PRotective Effect on the coronary microcirculation of patients with DIabetes by Clopidogrel or Ticagrelor (PREDICT): study rationale and design. A randomized multicenter clinical trial using intracoronary multimodal physiology

Abstract

BackgroundIn diabetic patients a predisposed coronary microcirculation along with a higher risk of distal particulate embolization during primary percutaneous intervention (PCI) increases the risk of peri-procedural microcirculatory damage. However, new antiplatelet agents, in particular Ticagrelor, may protect the microcirculation through its adenosine-mediated vasodilatory effects.MethodsPREDICT is an original, prospective, randomized, multicenter controlled study designed to investigate the protective effect of Ticagrelor on the microcirculation during PCI in patient with diabetes mellitus type 2 or pre-diabetic status. The primary endpoints of this study aim to test (i) the decrease in microcirculatory resistance with antiplatelet therapy (Ticagrelor > Clopidogrel; mechanistic effect) and (ii) the relative microcirculatory protection of Ticagrelor compared to Clopidogrel during PCI (Ticagrelor < Clopidogrel; protective effect).ConclusionsPREDICT will be the first multicentre clinical trial to test the adenosine-mediated vasodilatory effect of Ticagrelor on the microcirculation during PCI in diabetic patients. The results will provide important insights into the prospective beneficial effect of this drug in preventing microvascular impairment related to PCI (http://www.clinicaltrials.gov No. NCT02698618).Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0543-5) contains supplementary material, which is available to authorized users.

Mechanical and Pharmacological Revascularization Strategies for Prevention of Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction: Analysis from Index of Microcirculatory Resistance Registry Data

“…When compared with potent inhibition of platelet function, ticagrelor and prasugrel inhibit approximately 94% and 90%, respectively, in those with aspirin, whereas clopidogrel typically achieves a maximum of only 50% platelet inhibition in combination with aspirin in ACS. Ticagrelor and prasugrel are faster than clopidogrel in reaching its peak concentration (peak effect after loading dose at 2 hours for ticagrelor, 4 hours for prasugrel, and 6 hours for clopidogrel) and has been shown to increase adenosine plasma concentration associated with an inhibition of adenosine uptake of red blood cells, stimulating vasodilatation [ 35 – 37 ]. In our study, microvascular injury was reduced more in the third-generation P2Y12 inhibitors group.…”

An Examination of Clopidogrel in the Treatment of Coronary Microvascular Disease

“…Therefore, coronary microvascular dysfunction has been identified as one of the specific causes in 45% of dementia cases and 25% of strokes [8]. Through a review of several research pertaining to CMD, it was shown that clopidogrel was the most commonly prescribed medicine [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Its widespread use and prescription frequency can be linked to its anti-clotting actions and superior efficacy relative to other anti-platelet medications.…”

“…In a research study, it was observed that clopidogrel and ticagrelor are equally effective against acute coronary syndrome, although clopidogrel causes a much-reduced incidence of major and minor bleeding [29]. Clopidogrel was utilized in 14 of the studies that were evaluated in our inquiry [9][10][11][14][15][16][17][19][20][21][22][23][24][25][26][27]. In these 14 trials, clopidogrel was utilized in a range of therapeutic modalities, from antiplatelet therapy to vasodilation induction.…”

“…Six studies within the review do not report the usage of this treatment option which may suggest that while dual antiplatelet therapy is what is often used to help patients with microvascular issues, there may be instances where it is not the most conducive method of obtaining the desired outcome [9,[11][12][13]16,18]. For instance, for patients who are allergic or intolerant to aspirin, dual therapy may not be a viable option as the treatment method commonly requires the usage of both aspirin and clopidogrel to obtain the best effect [1][2][3].…”

Comparison of pharmacodynamic effects of ticagrelor vs prasugrel in type 2 diabetes mellitus patients with coronary heart disease

“…Importantly, increased platelet reactivity may account for reduced antiplatelet effects to oral antiplatelet agents, such as clopidogrel . The mechanisms leading to the high on‐treatment platelet reactivity of clopidogrel in patients with T2DM are not fully elucidated and may potentially involve genetic factors . Thus, after the introduction of new P2Y 12 agents, the influence of ticagrelor or prasugrel on platelet reactivity was the object of studies clarifying whether these regimens have better antiplatelet effects than clopidogrel in patients with T2DM.…”