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BACKGROUND: Rivaroxaban 2.5 mg twice daily plus acetylsalicylic acid (aspirin; ASA) 100 mg reduced the risk of cardiovascular events as compared with ASA monotherapy in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) but increased the risk of major bleedings. Analysis of net clinical benefit (NCB) is of key clinical relevance and represents an integrated measure of overall patient outcome.
METHODS: The current prespecified analysis was performed to assess the NCB of adding rivaroxaban 2.5 mg twice daily to ASA monotherapy in patients with chronic vascular disease in the COMPASS study cohort (intention-to-treat study population), with a specific focus on high-risk subgroups. The predefined NCB outcome was the composite of cardiovascular death, stroke, myocardial infarction, fatal bleeding, or symptomatic bleeding into a critical organ.
RESULTS: A lower number of NCB adverse outcomes was observed with rivaroxaban 2.5 mg twice daily plus ASA versus ASA alone (hazard ratio, 0.80 [95% CI, 0.70-0.91], P=0.0005), which became increasingly favorable with longer treatment duration. The main drivers of NCB outcomes were "efficacy" events, in particular stroke (0.5%/y versus 0.8%/y; hazard ratio, 0.58 [95% CI, 0.44-0.76], P<0.0001) and cardiovascular death (0.9%/y versus 1.2%/y; hazard ratio, 0.78 [95% CI, 0.64-0.96], P=0.02), whereas the bleeding components of the NCB, in particular fatal bleeding (0.09%/y versus 0.06%/y; hazard ratio, 1.49 [95% CI 0.67-3.33], P=0.32), only represented a minority of NCB events. In selected high-risk subgroups, including patients with polyvascular disease (=2 vascular beds affected with atherosclerosis), impaired renal function, heart failure, and/or diabetes mellitus, a larger absolute risk reduction for experiencing a NCB event was observed.
CONCLUSIONS: Compared with ASA monotherapy, the combination of rivaroxaban 2.5 mg twice daily plus ASA resulted in fewer NCB events primarily by preventing adverse efficacy events, particularly stroke and cardiovascular mortality, whereas severe bleedings were less frequent and with less clinical impact. The NCB was particularly favorable in high-risk subgroups and those with multiple risk characteristics. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01776424.
|Family Medicine (FM)/General Practice (GP)|
|General Internal Medicine-Primary Care(US)|
|Hemostasis and Thrombosis|
This study comparing rivaroxaban plus aspirin (RPA) vs aspirin was a re-analysis of a previous RCT that found RPA reduced major CV events but increased major bleeding events. This study defines the outcome of “net clinical benefit” (NCB), which is a composite of the benefits (e.g. reduced strokes) and the risks (e.g. major bleeding into a critical organ). RPA resulted in NCB. I am a family physician who frequently sees patients with cardiovascular disease. I have concerns about the study. The authors have ties to pharmaceutical companies. The authors claim that the current analysis was “pre-specified,” but this is a re-analysis of data from a 2017 publication. Finally, NCB is a composite score that adds and subtracts benefits and losses. Although this may be simple, it also can be misleading, especially for patient-centered care. It assumes that one values a stroke and a bleed equally, and that one values reaping gains and avoiding losses equally.
Relative numbers are pretty impressive, although absolute numbers were low.
The COMPASS trial reports favorable net clinical benefit for secondary prevention of vascular events in patients with established CVD by combining ASA and low-dose rivaroxaban. As expected, efficacy drove the NCB metric, while the bleeding subcomponent trended higher with combined therapy. Absolute event rates differed to a very small degree, calling into question whether the addition of rivaroxaban would be cost-effective.
The issue is definitely important to primary care practitioners. Whether I believe the results of this analysis is another story. .