Antithrombotic Treatments in Patients with Chronic Coronary Artery Disease or Peripheral Artery Disease: A Systematic Review of Randomised Controlled Trials

Abstract

Aims. Acetylsalicylic acid (ASA) is widely used for the prevention of atherothrombotic events in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD), but the risk of vascular events remains high. We aimed at identifying randomised controlled trials (RCTs) on antithrombotic treatments in patients with chronic CAD or PAD. Methods. Searches were conducted on MEDLINE, EMBASE, and CENTRAL on March 1st, 2018. This systematic review (SR) uses a narrative synthesis to summarize the evidence for the efficacy and safety of antiplatelet and anticoagulant therapies in the population of both chronic CAD or PAD patients. Results. Four RCTs from 27 publications were included. Study groups included 15,603 to 27,395 patients. ASA alone was the most extensively studied (n=3); other studies included rivaroxaban with or without ASA (n=1), vorapaxar alone (n=1), and clopidogrel with (n=1) or without ASA (n=1). Clopidogrel alone and clopidogrel plus ASA compared to ASA presented similar efficacy with comparable safety profile. Rivaroxaban plus ASA significantly reduced the risk of the composite of cardiovascular death, myocardial infarction, and stroke compared to ASA alone, although major bleeding with rivaroxaban plus ASA increased. Conclusion. There is limited and heterogeneous evidence on the prevention of atherothrombotic events in patients with chronic CAD or PAD. Clopidogrel alone and clopidogrel plus ASA did not demonstrate superiority over ASA alone. A combination of rivaroxaban plus ASA may offer significant additional benefit in reducing cardiovascular outcomes, yet it may increase the risk of bleeding, compared to ASA alone.

Combination anticoagulant or P2Y12 inhibitor with low-dose aspirin versus low-dose aspirin alone in patients at risk or with documented coronary and/or peripheral artery disease

“…CHARISMA's [4] primary bleeding outcome was severe GUSTO bleeding (ICH or bleeding resulting in substantial hemodynamic compromise requiring treatment), while COMPASS utilized a modified ISTH major bleeding definition (fatal or symptomatic critical organ bleeding, bleeding into a surgical site requiring reoperation, or bleeding requiring hospitalization) [3]. Prior antithrombotic trial analyses have suggested the GUSTO severe and ISTH major bleeding definitions are not in close agreement regarding bleed severity, with only ~25% of ISTH major bleeds categorized as GUSTO severe [11,17]. To address this issue, we utilized supplemental data from both RCTs, enabling us to compare a combined moderate-to-severe GUSTO bleeding outcome from CHARISMA [18] to either an a priori modified ISTH bleeding [3] or an adjudicated, investigator severity-ranked moderate-to-severe bleeding definition for COMPASS [17].…”

“…Bauersachs et al [11] previously performed a systematic review addressing a similar (though somewhat broader) key question with their literature search extending through February 2018. We updated the Cochrane CENTRAL, MEDLINE and EMBASE searches (Table S1) of Bauersachs et al from March 1, 2018 through August 23, 2021.…”

“…We subsequently reviewed full-text publications if both reviewers agreed it was eligible. All A c c e p t e d M a n u s c r i p t studies included in the prior systematic review by Bauersachs et al [11] were screened for inclusion.…”

“…Our updated search identified 1388 non-duplicate records, of which 18 required full-text review following title and abstract screening. After screening studies included in Bauersachs et al [11], we include a total of 6 publications [3,4,[16][17][18][19] reporting the results of 2 unique RCTs [3,4]. The two RCTs included in this analysis were the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial [4] and the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial (Figure 2) [3].…”

Rivaroxaban: Expanded Role in Cardiovascular Disease Management—A Literature Review

“…In the systematic review and meta-analysis on the use of rivaroxaban in coronary artery disease, it was concluded that patient's characteristics of ischemic and bleeding risk are critical in deciding about the addition of rivaroxaban [ 40 ]. The low-dose rivaroxaban in peripheral arterial disease was studied in the systematic review of randomized trials, and it was found to be effective in preventing cardiovascular events with a possible increase risk of bleeding [ 41 ].…”