University of South Alabama
Mobile, AL
G. Mustafa Awan, M.D.
Associate Professor of Cardiology
University of South Alabama
Mobile, AL
Sarina Sachdev, M.D.
Cardiology Fellow
University of South Alabama
Mobile, AL
Bassam Omar, M.D., PhD.
Professor of Cardiology
University of South Alabama
Mobile, AL
G. Mustafa Awan, M.D.
Associate Professor of Cardiology
University of South Alabama
Mobile, AL
Appraisal
Cardiofellows Newsletter; The First Six Months!
Manifest Scholarship at its Best
The Beginning
Our website, cardiofellow.com, was established approximately five years ago as a platform to post concise guideline information relevant to cardiology fellowship. Last year, and during a meeting of the curriculum committee, our cardiology fellows suggestive the establishment of a newsletter to be published online. The first thing that comes to mind when a newsletter is mentioned is a social forum of the fellows’ social activities, schedules, and announcements, as is the case with many training programs’ newsletters. Among the initial submissions to the newsletter, however, was an elegant journal review which could have otherwise been published in any reputable publication, with excellent scientific analysis and valuable appraisal of the findings. It was obvious following subsequent submissions that cardiofellows newsletter was shaping into a scientific platform of varying topics of interest to cardiology fellows and cardiologists in general.
Definition of newsletter according to the Merriam-Webster dictionary is: “a small publication (such as a leaflet or newspaper) containing news of interest chiefly to a special group.” Therefore, presence of newsletter in the title may imply the brevity of a publication, delivering specific news (message or point), but does not negate the scientific nature and the robust review process of the publication.
Scientific Newsletters
Pubmed included many journals over the years, some of which are obsolete, which contained newsletter in their titles. Some of these are listed below:
Newsl Am Acad Psychiatry Law
Newsl Macro Syst Inst Resour Dev Demogr Health Surv
Newsl Int Union Sci Study Popul
Newsl Womens Glob Netw Reprod Rights
Newsl Br Soc Hist Sci
Newsl Inter Afr Comm Tradit Pract Affect Health Women Child
Newsl Soc Anc Med
Newsl Am Acad Pediatr
Newsl Int Acad Periodontol
Newsl Med Sci Hist Soc
Newsl Ky Nurses Assoc
Newsl Int Coll Dent India Sect
Newsl Can Soc Hist Med
Newsl Wis League Nurs
Newsl Am Acad Implant Dent
Newsl Inst Interam Aff
Newsl Am Epilepsy Leag
Cardiofellows Newsletter Progress
In the inaugural July 2018 issue, the first publication in cardiofellows newsletter was a crossword puzzle [1], followed by journal review [2], find a word puzzle [3] and another journal review [4]. The August issue started with a topic review of psychocardiology [5], followed by two journal reviews [6, 7]. The September issue started with a historical perspective on angioplasty [8], followed by two challenging images [9, 10]. The October issue had two challenging images [11, 12]. The November issue was dedicated to an excellent module teaching angiography views, and videos were incorporated for the first time [13]. The December issue has one topic review [14], in addition to this appraisal [15].
Editorial Board
As the complexity of the publications increased, it was necessary to appoint an editorial board for the different clinical content received and reviewed. The current editorial board is comprised of faculty, in addition to fellows who serve on the curriculum committee (all the authors on this paper). Editorial board membership is open and can be requested online. Issues with the newsletter are discussed among the editorial board members during the curriculum committee meetings and the program evaluation committee meetings, when necessary.
Future Direction
Given the great success cardiofellows newsletter has seen in the first six months, efforts at archiving publications will be carried out during 2019. Inclusion in search engines will also be sought. Varied content will be encouraged, to include more educational modules pertinent to cardiology training. Submissions will also be encouraged from other departments and external sources, with stress on originality of work and adherence to copyright and HIPAA rules.
Credits
With the mounting responsibilities of patient care and administrative duties experienced by our faculty and fellows, the establishment of a successful scholarly online work such as cardiofellows newsletter is an praiseworthy effort. I am personally grateful to all my cardiology fellows; special mention goes to Dr. Sarina Sachdev and Dr. Landai Nguyen, who are the current representatives on the curriculum committee, and who spearheaded this effort. I would also express my gratitude to all the faculty who participate in this effort by either submissions, review or oversight.
References
Our website, cardiofellow.com, was established approximately five years ago as a platform to post concise guideline information relevant to cardiology fellowship. Last year, and during a meeting of the curriculum committee, our cardiology fellows suggestive the establishment of a newsletter to be published online. The first thing that comes to mind when a newsletter is mentioned is a social forum of the fellows’ social activities, schedules, and announcements, as is the case with many training programs’ newsletters. Among the initial submissions to the newsletter, however, was an elegant journal review which could have otherwise been published in any reputable publication, with excellent scientific analysis and valuable appraisal of the findings. It was obvious following subsequent submissions that cardiofellows newsletter was shaping into a scientific platform of varying topics of interest to cardiology fellows and cardiologists in general.
Definition of newsletter according to the Merriam-Webster dictionary is: “a small publication (such as a leaflet or newspaper) containing news of interest chiefly to a special group.” Therefore, presence of newsletter in the title may imply the brevity of a publication, delivering specific news (message or point), but does not negate the scientific nature and the robust review process of the publication.
Scientific Newsletters
Pubmed included many journals over the years, some of which are obsolete, which contained newsletter in their titles. Some of these are listed below:
Newsl Am Acad Psychiatry Law
Newsl Macro Syst Inst Resour Dev Demogr Health Surv
Newsl Int Union Sci Study Popul
Newsl Womens Glob Netw Reprod Rights
Newsl Br Soc Hist Sci
Newsl Inter Afr Comm Tradit Pract Affect Health Women Child
Newsl Soc Anc Med
Newsl Am Acad Pediatr
Newsl Int Acad Periodontol
Newsl Med Sci Hist Soc
Newsl Ky Nurses Assoc
Newsl Int Coll Dent India Sect
Newsl Can Soc Hist Med
Newsl Wis League Nurs
Newsl Am Acad Implant Dent
Newsl Inst Interam Aff
Newsl Am Epilepsy Leag
Cardiofellows Newsletter Progress
In the inaugural July 2018 issue, the first publication in cardiofellows newsletter was a crossword puzzle [1], followed by journal review [2], find a word puzzle [3] and another journal review [4]. The August issue started with a topic review of psychocardiology [5], followed by two journal reviews [6, 7]. The September issue started with a historical perspective on angioplasty [8], followed by two challenging images [9, 10]. The October issue had two challenging images [11, 12]. The November issue was dedicated to an excellent module teaching angiography views, and videos were incorporated for the first time [13]. The December issue has one topic review [14], in addition to this appraisal [15].
Editorial Board
As the complexity of the publications increased, it was necessary to appoint an editorial board for the different clinical content received and reviewed. The current editorial board is comprised of faculty, in addition to fellows who serve on the curriculum committee (all the authors on this paper). Editorial board membership is open and can be requested online. Issues with the newsletter are discussed among the editorial board members during the curriculum committee meetings and the program evaluation committee meetings, when necessary.
Future Direction
Given the great success cardiofellows newsletter has seen in the first six months, efforts at archiving publications will be carried out during 2019. Inclusion in search engines will also be sought. Varied content will be encouraged, to include more educational modules pertinent to cardiology training. Submissions will also be encouraged from other departments and external sources, with stress on originality of work and adherence to copyright and HIPAA rules.
Credits
With the mounting responsibilities of patient care and administrative duties experienced by our faculty and fellows, the establishment of a successful scholarly online work such as cardiofellows newsletter is an praiseworthy effort. I am personally grateful to all my cardiology fellows; special mention goes to Dr. Sarina Sachdev and Dr. Landai Nguyen, who are the current representatives on the curriculum committee, and who spearheaded this effort. I would also express my gratitude to all the faculty who participate in this effort by either submissions, review or oversight.
References
- Nguyen L, Omar B. Crossword Puzzle: Electrocardiographic (ECG) Signs. Cardiofel Newslet 2018 July;1(1):1-2.
- Nguyen L, Omar B, Awan GM. A Revascularization Conundrum: Who Owns the Radial? Cardiofel Newslet 2018 July;1(1):3-4.
- Sachdev S, Omar B. Find a Word: Cardiac Diagnosis Challenge. Cardiofel Newslet 2018 July;1(1):5-6.
- Sachdev S, Omar B, Malozzi C. Carvedilol: A Promising Tool in the Meager Armamentarium of the Cardio-Oncologist! Cardiofel Newslet 2018 July;1(1):7-9.
- Omar M, Sachdev S, Nguyen L, Omar B, Malozzi C. Psychocardiology: The Mysterious Brain-Heart Interaction Discipline! Cardiofel Newslet 2018 Aug; 1(2): 11-12.
- Nguyen L, Sachdev S, Omar B, Malozzi C, Awan GM. Oral Antibiotics for Endocarditis! Long-Awaited Novel Approach for an Old Diagnosis. Cardiofel Newslet 2018 August;1(2):13-14.
- Heron J, Ahmad S, Awan M, Omar B, Malozzi C. “Seeing is Believing”: Reduction of Coronary Events by CT Angiography Compared to Conventional Risk Stratification. Cardiofel Newslet 2018 August;1(2):15- 16.
- Sachdev S, Tahir H, Awan GM, Omar B. Angioplasty Beginnings..40 Years Later. Cardiofel Newslet 2018 September;1(3):17-18.
- Sachdev S, Nguyen L, Awan GM, Omar B. Circle of Vieussens: Got Collaterals? Cardiofel Newslet 2018 Sep; 1(3): 19-20.
- Sachdev S, Tahir H, Awan U, Nguyen L, Omar B, Awan GM,. Kommerell’s Diverticulum: Anomalous Anomaly! Cardiofel Newslet 2018 Sep; 1(3): 21-22.
- Nguyen L, Sachdev S, Tahir H, Rahimi F, Burckhartt B, Malozzi C, Omar B, Awan GM. Lost Stents..Peek-aBoo! Cardiofel Newslet 2018 October;1(4):23-24.
- Nguyen L, Sachdev S, Ahmad S, Rahimi F, Burckhartt B, Malozzi C, Omar B. Tumors Uptake Microbubbles..Gee Fizz! Cardiofel Newslet 2018 October;1(4):25-26.
- Sachdev S, Omar B, Awan GM, Eyrich G. Coronary Angiography: Basic Views. Cardiofel Newslet 2018 November;1(5):27–38.
- Sachdev S, Omar B, Awan GM. The Art of Switching P2Y12 Inhibitors: How to Mitigate Platelet Reactivation. Cardiofel Newslet 2018 Dec; 1(6): 39-41.
- Omar B, Awan GM, Burckhartt B, Malozzi C, Rahimi F, Sachdev S, Nguyen L. Cardiofellows Newsletter; The First Six Months! Manifest Scholarship at its Best. Cardiofel Newslet 2018 Dec; 1(6): 42-44.
Authors:
Bassam Omar, M.D., Ph.D.
Professor of Cardiology
University of South Alabama
Mobile, AL
G. Mustafa Awan, M.D.
Associate Professor of Cardiology
University of South Alabama
Mobile, AL
Barbara Burckhartt, M.D.
Associate Professor of Cardiology
University of South Alabama
Mobile, AL
Christopher Malozzi, D.O.
Assistant Professor of Cardiology
University of South Alabama
Mobile, AL
Farnoosh Rahimi, M.D.
Assistant Professor of Cardiology
University of South Alabama
Mobile, AL
Sarina Sachdev, M.D.
Cardiology Fellow
University of South Alabama
Mobile, AL
Landai Nguyen, D.O.
Cardiology Fellow
University of South Alabama
Mobile, AL
Bassam Omar, M.D., Ph.D.
Professor of Cardiology
University of South Alabama
Mobile, AL
G. Mustafa Awan, M.D.
Associate Professor of Cardiology
University of South Alabama
Mobile, AL
Barbara Burckhartt, M.D.
Associate Professor of Cardiology
University of South Alabama
Mobile, AL
Christopher Malozzi, D.O.
Assistant Professor of Cardiology
University of South Alabama
Mobile, AL
Farnoosh Rahimi, M.D.
Assistant Professor of Cardiology
University of South Alabama
Mobile, AL
Sarina Sachdev, M.D.
Cardiology Fellow
University of South Alabama
Mobile, AL
Landai Nguyen, D.O.
Cardiology Fellow
University of South Alabama
Mobile, AL