Are the COMPASS trial results applicable on a broader population in the REACH registry?
External applicability of the COMPASS trial: an analysis of the reduction of atherothrombosis for continued health (REACH) registryDarmon A, Bhatt DL, Elbez Y, et al. - Eur Heart J 2017; published online ahead of print
Aspirin is widely used for the prevention of CV events, however, a substantial residual ischemic risk remains for stable patients with atherothrombosis [1,2]. The randomized controlled COMPASS study showed that in patients with stable CAD or PAD, the combination of aspirin and rivaroxaban reduced the relative risk of CV death, stroke, or MI by 24%, compared with aspirin alone [3,4]. However, the applicability of these results on a broad CAD and PAD population is not known.
REACH was a large prospective, observational, international registry of patients ≥ 45 years old, with either established atherosclerotic disease (CAD, PAD, or CVD) or with at least three atherosclerotic risk factors. In this analysis of the REACH registry , the proportion of COMPASS-eligible patients with CAD or PAD was identified, the reasons for ineligibility were described, and the clinical characteristics, management and outcomes of COMPASS-eligible REACH patients were compared to those of the actual COMPASS trial participants, using patients in the aspirin arm of the trial.
For this analysis, the COMPASS-eligible study population in REACH was achieved after excluding patients with CVD alone or atherothrombotic risk factors alone. Moreover, patients were excluded if they had missing data, if they were at high bleeding risk or on oral anticoagulant treatment, if they had suffered an ischemic stroke or had received DAPT for ACS or PCI within the previous 12 months, and if they had severe renal failure. The inclusion criteria of the COMPASS-eligible population were:
1. PAD patients, regardless of age, defined as: history of intermittent claudication with an ankle/arm blood pressure ratio <0.9 or peripheral artery stenosis ≥50% at angiography or duplex ultrasound, previous limb or foot amputation for vascular disease, history of inferior limb revascularization (by surgery or PTA), previous carotid revascularization or asymptomatic carotid disease with at least 50% stenosis
2. CAD patients, aged > 65 years, defined as: previous MI within the last 20 years, history of stable or unstable angina with evidence of multivessel coronary disease, multivessel revascularization, either by PCI or CABG
3. CAD patients < 65 years if they had one of the following: documented atherosclerosis or documented prior revascularization involving at least two vascular beds, at least two additional risk factors out of the following: current smoker, DM, eGFR< 60 mL/min, HF, non-lacunar ischemic stroke >1 year
The primary outcome of COMPASS was the composite of CV death, MI, and stroke. For this analysis, the following secondary outcomes were additionally assessed: CV death, non-fatal MI, non-fatal stroke, all-cause mortality, bleeding, and HF hospitalization.
- Out of the 65531 patients in the REACH registry, 31873 patients comprised the study population with either CAD or PAD, and after applying the eligibility criteria, 16875 were COMPASS-eligible.
- There were important differences in baseline characteristics regarding age, gender, history of previous stroke or TIA, or history of remote MI between COMPASS-eligible and COMPASS participants. The rates of use of secondary prevention medications at baseline were higher in COMPASS participants.
- Based on the Recurrent Ischemic Event risk and Bleeding risk scores, COMPASS participants had a higher risk profile compared with the COMPASS-eligible patients in the REACH registry based on the Recurrent Ischemic Event risk score (12.1 ± 2.8 vs. 9.9 ± 2.4; P< 0.001) and Bleeding risk score (8.5 ± 2.2 vs. 7.2 ± 1.7; P< 0.001).
- Compared with COMPASS participants in the reference aspirin treatment arm, COMPASS-eligible patients in the REACH registry had a higher primary outcome event rate per 100 patients/year (4.2; 95% CI: 4.0-4.3 vs. 2.9; 95% CI: 2.6-3.2; P < 0,0001).
- The rates (per 100 patient/years) of all-cause mortality (3.2; 95% CI: 3.1–3.4 vs. 2.2; 95% CI: 1.9–2.4; P< 0,001] or CV death (1.9; 95% CI: 1.8–2.1 vs. 1.2; 95% CI: 1.0–1.3; P< 0.001) were also higher among COMPASS-eligible patients in REACH.
- The rate per 100 patient/years of HF hospitalization was 1.1 (95% CI: 0.8–1.1) in COMPASS participants, compared with 3.5% (95% CI: 3.2–3.8) at 1 year among COMPASS-eligible patients in REACH.
COMPASS-eligible patients represented a substantial part of the spectrum of stable CAD and PAD patients enrolled in the REACH registry. They had a higher risk of ischemic events compared with actual COMPASS participants in the aspirin alone treatment arm. These results should be interpreted with caution, due to important differences in the design between the 2 studies.