Strike early-strike strong lipid-lowering strategy with PCSK9i in ACS patients. Real-world evidence from AT-TARGET-IT registry.

AIMS: No data are available on early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with acute coronary syndrome (ACS) in real-world. This study investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. METHODS: The lipid control outcome was the percentage of patients reaching the LDL-C target of < 55 mg/dL at first lipid control. The clinical outcome was the incidence of composite major CV events (all cause death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization) during follow-up in relation to quartiles of LDL-C at first lipid control. RESULTS: We included 771 patients with ACS from AT-TARGET-IT registry, receiving PCSK9i prescription during hospitalization or at discharge. Median LDL-C was 137 mg/dL and decreased to 43 mg/dL at first lipid control. 527 (68.3%) patients achieved LDL-C target at the first lipid control at a median time of 37 days from hospitalization; of them, 404 (76.8%) were discharged on statin plus ezetimibe background therapy. Event curves through a median follow-up of 11 months across quartiles of LDL-C showed a stepwise lower risk of 4P-MACE, 3P-MACE, all-cause mortality, and ischemia-driven revascularization in lower quartile of LDL-C values at first lipid control (<23 mg/dL) and in patients reaching LDL-C <55 mg/dL. CONCLUSIONS: Intensive and early lipid-lowering therapy using PCSK9i in patients with ACS (strike early strike strong strategy) is safe and effective in clinical practice and associated with a reduction of residual CV risk.

This study, from AT-TARGET-IT registry, investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. Intensive and early PCSK9i therapy reduce composite major cardiovascular (CV) events in patients in reaching LDL-C target values. A strike early-strike strong strategy is safe and effective.

Achievement of target LDL-cholesterol level in patients with acute coronary syndrome undergoing percutaneous coronary intervention: The JET-LDL registry.

BACKGROUND: In patients with acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level < 1.4 mmol/L (<55 mg/dL). METHODS: The JET-LDL is a multicenter, observational, prospective registry created to investigate levels of LDL-C in consecutive patients with ACS undergoing PCI at 35 Italian hospitals, and to report their lipid lowering therapies (LLT). Follow-up was planned at 1 and 3 months. LDL-C reduction >50% from baseline or level < 55 mg/dL at 1-month was the primary endpoint. RESULTS: A total of 1095 patients were included: median age was 67 (58-75); 33.7% were already on LLT. Baseline LDL-C levels was 105 (76.5-137) mg/dL. At hospital discharge all patients were on LLT: 98.1% received statins (as mono or combination therapy), ezetimibe and PCSK9i were used in 60.1% and 8.5% of cases, respectively. Primary endpoint was achieved in 62% (95% CI 58-65) of cases. At 1-month LDL-C levels dropped to 53 (38-70) mg/dL (p < 0.001 vs baseline) and it was <55 mg/dL in 53% (95% CI 49-57) of patients; however, PCSK9i were added to 7 further cases. At 3-months 58% (95% CI 55-62) of patients achieved the target level, but PCSK9i was added to only 11 new patients. CONCLUSIONS: In this real-world registry of ACS patients undergoing PCI, recommend LDL-C levels were obtained in 62% of patients, but PCSK9i prescription was limited to 10% of cases. As LLT pattern appeared mainly improved at hospital discharge, an early and strong treatment should be considered.

Acute coronary syndromes: hospital management of dyslipidaemia with proprotein convertase subtilisin/kexin 9 inhibitors: time to act.

Atherosclerotic cardiovascular disease (ASCVD) in its countless clinical presentations is, in industrialized countries, the most frequent cause of death and, in recent years, a leading role in the prevention of ASCVD has been attributed to the treatment of dyslipidaemias. If statins and ezetimibe remain the cornerstone of pharmacological treatment, an increasingly relevant role is attributed to the inhibitors of the proprotein convertase subtilisin/kexin 9 (PCSK9i), as a result of the excellent results obtained in their respective trials, not only on the reduction of low-density lipoprotein (LDL) or LDL cholesterol (LDL-C) but also on plaque stabilization and regression. The addition of PCSK9 inhibitors leads to a further reduction in LDL levels and a consequent improvement in prognosis and it is recommended in 'fast-track' administration (intrahospital/discharge) in patients with acute coronary syndromes (ACSs) or multiple cardiovascular events already on statin therapy and LDL >70 mg/dL and in statin-naïve ACS patients and LDL >140 mg/dL. By applying guidelines and fast-track, ∼25% of patients with ACS should receive PCSK9i at discharge but unfortunately patients are currently undertreated.

[The importance of intensive lipid-lowering therapy after acute coronary syndrome: changing the paradigm to improve the achievement of targets]. / L'importanza di una terapia ipolipemizzante intensiva dopo sindrome coronarica acuta: cambiare il paradigma per migliorare il raggiungimento dei target.

BACKGROUND: Despite the availability of effective lipid-lowering drugs, only few high-risk patients attain their LDL cholesterol (LDL-C) guideline-recommended risk-based goal because of underprescription of combination therapy. We present an 18-month experience with variation of prescription protocols after publication of the 2019 ESC/EAS guidelines for the management of dyslipidemias. METHODS: Overall, 621 consecutive patients hospitalized for acute coronary syndrome at Mauriziano Hospital in Turin, Italy, between January 2020 and June 2021 were enrolled. Lipid-lowering therapy recommended at discharge was registered to evaluate how many patients received statin monotherapy, statin plus ezetimibe combination or triple therapy with high-intensity statin plus ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i). At 6-month follow-up, the reduction in LDL-C, adverse events, compliance and cardiovascular recurrences was analyzed. RESULTS: Of 621 patients enrolled, 7 died during hospitalization. During the entire study period, 33% of patients received statin monotherapy, 50% were discharged on statin-ezetimibe combination, and PCSK9i (evolocumab) was prescribed to 17% of patients. Between April 2020 and June 2021, when new recommendations were introduced into clinical practice, 20% of patients received evolocumab, 56% combination therapy and only 24% were discharged on statin monotherapy. At the beginning of observation, evolocumab was prescribed to 3% of patients hospitalized for acute coronary syndrome, while at the end of the study period 27% of patients were discharged on PCSK9i, with an increase of the prescription rate by 759%; in the same period, prescription of statin monotherapy decreased by 75%. At 6-month follow-up, LDL-C reduction was 77% in patients treated with PCSK9i vs 48% in patients taking statin-ezetimibe combination therapy (p<0.001). All patients on evolocumab reached the guideline-directed goals and a low rate of adverse events was reported, mainly represented by local injection site reactions. Six patients experienced acute coronary syndrome recurrence; only one of them was treated with evolocumab. CONCLUSION: Prescription of intensive lipid-lowering therapy after acute coronary syndrome, eventually with introduction of PCSK9i during hospitalization or at discharge, leads to attainment of guideline-recommended goals for all patients, with a low incidence of adverse events and optimal compliance.

Clinical value of left atrial appendage flow for prediction of long-term sinus rhythm maintenance in patients with nonvalvular atrial fibrillation.

OBJECTIVES: This study evaluated the role of various clinical and echocardiographic parameters, including the left atrial appendage (LAA) anterograde flow velocity, for prediction of the long-term preservation of sinus rhythm (SR) in patients with successful cardioversion (CV) of nonvalvular atrial fibrillation (AF). BACKGROUND: Echocardiographic parameters for assessing long-term SR maintenance after successful CV of nonvalvular AF are not accurately defined. METHODS: Clinical, transthoracic echocardiographic and transesophageal echocardiographic (TEE) data--measured in AF lasting >48 h--of 186 consecutive patients (116 men, mean age: 65 +/- 9 years) with successful CV (electrical or pharmacologic) were analyzed for assessment of one-year maintenance of SR. RESULTS: At one-year follow-up, 91 of 186 (49%) patients who underwent successful CV continued to have SR. Mean LAA peak emptying flow velocity was higher in patients remaining in SR for one year than in those with AF relapse (41.7 +/- 20.2 cm/s vs. 27.7 +/- 17.0 cm/s; p < 0.001). On multivariate logistic regression analysis, only the mean LAA peak emptying velocity >40 cm/s (p = 0.0001; chi(2): 23.9, odds ratio [OR] = 5.2, confidence interval [CI] 95% = 2.7 to 10.1) and the use of preventive antiarrhythmic drug treatment (p = 0.0398; chi(2): 4.2; OR = 2.0, CI 95% = 1.0 to 3.8) predicted the continuous preservation of SR during one year, outperforming other univariate predictors such as absence of left atrial spontaneous echocardiographic contrast during TEE, the left atrial parasternal diameter <44 mm, left ventricular ejection fraction >46% and AF duration <1 week before CV. The negative and positive predictive values of the mean LAA peak emptying velocity >40 cm/s for assessing preservation of SR were 66% (CI 95% = 56.9 to 74.2) and 73% (CI 95% = 62.4 to 83.3), respectively. CONCLUSIONS: In TEE-guided management of nonvalvular AF, high LAA flow velocity identifies patients with greater likelihood to remain in SR for one year after successful CV. Low LAA velocity is of limited value in identifying patients who will relapse into AF.