piperidines and Acute-Coronary-Syndrome

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Blood Proteins; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Galectin 3; Galectins; Growth Differentiation Factor 15; Heart Disease Risk Factors; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Piperidines; Prognosis; Risk Assessment; Troponin I; Uracil

The timing of enrolment following an acute coronary syndrome (ACS) may influence cardiovascular (CV) outcomes and potentially treatment effect in clinical trials. Understanding the timing and type of clinical events after an ACS will allow for clinicians to better tailor evidence-based treatments to optimize therapeutic effect. Using a large contemporary trial in patients with type 2 diabetes mellitus (T2DM) post-ACS, we examined the impact of timing of enrolment on subsequent CV outcomes.. EXAMINE was a randomized trial of alogliptin versus placebo in 5,380 patients with T2DM and a recent ACS from October 2009 to March 2013. The primary outcome was a composite of CV death, nonfatal myocardial infarction (MI), or nonfatal stroke. The median follow-up was 18 months. In this post hoc analysis, we examined the occurrence of subsequent CV events by timing of enrollment divided by tertiles of time from ACS to randomization: 8-34, 35-56, and 57-141 days.. Patients randomized early (compared to the latest times) had less comorbidities at baseline including a history of heart failure (HF; 24.7% vs 33.0%), prior coronary artery bypass graft (9.6% vs 15.9%), or atrial fibrillation (5.9% vs 9.4%). Despite the reduced comorbidity burden, the risk of the primary outcome was highest in patients randomized early compared to the latest time (adjusted hazard ratio 1.47; 95% CI 1.21-1.74). Similarly, patients randomized early had an increased risk of recurrent MI (adjusted hazard ratio 1.51; 95% CI 1.17-1.96) and HF hospitalization (1.49; 95% CI 1.05-2.10).. In a contemporary cohort of T2DM with a recent ACS, the risk for recurrent CV events including MI and HF hospitalization is elevated early after an ACS. Given the emergence of antihyperglycemic therapies that reduce the risk of MI and HF among patients with T2DM at high CV risk, future studies evaluating the initiation of these therapies in the early period following an ACS are warranted given the large burden of potentially modifiable CV events.

Topics: Acute Coronary Syndrome; Comorbidity; Diabetes Mellitus, Type 2; Evidence-Based Practice; Female; Heart Disease Risk Factors; Humans; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Outcome and Process Assessment, Health Care; Patient Selection; Piperidines; Random Allocation; Risk Assessment; Stroke; Time Factors; Uracil

We sought to assess the risk of major adverse cardiovascular events (MACE) by utilizing high-sensitivity C-reactive protein (hsCRP) level and low-density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and recent acute coronary syndrome.. Study participants enrolled in the EXAMINE trial (Clinical trials registration number: NCT00968708) and were stratified by baseline hsCRP levels (<1, 1-3 and >3 mg/L). They were also sub-divided into 4 groups according to baseline hsCRP (≤3 or >3 mg/L) and achieved LDL-C (<70 or ≥70 mg/dL) levels. Among 5380 patients, the MACE rate, a composite of cardiovascular death, non-fatal acute myocardial infarction and non-fatal stroke, was evaluated during the 30 months of follow-up.. Cumulative incidence of MACE was 11.5% (119 events), 14.6% (209 events) and 18.4% (287 events) in patients with hsCRP levels of <1, 1 to 3 and >3 mg/L, respectively (P < .001). In patients with hsCRP >3 mg/L, the adjusted hazard ratio (95% confidence interval) was 1.42 (1.13, 1.78; P = .002) for MACE compared with patients with hsCRP <1 mg/L. MACE cumulative incidences were 11.0% (128 events), 14.4% (100 events), 15.6% (194 events) and 21.3% (182 events) in patients with low LDL-C and low hsCRP, low LDL-C and high hsCRP, high LDL-C and low hsCRP, and high LDL-C and high hsCRP levels, respectively (P < .001).. Levels of hsCRP were associated with recurrent cardiovascular events in patients with type 2 diabetes and recent acute coronary syndrome, and this association appears to be independent of and additive to the achieved LDL-C level.

Topics: Acute Coronary Syndrome; C-Reactive Protein; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Female; Heart Failure; Humans; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Piperidines; Standard of Care; Treatment Outcome; Uracil

We evaluated the antihyperglycemic efficacy and safety of adding the dipeptidyl dipeptidase-4 inhibitor alogliptin to metformin and sulphonylurea in the treatment of type 2 diabetes in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care Trial.. Patients with type 2 diabetes and recent acute coronary syndrome were randomized to alogliptin or placebo and standard of care. Participants were followed for up to 40 (median 18) months. In a subgroup taking metformin and sulphonylurea at baseline, we evaluated change from baseline in glycated hemoglobin (HbA1c), adverse events, cardiovascular outcomes, laboratory data, and other safety parameters.. There were 1398 patients receiving baseline dual therapy (metformin and sulphonylurea only) randomized to alogliptin (N = 693) or placebo (N = 705); 550 patients receiving alogliptin and 505 patients receiving placebo completed the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care without addition of other antihyperglycemic therapies (P = .008). Changes from baseline to last visit in HbA1c were -0.4% on alogliptin and +0.1% on placebo (P < .001) in all those with baseline dual therapy and -0.4% for alogliptin and +0.2% for placebo (P < .001) in those without additional therapies. Reported rates of hypoglycemia were 8.8% for alogliptin and 6.7% for placebo (P = .16). Cardiovascular death and all-cause mortality rates were lower in those receiving alogliptin compared with those receiving placebo (hazard ratio, 0.49; 95% confidence interval, 0.28-0.84 and hazard ratio, 0.61; 95% confidence interval, 0.38-0.96, respectively).. Addition of the dipeptidyl peptidase-4 inhibitor alogliptin to dual therapy with metformin plus sulfonylurea significantly reduced HbA1c and was well tolerated. Lower mortality rates were seen in patients treated with alogliptin in this subgroup.

Topics: Acute Coronary Syndrome; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Piperidines; Sulfonylurea Compounds; Treatment Outcome; Uracil

Alogliptin, a dipeptidyl peptidase-4 inhibitor, is approved for the treatment of patients with type 2 diabetes (T2DM). EXAMINE was a randomized controlled clinical trial designed to demonstrate the cardiovascular (CV) safety of alogliptin. In the trial, 5380 patients with established T2DM who had a recent acute coronary syndrome event (between 15 and 90 days) were randomized to treatment with either alogliptin or placebo. To better understand and describe the CV safety of alogliptin, we analyzed data from the EXAMINE trial to determine whether treatment with alogliptin affected recurrent and total CV events. Poisson regression analysis compared the total number of occurrences of CV death, MI, stroke, unstable angina, and coronary revascularization between all patients randomized to alogliptin vs placebo groups. Patients with recurrent CV events were older and more likely to have renal disease and history of heart failure. There were 1100 first CV events and an additional 666 recurrent events over a median of 18 months of follow-up. There were no significant differences with regard to total number of events in patients treated with alogliptin (n = 873) or placebo (n = 893; P = 0.52). Furthermore, there were no differences in the types of events seen in patients treated with alogliptin or placebo. Alogliptin did not increase the risk of either first or recurrent CV events when compared with placebo in patients with T2DM and recent acute coronary syndrome. These data support the CV safety of alogliptin in patients who are at increased risk of future CV events.

Topics: Acute Coronary Syndrome; Aged; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Piperidines; Stroke; Survival Rate; Treatment Outcome; United States; Uracil

Antihyperglycemic therapies may increase the risk of cardiovascular events including hospitalization for heart failure. There is a paucity of data evaluating the cardiovascular safety of antihyperglycemic therapies in the high-risk period following an acute coronary syndrome (ACS).. The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial randomized 5380 patients who were 15 to 90 days post ACS to the dipeptidyl dipeptidase-IV (DPP-IV) inhibitor alogliptin versus placebo; mean follow-up was 18 months. Using a landmark analysis, we assessed the (1) burden of cardiovascular events from randomization to 6 months (early period) and from 6 months to the end of follow-up (late period) and (2) the risk of cardiovascular events associated with early (up to 6 months) and chronic (6 months to end of follow-up) DPP-IV inhibition with alogliptin. Patients with early versus late events had similar baseline demographic profiles. Overall, 42.1% of the composite of cardiovascular death/myocardial infarction/stroke and 47.5% of hospitalization for heart failure occurred in the early period. Early DPP-IV inhibition did not increase the risk of early cardiovascular death/myocardial infarction/stroke (hazard ratio 0.96, 95% confidence interval, 0.76-1.21) or hospitalization for heart failure (1.23, 95% confidence interval, 0.84-1.82). Similarly, chronic DPP-IV inhibition did not increase the risk of late cardiovascular death/myocardial infarction/stroke (hazard ratio 1.03, 95% confidence interval, 0.89-1.26) or hospitalization for heart failure (hazard ratio 1.02, 95% confidence interval, 0.85-1.22).. Early after an ACS, patients with type 2 diabetes mellitus experience a significant burden of HF events and recurrent ACS. DPP-IV inhibition with alogliptin appears to be safe even in the high-risk period following an ACS.

Topics: Acute Coronary Syndrome; Aged; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Piperidines; Recurrence; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome; Uracil

To investigate relationships between glycated haemoglobin (HbA1c) and reported hypoglycaemia and risk of major adverse cardiovascular events (MACE).. The EXAMINE trial randomized 5380 patients with type 2 diabetes (T2DM) and a recent acute coronary syndrome (ACS) event, in 49 countries, to double-blind treatment with alogliptin or placebo in addition to standard of care. We used Cox proportional hazards models to analyse relationships among MACE, HbA1c levels and hypoglycaemic events.. Patients randomized to alogliptin achieved lower HbA1c levels than the placebo group in all baseline HbA1c categories without differences in hypoglycaemia rates. No systematic change was found in MACE rates according to baseline HbA1c (P. There were no relationships between baseline HbA1c levels or HbA1c levels after 1 month of treatment and the risk of MACE. Alogliptin improved glycaemic control without increasing hypoglycaemia. Reported events of hypoglycaemia and serious hypoglycaemia were associated with MACE. These data underscore the safety of alogliptin in improving glycaemic control in T2DM post-ACS. Further study of hypoglycaemia as an independent risk factor for MACE in patients with T2DM and coronary disease is needed.

Topics: Acute Coronary Syndrome; Cardiovascular Diseases; Cohort Studies; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Male; Middle Aged; Piperidines; Risk Factors; Secondary Prevention; Severity of Illness Index; Uracil

To investigate adiponectin levels and cardiovascular (CV) outcomes in patients with diabetes and recent acute coronary syndrome (ACS).. We analysed baseline adiponectin concentration and CV outcomes in 5213 patients with type 2 diabetes enrolled in the EXAMINE trial of alogliptin vs placebo 15 to 90 days (median 45 days) after ACS. Event rates at 18 months are reported.. The median (interquartile range) baseline adiponectin concentration was 5.2 (3.5-7.9) μg/mL. Patients with the highest baseline adiponectin concentration (quartile [Q]4) were at significantly higher risk of death from a CV event (8.4% vs 1.7%; P < .0001), hospitalization for heart failure (HF; 7.5% vs 1.7%; P < .0001), and all-cause mortality (10.8% vs 2.4%; P < .0001) compared with those in Q1. After adjusting for age, sex, index event, HF, estimated glomerular filtration rate and hypertension, adiponectin concentration in Q4 remained associated with an increased risk of death from CV causes (hazard ratio [HR] 2.43, 95% confidence interval [CI] 1.52, 3.88), all-cause mortality (HR 2.45, 95% CI 1.65, 3.64), and HF (HR 2.44, 95% CI 1.47, 4.05), without change after stratification by body mass index. There was no significant difference in the rate of myocardial infarction or stroke.. In this contemporary population of patients with diabetes and ACS, adiponectin concentration was independently associated with increased risk of death from CV causes, all-cause mortality, and hospitalization for HF. The relationship between adiponectin and CV outcomes is complex and deserves further study.

Topics: Acute Coronary Syndrome; Adiponectin; Aged; Biomarkers; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Mortality; Piperidines; Proportional Hazards Models; Risk; Secondary Prevention; Uracil

We aimed to describe the relationship between changes in high-sensitivity cardiac troponin I (hsTnI) and cardiovascular outcomes.. The EXAMINE trial (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) was a phase IIIb clinical outcomes trial designed to evaluate the cardiovascular safety of alogliptin, a nonselective dipeptidyl peptidase 4 inhibitor. Patients with type 2 diabetes mellitus, glycohemoglobin between 6.5% and 11% (or between 7% and 11% if they were on insulin), and a recent acute coronary syndrome (between 15 and 90 days before randomization) were eligible for the trial. hsTnI was measured using the Abbott ARCHITECT assay at baseline and 6 months in patients randomized in the EXAMINE trial. This analysis was restricted to patients randomized ≥30 days after qualifying acute coronary syndrome to mitigate the potential for persistent hsTnI elevation after acute coronary syndrome (n=3808). The primary end point of the trial was cardiovascular death, myocardial infarction, or stroke. Cardiovascular death or heart failure was a prespecified, adjudicated secondary end point.. Serial assessment of hsTnI revealed a substantial proportion of patients with type 2 diabetes mellitus without clinically recognized events had dynamic or persistently elevated values and were at high risk of recurrent events. hsTnI may have a role in personalizing preventive strategies in patients with diabetes mellitus based on risk.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00968708.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Piperidines; Standard of Care; Treatment Outcome; Troponin I; Uracil

Concerns raised regarding adverse cardiovascular (CV) outcomes with new therapies for type 2 diabetes mellitus (T2DM) have led to several large-scale CV outcome trials. The EXAMINE trial confirmed noninferiority of the dipeptidyl dipeptidase 4 inhibitor alogliptin to placebo on major adverse cardiac event rates in a post-acute coronary syndrome (ACS) T2DM population. We present data on additional ischemic cardiac events and CV hospitalizations in EXAMINE.. Patients with T2DM and an ACS event in the previous 15 to 90 days were randomly assigned to alogliptin or placebo on a background of standard treatment for diabetes. The incident rates of a 5-component composite end point of CV death, stroke, myocardial infarction, unstable angina, and coronary revascularization as well as CV hospitalization were calculated in all participants and according to macrovascular disease at baseline.. There were no significant differences between alogliptin (n = 2,701) and placebo (n = 2,679) in the event rate of the 5-component composite endpoint with median follow-up 533 days (21.0% vs 21.5%, hazard ratio [HR] 0.98 [0.87-1.10], P = .72). No differences were observed in terms of CV hospitalization (25.0% vs 25.4%, HR 0.98 [0.88-1.09], P = .70) or coronary revascularization (10.6% vs 10.2%, HR 1.05 [0.88-1.09], P = .60). No interactions were observed for treatment and prior macrovascular disease.. EXAMINE demonstrates that there was no increase in the risk of cardiac ischemic events and CV hospitalizations with alogliptin in a high-risk post-ACS patient population. Because these are major driver of overall health care costs, these data suggest that there would be no adverse impact on health care resource utilization.

Topics: Acute Coronary Syndrome; Aged; Diabetes Mellitus, Type 2; Female; Hospitalization; Humans; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Outcome and Process Assessment, Health Care; Piperidines; Risk Assessment; Standard of Care; Stroke; Uracil

Activation of the sympathetic nervous system when there is dipeptidyl peptidase 4 inhibition in the presence of high-dose angiotensin-converting enzyme (ACE) inhibition has led to concerns of potential increases in cardiovascular events when the 2 classes of drugs are coadministered. We evaluated cardiovascular outcomes from the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care) trial according to ACE inhibitor use. Patients with type 2 diabetes mellitus and a recent acute coronary syndrome were randomly assigned to receive the dipeptidyl peptidase 4 inhibitor alogliptin or placebo added to existing antihyperglycemic and cardiovascular prophylactic therapies. Risks of adjudicated cardiovascular death, nonfatal myocardial infarction and stroke, and hospitalized heart failure were analyzed using a Cox proportional hazards model in patients according to ACE inhibitor use and dose. There were 3323 (62%) EXAMINE patients treated with an ACE inhibitor (1681 on alogliptin and 1642 on placebo). The composite rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were comparable for alogliptin and placebo with ACE inhibitor (11.4% versus 11.8%; hazard ratio, 0.97; 95% confidence interval, 0.79-1.19; P=0.76) and without ACE inhibitor use (11.2% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=0.62). Composite rates for cardiovascular death and heart failure in patients on ACE inhibitor occurred in 6.8% of patients on alogliptin versus 7.2% on placebo (hazard ratio, 0.93; 95% confidence interval, 0.72-1.2; P=0.57). There were no differences for these end points nor for blood pressure or heart rate in patients on higher doses of ACE inhibitor. Cardiovascular outcomes were similar for alogliptin and placebo in patients with type 2 diabetes mellitus and coronary disease treated with ACE inhibitors.

Topics: Acute Coronary Syndrome; Aged; Angiotensin-Converting Enzyme Inhibitors; Confidence Intervals; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Piperidines; Prognosis; Proportional Hazards Models; Prospective Studies; Reference Values; Risk Assessment; Survival Rate; Treatment Outcome; Uracil

The EXAMINE trial showed non-inferiority of the DPP-4 inhibitor alogliptin to placebo on major adverse cardiac event (MACE) rates in patients with type 2 diabetes and recent acute coronary syndromes. Concerns about excessive rates of in-hospital heart failure in another DPP-4 inhibitor trial have been reported. We therefore assessed hospital admission for heart failure in the EXAMINE trial.. Patients with type 2 diabetes and an acute coronary syndrome event in the previous 15-90 days were randomly assigned alogliptin or placebo plus standard treatment for diabetes and cardiovascular disease prevention. The prespecified exploratory extended MACE endpoint was all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, urgent revascularisation due to unstable angina, and hospital admission for heart failure. The post-hoc analyses were of cardiovascular death and hospital admission for heart failure, assessed by history of heart failure and brain natriuretic peptide (BNP) concentration at baseline. We also assessed changes in N-terminal pro-BNP (NT-pro-BNP) from baseline to 6 months. This study is registered with ClinicalTrials.gov, number NCT00968708.. 5380 patients were assigned to alogliptin (n=2701) or placebo (n=2679) and followed up for a median of 533 days (IQR 280-751). The exploratory extended MACE endpoint was seen in 433 (16·0%) patients assigned to alogliptin and in 441 (16·5%) assigned to placebo (hazard ratio [HR] 0·98, 95% CI 0·86-1·12). Hospital admission for heart failure was the first event in 85 (3·1%) patients taking alogliptin compared with 79 (2·9%) taking placebo (HR 1·07, 95% CI 0·79-1·46). Alogliptin had no effect on composite events of cardiovascular death and hospital admission for heart failure in the post hoc analysis (HR 1·00, 95% CI 0·82-1·21) and results did not differ by baseline BNP concentration. NT-pro-BNP concentrations decreased significantly and similarly in the two groups.. In patients with type 2 diabetes and recent acute coronary syndromes, alogliptin did not increase the risk of heart failure outcomes.. Takeda Development Center Americas.

Topics: Acute Coronary Syndrome; Aged; Angina, Unstable; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Piperidines; Risk Factors; Stroke; Uracil

Comprehensive safety evaluation of new drugs for diabetes mellitus is needed in the area of cardiovascular (CV) outcomes, particularly in populations with high CV risk. Alogliptin, a dipeptidyl peptidase 4 inhibitor, is under development for the treatment of type 2 diabetes mellitus alone or in combination with other antidiabetic therapies. Long-term CV safety of alogliptin is being established in a randomized, placebo-controlled clinical study in patients with acute coronary syndrome (ACS) using an analytical approach that has both an interim and final assessment. The primary CV end point for this trial is a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Approximately 5,400 men and women with type 2 diabetes and ACS (acute myocardial infarction or unstable angina) are being recruited and will be followed up for up to 4.5 years postrandomization. The statistical plan for the trial uses a design that evaluates the hazard ratio (HR) of alogliptin to placebo first based on the primary CV composite end point after accrual of 80 to 150 primary CV events and again when there are 550 to 650 primary CV events. In the first series of analyses, the upper bound of a group-sequential 1-sided repeated CI for the HR must be ≤1.8 for registration in the United States. At end of study, the upper bound of a subsequent group-sequential 1-sided repeated CI for the HR must be ≤1.3. For both group sequential analyses, the repeated CIs are calculated to insure simultaneous coverage probabilities of 97.5% for the true HR. Study progress: More than 2,000 ACS patients were randomized as of June 2011. EXAMINE will define the CV safety profile of this dipeptidyl peptidase 4 inhibitor in patients at high risk for CV events.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Treatment Outcome; Uracil

Patients with type 2 diabetes (T2D) may experience frequent body weight changes over time. The prognostic impact of these weight changes (gains or losses) requires further study.. To study the associations between changes in body weight (intentional or unintentional) with subsequent outcomes.. The EXAMINE trial included 5380 patients with T2D and a recent acute coronary syndrome, who were randomized to alogliptin or placebo. Time-updated Cox models and mixed effects models were used to test the associations between changes in body weight and subsequent outcomes over a median follow-up of 1.6 (1.0-2.1) years.. During the post-randomization follow-up period, 1044 patients (19.4%) experienced a weight loss ≥ 5% of baseline weight, 2677 (49.8%) had a stable weight, and 1659 (30.8%) had a ≥ 5 % weight gain. Patients with weight loss were more frequently women and had more co-morbid conditions. In contrast, patients who gained ≥ 5% weight were more frequently men with less co-morbid conditions. A weight loss ≥ 5% was independently associated with a higher risk of subsequent adverse outcomes, including all-cause mortality: adjusted HR (95% CI) = 1.79 (1.33-2.42), P < 0.001. Similar associations were found for cardiovascular mortality, the composite of cardiovascular mortality or heart failure hospitalization, and the primary outcome. A weight gain ≥ 5% was independently associated with an increase in the risk of subsequent cardiovascular mortality or heart failure hospitalization only: adjusted HR (95% CI) = 1.34 (1.02-1.76), P = 0.033.. In patients with T2D who had a recent ACS/MI, a ≥ 5% loss of body weight was associated with a higher risk of subsequent cardiovascular events and mortality.

Topics: Acute Coronary Syndrome; Aged; Body Mass Index; Comorbidity; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Incidence; Male; Middle Aged; Piperidines; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Uracil; Weight Gain; Weight Loss

Topics: Acute Coronary Syndrome; Angina, Unstable; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Male; Myocardial Infarction; Peptides; Piperidines; Uracil

Topics: Acute Coronary Syndrome; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Heart Failure; Humans; Hypoglycemic Agents; Male; Piperidines; Uracil

Topics: Acute Coronary Syndrome; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Heart Failure; Humans; Hypoglycemic Agents; Male; Piperidines; Uracil

Topics: Acute Coronary Syndrome; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Heart Failure; Humans; Hypoglycemic Agents; Male; Piperidines; Uracil

Topics: Acute Coronary Syndrome; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Heart Failure; Humans; Hypoglycemic Agents; Male; Piperidines; Uracil

Topics: Acute Coronary Syndrome; Aged; Editorial Policies; Female; Humans; Medical Records, Problem-Oriented; Migraine Disorders; Periodicals as Topic; Piperidines; Publishing; Research Report; Switzerland; Tryptamines; Vasoconstrictor Agents; Writing

This case report describes for the first time acute coronary syndrome in a 67-year old patient after oral intake of naratriptan for migraine. So far in the literature, only sumatriptan, zolmitriptan and frovatriptan have been described to cause acute coronary syndromes. A 67-year old Swiss woman with thoracic pain after intake of 2.5 mg naratriptan presented with T-wave inversions in the ECG and a positive troponin-T at our hospital. Coronary angiography showed normal coronary arteries. Naratriptan-induced coronary vasospasms were thought to have caused the acute coronary syndrome.Triptans should not be prescribed in patients with pre-existing coronary heart disease. However, triptans can also cause acute coronary syndromes in patients without coronary heart disease--as described in our case report. Severe or persistent thoracic pain after intake of triptans should therefore be investigated accordingly.

Topics: Acute Coronary Syndrome; Aged; Electrocardiography; Female; Humans; Migraine Disorders; Piperidines; Serotonin Agents; Treatment Outcome; Troponin T; Tryptamines