Reduction Of Atherothrombosis For Continued Health Registry Research Articles

A Web-Based Application for Risk Stratification and Optimization in Patients With Cardiovascular Disease: Pilot Study.

In addition to aspirin, angiotensin-converting enzyme inhibitors, statins, and lifestyle modification interventions, novel pharmacological agents have been shown to reduce morbidity and mortality in atherosclerotic cardiovascular disease patients, including new antithrombotics, antihyperglycemics, and lipid-modulating therapies. Despite their benefits, the uptake of these guideline-directed therapies remains a challenge. There is a need to develop strategies to support knowledge translation for the uptake of secondary prevention therapies. The goal of this study was to test the feasibility and usability of Stratification and Optimization in Patients With Cardiovascular Disease (STOP-CVD), a point-of-care application that was designed to facilitate knowledge translation by providing individualized risk stratification and optimization guidance. Using the REACH (Reduction of Atherothrombosis for Continued Health) Registry trial and predictive modeling (which included 67,888 patients), we designed a free web-based secondary risk calculator. Based on demographic and comorbidity profiles, the application was used to predict an individual's 20-month risk of cardiovascular events and cardiovascular mortality and provides a comparison to an age-matched control with an optimized cardiovascular risk profile to illustrate the modifiable residual risk. Additionally, the application used the patient's risk profile to provide specific guidance for possible therapeutic interventions based on a novel algorithm. During an initial 3-month adoption phase, 1-time invitations were sent through email and telephone to 240 physicians that refer to a regional cardiovascular clinic. After 3 months, a survey of user experience was sent to all users. Following this, no further marketing of the application was performed. Google Analytics was collected postimplementation from January 2021 to December 2021. These were used to tabulate the total number of distinct users and the total number of monthly uses of the application. During the 1-year pilot, 47 of the 240 invited clinicians used the application 1573 times, an average of 131 times per month, with sustained usage over time. All 24 postimplementation survey respondents confirmed that the application was functional, easy to use, and useful. This pilot suggests that the STOP-CVD application is feasible and usable, with high clinician satisfaction. This tool can be easily scaled to support the uptake of guideline-directed medical therapy, which could improve clinical outcomes. Future research will be focused on evaluating the impact of this tool on clinician management and patient outcomes.

Generalizability of the REDUCE-IT trial and cardiovascular outcomes associated with hypertriglyceridemia among patients potentially eligible for icosapent ethyl therapy: An analysis of the REduction of Atherothrombosis for Continued Health (REACH) registry

BackgroundThe REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial) trial demonstrated that high-dose icosapent-ethyl reduced the risk of ischemic events in statin-treated patients with elevated triglycerides (TG) and either atherosclerotic cardiovascular disease (ASCVD) or diabetes plus at least one risk factor. Methods and resultsUsing data from REACH (Reduction of Atherothrombosis for Continued Health), a large international registry of outpatients with or at risk of ASCVD, we evaluated the proportion of patients potentially eligible for enrolment in REDUCE-IT and compared their outcomes to those excluded because of low TG. Among 62,464 patients with either ASCVD or diabetes enrolled in the REACH Registry, 1036/8418 (12.3%) patients in primary prevention and 6049/54046 (11.2%) patients in secondary prevention (11.3% overall) would have been eligible for inclusion in REDUCE-IT. Compared with patients excluded for low TG level, adjusted risk of the primary composite outcome of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, unstable angina, or coronary revascularization was higher in the REDUCE-IT eligible group (HR:1.06, 95%CI:1.00–1.13, p = 0.04). In addition, unstable angina, non-fatal MI, percutaneous coronary intervention and coronary artery bypass grafting were also more frequent in the REDUCE-IT eligible group (HR:1.17, 95%CI:1.07–1.27, p < 0.001; HR:1.25, 95%CI:1.07–1.45, p < 0.001; HR:1.42, 95%CI:1.27–1.57, p < 0.001; HR:1.43, 95%CI:1.19–1.71, p < 0.001, respectively), whereas the adjusted risk of non-fatal stroke was lower (HR:0.64, 95%CI:0.54–0.75, p < 0.001). ConclusionIn this large international registry of patients with or at high-risk of ASCVD, 11.3% met the REDUCE-IT trial selection criteria. REDUCE-IT eligible patients were found to be at higher risk of cardiac atherothrombotic events, but at lower risk of stroke than trial-ineligible patients with lower TG.

Clinical characteristics and outcomes of COMPASS eligible patients in France. An analysis from the REACH Registry

BackgroundFollowing the publication of the COMPASS trial, the European Medicines Agency has approved a regimen of combination of rivaroxaban 2.5mg twice daily and a daily dose of 75–100mg acetylsalicylic acid (ASA) for patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events. However, the applicability of such a therapeutic strategy in France is currently unknown. AimsTo describe the proportion of patients eligible to COMPASS in France, their baseline clinical characteristics and the rate of major adverse cardiovascular events, using the REACH registry. MethodsFrom the the REduction of Atherothrombosis for Continued Health (REACH) registry database, a large international registry of patients with, or at risk, of atherothrombosis, we analyzed patients included in France with either established CAD and/or PAD and fulfilling the inclusion and exclusion criteria of the COMPASS trial. The ischemic outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke, and serious bleeding were defined as haemorrhagic stroke or bleeding leading to hospitalization or transfusion. ResultsAmong more than 65000 patients enrolled in REACH, 2.012 patients were evaluable and enrolled in France. Among them, 1194 patients (59.3%) were eligible to COMPASS. The main reasons for exclusion of the COMPASS trial, were high bleeding risk (59.1%), anticoagulant use (43.4%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI (24.7%). In the “COMPASS eligible population”, the rate of MACE (CV, MI and stroke) at 4 years follow-up was 13.4% [11.3–15.8], and serious bleeding was 2.5% at 4 years [1.6–3.4]. Patients with polyvascular disease (n=219) had the highest rate of MACE, compared with patients with CAD only and PAD only (19.1% [13.9–26.1] vs. 11.6% [9.1–14.8] vs 13.2% [9.2–18.8], P<0.0001, respectively). ConclusionThe COMPASS therapeutic strategy in France appears to be applicable to more than half of CAD or PAD patients. This population appears at high residual risk of atherothrombotic events, and patients with polyvascular disease experienced the highest rate of events.

Association of Multiple Enrichment Criteria With Ischemic and Bleeding Risks Among COMPASS-Eligible Patients

BackgroundThe COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial found clinical benefit of low-dose rivaroxaban plus aspirin, but at the expense of increased bleeding risk in patients with stable vascular disease. ObjectivesThis study evaluated the balance of ischemic and bleeding risks according to the presence of ≥1 enrichment criteria in “COMPASS-eligible” patients. MethodsKey COMPASS selection criteria were applied to identify a COMPASS-eligible population (n = 16,875) from the REACH (REduction of Atherothrombosis for Continued Health) Registry of stable atherothrombotic patients. Ischemic outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Bleeding outcome was serious bleeding (hemorrhagic stroke, hospitalization for bleeding, transfusion). ResultsPatients were categorized according to the enrichment criteria: age >65 years (81.5%), diabetes (41.0%), moderate renal failure (40.2%), peripheral artery disease (33.7%), current smoker (13.8%), heart failure (13.3%), ischemic stroke (11.1%), and asymptomatic carotid stenosis (8.7%). Each criterion was associated with a consistent increase in ischemic and bleeding events, but no individual subgroup derived a more favorable trade-off. Patients with multiple criteria had a dramatic increase in ischemic risk (7.0% [95% confidence interval (CI): 5.6% to 8.7%], 12.5% [95% CI: 11.1% to 14.1%], 16.6% [95% CI: 14.7% to 18.6%], and 21.8% [95% CI: 19.9% to 23.9%] with 1, 2, 3, and ≥4 enrichment criteria, respectively), but a more modest absolute increase in bleeding risk (1.5% [95% CI: 0.9% to 2.1%], 1.8% [95% CI: 1.3% to 2.2%], 2.0% [95% CI: 1.5% to 2.6%], 3.2% [95% CI: 2.6% to 3.9%]). ConclusionsIn a population of stable vascular patients at high risk of atherothrombotic events, the subset with multiple enrichment criteria had a greater absolute increase in ischemic than in bleeding risk and may be good candidates for low-dose rivaroxaban in addition to aspirin.

Identifying higher risk patients among the COMPASS-Eligible population: An analysis from the REduction of Atherothrombosis for Continued Health (REACH) Registry

The COMPASS trial showed that a combination of rivaroxaban and aspirin improved outcomes in patients with stable vascular disease compared with aspirin alone, but at the cost of an overall increase in bleeding. Describe the baseline characteristics and outcomes of relevant subgroups within the COMPASS-eligible population (CEP) in the REACH Registry and identify subgroups with higher ischemic and lower bleeding risk profile. Within the CEP, (fulfilling COMPASS inclusion and exclusion criteria) we identified the following subgroups: diabetes, MI < 1 year, age > 65 years, asymptomatic carotid stenosis > 70%, heart failure (HF), and stage III chronic kidney disease (CKD). We describe the composite outcome of MI, stroke or CV death, expressed as rates per 100 patient-years and serious bleeding rate at 1 year (bleeding requiring transfusion, hospitalization or hemorrhagic stroke) From the overall CEP ( n = 16.875), 81.5% were aged > 65 years, 41.0% had diabetes, 40.2% had stage III CKD, 13.3% had HF, 8.7% had asymptomatic carotid stenosis and 5.9% had a history of MI < 1 year. Patients with HF, MI < 1 year, and stage III CKD had the higher incidence rates of the primary outcome, compared with the overall CEP (7.5, 5.6, and 5.3 vs. 4.2 respectively) ( Fig. 1 ). Patients with a history of MI < 1 year, stage III CKD or diabetes had a higher incidence of CV Death/MI/Stroke compared with those who did not (5.6 vs. 3.6, 5.3 vs. 3.4, and 5.0 vs. 3.4, respectively, P < 0.05). Patients with history of MI < 1 year, stage III CKD or diabetes had similar rates of serious bleeding than the overall CEP at 1 year ( Table 1 ). Within the COMPASS-eligible patients, those with a history of MI < 1 year, stage III CKD or diabetes, experience a higher risk of ischemic events, with no excess in serious bleedings and appear potentially attractive candidates to more potent treatment such as addition of low dose rivaroxaban to single antiplatelet therapy.

How frequent are COMPASS-like patients in the real world? Insights from the reduction of atherothrombosis for continued health (REACH) registry

The COMPASS trial compared 3 antithrombotic strategies in patients with stable CAD or PAD: Aspirin alone or a combination of Aspirin and different dose of Rivaroxaban. This trial has been stopped prematurely, due to overwhelming efficacy. These could potentially change the management of stable CAD and PAD patients. To describe the proportion of COMPASS-eligible patients in the REACH registry. To describe the reasons for ineligibility, and to compare the clinical characteristics, management and outcomes of COMPASS-eligible vs ineligible patients. REACH is an international prospective registry of patients with established stable CAD or PAD. The COMPASS inclusion and exclusion criteria were applied to the REACH population. The primary outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI) and stroke. From the 65,351 patients in the overall REACH population, 24,677 were excluded because they did not have CAD or PAD, 15,885 were excluded because of missing information. The 24,969 remaining patients constituted the evaluable population. Among these, 10,983 patients were excluded because of exclusion criteria. The COMPASS-eligible population included 13,986 patients (56% of COMPASS-evaluable). Patients were excluded because: 4902 (19.6%) had a high bleeding risk (REACH score > 10), 3707 (14.9%) required AC, 5324 (21.3%) had HF, 1597 (6.4%) required DAPT due to ACS/PCI in the prior 12 months. The COMPASS-eligible population had a lower 4-year rate of CV death, non-fatal MI, or non-fatal stroke (14% [13.26–14.73] vs. 23.6% [22.54–24.64]); all-cause mortality (10.9% [10.2–11.5] vs. 22.5% [21.5–23.6]); or hospitalization for atherothrombotic events (26.7% [25.8–27.6] vs. 32.9% [31.8–34.0]), P < 0.001 ( Table 1 , Fig. 1 ). COMPASS-eligible patients represent approximately half of the spectrum of CAD/PAD patients in the real world REACH registry. COMPASS-eligible patients have a lower risk profile, and lower event rates compared to COMPASS-ineligible patients.

Risk Assessment in Patients With Diabetes With the TIMI Risk Score for Atherothrombotic Disease.

OBJECTIVEImproved risk assessment for patients with type 2 diabetes and elevated cardiovascular (CV) risk is needed. The Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P) predicts a gradient of risk in patients with prior myocardial infarction (MI) but has not been evaluated in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSCV event rates were compared by baseline TRS 2°P in 16,488 patients enrolled in SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53) with type 2 diabetes and high CV risk or established CV disease. Calibration was tested in the diabetes cohort from the REACH (REduction of Atherothrombosis for Continued Health) Registry.RESULTSTRS 2°P revealed a robust risk gradient for the composite of CV death, MI, and ischemic stroke in the full trial population, with 2-year event rates of 0.9% in the lowest- and 19.8% in the highest-risk groups (Ptrend < 0.001). A clear risk gradient was present within the subgroups of all coronary artery disease (CAD), CAD without prior MI, CAD with prior MI, peripheral artery disease, and prior stroke (Ptrend < 0.001 for each), with consistent risk relationships across subgroups. The C-statistic (0.71 for CV death and 0.66 for the composite end point) was consistent in each subgroup. There was close calibration with the type 2 diabetes cohort from the REACH Registry (goodness-of-fit P = 0.78).CONCLUSIONSThe expanded TRS 2°P provides a practical and well-calibrated risk prediction tool for patients with type 2 diabetes.

External applicability of the COMPASS trial: an analysis of the reduction of atherothrombosis for continued health (REACH) registry.

The aims of the present study were to describe the proportion of patients eligible for the COMPASS trial within the Reduction of Atherothrombosis for Continued Health (REACH) registry, the reasons for ineligibility, and to put in perspective the characteristics and outcomes of trial-eligible patients from the REACH registry compared with those of patients enrolled in the reference aspirin arm of the COMPASS trial. The COMPASS selection and exclusion criteria were applied to REACH patients with either coronary artery disease (CAD) or peripheral artery disease (PAD). We used the COMPASS primary composite outcome of cardiovascular (CV) death, myocardial infarction (MI), or stroke. In REACH, 31 873 patients had CAD or PAD and detailed information allowing evaluation of eligibility. Among these, 9518 (29.9%) patients had exclusion criteria and an additional 5480 patients (17.2%) did not fulfil the inclusion criteria and thus were not eligible. The 'COMPASS-Eligible' population therefore comprised 52.9% of the evaluable REACH patients (n = 16 875). The main reasons for exclusion were high-bleeding risk (51.8%), anticoagulant use (44.8%), requirement for dual antiplatelet therapy within 1year of an ACS or PCI with stent, (25.9%), history of ischaemic stroke <1 year (12.4%), and severe renal failure (2.2%). Eligibility was highest among patients with PAD alone (68.4%). COMPASS-Eligible patients from REACH experienced higher annualized primary outcome event rates than patients actually enrolled in the reference aspirin arm of COMPASS (4.2% vs. 2.9% per year, P < 0.001). COMPASS-Eligible patients represent a substantial fraction of stable CAD/PAD patients encountered in routine clinical practice in the large international REACH registry suggesting good external applicability. COMPASS-Eligible patients experienced a higher rate of the primary outcome compared with COMPASS participants in the aspirin alone treatment arm.

Four-Year Clinical Outcomes of Filipino Patients with or at Risk for Atherothrombotic Events from the REACH Registry

Background: Patients with established atherothrombotic disease (EAD) or those with atherothrombotic risk factors are at high risk for cardiovascular events and death. There are scant data on the clinical profile of stable Filipino patients with risk factors for atherothrombosis, and their long-term outcomes. Objective: To present the baseline clinical profile and four-year cardiovascular outcomes of Filipino out patients with EAD and those with multiple atherothrombotic risk factors. Methodology: The Reduction of Atherothrombosis for Continued Health (REACH) Registry is an international, prospective cohort of 68,236 patients aged at least 45 years old with either EAD or at least three atherothrombotic risk factors enrolled from 44 countries from 2003 to 2004. The Philippine cohort consists of 913 patients with EAD and 127 subjects with at least three atherothrombotic risk factors, who were consecutively enrolled and followed up for at least one to four years for the occurrence of cardiovascular (CV) death, myocardial infarction (MI) or stroke. Results: Of the 1,040 Filipino patients enrolled, 995 completed the four-year follow-up (96%). Their mean age was 65.5 years, with a balanced sex distribution. Forty-six percent have diabetes, 87.4% have hypertension, 62.9% have hypercholesterolemia, and 29.7% are ever-smokers. Ninety two percent had EAD (43% with coronary artery disease, 45% with cerebrovascular disease and 4% with peripheral artery disease or PAD). The rate of the combined primary endpoint of CV death/MI/stroke was 14.7%, but was higher (19.8%) among those with poly-vascular disease. Cerebrovascular disease patients had the highest CV death/MI/stroke rates (17.6%). PAD patients had the highest CV death/MI/stroke and hospitalization rate (33.2%). At baseline, 81.1% were receiving antiplatelet agents, 62.6% were receiving statins and 69% were receiving either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. After the fourth year of follow-up, medication usage rates were lower at 72.6%, 62.3%, and 37.2%, respectively. Conclusions: Filipino outpatients with, or at risk for, atherothrombosis experienced high long-term rates of CV events. This is the first report of long-term CV outcomes of stable Filipino outpatients with this high-risk profile.

Pulse Pressure and Risk for Cardiovascular Events in Patients With Atherothrombosis: From the REACH Registry

BackgroundPulse pressure (PP) provides valuable prognostic information in specific populations, but few studies have assessed its value on cardiovascular outcomes in a broad, worldwide population. ObjectivesThe aim of this study was to determine whether PP is associated with major adverse cardiovascular outcomes, independently of mean arterial pressure. MethodsParticipants from the international REACH (Reduction of Atherothrombosis for Continued Health) registry, which evaluates subjects with clinical atherothrombotic disease or risk factors for its development, were examined. Those with incomplete 4-year follow-up or PP data (final n = 45,087) were excluded. Univariate and multivariate regression analyses were performed to determine the association between PP and cardiovascular outcomes, including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, all myocardial infarction, all stroke, cardiovascular hospitalization, and a combined outcome. PP was analyzed as a continuous and categorical (i.e., by quartile) variable. ResultsThe mean age of the cohort was 68 ± 10 years, 35% were women, and 81% were treated for hypertension. The mean blood pressure was 138 ± 19/79 ± 11 mm Hg, rendering a mean PP of 49 ± 16 mm Hg. On univariate analysis, increasing PP quartile was associated with worse outcomes (p < 0.05 for all comparisons). After adjusting for sex, age, current smoking status, history of hypercholesterolemia, history of diabetes, aspirin use, statin use, blood pressure medication use, and mean arterial pressure, PP quartile was still associated with all outcomes except all stroke and cardiovascular death (p < 0.05 for all comparisons). Analysis of PP as a continuous variable yielded similar results. ConclusionsIn an international cohort of high-risk subjects, PP, a readily available hemodynamic parameter, is associated with multiple adverse cardiovascular outcomes and provides prognostic utility beyond that of mean arterial pressure.

Abstract 11669: Pulse Pressure and Risk of Cardiovascular Events in Patients With Atherothrombosis: Findings From the REACH Registry

Background: Pulse pressure (PP) provides valuable prognostic information in specific populations, but few studies have assessed its prognostic value on cardiovascular outcomes in a broad, worldwide population. Hypothesis: PP is associated with adverse outcomes independent of mean arterial pressure. Methods: We examined participants from the REACH (Reduction of Atherothrombosis for Continued Health) registry, an international study of individuals with atherothrombotic disease or risk factors for its development. We excluded those with incomplete four-year follow-up or PP data (final N=45,087). Univariable and multivariable regression analyses (using stepwise modeling) were performed to determine the association between PP and cardiovascular outcomes, including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, cardiovascular hospitalization, and a combined outcome. Model 1 covariates included sex, age, smoking status, hyperlipidemia, diabetes mellitus, aspirin use, statin use. Model 2 further adjusted for history of atherothrombosis. Model 3 additionally adjusted for blood pressure medications. Model 4 finally adjusted for mean arterial pressure. Results: The mean age of the cohort was 68±10 years, 35% were female, and 81% were treated for hypertension. The mean blood pressure was 138±19/79±11 mmHg (mean PP of 49±16 mmHg). On univariable analysis, increasing PP quartile was associated with worse outcomes (p&lt;0.05 for all comparisons). The Figure displays hazard ratios per 10 mmHg increase in PP, and shows an increased risk of the combined outcome. Similar findings were demonstrated for non-fatal myocardial infarction and cardiovascular hospitalization (p&lt;0.01). Conclusions: In a large international cohort of high-risk individuals, PP, a readily available hemodynamic parameter, is associated with multiple adverse cardiovascular outcomes and provides prognostic utility beyond that of mean arterial pressure.

Abstract 14844: Regional Variations on Cardiovascular Outcomes in Stable Chronic Heart Failure Outpatients at Risk of or With Atherothrombosis - Insights From REACH Registry

Background: There is a growing recognition of geographic variation for clinical trial outcomes in patients with chronic HF. This study sought to investigate regional variation among patients with a history of HF in a registry population with or at risk for atherothrombosis. Methods: 4 year CV outcomes of chronic HF patients (n=8,962) in Reduction of Atherothrombosis for Continued Health (REACH) Registry, an international, prospective cohort of stable outpatients with established ischemic events (CAD, CVD, and/or PAD) or multiple risk factors for atherothrombosis, were analyzed by geographic regions (North America (NA), Western Europe (WE), Eastern Europe (EE), Latin America (LA), Middle East (ME), and Asia Pacific (AP)). Results: Among 68,236 patients enrolled, 18.1% (n=1,311) of EE patients, 15.0% (n=4,158) of NA patients, 13.9% (n=118) of ME patients, 13.1% (n=2,161) of WE patients, 7.8% (n=150) of LA patients, and 7.6% (n=1,064) of AP patients had a history of HF at baseline. The prevalence of traditional cardiovascular risk factors and the use of medical therapies varied significantly among regions. At 4 year, the rate of CV death, MI, stroke, or hospitalization for HF ranged from 27.1% in AP to 53.4% in ME (p&lt;0.001). Similarly, a significant regional disparity was observed in recurrent HF hospitalization and CV death, however, with a different pattern for CV death (p&lt;0.001 for both, fig.). These differences among regions persisted after adjustment for regional differences in key prognostic variables. Conclusions: This large long term international database demonstrated regional heterogeneity in CV event rates, including hospitalization for heart failure, in patients with or at risk for atherothrombosis and a reported history of heart failure. These findings may have implications for estimating event rates and planning clinical trials of patients with heart failure.

Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death: Outcomes at 4 Years From the Reduction of Atherothrombosis for Continued Health (REACH) Registry.

Despite the known association of diabetes mellitus with cardiovascular events, there are few contemporary data on the long-term outcomes from international cohorts of patients with diabetes mellitus. We sought to describe cardiovascular outcomes at 4 years and to identify predictors of these events in patients with diabetes mellitus. The Reduction of Atherothrombosis for Continued Health (REACH) registry is an international registry of patients at high risk of atherothrombosis or established atherothrombosis. Four-year event rates in patients with diabetes mellitus were determined with the corrected group prognosis method. Of the 45 227 patients in the REACH registry who had follow-up at 4 years, 43.6% (n=19 699) had diabetes mellitus at baseline. The overall risk and hazard ratio (HR) of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were greater in patients with diabetes compared with patients without diabetes (16.5% versus 13.1%; adjusted HR, 1.27; 95% confidence interval [CI] 1.19-1.35). There was also an increase in both cardiovascular death (8.9% versus 6.0%; adjusted HR, 1.38; 95% CI, 1.26-1.52) and overall death (14.3% versus 9.9%; adjusted HR, 1.40; 95% CI, 1.30-1.51). Diabetes mellitus was associated with a 33% greater risk of hospitalization for heart failure (9.4% versus 5.9%; adjusted odds ratio, 1.33; 95% CI, 1.18-1.50). In patients with diabetes mellitus, heart failure at baseline was independently associated with cardiovascular death (adjusted HR, 2.45; 95% CI, 2.17-2.77; P<0.001) and hospitalization for heart failure (adjusted odds ratio, 4.72; 95% CI, 4.22-5.29; P<0.001). Diabetes mellitus substantially increases the risk of death, ischemic events, and heart failure. Patients with both diabetes mellitus and heart failure are at particularly elevated risk of cardiovascular death, highlighting the need for additional therapies in this high-risk population.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Metabolic syndrome, diabetes mellitus, or both and cardiovascular risk in outpatients with or at risk for atherothrombosis

The incidence of metabolic syndrome (MetS), diabetes mellitus (DM), and their coexistence is increasing but whether MetS increases cardiovascular risk beyond component risk factors is controversial. We compared the risk of cardiovascular death, myocardial infarction, or stroke among patients with MetS, newly detected DM, established DM, or coexistent MetS and DM in the global REduction of Atherothrombosis for Continued Health (REACH) registry. Outpatients with or at risk for atherothrombosis were recruited between 1 December 2003 and 31 December 2004 and followed up to 4 years for cardiovascular events. Risk was compared in patients with or without MetS or DM after adjustment for age, sex, risk factors, vascular disease, fasting blood glucose, therapy, and region. Among 44,548 REACH participants, 17,887 (40%) were without MetS or DM; 6459 had MetS (15%); 12,059 had established DM (27%); 7503 had both (17%); and 640 had newly detected DM (1%). Presence of MetS was not associated with higher cardiovascular events (12.6%, adjusted HR 0.98, 95% CI 0.89-1.08). In addition, once DM was evident, patients with coexistent MetS had similar increased risk (16.1%, adjusted HR 1.33, 95% CI 1.21-1.47) as DM alone (16.7%, adjusted HR 1.36, 95% CI 1.24-1.48). Newly detected DM was associated with increased cardiovascular risk (18.5%, adjusted HR 1.26, 95% CI 1.02-1.57), similar to longstanding DM. MetS was associated with incident DM (adjusted OR 1.94). In the REACH registry, presence of newly detected DM but not metabolic syndrome was associated with an increased risk of cardiovascular events.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Lessons from the REACH Registry in Europe

Among patients with atherothrombosis, including coronary artery disease (CAD), cerebrovascular disease (CVD), and peripheral arterial disease (PAD), patients with PAD generally have the worse prognosis. The Reduction of Atherothrombosis for Continued Health (REACH) Registry characterized the atherothrombotic risk factor profile, and evaluated treatment intensity and cardiovascular events among different atherothrombotic patient populations worldwide. Two thirds of PAD patients had polyvascular disease, defined as symptomatic involvement of more than one vascular bed. The risk factor profile in patients with CAD, CVD and PAD was very much similar. However, optimal risk factor control by medical treatment and lifestyle interventions was least accomplished in PAD patients. Furthermore, PAD patients and patients with polyvascular disease showed the highest cardiovascular event rates. Of note, therapeutic strategies are similar for all atherothrombotic disease categories, irrespective of the presence of polyvascular disease. Therefore, it is of the utmost importance to achieve optimal risk factor control, particularly for PAD patients and for those with polyvascular disease, in order to prevent future cardiovascular events.

An evidence-based score to detect prevalent peripheral artery disease (PAD)

Detection of peripheral artery disease (PAD) typically entails collection of medical history, physical examination, and noninvasive imaging, but whether a risk factor-based model has clinical utility in population screening is unclear. Our objective was to derive and validate a new score for estimating PAD probability in individuals or populations. PAD presence was determined by a history of previous or current intermittent claudication associated with an ankle-brachial index (ABI) of < 0.9 or previous lower extremity arterial intervention. Multivariable stepwise logistic regression identified cross-sectional correlates of PAD from demographic, clinical, and laboratory variables. Analyses were derived from 18,049 US REACH (REduction of Atherothrombosis for Continued Health) Registry outpatients with a complete baseline risk factor profile (enrolled from December 2003 to June 2004). Model performance was assessed internally using 10-fold cross validation, and effect estimates were used to generate the score. The model was externally validated using the Framingham Offspring Study. Age, sex, smoking, diabetes mellitus, body mass index, hypertension stage, and history of heart failure, coronary artery disease, and cerebrovascular disease were predictive of PAD prevalence. The model had reasonable discrimination on derivation and internal validation (c-statistic = 0.61 and 0.60, respectively) and external validation (c-statistic = 0.63 [ABI < 0.9] or 0.64 [clinical PAD]). The model-estimated PAD prevalence varied more than threefold from lowest to highest decile (range, 4.5-16.7) and corresponded closely with actual PAD prevalence in each population. In conclusion, this new tool uses clinical variables to estimate PAD prevalence. While predictive power may be limited, it may improve PAD detection in vulnerable, at-risk populations.

Fate of individuals with ischemic amputations in the REACH Registry: Three-year cardiovascular and limb-related outcomes

ObjectiveTo evaluate systemic and limb ischemic event rates of PAD patients with prior leg amputation and determine predictors of adverse outcomes. MethodsThe REduction of Atherothrombosis for Continued Health (REACH) Registry provided a prospective multinational cohort of 7996 outpatients with PAD enrolled from primary medical clinics in 44 countries in 2003–2004. 1160 patients (14.5%) had a prior leg amputation at any level. Systemic (myocardial infarction [MI], stroke, cardiovascular death) and limb (angioplasty, surgery, amputation) ischemic event rates were determined in a 3-year follow-up. ResultsPAD patients with leg amputations on entry had a 5-fold higher rate of a subsequent amputation (12.4% vs. 2.4%, P<.001), lower rate of peripheral angioplasty (8.3% vs. 10.7%, P=.005), and similar rates of surgical revascularization procedures compared with PAD patients without amputation. A nearly 2-fold increase in rates of cardiovascular death (14.5% vs. 7.7%, P<.001) and all-cause mortality (21.8% vs. 12.6%, P<.001) and an increase in the composite outcome of MI, stroke, cardiovascular death, or hospitalization (48.7% vs. 40.0%, P<.001) were noted. Recent (≤1 year) amputation was associated with higher rates of worsening PAD, subsequent lower extremity surgical revascularization procedures, re-amputation, non-fatal MI, and the composite outcome, including hospitalization. Adverse systemic and limb ischemic outcomes were similar regardless of amputation level. ConclusionsIndividuals with a history of leg amputations have markedly elevated rates of systemic and limb-related outcomes. PAD patients with recent ischemic amputation have the highest risk of adverse events. A history of “minor” ischemic amputation may confer an identical systemic risk as “major” leg amputation.

Ethnic Differences in Cardiovascular Risks and Mortality in Atherothrombotic Disease: Insights From the REduction of Atherothrombosis for Continued Health (REACH) Registry

OBJECTIVE To determine whether ethnic-specific differences in the prevalence of cardiovascular risk factors and outcomes exist worldwide among individuals with stable arterial disease. PATIENTS AND METHODS From December 1, 2003, to June 30, 2004, the prospective, observational REduction of Atherothrombosis for Continued Health (REACH) Registry enrolled 49,602 outpatients with coronary artery disease, cerebrovascular disease, and/or peripheral arterial disease from 7 predefined ethnic/racial groups: white, Hispanic, East Asian, South Asian, Other Asian, black, and Other (comprising any race distinct from those specified). The baseline demographic and risk factor profiles, medication use, and 2-year cardiovascular outcomes were assessed among these groups. RESULTS The prevalence of traditional atherothrombotic risk factors varied significantly among the ethnic/racial groups. The use of medical therapies to reduce risk was comparable among all groups. At 2-year follow-up, the rate of cardiovascular death was significantly higher in blacks (6.1%) compared with all other ethnic/racial groups (3.9%; P=.01). Cardiovascular death rates were significantly lower in all 3 Asian ethnic/racial groups (overall, 2.1%) compared with the other groups (4.5%; P<.001). CONCLUSION The REACH Registry, a large international study of individuals with atherothrombotic disease, documents the important ethnic-specific differences in cardiovascular risk factors and variations in cardiovascular mortality that currently exist worldwide.