Putting the future in service of the present: Risk assessment in acute coronary syndrome patients

Risk, the possibility of loss or injury, is indeed a fixture in all aspects of our lives, from investing in the stock market to crossing the street. This concept that we now take for granted is in fact relatively novel. Some have argued that the ability to describe, estimate and control risk is a key distinction between past and modern times.1 In early civilization, the future of human beings was largely thought to be at the whim of the gods. The turning point came during the Renaissance when Chevalier de Méré, a French nobleman with an affinity for gambling and mathematics, challenged the famed French mathematician Blaise Pascal to solve an infamous puzzle: How to divide the stakes of an unfinished game of chance between two players when one of them is ahead.1,2 Collaboration between Pascal and Pierre de Fermat, a lawyer and a talented mathematician, resulted in a solution and consequently, the theory of probability was born. And it is this concept that is at the heart of modern cardiovascular medicine and research

Association between glycated haemoglobin levels and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the TECOS randomized clinical trial

Aims: Whether glycaemic control is associated with cardiovascular outcomes in patients with type 2 diabetes (T2D) is unclear. Consequently, we assessed the relationship between glycated haemoglobin (HbA1c) and cardiovascular outcomes in a placebo-controlled randomized trial which demonstrated no cardiovascular effect of sitagliptin in patients with T2D and atherosclerotic vascular disease. Methods and results: Secondary analysis of 14 656 TECOS participants with time to event analyses using multivariable Cox proportional hazard models. During a median 3.0 (interquartile range 2.3–3.8) year follow-up, 456 (3.1% of 14 656) patients had first hospitalization for heart failure (HF), 1084 (11.5%) died, 1406 (9.6%) died or were hospitalized for HF, and 1689 (11.5%) had a non-HF cardiovascular event (cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, or hospitalization for unstable angina). Associations between baseline or time-varying HbA1c and cardiovascular outcomes were U-shaped, with the lowest risk when HbA1c was around 7%. Each one-unit increase in the time-varying HbA1c above 7% was associated with an adjusted hazard ratio (HR) of 1.21 [95% confidence interval (CI) 1.11–1.33] for first HF hospitalization, 1.11 (1.03–1.21) for all-cause death, 1.18 (1.09–1.26) for death or HF hospitalization, and 1.10 (1.02–1.17) for non-HF cardiovascular events. Each one-unit decrease in the time-varying HbA1c below 7% was associated with an adjusted HR of 1.35 (95% CI 1.12–1.64) for first HF hospitalization, 1.37 (1.16–1.61) for death, 1.42 (1.23–1.64) for death or HF hospitalization, and 1.22 (1.06–1.41) for non-HF cardiovascular events. Conclusion: Glycated haemogobin exhibits a U-shaped association with cardiovascular outcomes in patients with T2D and atherosclerotic vascular disease, with nadir around 7%. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT00790205

Effect of left ventricular hypertrophy on long-term survival of patients with coronary artery disease following percutaneous coronary intervention

The impact of left ventricular hypertrophy (LVH) on survival among patients with established coronary artery disease (CAD) is not well understood. We sought to evaluate the effect of LVH on the survival of patients with CAD following percutaneous coronary intervention (PCI). Three hospitals in New York City contributed prospectively defined data on 4284 consecutive patients undergoing PCI. Allcause mortality at a mean follow-up of three years was the primary endpoint. LVH was present in 383 patients (8.9%). LVH patients had a greater prevalence of hypertension (88% vs. 68%, p<0.001), vascular disease (21% vs. 6.6%, p=0.001), and prior heart failure (10% vs. 5.5%, p<0.001). LVH patients presented less often with one-vessel disease (38% vs. 50%, p=0.040) and more often with two- (34% vs. 29%, p=0.014) or three-vessel (22% vs. 18%, p=0.044) disease. Ejection fractions and angiographic success were similar in both groups. In-hospital mortality did not differ between groups. At three-year follow-up, the survival rate for patients with LVH was 86% vs. 91% in patients without LVH (log-rank p=0.001). However, after adjustment for differences in baseline characteristics using Cox proportional hazards analysis, LVH was found not to be an independent predictor of mortality (hazard ratio, 0.93; 95% confidence interval, 0.68–1.28; p=0.67). We conclude that LVH at the time of PCI is not independently associated with an increase in the hazard of death at three years

Sitagliptin and risk of fractures in type 2 diabetes: Results from the TECOS trial

Aim: To examine fracture incidence among participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Research design and methods: We used data from 14 671 participants in the TECOS study who were randomized double-blind to sitagliptin (n = 7332) or placebo (n = 7339). Cumulative fracture incidence rates were calculated and their association with study treatment assignment was examined using multivariable Cox proportional hazards regression. Results: The baseline mean (standard deviation) participant age was 65.5 (8.0) years, diabetes duration was 11.6 (8.1) years and glycated haemoglobin level was 7.2 (0.5)% [55.2 (5.5) mmol/mol], and 29.3% of participants were women and 32.1% were non-white. During 43 222 person-years’ follow-up, 375 (2.6%; 8.7 per 1000 person-years) had a fracture; 146 were major osteoporotic fractures (hip, n = 34; upper extremity, n = 81; and clinical spine, n = 31). Adjusted analyses showed fracture risk increased independently with older age (P <.001), female sex (P <.001), white race (P <.001), lower diastolic blood pressure (P <.001) and diabetic neuropathy (P =.003). Sitagliptin, compared with placebo, was not associated with a higher fracture risk [189 vs 186 incident fractures: unadjusted hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.82 to 1.23, P =.944; adjusted HR 1.03, P =.745], major osteoporotic fractures (P =.673) or hip fractures (P =.761). Insulin therapy was associated with a higher fracture risk (HR 1.40, 95% CI 1.02-1.91; P =.035), and metformin with a lower risk (HR 0.76, 95% CI 0.59-0.98; P =.035). Conclusion: Fractures were common among people with diabetes in the TECOS study, but were not related to sitagliptin therapy. Insulin and metformin treatment were associated with higher and lower fracture risks, respectively

Cluster Analysis of Cardiovascular Phenotypes in Patients With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Potential Approach to Precision Medicine

OBJECTIVE Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined. We used cluster analysis machine-learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD. RESEARCH DESIGN AND METHODS We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n = 14,671), a cardiovascular outcome safety trial comparing sitagliptin with placebo in patients with T2DM and ASCVD (median follow-up 3.0 years). Cluster analysis using 40 baseline variables was conducted, with associations between clusters and the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina) assessed by Cox proportional hazards models. We replicated the results using the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. RESULTS Four distinct phenotypes were identified: Cluster I included Caucasian men with a high prevalence of coronary artery disease; cluster II included Asian patients with a low BMI; cluster III included women with noncoronary ASCVD disease; and cluster IV included patients with heart failure and kidney dysfunction. The primary outcome occurred, respectively, in 11.6%, 8.6%, 10.3%, and 16.8% of patients in clusters I to IV. The crude difference in cardiovascular risk for the highest versus lowest risk cluster (cluster IV vs. II) was statistically significant (hazard ratio 2.74 [95% CI 2.29–3.29]). Similar phenotypes and outcomes were identified in EXSCEL. CONCLUSIONS In patients with T2DM and ASCVD, cluster analysis identified four clinically distinct groups. Further cardiovascular phenotyping is warranted to inform patient care and optimize clinical trial designs

Associations between beta-blocker therapy and cardiovascular outcomes in patients with diabetes and established cardiovascular disease

Contains fulltext : 215191.pdf (publisher's version ) (Closed access)BACKGROUND: The effects of beta-blocker therapy in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) are unclear. We sought to evaluate associations between beta-blocker use in T2D with ASCVD and cardiovascular (CV) outcomes. METHODS: In patients with T2D and ASCVD enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), an inverse probability of treatment-weighted Cox proportional hazards model was used to examine the association between baseline beta-blocker therapy (at randomization) and the primary CV composite (defined as CV death, non-fatal myocardial infarction [MI], non-fatal stroke, or hospitalization for unstable angina), including in subgroups with prior MI and heart failure (HF); other outcomes evaluated included individual components of the primary composite, hospitalization for HF, and severe hypoglycemic events. RESULTS: Of the 14,671 patients randomized, 9322 (64%) were on a beta-blocker at baseline; these patients were more likely to have prior MI or HF. Over a median 3.0 (25th, 75th percentile: 2.2, 3.6) years, the risk of the primary CV composite was significantly higher with baseline beta-blocker use versus no beta-blocker use (4.5 vs. 3.4 events/100-patient years, adjusted hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05-1.29); no significant interaction was noted for patients with versus without prior MI or HF. Baseline beta-blocker use was not associated with risks for severe hypoglycemic events (HR 1.14, 95% CI 0.88-1.48). CONCLUSIONS: In this observational analysis of T2D and ASCVD, baseline beta-blocker use was not associated with risks for severe hypoglycemia yet also was not associated with CV risk reduction over 3 years of follow-up, supporting a randomized examination of chronic beta-blocker therapy in this patient population. (TECOS ClinicalTrials.gov number, NCT00790205)

High-risk patients with ST-elevation myocardial infarction derive greatest absolute benefit from primary percutaneous coronary intervention: results from the Primary Coronary Angioplasty Trialist versus thrombolysis (PCAT)-2 collaboration

Item does not contain fulltextBACKGROUND: Meta-analyses of randomized trials show that primary percutaneous coronary intervention (PPCI) results in lower mortality than fibrinolytic therapy in patients with myocardial infarction. We investigated which categories of patients with myocardial infarction would benefit most from the strategy of PPCI and, thus, have lowest numbers needed to treat to prevent a death. METHODS: Individual patient data were obtained from 22 (n = 6,763) randomized trials evaluating efficacy and safety of PPCI versus fibrinolysis. A risk score was developed and validated to estimate the probability of 30-day death in individuals. Patients were then divided in quartiles according to risk. Subsequent analyses were performed to evaluate if the treatment effect was modified by estimated risk. RESULTS: Overall, 446 patients (6.6%) died within 30 days after randomization. The mortality risk score contained clinical characteristics, including the time from symptom onset to randomization. The c-index was 0.76, and the Hosmer-Lemeshow test was nonsignificant, reflecting adequate discrimination and calibration. Patients randomized to PPCI had lower mortality than did patients randomized to fibrinolysis (5.3% vs 7.9%, adjusted odds ratio 0.63, 95% CI 0.42-0.84, P 2 hours, fibrinolysis remains a legitimate option in low-risk patients because of the small absolute risk reduction by PPCI in this particular cohort