Angina and Future Cardiovascular Events in Stable Patients With Coronary Artery Disease : Insights From the Reduction of Atherothrombosis for Continued Health (REACH) Registry

The REACH Registry was sponsored by Sanofi‐Aventis, Bristol‐Myers Squibb, and the Waksman Foundation (Tokyo, Japan) and is endorsed by the World Heart Federation.Peer reviewedPublisher PD

External applicability of the Effect of ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) trial: An analysis of patients with diabetes and coronary artery disease in the REduction of Atherothrombosis for Continued Health (REACH) registry

Aims: THEMIS is a double-blind, randomized trial of 19,220 patients with diabetes mellitus and stable coronary artery disease (CAD) comparing ticagrelor to placebo, in addition to aspirin. The present study aimed to describe the proportion of patients eligible and reasons for ineligibility for THEMIS within a population of patients with diabetes and CAD included in the Reduction of Atherothrombosis for Continued Health (REACH) registry. Methods and results: The THEMIS eligibility criteria were applied to REACH patients. THEMIS included patients ≥50 years with type 2 diabetes and stable CAD as determined by either a history of previous percutaneous coronary intervention, coronary artery bypass grafting, or documentation of angiographic stenosis of ≥50% of at least one coronary artery. Patients with prior myocardial infarction or stroke were excluded. In REACH, 10,156 patients had stable CAD and diabetes. Of these, 6515 (64.1%) patients had at least one exclusion criteria. From the remaining population, 784 patients did not meet inclusion criteria (7.7%) mainly due to absence of aspirin treatment (7.2%), yielding a ‘THEMIS-eligible population’ of 2857 patients (28.1% of patients with diabetes and stable CAD). The main reasons for exclusion were a history of myocardial infarction (53.1%), use of oral anticoagulation (14.5%), or history of stroke (12.9%). Among the 4208 patients with diabetes and a previous PCI, 1196 patients (28.4%) were eligible for inclusion in the THEMIS-PCI substudy. Conclusions: In a population of patients with diabetes and stable coronary artery disease, a sizeable proportion appear to be ‘THEMIS eligible.’ Clinical trial registration: http://www.clinicaltrials.gov identifier: NCT0199179

Individual lifetime benefit from low-dose colchicine in patients with chronic coronary artery disease

Aims Low-dose colchicine reduces cardiovascular risk in patients with coronary artery disease (CAD), but absolute benefits ma vary between individuals. This study aimed to assess the range of individual absolute benefits from low-dose colchicine ac cording to patient risk profile. Methods and results The European Society of Cardiology (ESC) guideline–recommended SMART-REACH model was combined with the relative treatment effect of low-dose colchicine and applied to patients with CAD from the Low-Dose Colchicine 2 (LoDoCo2) trial and the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease (UCC-SMART) study (n = 10 830). Individual treatment benefits were expressed as 10-year absolute risk reductions (ARRs) for myocardial infarction, stroke, or cardiovascular death (MACE), and MACE-free life-years gained. Predictions were also performed for MACE plus coronary revascularization (MACE+), using a new lifetime model derived in the REduction of Atherothrombosis for Continued Health (REACH) registry. Colchicine was compared with other ESC guideline–recommended intensified (Step 2) prevention strategies, i.e. LDL cholesterol (LDL-c) reduction to 1.4 mmol/L and systolic blood pressure (SBP) reduction to 130 mmHg. The generalizability to other populations was assessed in patients with CAD from REACH North America and Western Europe (n = 25 812). The median 10-year ARR from low-dose colchicine was 4.6% [interquartile range (IQR) 3.6–6.0%] for MACE and 8.6% (IQR 7.6–9.8%) for MACE+. Lifetime benefit was 2.0 (IQR 1.6–2.5) MACE-free years, and 3.4 (IQR 2.6–4.2) MACE+-free life-years gained. For LDL-c and SBP reduction, respectively, the median 10-year ARR for MACE was 3.0% (IQR 1.5–5.1%) and 1.7% (IQR 0.0–5.7%), and the lifetime benefit was 1.2 (IQR 0.6–2.1) and 0.7 (IQR 0.0–2.3) MACE-free life-years gained. Similar results were obtained for MACE+ and in American and European patients from REACH. Conclusion The absolute benefits of low-dose colchicine vary between individual patients with chronic CAD. They may be expected to be of at least similar magnitude to those of intensified LDL-c and SBP reduction in a majority of patients already on conventional lipid-lowering and blood pressure–lowering therapy

Effects of adherence to guidelines for the control of major cardiovascular risk factors on outcomes in the REduction of Atherothrombosis for Continued Health (REACH) Registry Europe

To examine the impact of cardiovascular risk factor control on 3-year cardiovascular event rates in patients with stable symptomatic atherothrombotic disease in Europe

Carotid atherosclerosis and risk of subsequent coronary event in outpatients with atherothrombosis.

The presence of carotid plaque reflects overall atherosclerotic burden and may predict coronary artery disease events. We examined the association among carotid atherosclerosis, history of atherothrombotic events, and risk of coronary events. Among 45 227 patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry with 4-year follow-up, 23 364 patients with information on carotid atherosclerosis at baseline were analyzed. The primary outcome was the composite of first occurrence of cardiovascular death, myocardial infarction, or coronary hospitalization. The carotid atherosclerosis was present in 46% of patients (n=10 725) and was associated with increasing conventional cardiovascular risk factors and extent of symptomatic vascular disease. During 4-year follow-up, 4304 patients experienced ≥1 coronary event. After adjustment for cardiovascular risk factors and geographic region, the risk of coronary events increased by 22% (95% confidence interval [CI], 14%-30%) in patients with versus without carotid atherosclerosis. The relative increase was 18% (95% CI, -7%-51%) in patients enrolled with multiple risk factors only, 25% (95% CI,16%-35%) in patients with coronary artery disease, 46% (95% CI,28%-65%) in patients with cerebrovascular disease, and 37% (95% CI,17%-60%) in patients with peripheral artery disease. Carotid atherosclerosis was associated with increased risk, even among patients with previous myocardial infarction but no known stroke (P=0.001) or among patients with previous stroke but no known myocardial infarction (P<0.001). Carotid atherosclerosis was an independent predictor of coronary events across all types of symptomatic vascular disease and had an incremental effect on risk regardless of risk factors or location of vessel disease

Carotid plaque and intima-media thickness and the incidence of ischemic events in patients with atherosclerotic vascular disease

We aimed to evaluate whether carotid intima-media thickness (CIMT) or the presence of plaque can confer additional predictive value of future cardiovascular (CV) ischemic events in patients with pre-existing atherosclerotic vascular disease. We identified 2317 patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry who had atherosclerotic vascular disease and baseline CIMT measurements. The entire range of CIMT was divided into quartiles and the fourth quartile (? 1.5 mm) was defined as carotid plaque. Mean ± standard deviation baseline CIMT was 1.31 ± 0.65 mm. Associated CV ischemic events and vascular-related hospitalizations were evaluated over a 2-year follow-up. There was a positive increase in adjusted hazard ratios (HRs) for all-cause mortality (p = 0.04 for trend) and the quadruple endpoint (CV death, myocardial infarction (MI), stroke, hospitalization for CV events) with increasing quartiles of CIMT (p = 0.0008 for trend), which was mainly driven by the fourth quartile (carotid plaque). HRs for all-cause mortality, CV death, CV death/MI/stroke and the quadruple endpoint comparing the highest (carotid plaque) with the lowest CIMT quartile were 2.09 (95% CI, 1.07-4.10; p = 0.03); 2.49 (1.10-5.67; p = 0.03); 1.71 (1.10-2.67; p = 0.02); and 1.73 (1.31-2.27; p = 0.0001). In conclusion, our analyses suggest that the presence of carotid plaque, rather than the thickness of intima-media, appears to be associated with increased risk of CV morbidity and mortality, but confirmation of these findings in other population and prospective studies is required

Cardiovascular risk in relation to body mass index and use of evidence-based preventive medications in patients with or at risk of atherothrombosis.

International audienceAim Explore the relation between body mass index (BMI) and cardiovascular disease, and the influence of optimal medical therapy (OMT) on this relationship. Methods and results Patients from the REACH cohort, an international, prospective cohort of patients with or at high risk of atherosclerosis with documentation of potential confounders, including treatments and risk factors, were followed up to 4 years (n = 54 285). Patients were categorized according to baseline BMI (ranging from underweight to Grade III obesity). Optimal medical therapy was defined as the use of the four cardioprotective medication classes (statins, ACE inhibitors/angiotensin II receptor blockers, β-blockers, and antiplatelet agents). The main outcomes were all-cause mortality, cardiovascular (CV) mortality, and CV events. In primary and secondary prevention, a reverse J-shaped curve best described the relationship between BMI categories and the incidence of the various outcomes. In secondary prevention, the highest adjusted risks were observed for underweight patients (1.97, P < 0.01, and 1.29, P = 0.03, for CV mortality and CV events) and the lowest HRs were observed, respectively, in Grade II and Grade III obese patients (0.73, P < 0.01 and 0.80, P < 0.01). The proportion of patients on OMT increased with BMI from 10.1 to 36% (P < 0.001). The apparent CV protection conferred by obesity persisted in patients receiving OMT. Conclusion An obesity paradox was observed in both primary and secondary CV prevention patients. The intensity of use of evidence-based preventive medications does not account for the paradoxical CV protection associated with obesity. At extremes of BMI, further interventions beyond OMT may be needed to reduce CV risk

Geographic variation and risk factors for systemic and limb ischemic events in patients with symptomatic peripheral artery disease: Insights from the REACH Registry

Background: Patients with symptomatic peripheral artery disease (PAD) are at high risk of ischemic events. However, data about predictors of this risk are limited. Hypothesis: We analyzed baseline characteristics and 4-year follow-up of patients enrolled in the international REduction of Atherothrombosis for Continued Health (REACH) Registry with symptomatic PAD and no history of stroke/transient ischemic attack to describe annual rates of recurrent ischemic events globally and geographically. Methods: The primary outcome was systemic ischemic events (composite of cardiovascular death, myocardial infarction, or stroke) at 4 years. The secondary outcome was limb ischemic events (composite of lower limb amputation, peripheral bypass graft, and percutaneous intervention for PAD) at 2 years. Multivariate analysis identified risk factors associated with recurrent ischemic events. Results: The primary endpoint rate reached 4.7% during the first year and increased continuously (by 4%-5% each year) to 17.6% by year 4, driven mainly by cardiovascular mortality (11.1% at year 4). Japan experienced lower adjusted ischemic rates (P < 0.01) vs North America. Renal impairment (P < 0.01), congestive heart failure (P < 0.01), history of diabetes (P < 0.01), history of myocardial infarction (P = 0.01), vascular disease (single or poly, P < 0.01), and older age (P < 0.01) were associated with increased risk of systemic ischemic events, whereas statin use was associated with lower risk (P = 0.03). The limb ischemic event rate was 5.7% at 2 years. Conclusions: Four-year systemic ischemic risk in patients with PAD and no history of stroke or transient ischemic attack remains high, and was mainly driven by cardiovascular mortality