Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Arritmias potenciadas por isquemia sub-epicárdica en pared transmural heterogénea cardiaca: un estudio teórico de simulación

La fibrilación ventricular, la isquemia miocárdica y la muerte súbita son fisiopatologías cardiacas inseparables. La influencia de la distribución de células del medio miocardio en la formación de arritmias en la pared heterogénea cardiaca en presencia de isquemia sub-epicárdica, no está del todo dilucidada. En este estudio se modela una porción plana de la pared transmural con diferentes configuraciones de células del medio miocardio que se adjuntan a las heterogeneidades bioquímicas presentes en isquemia sub-epicárdica para cuantificar su influencia en la formación de arritmias. Se obtuvieron reentradas lobulares no sostenidas en torno de la lesión isquémica que interfieren con las células M, alterando la repolarización del tejido. La función de vulnerabilidad que cuantifica la prospección a reentradas es aproximada por una función logística, y su mayor expresión ocurre en el minuto 8,75 de isquemia modelada. La heterogeneidad bioquímica y morfológica en el tejido virtual estudiado dan como resultado una arritmia por reentrada; su secuela en la vulnerabilidad del tejido aumenta a medida que crece la severidad de la hiperkalemia. Los electrogramas obtenidos muestran depresión TQ y elevación ST con una morfología de taquicardia ventricular polimórfica

Intra-variability in IB4- and IB4+ DRG neurons: a population of models study

[EN] The neural action potential (AP) depends on the level of expression of the different channel families, decisively influencing neuronal excitability. Since the experimental study of these phenomena has considerable limitations, the contributions of computational models are increasingly useful. In this study, a population of models of cultured dorsal root ganglion (DRG) neurons has been developed allowing the identification of parameter sets that give rise to APs congruent with the experimental ones regarding two types of DRG neurons: IB4- and IB4+. The results show a high degree of consistency with the experimental results reproducing the greater excitability of IB4- DRG neurons over IB4+ neurons. The intra-species APs have been successfully simulated by considering the intrinsic variability of the expression levels of the different families of channels. This methodology allows the determination of the correct ion channel expression levels to model the neuron AP.Puche-García, V.; López-Sánchez, N.; Villalba-Riquelme, E.; Hingorani-Jai Prakash, S.; Ferrer-Montiel, A.; Moreno-Manzano, V.; Ferrero De Loma-Osorio, JM. (2022). Intra-variability in IB4- and IB4+ DRG neurons: a population of models study. Universidad de Valladolid. 361-364. http://hdl.handle.net/10251/19168136136

"Impact of age on management and prognosis of resuscitated sudden cardiac death patients"

Background: Sudden cardiac death (SCD) has a great impact on healthcare due to cardiologic and neurological complications. Admissions of elderly people in Cardiology Intensive Care Units have increased. We assessed the impact of age in presentation, therapeutic management and in vital and neurological prognosis of SCD patients. Methods: We carried out a retrospective, observational, multicenter registry of patients who were admitted with a SCD in 5 tertiary hospitals from January 2013 to December 2020. We divided our cohort into two groups (patients 1 at admission, time to CPR initiation > 5 min, time to ROSC > 20 min and lactate > 2 mmol/L were independent predictors for in-hospital mortality. Non-shockable rhythm, Killip class > 1 at admission, time to CPR initiation > 5 min and time to ROSC > 20 min but not age were independent predictors for poor neurological outcomes. Conclusions: Age determined a less aggressive management and it was associated with a worse vital prognosis in patients admitted with a SCD. Nevertheless, age was not associated with worse neurological outcomes