Cognitive impairment and risk of cardiovascular events and mortality.

BACKGROUND: Cognitive impairment may increase the risk of all cardiovascular (CV) events. We prospectively evaluated the independent association between Mini-Mental State Examination (MMSE) score and myocardial infarction, stroke, hospital admission for heart failure and mortality, and their CV composite (major CV events), in a large high-risk CV population. METHODS AND RESULTS: Mini-Mental State Examination was recorded at baseline in 30 959 individuals enrolled into two large parallel trials of patients with prior cardiovascular disease or high-risk diabetes and followed for a median of 56 months. We used a Cox regression model to determine the association between MMSE score and incident CV events and non-CV mortality, adjusted for age, sex, education, history of vascular events, dietary factors, blood pressure, smoking, glucose, low-density lipoprotein, high-density lipoprotein, CV medications, exercise, alcohol intake pattern, depression, and psychosocial stress. Patients were categorized into four groups based on baseline MMSE; 30 (reference), 29-27, 26-24, and <24. Compared with patients with an MMSE of 30 (n = 9624), those with scores of 29-27 [n = 13 867; hazard ratio (HR) 1.08; 95% confidence intervals (CI) 1.01-1.16], 26-24 (n = 4764; HR: 1.15; 95% CI: 1.05-1.26) and <24 (n = 2704; HR: 1.35; 95% CI: 1.21-1.50) had a graded increase in the risk of major vascular events (P < 0.0001). Mini-Mental State Examination score was significantly associated with each of the individual components of the composite, except myocardial infarction. There was also no association between baseline MMSE and hospitalization for unstable or new angina. Within MMSE domains, impairments in orientation to place (HR: 1.52; 1.25-1.85), attention-calculation (HR: 1.10; 1.02-1.18), recall (HR: 1.10; 1.04-1.16), and design copy (HR: 1.15; 1.06-1.24) were the most predictive of major vascular events and mortality. The magnitude of increased risk of CV events associated with an MMSE <24 was similar to a previous history of stroke. CONCLUSION: In people at increased CV risk, impairments on baseline cognitive testing are associated with a graded increase in the risk of stroke, congestive heart failure, and CV death, but not coronary events. An MMSE score of <24 increased CV disease risk to the same extent as a previous stroke.

The cost-effectiveness of rivaroxaban with or without aspirin in the COMPASS trial.

AIMS: The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial demonstrated that rivaroxaban 2.5 mg BID with aspirin 100 mg was more effective than aspirin 100 mg daily alone for the prevention of cardiovascular (CV) death, stroke, or myocardial infarction in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). We aimed to examine the cost-effectiveness of rivaroxaban using patient-level data from the COMPASS trial. METHODS AND RESULTS: We performed an in-trial analysis and extrapolated our results for 33 years using a two-state Markov model with a 1-year cycle length. Hospitalization events, procedures, and study drugs were documented for patients. We applied country-specific (Canada, France, and Germany) direct healthcare system costs (in USD) to healthcare resources consumed by patients. Average cost per patient during the trial (mean follow-up of 23 months), quality-adjusted life years (QALYs), and lifetime cost-effectiveness were calculated. Costs of events and procedures were reduced with rivaroxaban 2.5 mg BID with aspirin. The addition of rivaroxaban 2.5 mg BID increased total costs for the combination group. Over a lifetime horizon (in trial +33 years), rivaroxaban plus aspirin was associated with 1.17 QALYs gained, yielding an incremental cost-effectiveness ratio (ICER) of $3946/QALY, $9962/QALY, and $10 264/QALY in Canada, France, and Germany, respectively. PAD and polyvascular disease subgroups had lower ICERs. CONCLUSION: Rivaroxaban 2.5 mg twice daily plus aspirin compared with aspirin alone reduces direct healthcare costs. After acquisition costs of rivaroxaban, the lifetime cost-effectiveness of 2.5 mg twice daily plus aspirin is highly cost-effective in Canada, France, and Germany.(COMPASS ClinicalTrials.gov identifier: NCT01776424).

Chronic Kidney Disease, Basal Insulin Glargine, and Health Outcomes in People with Dysglycemia: The ORIGIN Study.

BACKGROUND: Early stages of chronic kidney disease are associated with an increased cardiovascular risk in patients with established type 2 diabetes and macrovascular disease. The role of early stages of chronic kidney disease on macrovascular outcomes in prediabetes and early type 2 diabetes mellitus is not known. In the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial, the introduction of insulin had no effect on cardiovascular outcomes compared with standard therapy. In this post hoc analysis of ORIGIN, we compared cardiovascular outcomes in subjects without to those with mild (Stages 1-2) or moderate chronic kidney disease (Stage 3). METHODS: Τwo co-primary composite cardiovascular outcomes were assessed. The first was the composite end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes; and the second was a composite of any of these events plus a revascularization procedure, or hospitalization for heart failure. Several secondary outcomes were prespecified, including microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers. RESULTS: Complete renal function data were available in 12,174 of 12,537 ORIGIN participants. A total of 8114 (67%) had no chronic kidney disease, while 4060 (33%) had chronic kidney disease stage 1-3. When compared with nonchronic kidney disease participants, the risk of developing the composite primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) in those with mild to moderate chronic kidney disease was 87% higher; hazard ratio (HR) 1.87; 95% confidence interval (CI), 1.71-2.04 (P < .0001). The presence of chronic kidney disease 1-3 was also associated with a greater than twofold higher risk for both all-cause mortality (HR 2.17; 95% CI, 1.98-2.38; P < .0001) and cardiovascular mortality (HR 2.39; 95% CI, 2.13-2.69; P < .0001). Moreover, patients with mild to moderate chronic kidney disease had significantly higher risk for nonfatal myocardial infarction (50%), nonfatal stroke (68%), any stroke (84%), the above composite primary end point plus revascularization or heart failure requiring hospitalization (59%), or a major coronary artery disease event (56%). Furthermore, in patients with chronic kidney disease and early diabetes mellitus type 2, the primary end point occurred 83% more frequently as compared with nonchronic kidney disease participants (HR 1.83; 95% CI, 1.67-2.01; P < .001) and in patients with prediabetes and chronic kidney disease 67% more frequently (HR 1.67; 95% CI,1.25-2.24; P < .001). CONCLUSIONS: In high-risk patients with dysglycemia (prediabetes and early diabetes), mild and moderate chronic kidney disease significantly increased cardiovascular events.

Use of ramipril in preventing stroke: double blind randomised trial.

OBJECTIVE: To determine the effect of the angiotensin converting enzyme inhibitor ramipril on the secondary prevention of stroke. DESIGN: Randomised controlled trial with 2x2 factorial design. SETTING: 267 hospitals in 19 countries. PARTICIPANTS: 9297 patients with vascular disease or diabetes plus an additional risk factor, followed for 4.5 years as part of the HOPE study. OUTCOME MEASURES: Stroke (confirmed by computed tomography or magnetic resonance imaging when available), transient ischaemic attack, and cognitive function. Blood pressure was recorded at entry to the study, after 2 years, and at the end of the study. RESULTS: Reduction in blood pressure was modest (3.8 mm Hg systolic and 2.8 mm Hg diastolic). The relative risk of any stroke was reduced by 32% (156 v 226) in the ramipril group compared with the placebo group, and the relative risk of fatal stroke was reduced by 61% (17 v 44). Benefits were consistent across baseline blood pressures, drugs used, and subgroups defined by the presence or absence of previous stroke, coronary artery disease, peripheral arterial disease, diabetes, or hypertension. Significantly fewer patients on ramipril had cognitive or functional impairment. CONCLUSION: Ramipril reduces the incidence of stroke in patients at high risk, despite a modest reduction in blood pressure.