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Review
. 2023 Apr 6:10:1040936.
doi: 10.3389/fcvm.2023.1040936. eCollection 2023.

Antithrombotic regimens for the prevention of major adverse cardiac events in chronic coronary syndrome: A systematic review and network meta-analysis

Affiliations
Review

Antithrombotic regimens for the prevention of major adverse cardiac events in chronic coronary syndrome: A systematic review and network meta-analysis

Gustavo Lenci Marques et al. Front Cardiovasc Med. .

Abstract

Backgroud: Antithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and efficacy remains undefined. Our objective was to evaluate the effectiveness and safety of antithrombotic options and identify the optimal treatment option for patients with CCS.

Methods: We used the MEDLINE, CENTRAL and Embase databases to search for randomized controlled trials with follow-up periods longer than 12 months that compared aspirin (ASA) monotherapy with other antithrombotic therapies in patients with CCS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Extracted data [hazard ratios (HR)] were pooled using Bayesian fixed-effect models, allowing the estimation of credible intervals (CrI) and posterior probabilities of benefit, harm, and practical equivalence. Confidence in the results was assessed with the Confidence In Network Meta-Analysis (CINeMA) tool. The primary efficacy and safety outcomes were major adverse cardiovascular events (MACE) and primary bleeding, respectively. Secondary outcomes were acute myocardial infarction, ischemic stroke, all-cause, and cardiovascular-specific mortality.

Results: Five trials with a total of 80,605 patients were included. Mean patient age ranged from 61 to 69 years, while 20.3% to 31.4% were women. The reference treatment was ASA monotherapy. ASA + prasugrel 10 mg and clopidogrel 75 mg monotherapy presented the greatest benefit for MACE [HR 0.52 (95% CrI, 0.39-0.71); and 0.68 (95% CrI, 0.54-0.88)]. There was a probability of 98.8% that ASA + ticagrelor was practically equivalent to ASA monotherapy. Regarding the primary bleeding outcome, clopidogrel 75 mg monotherapy performed best [HR 0.64 (0.42, 0.99)]. There was a probability of 97.4% that ASA + Prasugrel 10 mg increases bleeding (HR > 1.0). Secondary outcome results followed a similar treatment ranking pattern as in primary outcomes. Overall, CINeMA confidence ratings were judged as either low or very low.

Conclusions: These results revealed that clopidogrel monotherapy might provide the best risk-benefit balance in treating CCS. However, low CINeMA confidence ratings may preclude more forceful conclusions. Our analysis suggests that current guidelines recommending ASA as first-line therapy for CCS management need to be revised to include additional pharmacological options.

Keywords: anticoagulants; coronary arter disease; major adverse cardiac event (MACE); platelet aggregation inhibitors; secondary prevention.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart of articles included in network meta-analysis. From 7,492 unique articles, we screened titles and abstracts and excluded 7,470 articles that did not meet inclusion criteria. The full-text of eligible articles (n = 22), including an article included by cross-referencing, was reviewed using inclusion and exclusion criteria to identify articles for data extraction (n = 5). All stages were conducted independently by 2 investigators.
Figure 2
Figure 2
Network plot. Treatment effects compared with ASA on MACE and Bleeding outcomes, ordered according to underlying SUCRA values. HR below 1.0 favors the experimental treatment. On the left, treatment names are depicted. In the middle, forest plot shows each treatment effect median and 95% credible intervals. Gray area corresponds to the ROPE (from 0.8 to 1.25 HR). On the right, exact effect sizes along with posterior probabilities are shown. ROPE, region of practical equivalence; HR, hazard ratio.
Figure 3
Figure 3
(A) ranking probabilities for MACE (solid line) and bleeding (dotted line) outcomes for each treatment. (B) heatmap with corresponding SUCRA values. While each row corresponds to a treatment, each column depicts one outcome.

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