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The dogma of aspirin: a critical review of evidence on the best monotherapy after dual antiplatelet therapy.

Polo Friz H, Molteni M, Cimminiello C - Thromb J (2015)

Bottom Line: Dual antiplatelet therapy based on the combination of an adenosine diphosphate (ADP)-receptor antagonist plus aspirin has demonstrated to be more effective in reducing the rate of major ischemic vascular events compared to aspirin monotherapy in some clinical settings.We conclude that, whether ADP-receptor antagonist rather than aspirin may be proposed as monotherapy seems not only have no answer but also not place in the current specialists' analysis, as if a dogmatic approach were prevalent.Perhaps the time for an open debate on these topics is ripe.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Vimercate Hospital Azienda Ospedaliera di Desio e Vimercate, Vimercate, Italy.

ABSTRACT
Dual antiplatelet therapy based on the combination of an adenosine diphosphate (ADP)-receptor antagonist plus aspirin has demonstrated to be more effective in reducing the rate of major ischemic vascular events compared to aspirin monotherapy in some clinical settings. The current controversy on the duration of dual antiplatelet therapy should not conceal another major issue: the choice of the more appropriate antiplatelet monotherapy after the dual treatment phase. The aim of this article is to critically analyze the available evidence in this topic. Data from studies like CAPRIE, MATCH, PROFESS, CHANCE, DAPT and others, raise questions as why antiplatelet monotherapy after the dual phase should only be based on aspirin, in spite of a lack of evidence surprisingly not highlighted by key opinion leaders and experts. We conclude that, whether ADP-receptor antagonist rather than aspirin may be proposed as monotherapy seems not only have no answer but also not place in the current specialists' analysis, as if a dogmatic approach were prevalent. Perhaps the time for an open debate on these topics is ripe.

No MeSH data available.


Related in: MedlinePlus

DAPT study [24]: risk of stent thrombosis in patients treated for 12 and 30 months during the 3 months after discontinuation of thienopyridine treatment
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Related In: Results  -  Collection

License 1 - License 2
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Fig2: DAPT study [24]: risk of stent thrombosis in patients treated for 12 and 30 months during the 3 months after discontinuation of thienopyridine treatment

Mentions: With regard to antiplatelet therapy following PCI, the use of dual therapy is critically important for the prevention of coronary stent thrombosis, and this therapy is currently recommended for 6 to 12 months after implantation of a drug-eluting stent (DES) [22, 23]. However, the optimal duration remains unknown. To test the hypothesis that a 30-month duration of therapy with aspirin plus an ADP-receptor antagonist would be superior to a 12-month duration in patients undergoing PCI, DAPT trial was carried out and results recently published by Mauri et al. [24]. All patients received aspirin with 5020 patients randomized to prolonged DAPT and 4941 to placebo. Approximately two thirds of the patients received clopidogrel, whereas the rest received prasugrel. The primary endpoint of major adverse cardiac and cerebrovascular events was significantly lower in the continued DAPT arm compared with placebo (4.3 % vs. 5.9 %, hazard ratio 0.71, 95 % confidence interval 0.59–0.85, p < 0.001). There were reductions in all MI (2.1 % vs. 4.1 %, p < 0.001) and stent thrombosis (0.4 % vs. 1.4 %, p < 0.001), but all-cause mortality was higher (2.0 % vs. 1.5 %, p = 0.05), driven mostly by an increase in non-cardiovascular deaths (1 % vs. 0.5 %, p = 0.002), including cancer-related death (0.62 % vs. 0.28 %, p = 0.02) and bleeding-related death (0.22 % vs. 0.06 %, p = 0.06). GUSTO moderate and severe bleeding was also higher with DAPT (2.5 % vs. 1.6 %, p = 0.001). The results of the DAPT trial indicate that prolonged duration of DAPT up to 30 months following index PCI with a DES results in lower stent thrombosis and recurrent MIs compared with a 12-month duration of DAPT, although bleeding and all-cause mortality were higher with prolonged therapy. The excess in mortality is concerning, but appears to be a combination of cancer-related and bleeding-related mortality. However, an important finding of the study risks of going unnoticed. In the mentioned trial, the interruption of ADP-receptor antagonists therapy both in the group of early discontinuation and in those receiving extended dual therapy was followed in the next quarter by an important increase of stent thrombosis and MI, suggesting that an ADP-receptor antagonist instead of aspirin might be the best choice as monotherapy after dual phase antiplatelet treatment, Fig. 2. Yet is easy to refer to the evidence which made possible [24, 25] the large-scale use of coronary stents in clinical practice thanks to the addiction of ADP-receptor antagonists to aspirin which alone had failed in preventing stent occlusion. The question that arises from DAPT and a number of previous studies [26] is why antiplatelet monotherapy after the dual phase should only be based on aspirin? What is the evidence supporting that patients after a period of dual antiplatelet therapy for having received a coronary stent must return to antiplatelet monotherapy with aspirin? Instead, in these patients it may make sense to think about the use of an ADP-receptor antagonist rather than aspirin as monotherapy.Fig 2


The dogma of aspirin: a critical review of evidence on the best monotherapy after dual antiplatelet therapy.

Polo Friz H, Molteni M, Cimminiello C - Thromb J (2015)

DAPT study [24]: risk of stent thrombosis in patients treated for 12 and 30 months during the 3 months after discontinuation of thienopyridine treatment
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4561422&req=5

Fig2: DAPT study [24]: risk of stent thrombosis in patients treated for 12 and 30 months during the 3 months after discontinuation of thienopyridine treatment
Mentions: With regard to antiplatelet therapy following PCI, the use of dual therapy is critically important for the prevention of coronary stent thrombosis, and this therapy is currently recommended for 6 to 12 months after implantation of a drug-eluting stent (DES) [22, 23]. However, the optimal duration remains unknown. To test the hypothesis that a 30-month duration of therapy with aspirin plus an ADP-receptor antagonist would be superior to a 12-month duration in patients undergoing PCI, DAPT trial was carried out and results recently published by Mauri et al. [24]. All patients received aspirin with 5020 patients randomized to prolonged DAPT and 4941 to placebo. Approximately two thirds of the patients received clopidogrel, whereas the rest received prasugrel. The primary endpoint of major adverse cardiac and cerebrovascular events was significantly lower in the continued DAPT arm compared with placebo (4.3 % vs. 5.9 %, hazard ratio 0.71, 95 % confidence interval 0.59–0.85, p < 0.001). There were reductions in all MI (2.1 % vs. 4.1 %, p < 0.001) and stent thrombosis (0.4 % vs. 1.4 %, p < 0.001), but all-cause mortality was higher (2.0 % vs. 1.5 %, p = 0.05), driven mostly by an increase in non-cardiovascular deaths (1 % vs. 0.5 %, p = 0.002), including cancer-related death (0.62 % vs. 0.28 %, p = 0.02) and bleeding-related death (0.22 % vs. 0.06 %, p = 0.06). GUSTO moderate and severe bleeding was also higher with DAPT (2.5 % vs. 1.6 %, p = 0.001). The results of the DAPT trial indicate that prolonged duration of DAPT up to 30 months following index PCI with a DES results in lower stent thrombosis and recurrent MIs compared with a 12-month duration of DAPT, although bleeding and all-cause mortality were higher with prolonged therapy. The excess in mortality is concerning, but appears to be a combination of cancer-related and bleeding-related mortality. However, an important finding of the study risks of going unnoticed. In the mentioned trial, the interruption of ADP-receptor antagonists therapy both in the group of early discontinuation and in those receiving extended dual therapy was followed in the next quarter by an important increase of stent thrombosis and MI, suggesting that an ADP-receptor antagonist instead of aspirin might be the best choice as monotherapy after dual phase antiplatelet treatment, Fig. 2. Yet is easy to refer to the evidence which made possible [24, 25] the large-scale use of coronary stents in clinical practice thanks to the addiction of ADP-receptor antagonists to aspirin which alone had failed in preventing stent occlusion. The question that arises from DAPT and a number of previous studies [26] is why antiplatelet monotherapy after the dual phase should only be based on aspirin? What is the evidence supporting that patients after a period of dual antiplatelet therapy for having received a coronary stent must return to antiplatelet monotherapy with aspirin? Instead, in these patients it may make sense to think about the use of an ADP-receptor antagonist rather than aspirin as monotherapy.Fig 2

Bottom Line: Dual antiplatelet therapy based on the combination of an adenosine diphosphate (ADP)-receptor antagonist plus aspirin has demonstrated to be more effective in reducing the rate of major ischemic vascular events compared to aspirin monotherapy in some clinical settings.We conclude that, whether ADP-receptor antagonist rather than aspirin may be proposed as monotherapy seems not only have no answer but also not place in the current specialists' analysis, as if a dogmatic approach were prevalent.Perhaps the time for an open debate on these topics is ripe.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Vimercate Hospital Azienda Ospedaliera di Desio e Vimercate, Vimercate, Italy.

ABSTRACT
Dual antiplatelet therapy based on the combination of an adenosine diphosphate (ADP)-receptor antagonist plus aspirin has demonstrated to be more effective in reducing the rate of major ischemic vascular events compared to aspirin monotherapy in some clinical settings. The current controversy on the duration of dual antiplatelet therapy should not conceal another major issue: the choice of the more appropriate antiplatelet monotherapy after the dual treatment phase. The aim of this article is to critically analyze the available evidence in this topic. Data from studies like CAPRIE, MATCH, PROFESS, CHANCE, DAPT and others, raise questions as why antiplatelet monotherapy after the dual phase should only be based on aspirin, in spite of a lack of evidence surprisingly not highlighted by key opinion leaders and experts. We conclude that, whether ADP-receptor antagonist rather than aspirin may be proposed as monotherapy seems not only have no answer but also not place in the current specialists' analysis, as if a dogmatic approach were prevalent. Perhaps the time for an open debate on these topics is ripe.

No MeSH data available.


Related in: MedlinePlus