European Heart Journal - Cardiovascular Pharmacotherapy最新文献

Aims: Our study aimed to assess whether a single pill concept (SPC) is superior to a multi pill concept (MPC) in reducing cardiovascular (CV) events, all-cause death, and costs in CV patients.

Method and results: Anonymized medical claims data covering 2012-2018, including patients with hypertension, dyslipidemia, and CV diseases who started a drug therapy either as SPC or identical MPC were analyzed after 1:1-Propensity Score Matching (PSM). Hospitalizations with predefined CV events, all-cause mortality, and costs were studied in 25,311 patients with SPC and 25,311 patients with MPC using incidence rate ratios (IRRs) and non-parametric tests for continuous variables.IRRs were significantly lower for SPC: stroke (IRR=0.77; 95% CI 0.67-0.88; p<0.001), transitory ischemic attack (IRR=0.61; 95% CI 0.48-0.78; p<0.001), myocardial infarction (IRR=0.76; 95% CI 0.63-0.90; p=0.0016), coronary artery disease (IRR=0.66; 95% CI 0.57-0.77; p<0.001), heart failure (IRR=0.59; 95% CI 0.54-0.64; p<0.001), acute renal failure (IRR=0.54; 95% CI 0.56-0.64; p<0.001), all cause hospitalization (IRR=0.72; 95% CI 0.71-0.74; p<0.001), CV hospitalization (IRR=0.63; 95% CI 0.57-0.69; p<0.001), and all-cause mortality (IRR=0.62; 95% CI 0.57-0.68; p<0.001). Mean time to first events and time to death were also in favor of SPC. Mean total costs were 4,708 € for SPC vs. 5.669 € for MPC, respectively (MR 0.830, p<0.001).

Conclusion: SPC is associated with lower incidence rates of CV events, time to CV events, and all-cause death, and is superior regarding pharmacoeconomic parameters and should therefore become standard of care to improve outcomes and reduce healthcare costs.

Aims: To assess the use and associations with outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in a real-world population with heart failure (HF) and type 2 diabetes mellitus (T2DM).

Methods and results: The Swedish HF Registry was linked with the National Diabetes Registry and other national registries. Independent predictors of GLP-1 RA use were assessed by multivariable logistic regressions and associations with outcomes were assessed by Cox regressions in a 1:1 propensity score-matched cohort. Of 8188 patients enrolled in 2017-21, 9% received a GLP-1 RA. Independent predictors of GLP-1 RA use were age <75 years, worse glycaemic control, impaired renal function, obesity, and reduced ejection fraction (EF). GLP-1 RA use was not significantly associated with a composite of HF hospitalization (HHF) or cardiovascular (CV) death regardless of EF, but was associated with a lower risk of major adverse CV events (CV death, non-fatal stroke/transient ischaemic attack, or myocardial infarction), and CV and all-cause death. In patients with body mass index ≥30 kg/m2, GLP-1 RA use was also associated with a lower risk of HHF/CV death and HHF alone.

Conclusions: In patients with HF and T2DM, GLP-1 RA use was independently associated with more severe T2DM, reduced EF, and obesity and was not associated with a higher risk of HHF/CV death but with longer survival and less major CV adverse events. An association with lower HHF/CV death and HHF was observed in obese patients. Our findings provide new insights into GLP-1 RA use and its safety in HF and T2DM.

Aims: Large outcome trials have demonstrated cardiovascular benefits of selected glucagon-like peptide-1 (GLP-1) receptor agonists. We examined coronary disease outcomes in the Harmony Outcomes trial of the GLP-1 receptor agonist albiglutide.

Methods and results: Harmony Outcomes was an event-driven, multicenter, double-blind, and placebo-controlled trial involving 9463 patients >40 years of age with type-2 diabetes and established atherosclerotic cardiovascular disease. It tested the effects of albiglutide on the occurrence of a composite primary endpoint, consisting of cardiovascular death, myocardial infarction (MI), or stroke. Within this post-hoc analysis, the effects of albiglutide on MI subtypes and other ischaemic endpoints were analysed.During the median-follow up of 1.6 years, a total of 421 patients (4.5%) experienced at least one MI, with 72 patients having more than one event. Treatment with albiglutide reduced both first events [hazard ratio (HR) 0.75 (0.62-0.91)] and overall events [HR 0.75 (0.61-0.91)] as well as first type 1 [HR 0.73 (0.57-0.92)] and type 2 myocardial infarctions [HR 0.65 (0.46-0.92)]. The effect of albiglutide treatment was consistent for ST-segment elevation [HR 0.69 (0.38-1.26)] and non-ST elevation (HR 0.86 (0.66-1.2) MI.

Conclusion: Treatment with the GLP-1 receptor agonist albiglutide resulted in a 25% relative risk reduction in MI that was consistent for type of infarction and presence or absence of ST elevation. Our findings add novel information about the effects of GLP-1 receptor agonists on ischaemic events in patients with type 2 diabetes.

Background: An increasing number of hypertensive persons travel to high altitude (HA) while using antihypertensive medications such as beta-blockers. Nevertheless, while hypoxic exposure initiates an increase in pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR), the contribution of the autonomic nervous system is unclear. In animals, beta-adrenergic blockade has induced pulmonary vasoconstriction in normoxia and exaggerated hypoxic pulmonary vasoconstriction (HPV) and both effects were abolished by muscarinic blockade. We thus hypothesized that in humans, propranolol (PROP) increases Ppa and PVR in normoxia and exaggerates HPV, and that these effects of PROP are abolished by glycopyrrolate (GLYC).

Methods: In seven healthy male lowlanders, Ppa was invasively measured without medication, with PROP and PROP + GLYC, both at sea level (SL, 488 m) and after a 3-week sojourn at 3454 m altitude (HA). Bilateral thigh-cuff release manoeuvres were performed to derive pulmonary pressure-flow relationships and pulmonary vessel distensibility.

Results: At SL, PROP increased Ppa and PVR from (mean ± SEM) 14 ± 1 to 17 ± 1 mmHg and from 69 ± 8 to 108 ± 11 dyn s cm-5 (21% and 57% increase, P = 0.01 and P < 0.0001). The PVR response to PROP was amplified at HA to 76% (P < 0.0001, P[interaction] = 0.05). At both altitudes, PROP + GLYC abolished the effect of PROP on Ppa and PVR. Pulmonary vessel distensibility decreased from 2.9 ± 0.5 to 1.7 ± 0.2 at HA (P < 0.0001) and to 1.2 ± 0.2 with PROP, and further decreased to 0.9 ± 0.2% mmHg-1 with PROP + GLYC (P = 0.01).

Conclusions: Our data show that beta-adrenergic blockade increases, and muscarinic blockade decreases PVR, whereas both increase pulmonary artery elastance. Future studies may confirm potential implications from the finding that beta-adrenergic blockade exaggerates HPV for the management of mountaineers using beta-blockers for prevention or treatment of cardiovascular conditions.

The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

Aims: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have a direct cardiac effect that is likely to be independent of its glucose lowering renal effect. Previous research has shown that SGLT2-is mitigate heart failure and prevent arrhythmic cardiac death. Our objective is to determine whether SGLT-2is reduce atrial fibrillation (AF) in comparison to other second-to third-line antidiabetic drugs in type 2 diabetes.

Methods and results: We conducted a population-based, new-user active comparator cohort study using data from the UK Clinical Practice Research Datalink. We identified a cohort of patients initiating a new antidiabetic drug class between January 2013 and September 2020. This cohort included patients initiating their first ever non-insulin antidiabetic drug, as well as those who switched to or added-on an antidiabetic drug class not previously used in their treatment history. Individuals with a diagnosis of AF or atrial flutter at any time before cohort entry were excluded. Cox regression analysis with time-dependent covariates was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of AF comparing SGLT-2-is with other second-line to third-line antidiabetic drugs. Stratified analyses were performed according to sex, diabetes duration (<5 or ≥ 5 years), body mass index (BMI), HbA1c, and presence of heart failure.The cohort comprised 142 447 patients. SGLT-2is were associated with a statistically significant reduced hazard of AF compared to other second-line to third-line antidiabetic drugs (adjusted HR: 0.77 [95% CI: 0.68-0.88]). This reduced risk was present in both sexes but was more prominently among women (adjusted HRwomen: 0.60 [95% CI: 0.45-0.79]; HRmen: 0.85 [95% CI: 0.73-0.98]; P-value interaction: 0.012). There was no evidence for effect modification when stratifying on duration of diabetes, BMI, HbA1c, or presence of heart failure.

Conclusion: SGLT-2is were associated with a reduced risk of AF in patients with type 2 diabetes compared to other second-line to third-line antidiabetic drugs. This reduced risk occurs in both sexes but more prominently among women.