Resting heart rate and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk analysis from the ONTARGET/TRANSCEND trials

2018 ◽  
Vol 41 (2) ◽  
pp. 231-238 ◽  
Author(s):  
Michael Böhm ◽  
Helmut Schumacher ◽  
Koon K Teo ◽  
Eva M Lonn ◽  
Felix Mahfoud ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Heart Rate ◽  
Primary Outcome ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Diabetic Patients ◽  
Resting Heart Rate ◽  
High Cardiovascular Risk ◽  
Patients With Diabetes

Abstract Aims Resting heart rate (RHR) has been shown to be associated with cardiovascular outcomes in various conditions. It is unknown whether different levels of RHR and different associations with cardiovascular outcomes occur in patients with or without diabetes, because the impact of autonomic neuropathy on vascular vulnerability might be stronger in diabetes. Methods and results We examined 30 937 patients aged 55 years or older with a history of or at high risk for cardiovascular disease and after myocardial infarction, stroke, or with proven peripheral vascular disease from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination followed for a median of 56 months. We analysed the association of mean achieved RHR on-treatment with the primary composite outcome of cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, the components of the composite primary outcome, and all-cause death as continuous and categorical variables. Data were analysed by Cox regression analysis, ANOVA, and χ2 test. These trials were registered with ClinicalTrials.gov.number NCT00153101. Patients were recruited from 733 centres in 40 countries between 1 December 2001 and 31 July 2008 (ONTARGET) and 1 November 2001 until 30 May 2004 (TRANSCEND). In total, 19 450 patients without diabetes and 11 487 patients with diabetes were stratified by mean RHR. Patients with diabetes compared to no diabetes had higher RHRs (71.8 ± 9.0 vs. 67.9 ± 8.8, P < 0.0001). In the categories of <60 bpm, 60 ≤ 65 bpm, 65 ≤ 70 bpm, 70 ≤ 75 bpm, 75 ≤ 80 bpm and ≥80 bpm, non-diabetic patients had an increased hazard of the primary outcome with mean RHR of 75 ≤ 80 bpm (adjusted hazard ratio [HR] 1.17 (1.01–1.36)) compared to RHR 60 ≤ 65 bpm. For patients with in-trial RHR ≥80 bpm the hazard ratios were highest (diabetes: 1.96 (1.64–2.34), no diabetes: 1.73 (1.49–2.00), For cardiovascular death hazards were also clearly increased at RHR ≥80 bpm (diabetes [1.99, (1.53–2.58)], no diabetes [1.73 (1.38–2.16)]. Similar results were obtained for hospitalization for heart failure and all-cause death while the effect of RHR on myocardial infarction and stroke was less pronounced. Results were robust after adjusting for various risk indicators including beta-blocker use and atrial fibrillation. No significant association to harm was observed at lower RHR. Conclusion Mean RHR above 75–80 b.p.m. was associated with increased risk for cardiovascular outcomes except for stroke. Since in diabetes, high RHR is associated with higher absolute event numbers and patients have higher RHRs, this association might be of particular clinical importance in diabetes. These data suggest that RHR lowering in patients with RHRs above 75–80 b.p.m. needs to be studied in prospective trials to determine if it will reduce outcomes in diabetic and non-diabetic patients at high cardiovascular risk. Clinical Trial registration http://clinicaltrials.gov.Unique identifier: NCT00153101.

Cardiovascular outcomes and achieved blood pressure in patients with and without diabetes at high cardiovascular risk

2019 ◽  
Vol 40 (25) ◽  
pp. 2032-2043 ◽  
Author(s):  
Michael Böhm ◽  
Helmut Schumacher ◽  
Koon K Teo ◽  
Eva M Lonn ◽  
Felix Mahfoud ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Risk ◽  
Primary Outcome ◽  
Cox Regression ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Composite Outcome ◽  
High Cardiovascular Risk ◽  
Increased Risk ◽  
Patients With Diabetes

Abstract Aims Studies have shown a non-linear relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) and outcomes, with increased risk observed at both low and high blood pressure (BP) levels. We hypothesized that the BP-risk association is different in individuals with and without diabetes at high cardiovascular risk. Methods and results We identified patients with (N = 11 487) or without diabetes (N = 19 450), from 30 937 patients, from 133 centres in 44 countries with a median follow-up of 56 months in the ONTARGET/TRANSCEND studies. Patients had a prior history of stroke, myocardial infarction (MI), peripheral artery disease, or were high-risk diabetics. Patients in ONTARGET had been randomized to ramipril 10 mg daily, telmisartan 80 mg daily, or the combination of both. Patients in TRANSCEND were ACE intolerant and randomized to telmisartan 80 mg daily or matching placebo. We analysed the association of mean achieved in-trial SBP and DBP with the composite outcome of cardiovascular death, MI, stroke and hospitalization for congestive heart failure (CHF), the components of the composite, and all-cause death. Data were analysed by Cox regression and restricted cubic splines, adjusting for risk markers including treatment allocation and accompanying cardiovascular treatments. In patients with diabetes, event rates were higher across the whole spectrum of SBP and DBP compared with those without diabetes (P < 0.0001 for the primary composite outcome, P < 0.01 for all other endpoints). Mean achieved in-trial SBP ≥160 mmHg was associated with increased risk for the primary outcome [diabetes/no diabetes: adjusted hazard ratio (HR) 2.31 (1.93–2.76)/1.66 (1.36–2.02) compared with non-diabetics with SBP 120 to <140 mmHg], with similar findings for all other endpoints in patients with diabetes, and for MI and stroke in patients without diabetes. In-trial SBP <120 mmHg was associated with increased risk for the combined outcome in patients with diabetes [HR 1.53 (1.27–1.85)], and for cardiovascular death and all-cause death in all patients. In-trial DBP ≥90 mmHg was associated with increased risk for the primary outcome [diabetes/no diabetes: HR 2.32 (1.91–2.82)/1.61 (1.35–1.93) compared with non-diabetics with DBP 70 to <80 mmHg], with similar findings for all other endpoints, but not for CHF hospitalizations in patients without diabetes. In-trial DBP <70 mmHg was associated with increased risk for the combined outcome in all patients [diabetes/no diabetes: HR 1.77 (1.51–2.06)/1.30 (1.16–1.46)], and also for all other endpoints except stroke. Conclusion High on treatment BP levels (≥160 or ≥90 mmHg) are associated with increased risk of cardiovascular outcomes and death. Also low levels (<120 or <70 mmHg) are associated with increased cardiovascular outcomes (except stroke) and death. Patients with diabetes have consistently higher risks over the whole BP range, indicating that achieving optimal BP goals is most impactful in this group. These data favour guidelines taking lower BP boundaries into consideration, in particular in diabetes. Clinical trial registration http://clinicaltrials.gov.Unique identifier: NCT00153101.

scholarly journals Treatment of Heart Failure with Sodium-Glucose Cotransporter 2 Inhibitors and Other Anti-diabetic Drugs

2019 ◽  
Vol 5 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Thomas A Zelniker ◽  
Eugene Braunwald
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Renal Failure ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide 1

Patients with type 2 diabetes are at increased risk of developing heart failure, cardiovascular death and renal failure. The recent results of three large sodium-glucose cotransporter 2 inhibitor cardiovascular outcomes trials have demonstrated a reduction in heart failure hospitalisation and progressive renal failure. One trial also showed a fall in cardiovascular and total death. A broad spectrum of patients with diabetes benefit from these salutary effects in cardiac and renal function and so these trials have important implications for the management of patients with type 2 diabetes. Selected glucagon-like peptide 1 receptor agonists have also been shown to reduce adverse cardiovascular outcomes.

scholarly journals A genetic model of ivabradine recapitulates results from randomized clinical trials

2020 ◽  
Author(s):  
Marc-André Legault ◽  
Johanna Sandoval ◽  
Sylvie Provost ◽  
Amina Barhdadi ◽  
Louis-Philippe Lemieux Perreault ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Rate ◽  
Drug Target ◽  
Drug Targets ◽  
Risk Model ◽  
Cardiovascular Death ◽  
Increased Risk ◽  
The Uk

ABSTRACTBackgroundNaturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects. This study evaluates the effect of a mutation in HCN4, ivabradine’s drug target, on safety and efficacy endpoints.MethodsWe used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes.ResultsUsing data from the UK Biobank and large GWAS consortia, we evaluated the effect of a heart rate-reducing genetic variant at the HCN4 locus encoding ivabradine’s drug target. These genetic association analyses showed increases in risk for atrial fibrillation (OR 1.09, 95% CI: 1.06-1.13, P=9.3 ×10−9) in the UK Biobank. In a cause-specific competing risk model to account for the increased risk of atrial fibrillation, the HCN4 variant reduced incident heart failure in participants that did not develop atrial fibrillation (HR 0.90, 95% CI: 0.83-0.98, P=0.013). In contrast, the same heart rate reducing HCN4 variant did not prevent a composite endpoint of myocardial infarction or cardiovascular death (OR 0.99, 95% CI: 0.93-1.04, P=0.61).ConclusionGenetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.CONDENSED ABSTRACTThe effects of drugs can sometimes be predicted from the effects of mutations in genes encoding drug targets. We tested the effect of a heart rate reducing allele at the HCN4 locus encoding ivabradine’s drug target and found results coherent with the SHIFT and SIGNIFY clinical trials of ivabradine. The genetic variant increased the risk of atrial fibrillation and cardioembolic stroke and protected against heart failure in a competing risk model accounting for the increased risk of atrial fibrillation. The variant had a neutral effect on a composite of myocardial infarction and cardiovascular death.

88Oxygen therapy in myocardial infarction patients with or without diabetes mellitus - A predefined subgroup analysis from the DETO2X-AMI trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Hofmann ◽  
T Jernberg ◽  
B Lindahl ◽  
O Ostlund ◽  
D Erlinge ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Oxygen Therapy ◽  
Composite Endpoint ◽  
Ambient Air ◽  
Supplemental Oxygen ◽  
Cardiovascular Death ◽  
Patients With Diabetes ◽  
One Year ◽  
Event Rates

Abstract Background In diabetes, there is an interaction between hyperglycaemia and cellular hypoxia, which may induce oxidative stress. Oxygen therapy in patients with diabetes and myocardial infarction (MI) has not been studied. Purpose Our aim was to determine the effects of supplemental oxygen in MI patients with or without diabetes. Methods The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomised 6629 patients with suspected myocardial infarction (MI) to receive oxygen at 6 L/min for 6–12 hours or ambient air. In this prespecified analysis involving 5010 patients with confirmed MI, 934 had known diabetes (19%). The main composite endpoint was the effect of supplemental oxygen on all-cause death, rehospitalisation with MI, or heart failure at one year in patients with diabetes. Key secondary endpoint was the comparison between patients with or without diabetes. Results In patients with diabetes, the main composite endpoint occurred in 16.2% (72 of 445) of patients allocated to oxygen compared to 16.6% (81 of 489) allocated to ambient air (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.67–1.27, P=0.81) at one year (figure). There was no statistically significant difference for the individual components of the main composite endpoint, or the rate of cardiovascular death up to one year. In comparison, corresponding endpoints in patients without diabetes were similar between the treatment groups. However, when comparing patients according to diabetes status, event rates were significantly higher in the diabetic population (main composite endpoint: HR 1.60; 95% CI, 1.32–1.93, P<0.01). Kaplan-Meier curves for main endpoint Conclusions Oxygen therapy in normoxemic MI patients did not significantly affect 1-year all-cause death, cardiovascular death, rehospitalisation with MI or heart failure, irrespective of underlying diabetes. Noteworthy, despite that the incidence of cardiovascular outcomes has declined substantially in patients with diabetes over the last decades, we still observed markedly increased event rates in patients with diabetes. Acknowledgement/Funding Swedish Heart-Lung Foundation; Swedish Research Council; Stockholm County Council

scholarly journals Hypertension Management in the High Cardiovascular Risk Population

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Ilir Maraj ◽  
John N. Makaryus ◽  
Anthony Ashkar ◽  
Samy I. McFarlane ◽  
Amgad N. Makaryus
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Blood Pressure ◽  
Cardiovascular Risk ◽  
Diabetic Patients ◽  
Hypertension Management ◽  
High Cardiovascular Risk ◽  
Risk Population ◽  
Real Challenge ◽  
Prevention Of Cardiovascular Disease

The incidence of hypertension is increasing every year. Blood pressure (BP) control is an important therapeutic goal for the slowing of progression as well as for the prevention of Cardiovascular disease. The management of hypertension in the high cardiovascular risk population remains a real challenge as the population continues to age, the incidence of diabetes increases, and more and more people survive acute myocardial infarction. We will review hypertension management in the high cardiovascular risk population: patients with coronary heart disease (CHD) and heart failure (HF) as well as in diabetic patients.

scholarly journals Comparative Effectiveness of Early Rhythm Control Versus Rate Control for Cardiovascular Outcomes in Patients With Atrial Fibrillation

2021 ◽  
Author(s):  
Daehoon Kim ◽  
Pil‐Sung Yang ◽  
Seng Chan You ◽  
Eunsun Jang ◽  
Hee Tae Yu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Rate Control ◽  
Cardiovascular Death ◽  
Population Based ◽  
Cardiovascular Outcomes ◽  
Rhythm Control ◽  
Control Treatment ◽  
Control Rhythm

Background Rhythm control is associated with better cardiovascular outcomes than usual care among patients with recently diagnosed atrial fibrillation (AF). This study investigated the effects of rhythm control compared with rate control on the incidence of stroke, heart failure, myocardial infarction, and cardiovascular death stratified by timing of treatment initiation. Methods and Results We conducted a retrospective population‐based cohort study including 22 635 patients with AF newly treated with rhythm control (antiarrhythmic drugs or ablation) or rate control in 2011 to 2015 from the Korean National Health Insurance Service database. Propensity overlap weighting was used. Compared with rate control, rhythm control initiated within 1 year of AF diagnosis decreased the risk of stroke. The point estimates for rhythm control initiated at selected time points after AF diagnosis are as follows: 6 months (hazard ratio [HR], 0.76; 95% CI, 0.66–0.87), 1 year (HR, 0.78; 95% CI, 0.66–0.93), and 5 years (HR, 1.00; 95% CI, 0.45–2.24). The initiation of rhythm control within 6 months of AF diagnosis reduced the risk of hospitalization for heart failure: 6 months (HR, 0.84; 95% CI, 0.74–0.95), 1 year (HR, 0.96; 95% CI, 0.82–1.13), and 5 years (HR, 2.88; 95% CI, 1.34–6.17). The risks of myocardial infarction and cardiovascular death did not differ between rhythm and rate control regardless of treatment timing. Conclusions Early initiation of rhythm control was associated with a lower risk of stroke and heart failure–related admission than rate control in patients with recently diagnosed AF. The effects were attenuated as initiating the rhythm control treatment later.

scholarly journals Cardiovascular outcomes in patients who experienced a myocardial infarction while treated with liraglutide versus placebo in the LEADER trial

2018 ◽  
Vol 15 (5) ◽  
pp. 465-468 ◽  
Author(s):  
Michael A Nauck ◽  
Karen Tornøe ◽  
Søren Rasmussen ◽  
Marianne Bach Treppendahl ◽  
Steven P Marso
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Confidence Interval ◽  
Animal Studies ◽  
Cox Regression ◽  
Myocardial Necrosis ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Hazard Ratio

Objective: Animal studies demonstrated that glucagon-like peptide-1 receptor agonists reduce myocardial necrosis following regional ischaemia induction. This effect may improve cardiovascular outcomes after myocardial infarction. Risk of cardiovascular death or hospitalisation for heart failure after myocardial infarction was evaluated in patients with type 2 diabetes at high cardiovascular risk in the LEADER trial. Methods: Data from patients randomised to liraglutide or placebo, in addition to standard of care, in Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) (NCT01179048) were analysed post hoc. Cox regression, with myocardial infarction as a time-dependent covariate, was used to analyse time from randomisation to a composite of cardiovascular death or hospitalisation for heart failure. Results: Patients who experienced myocardial infarction had a sevenfold higher risk of the composite endpoint (with myocardial infarction: n = 148, 25.0%; without myocardial infarction: n = 716, 8.2%; hazard ratio: 7.0; 95% confidence interval: 5.8, 8.4). The risk of the composite endpoint after myocardial infarction was not significantly lower in the liraglutide group ( n = 63, 23.0%) compared with placebo ( n = 85, 26.7%; hazard ratio: 0.91; 95% confidence interval: 0.66, 1.26). Conclusion: The data demonstrated that having myocardial infarction significantly increased the risk of subsequent cardiovascular death or hospitalisation for heart failure. However, we did not find evidence for a reduced risk in these cardiovascular outcomes following myocardial infarction in patients treated with liraglutide versus placebo.

scholarly journals Impact of Insulin Treatment on the Effect of Eplerenone: Insights From the EMPHASIS-HF Trial

2021 ◽  
Vol 14 (6) ◽  
Author(s):  
João Pedro Ferreira ◽  
Zohra Lamiral ◽  
John J.V. McMurray ◽  
Karl Swedberg ◽  
Dirk J. van Veldhuisen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Primary Outcome ◽  
Systolic Heart Failure ◽  
Cardiovascular Death ◽  
Cardiovascular Complications ◽  
Number Needed To Treat ◽  
Unique Identifier ◽  
Cox Models ◽  
Reduced Ejection Fraction ◽  
Patients With Diabetes

Background: Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, including those treated with insulin in the EMPHASIS-HF trial (Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms). Methods: The primary outcome was the composite of heart failure hospitalization or cardiovascular death. Cox models with treatment-by-diabetes subgroup interaction terms were used. Results: The median follow-up was 21 (10–33) months. Of the 2737 patients included, 623 (23%) had non-insulin-treated diabetes, 236 (9%) had insulin-treated diabetes and 1878 did not have diabetes. Patients with insulin-treated diabetes were younger, more often women, with higher body mass index, waist circumference, more frequent ischemic heart failure cause, impaired kidney function, and longer diabetes duration. Compared with patients without diabetes, those with insulin-treated diabetes had a 2-fold higher risk of having a primary outcome event. The hazard ratio (95% CI) for the effect of eplerenone, compared with placebo, on the primary outcome was 0.31 (0.19–0.50) in insulin-treated diabetes, 0.69 (0.50–0.93) in non-insulin-treated diabetes, and 0.72 (0.58–0.88) in patients without diabetes; interaction P =0.007. The annualized number needed-to-treat-to-benefit with regards to the primary outcome was 3 (95% CI, 3–4) in patients with insulin-treated diabetes, 16 (13–19) in patients with diabetes not receiving insulin, and 26 (24–28) in patients without diabetes. Conclusions: Patients with insulin-treated diabetes experienced a greater benefit from eplerenone than those with diabetes not treated with insulin and people without diabetes. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00232180.

Sign in / Sign up

Export Citation Format

Share Document