The Effect of Ticagrelor on Endothelial Function Compared to Prasugrel, Clopidogrel, and Placebo: A Systematic Review and Meta-Analysis

Abstract

Background/ObjectiveEndothelial dysfunction is associated with the long-term outcomes in patients with coronary artery disease (CAD). Recent evidence suggests that ticagrelor, a potent antiplatelet agent, improves endothelial function. However, several studies demonstrated contrasting results. The objective of this meta-analysis was to determine the efficacy of ticagrelor treatment on endothelial function.Materials and MethodsA systematic literature study was conducted on databases including PubMed, Web of Science, EMBASE, Scopus, and the Cochrane Library. A historical search was performed for a reference list of the selected studies as of August 2021. The randomized controlled trials (RCTs) were assessed using the Cochrane tool. The weighted mean difference (WMD) 95% CI was treated as the overall effect size, and data were pooled using the fixed-effect model or random-effect model according to the heterogeneity. Subgroup and sensitivity analyses were performed to measure the effects of potential confounders.ResultsA total of 21 studies were included. The meta-analysis indicated that ticagrelor resulted in a significant increase of flow-mediated dilation (FMD) (WMD: 1.48; 95% CI: 0.36, 2.60), reactive hyperemia index (RHI) (WMD: 0.06; 95% CI: 0.00, 0.13), and circulating progenitor endothelial cells (CEPCs) (WMD: 13.84; 95% CI: 5.70, 21.98), and a reduction in the index of microvascular resistance (IMR) (WMD: −15.39; 95% CI: −25.11, −5.68).ConclusionTicagrelor has a significant effect on some markers of endothelial function in patients with CAD. However, the results should be interpreted with caution due to the heterogeneity and limited studies.

An Examination of Clopidogrel in the Treatment of Coronary Microvascular Disease

“…Therefore, to prevent these complications from arising in patients who have vascular problems, physicians usually prescribe treatment methods that either decrease cholesterol production or blood coagulation. Although numerous physicians tend to prescribe treatment options that decrease both of these factors for patients, medications that inhibit cholesterol synthesis, such as statins, tend to have more side effects than pharmaceuticals that hinder thrombosis [ 16 ]. This could potentially explain why anti-platelet therapy is the preferred solution to this issue.…”

“…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].…”

“…The most commonly used treatment method for patients who had microvasculature issues was antiplatelet therapy. The data from Table 1 reports that 17 studies within the review reported that antiplatelet therapy was chosen by physicians as the primary method of handling coronary microvasculature issues [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. The treatment modality used for clopidogrel in each study is also mentioned in Table 1.…”