In this randomized study, the addition of lixisenatide, a glucagon-like peptide 1–receptor agonist, to usual care in patients with type 2 diabetes and a recent cardiovascular event did not alter the ...rate of subsequent major cardiovascular or other serious adverse events.
Randomized trials involving patients with new or established type 2 diabetes have shown that improved glucose control reduces the risk of microvascular complications,
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with modest cardiovascular benefits suggested by meta-analyses and extended follow-up of clinical trials.
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However, various studies indicate that, despite being effective in lowering the glucose and glycated hemoglobin levels, some hypoglycemic medications may increase, rather than reduce, the risk of cardiovascular events.
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These unexpected findings prompted the reexamination of the regulatory approval processes for new antidiabetic therapies, which had been based primarily on the surrogate measure of glucose lowering with limited clinical-outcomes data. Since . . .
In a randomized trial, more than 1100 patients with nonischemic heart failure (left ventricular ejection fraction ≤35%) were assigned either to receive or not to receive an ICD. At a median of 67.6 ...months, there was no significant difference in mortality between the two groups.
In both European and U.S. guidelines, prophylactic implantation of an implantable cardioverter–defibrillator (ICD) is a class 1 recommendation for patients with heart failure and reduced left ventricular systolic function.
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However, the evidence for a benefit is much stronger for patients with ischemic heart disease than it is for patients with heart failure from other causes. Over the past two decades, ICD implantation has been shown to be associated with substantial reductions in the rate of sudden cardiac death and total mortality in patients with ischemic heart disease.
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In the case of patients without ischemic heart disease, one trial . . .
AbstractObjectiveTo investigate the association between SARS-CoV-2 vaccination and myocarditis or myopericarditis.DesignPopulation based cohort study.SettingDenmark.Participants4 931 775 individuals ...aged 12 years or older, followed from 1 October 2020 to 5 October 2021.Main outcome measuresThe primary outcome, myocarditis or myopericarditis, was defined as a combination of a hospital diagnosis of myocarditis or pericarditis, increased troponin levels, and a hospital stay lasting more than 24 hours. Follow-up time before vaccination was compared with follow-up time 0-28 days from the day of vaccination for both first and second doses, using Cox proportional hazards regression with age as an underlying timescale to estimate hazard ratios adjusted for sex, comorbidities, and other potential confounders.ResultsDuring follow-up, 269 participants developed myocarditis or myopericarditis, of whom 108 (40%) were 12-39 years old and 196 (73%) were male. Of 3 482 295 individuals vaccinated with BNT162b2 (Pfizer-BioNTech), 48 developed myocarditis or myopericarditis within 28 days from the vaccination date compared with unvaccinated individuals (adjusted hazard ratio 1.34 (95% confidence interval 0.90 to 2.00); absolute rate 1.4 per 100 000 vaccinated individuals within 28 days of vaccination (95% confidence interval 1.0 to 1.8)). Adjusted hazard ratios among female participants only and male participants only were 3.73 (1.82 to 7.65) and 0.82 (0.50 to 1.34), respectively, with corresponding absolute rates of 1.3 (0.8 to 1.9) and 1.5 (1.0 to 2.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 1.48 (0.74 to 2.98) and the absolute rate was 1.6 (1.0 to 2.6) per 100 000 vaccinated individuals within 28 days of vaccination. Among 498 814 individuals vaccinated with mRNA-1273 (Moderna), 21 developed myocarditis or myopericarditis within 28 days from vaccination date (adjusted hazard ratio 3.92 (2.30 to 6.68); absolute rate 4.2 per 100 000 vaccinated individuals within 28 days of vaccination (2.6 to 6.4)). Adjusted hazard ratios among women only and men only were 6.33 (2.11 to 18.96) and 3.22 (1.75 to 5.93), respectively, with corresponding absolute rates of 2.0 (0.7 to 4.8) and 6.3 (3.6 to 10.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 5.24 (2.47 to 11.12) and the absolute rate was 5.7 (3.3 to 9.3) per 100 000 vaccinated individuals within 28 days of vaccination.ConclusionsVaccination with mRNA-1273 was associated with a significantly increased risk of myocarditis or myopericarditis in the Danish population, primarily driven by an increased risk among individuals aged 12-39 years, while BNT162b2 vaccination was only associated with a significantly increased risk among women. However, the absolute rate of myocarditis or myopericarditis after SARS-CoV-2 mRNA vaccination was low, even in younger age groups. The benefits of SARS-CoV-2 mRNA vaccination should be taken into account when interpreting these findings. Larger multinational studies are needed to further investigate the risks of myocarditis or myopericarditis after vaccination within smaller subgroups.
In this randomized, controlled trial conducted at Danish cardiac centers, intravenous antibiotic therapy was compared with partial oral antibiotic therapy for the treatment of bacterial endocarditis. ...The outcomes were similar in the two groups.
In this trial, 7016 patients with heart failure were assigned to aliskiren, enalapril, or both. At 36 months, the rate of cardiovascular death or heart-failure hospitalization was not lower with ...combination therapy than with enalapril. Aliskiren was not noninferior to enalapril.
Angiotensin-converting–enzyme (ACE) inhibitors are effective in lowering the risks of death and hospitalization among patients with chronic heart failure and reduced ejection fraction.
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As a consequence, there has been interest in other approaches to interruption of the renin–angiotensin system in patients with heart failure. Angiotensin-receptor blockers (ARBs) were the first alternative tested, and in one placebo-controlled trial, candesartan was associated with lower risks of death from cardiovascular causes and hospitalization for heart failure among patients who could not take ACE inhibitors.
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However, in a head-to-head comparison, losartan was not as effective as captopril.
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Objectives The purpose of this study was to investigate the risk of thrombosis and bleeding according to multiple antithrombotic treatment regimens in atrial fibrillation (AF) patients after ...myocardial infarction (MI) or percutaneous coronary intervention (PCI). Background The optimal antithrombotic treatment strategy is unresolved in patients with multiple indications. Methods A total of 12,165 AF patients hospitalized with MI and/or undergoing PCI between 2001 and 2009 were identified by nationwide registries (60.7% male; mean age 75.6 years). Risk of MI/coronary death, ischemic stroke, and bleeding according to antithrombotic treatment regimen was estimated by Cox regression models. Results Within 1 year, MI or coronary death, ischemic stroke, and bleeding events occurred in 2,255 patients (18.5%), 680 (5.6%), and 769 (6.3%), respectively. Relative to triple therapy (oral anticoagulation OAC plus aspirin plus clopidogrel), no increased risk of recurrent coronary events was seen for OAC plus clopidogrel (hazard ratio HR: 0.69, 95% confidence interval CI: 0.48 to 1.00), OAC plus aspirin (HR: 0.96, 95% CI: 0.77 to 1.19), or aspirin plus clopidogrel (HR: 1.17, 95% CI: 0.96 to 1.42), but aspirin plus clopidogrel was associated with a higher risk of ischemic stroke (HR: 1.50, 95% CI: 1.03 to 2.20). Also, OAC plus aspirin and aspirin plus clopidogrel were associated with a significant increased risk of all-cause death (HR: 1.52, 95% CI: 1.17 to 1.99 and HR: 1.60, 95% CI: 1.25 to 2.05, respectively). When compared to triple therapy, bleeding risk was nonsignificantly lower for OAC plus clopidogrel (HR: 0.78, 95% CI: 0.55 to 1.12) and significantly lower for OAC plus aspirin and aspirin plus clopidogrel. Conclusions In real-life AF patients with indication for multiple antithrombotic drugs after MI/PCI, OAC and clopidogrel was equal or better on both benefit and safety outcomes compared to triple therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patients undergoing surgical aortic valve replacement (SAVR) are considered at high risk of infective endocarditis (IE). However, data on the risk of IE following transcatheter aortic valve ...replacement (TAVR) are sparse and limited by the lack of long-term follow-up as well as a direct comparison with patients undergoing SAVR.
This study sought to investigate the long-term incidence of IE in patients undergoing TAVR and to compare the long-term risk of IE with patients undergoing isolated SAVR.
In this nationwide observational cohort study, all patients undergoing TAVR and isolated SAVR from January 1, 2008, to December 31, 2016, with no history of IE and alive at discharge were identified using data from Danish nationwide registries.
A total of 2,632 patients undergoing TAVR and 3,777 patients undergoing isolated SAVR were identified. During a mean follow-up of 3.6 years, 115 patients (4.4%) with TAVR and 186 patients (4.9%) with SAVR were admitted with IE. The median time from procedure to IE hospitalization was 352 days (25th to 75th percentile: 133 to 778 days) in the TAVR group and 625 days (25th to 75th percentile: 209 to 1,385 days) in the SAVR group. The crude incidence rates of IE were 1.6 (95% confidence interval CI: 1.4 to 1.9) and 1.2 (95% CI: 1.0 to 1.4) events per 100 person-years in TAVR and SAVR patients, respectively. The cumulative 1-year risk of IE was 2.3% (95% CI: 1.8% to 2.9%) and 1.8% (95% CI: 1.4% to 2.3%) in TAVR and SAVR patients, respectively. Correspondingly, the cumulative 5-year risk of IE was 5.8% (95% CI: 4.7% to 7.0%) and 5.1% (95% CI: 4.4% to 6.0%), respectively. In multivariable Cox proportional hazard analysis, TAVR was not associated with a statistically significant different risk of IE compared with SAVR (hazard ratio: 1.12; 95% CI: 0.84 to 1.49).
The 5-year incidence of IE following TAVR was 5.8% and not significantly different than the incidence following SAVR.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Among patients in Denmark who survived for 30 days after out-of-hospital cardiac arrest, bystander CPR and bystander defibrillation were associated with significantly lower risks of brain damage or ...nursing home admission and of death from any cause than no bystander intervention.
Summary Background Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. ...We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only. Methods We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularisation of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov , number NCT01960933. Findings From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularisation guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0·56, 95% CI 0·38–0·83; p=0·004). Interpretation In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularisation should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints. Funding Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Aims
In observational studies, non-alcoholic fatty liver disease (NAFLD) is associated with high risk of ischaemic heart disease (IHD). We tested the hypothesis that a high liver fat content ...or a diagnosis of NAFLD is a causal risk factor for IHD.
Methods and results
In a cohort study of the Danish general population (n = 94 708/IHD = 10 897), we first tested whether a high liver fat content or a diagnosis of NAFLD was associated observationally with IHD. Subsequently, using Mendelian randomization, we tested whether a genetic variant in the gene encoding the protein patatin-like phospholipase domain containing 3 protein (PNPLA3), I148M (rs738409), a strong and specific cause of high liver fat content and NAFLD, was causally associated with the risk of IHD. We found that the risk of IHD increased stepwise with increasing liver fat content (in quartiles) up to an odds ratio (OR) of 2.41 (1.28–4.51)(P-trend = 0.004). The corresponding OR for IHD in individuals with vs. without NAFLD was 1.65 (1.34–2.04)(P = 3×10−6). PNPLA3 I148M was associated with a stepwise increase in liver fat content of up to 28% in MM vs. II-homozygotes (P-trend = 0.0001) and with ORs of 2.03 (1.52–2.70) for NAFLD (P = 3×10−7), 3.28 (2.37–4.54) for cirrhosis (P = 4×10−12), and 0.95 (0.86–1.04) for IHD (P = 0.46). In agreement, in meta-analysis (N = 279 013/IHD = 71 698), the OR for IHD was 0.98 (0.96–1.00) per M-allele vs. I-allele. The OR for IHD per M-allele higher genetically determined liver fat content was 0.98 (0.94–1.03) vs. an observational estimate of 1.05 (1.02–1.09)(P for comparison = 0.02).
Conclusion
Despite confirming the known observational association of liver fat content and NAFLD with IHD, lifelong, genetically high liver fat content was not causally associated with risk of IHD. These results suggest that the observational association is due to confounding or reverse causation.
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