Lipid-lowering Therapy For Secondary Prevention Research Articles

Early, Intensive and Persistent Lipid-Lowering Therapy for Secondary Prevention of Acute Coronary Syndrome.

Early and intensive low-density lipoprotein (LDL-C)-lowering therapy plays important roles in secondary prevention of acute coronary syndrome (ACS), but the treatment period for further clinical benefit remains undefined. This single-center, retrospective study explored LDL-C trajectory after ACS and its associations with subsequent cardiovascular events (CVE). In 831 patients with ACS, we evaluated LDL-C reduction during the first 2 months post-ACS as an index of early intervention and the area over the curve for LDL-C using 70 mg/dl as the threshold in the next 6 months (AOC-70) as a persistent intensity index. Patients were followed for a median of 3.0 (1.1-5.2) years for CVE, defined as the composite of cardiovascular death, non-fatal myocardial infarction, angina pectoris requiring revascularization, cerebral infarction, and coronary bypass grafting. LDL-C decreased from baseline to 2 months post-ACS (107±38 mg/dl to 78±25 mg/dl, p＜0.001) through high-intensity statin prescription (91.8%), while achieving rates of LDL-C ＜70 mg/dl at 2 months remained only 40.2% with no significant changes thereafter. During the follow-up period, CVE occurred in 200 patients. LDL-C reduction during the first 2 months and AOC-70 in the next 6 months were both associated with subsequent CVE risk (sub-HR [hazard ratio] [95% confidence interval]: 1.48 [1.16-1.89] and 1.22 [1.05-1.44]). Furthermore, early intervention followed by persistently intensive LDL-C-lowering therapy resulted in further CVE risk reduction. The present study observed that achieving early and intensive LDL-C reduction within the first two months after ACS and maintaining it for the next six months suppressed subsequent CVE risk, suggesting the importance of early, intensive, and persistent LDL-C-lowering therapy in the secondary prevention of ACS.

New possibilities for lipid level control using inclisiran — prospects for interaction between a cardiologist and a neurologist

Dyslipidemia is one of the most significant modifiable cardiovascular risk factors. The change in the modern paradigm for dyslipidemia treatment from high-intensity statin therapy to high-intensity lipid-lowering therapy makes it possible to more often use new drug classes to achieve the target level of low-density lipoprotein cholesterol. The article presents two case reports on the use of inclisiran as part of combination lipid-lowering therapy for secondary prevention in patients at very high cardiovascular risk. Based on the presented cases, following clinical aspects of the management of cardiovascular patients are discussed: the safety of achieving low-density lipoprotein cholesterol levels below 1 mmol/l in a patient with asymptomatic cerebral infarction, the need for adequate dyslipidemia treatment after revascularization, the strategic importance of prescribing lipid-lowering therapy in patients with cerebrovascular disease to reduce the cardiovascular risk, adherence to therapy as a significant aspect of effective dyslipidemia control.

Gaps in Guideline-Based Lipid-Lowering Therapy for Secondary Prevention in the United States: A Retrospective Cohort Study of 322 153 Patients.

Many patients with atherosclerotic cardiovascular disease (ASCVD) are not on guideline-recommended statin therapy. We evaluated utilization of statins and other lipid-lowering therapy (LLT), and changes in low-density lipoprotein cholesterol (LDL-C), among patients with ASCVD over a 1-year period. LLT and LDL-C levels at the first outpatient visit (January 1, 2017-December 31, 2018) and 1-year follow-up were evaluated using data from Cerner Real-World Data, an electronic health record-derived data set from 92 US health systems. Logistic regression was used to evaluate factors associated with high-intensity statin use. We identified 322 153 patients with ASCVD (median age 69 years, 58.8% men, 81.8% White). Overall, 76.1% of patients were on statins, with only 39.4% on high-intensity statins. Men were more likely to receive high-intensity statins than women (multivariable-adjusted odds ratio, 1.34 [95% CI, 1.30-1.38]). Increasing age was associated with lower odds of statin use (odds ratio, 0.79 per 5-year increase at 60 years [95% CI, 0.78-0.81]). Patients with peripheral artery disease (odds ratio, 0.40 [95% CI, 0.37-0.42]) and cerebrovascular disease (odds ratio, 0.75 [95% CI, 0.70-0.80]) had lower odds of using high-intensity statins than those with coronary artery disease. At baseline, most patients (61.3%) had elevated LDL-C (≥70 mg/dL), including 59.8% of those on low/moderate-intensity statins and 76.1% on no statin; only 45.3% achieved an LDL-C <70 mg/dL at 1 year. Nonstatin LLT use was low (ezetimibe, 4.4%; proprotein convertase subtilisin/kexin type 9 inhibitors, 0.7%). Among patients on no statin or low/moderate-intensity statin at baseline, 14.8% and 13.4%, respectively, were on high-intensity statins at 1 year. Among patients with ASCVD in routine care, high-intensity statins are underutilized, and uptitration and use of nonstatin therapy are uncommon. Women, older adults, and individuals with noncardiac ASCVD are particularly undertreated. Concerted efforts are needed to address therapeutic inertia for lipid management in patients with ASCVD.

Uptake of non-statin lipid-lowering therapies for secondary prevention in community practice

Nearly two-thirds of individuals with atherosclerotic cardiovascular disease (ASCVD) do not reach target low-density lipoprotein cholesterol despite statin therapy. Three novel lipid-lowering therapies have proven to further reduce ASCVD beyond statins, including: ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), and icosapent ethyl. This study evaluated the use of these three agents in 728,423 individuals with ASCVD from 89 US health systems from 01/2018 through 03/2021 using the electronic health record. As of 2021, only 6.0% of ASCVD patients were on ezetimibe, 1.6% were on a PCSK9i, and 1.3% on icosapent ethyl, with utilization only marginally increasing over the study period. Addressing the underutilization of non-statin lipid-lowering therapy for secondary prevention is a critical step in improving the treatment gap of patients with residual risk of ASCVD.

Have the ESC guidelines improved the identification and prevention of individuals at risk of premature myocardial infarction?

Abstract Background Over the last 20 years, the proportion of young patients admitted for MI has increased. It is unknown whether the 5-year changes in ESC/EAS guidelines and the new SCORE2 can improve the detection and treatment of individuals at risk of premature MI. Purpose To determine how consecutive changes in the ESC/EAS guidelines affected the identification and treatment of young adults premature STEMI. Methods Patients admitted for a first STEMI in the ePARIS between 2010 and 2018 were included (n=2757) and stratified by age categories (&amp;lt;55 y-o; 55–65 y-o; &amp;gt;65 y-o). Using baseline characteristics, we evaluated whether patients in each age group would have been detected as high risk and treated with primary prevention statins before their first STEMI based on the 2021 EAS/ESC guidelines versus 2019 and 2016 guidelines (class I, IIA and IIB recommandations). Eligibility for intensive lipid-lowering therapy in secondary prevention according to age was also assessed. Results Among the 2757 individuals admitted for a first STEMI, 1253 (45,7%) were &amp;lt;55 y.o, 633 (22.9%) were [55–65] and 871 (31.4%) were &amp;gt;65. Only 17% and 18% of young individuals would have been considered as high risk and eligible for primary prevention statins prior to their first STEMI according to 2016 and 2019 EAS/ESC guidelines respectively, compared with individuals aged 55–65 years (41% and 35%) and &amp;gt;65 years old (21% and 72%), p&amp;lt;0.01. Following 2021 ESC guidelines, 62.5% of individuals aged &amp;lt;55 y.o would have been detected as eligible for primary prevention statins, without difference with individuals aged 55 to 65 years old (61.7%) and &amp;gt;65 y.o (62.1%) (figure). At discharge, based on the expected reduction of baseline LDL-C with maximal dose statins and ezetimibe, 47% of patients with premature STEMI would be eligible for PCSK9i compared with 50% and 37% in individuals aged 55–65 y-o and &amp;gt;65 y-o, respectively. Conclusions While 2016 and 2019 ESC guidelines poorly detected young individuals at risk of premature MI, the 2021 ESC guidelines using the new SCORE2 allowed a much better detection of young individuals at risk for a first STEMI. Young patients were also more likely to be eligible for intensive lipid-lowering therapy after their first premature STEMI. Funding Acknowledgement Type of funding sources: None.

ESC/EAS guidelines for the detection, prevention, and treatment of individuals at risk of a first myocardial infarction: effect of 5 years of updates and the new SCORE2.

The European Society of Cardiology (ESC) has released three consecutive guidelines within 5 years addressing cardiovascular prevention, risk scores, and cholesterol treatment. This study aims to evaluate whether the 2021 ESC guidelines improved the eligibility of individuals for primary prevention statin therapy before their first ST-segment elevation myocardial infarction (STEMI), and for intensive lipid-lowering treatments in secondary prevention. The cardiovascular risk category of 2757 consecutive individuals admitted for a first STEMI was evaluated to assess whether they would have been eligible for primary prevention statins according to 2021 vs. 2019 and 2016 ESC guidelines. Eligibility for intensive lipid-lowering therapy in secondary prevention was assessed according to the real-life follow-up low-density lipoprotein cholesterol (LDL-C) and the expected follow-up LDL-C. More individuals would have been eligible for primary prevention statins according to 2021 and 2019 vs. 2016 guidelines (61.8% vs. 38.7% vs. 23.6%, P&lt;0.01), a finding observed in both men (62.3% vs. 35.0% vs. 24.9%, P&lt;0.01) and women (60.2% vs. 50.7% vs. 19.3%, P=0.18). Only 27% of individuals reached the LDL-C objective of 55mg/L in secondary prevention: using the ESC stepwise approach, 61.7% were eligible for higher doses of statins, 26.2% for ezetimibe, and 12.1% for a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (PCSK9i). Based on expected LDL-C reductions, eligibility for a PCSK9i in secondary prevention was greater with 2021 vs. 2016 guidelines (44.5% vs. 22.5%, P&lt;0.01). The 2021 ESC guidelines improved the detection and treatment of individuals at risk for a first myocardial infarction. In secondary prevention, 70% of patients kept LDL-C levels above 55mg/dL: increasing the statin dose and adding ezetimibe were the most frequently recommended therapeutic actions.

Suboptimal lipid-lowering therapy in secondary prevention of atherosclerotic CVD incurs high cost in Italy

Suboptimal lipid-lowering therapy in secondary prevention of atherosclerotic CVD incurs high cost in Italy

Echolucency of carotid plaque is useful for selecting high-risk patients with chronic coronary artery disease who benefit from intensive lipid-lowering therapy

BackgroundUltrasound assessment of the carotid artery provides prognostic information on coronary events. This study examined whether ultrasound assessments of plaque echolucency of the carotid artery are useful for identifying patients with coronary artery disease (CAD) who are at high risk but could benefit from lipid-lowering therapy for secondary prevention. MethodsUltrasound assessment of carotid plaque echolucency with integrated backscatter (IBS) analysis was performed in 393 chronic CAD patients with low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dL on statin therapy. All patients were prospectively followed up for a maximum of 96 months or until the occurrence of one of the following coronary events: cardiac death, nonfatal myocardial infarction, or unstable angina pectoris requiring unplanned revascularization. ResultsDuring the follow-up period, 45 coronary events occurred. Patients were stratified by IBS (≤-16.3 or >-16.3 dB, median value) and LDL-C level (<70 or 70–99 mg/dL). Multivariate Cox proportional hazards analysis showed that patients with lower IBS and LDL-C 70–99 mg/dL had significantly higher probabilities of coronary events compared with those with higher IBS and LDL-C <70 mg/dL, after adjustment for a baseline model of risk factors (hazard ratio 5.15; 95% confidence interval 1.21–22.0, p = 0.03). In contrast, patients with lower IBS and LDL-C <70 mg/dL had an improved prognosis comparable with those with higher IBS. Addition of LDL-C levels to the baseline model of risk factors improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI) in patients with lower IBS (NRI, 0.44, p = 0.04; and IDI, 0.035, p < 0.01), but not in those with higher IBS. ConclusionsEvaluation of echolucency of the carotid artery was useful for selecting CAD patients at high risk of secondary coronary events but who could benefit from lipid-lowering therapy.

Familial Hypercholesterolemia in Premature Acute Coronary Syndrome. Insights from CholeSTEMI Registry.

Familial hypercholesterolemia (FH) is an underdiagnosed genetic inherited condition that may lead to premature coronary artery disease (CAD). FH has an estimated prevalence in the general population of about 1:313. However, its prevalence in patients with premature STEMI (ST-elevation myocardial infarction) has not been widely studied. This study aimed to evaluate the prevalence of FH in patients with premature STEMI. Cardiovascular risk factors, LDLc (low-density lipoprotein cholesterol) evolution, and differences between genders were also evaluated. Consecutive patients were referred for cardiac catheterization to our center due to STEMI suspicion in 2018. From the 80 patients with confirmed premature CAD (men < 55 and women < 60 years old with confirmed CAD), 56 (48 men and eight women) accepted to be NGS sequenced for the main FH genes. Clinical information and DLCN (Dutch Lipid Clinic Network) score were analyzed. Only one male patient had probable FH (6–7 points) and no one reached a clinically definite diagnosis. Genetic testing confirmed that the only patient with a DLCN score ≥6 has HF (1.8%). Smoking and high BMI the most frequent cardiovascular risk factors (>80%). Despite high doses of statins being expected to reduce LDLc levels at STEMI to current dyslipidemia guidelines LDL targets (<55 mg/dL), LDLc control levels were out of range. Although still 5.4 times higher than in general population, the prevalence of FH in premature CAD is still low (1.8%). To improve the genetic yield, genetic screening may be considered among patients with probable or definite FH according to clinical criteria. The classical cardiovascular risk factors prevalence far exceeds FH prevalence in patients with premature STEMI. LDLc control levels after STEMI were out range, despite intensive hypolipemiant treatment. These findings reinforce the need for more aggressive preventive strategies in the young and for intensive lipid-lowering therapy in secondary prevention.

Contemporary use of lipid-lowering therapy for secondary prevention in Korean patients with atherosclerotic cardiovascular diseases.

Background/AimsWe evaluated the contemporary use of lipid-lowering therapy (LLT) in Korean patients with atherosclerotic cardiovascular disease (ASCVD), and identified factors associated with statin non-prescription.MethodsUsing the Korean Health Insurance Review and Assessment data, we identified LLT-naïve subjects newly diagnosed with ASCVD between 2011 and 2012, and followed up until 2015. LLT-naïve status was defined as no LLT prescription for 1 year before ASCVD diagnosis. ASCVD was defined as first hospitalization or emergency room visit for coronary artery disease (CAD), acute cerebrovascular disease (CVD), or peripheral artery disease (PAD). Statin intensity was defined per the 2013 American College of Cardiology/American Heart Association guideline for cholesterol treatment.ResultsThe study enrolled 80,884 subjects newly diagnosed with ASCVD, of whom only 48,725 (60.2%) received LLT during the follow-up period. Statin, combination of statin and non-statin, and non-statin LLT were administered in 50.5%, 9.7%, and 0.1% of all subjects, respectively. Statins were prescribed to 80.4% of CAD patients but only to 50.2% and 46.8% of CVD and PAD patients. Statin-based LLT usually had moderate- (77.2%) or high-intensity (18.5%). Subjects not prescribed statins were younger or older (< 40 or ≥ 70 years), more commonly female, and more likely to have comorbidities. Statins were prescribed at the time of ASCVD diagnosis in 45.5% of all subjects, and in 53.0% within 90 days of diagnosis.ConclusionsOnly 60% of LLT-naïve Korean patients newly diagnosed with ASCVD received statins. Statins were often prescribed in subjects with CAD but less commonly in those with CVD or PAD. Moderate-intensity statins were most frequently used.

The use of lipid-lowering therapy for secondary prevention in patients undergoing percutaneous coronary intervention

Recent literature suggests that lipid-lowering therapy may have an early beneficial effect among patients undergoing percutaneous coronary intervention (PCI) because the therapy decreases cardiac mortality, morbidity and possibly restenosis. The primary objective of the present study was to determine the proportion of PCI patients receiving lipid-lowering therapy at a large, tertiary-care referral centre. Patients undergoing a first PCI between August 2000 and August 2002 with corresponding inpatient medication information were included in the study. Patient demographics, procedural variables, and lipid-lowering and other evidence-based cardiac medication data were collected. A multiple logistical regression model was constructed to evaluate the factors associated with the use of lipid-lowering therapy. Of the 3254 cases included in the analyses, 52% were elective, 44% were urgent or salvage, and 4% were emergent. The mean patient age was 63 years, and 73% of patients were male. Over 76% of patients were receiving lipid-lowering therapy at the time of PCI. Patient use of other medications was as follows: acetylsalicylic acid in 96%, beta-blocker in 80% and angiotensin-converting enzyme inhibitor in 59%. In the multiple regression analysis, variables significantly associated with lipid-lowering therapy use included hypercholesterolemia, beta-blocker use, angiotensin-converting enzyme inhibitor use, case urgency, prior coronary artery bypass graft surgery, age and sex. Lipid-lowering therapy use rates exceeded those previously reported in the literature. Women and patients undergoing elective procedures appear to be treated less often with lipid-lowering therapy. There remains an opportunity to further optimize use in this high-risk cohort at time of PCI.

Paradoxical under-prescription of lipid-lowering therapy for secondary prevention of coronary heart disease in high-risk subjects

Paradoxical under-prescription of lipid-lowering therapy for secondary prevention of coronary heart disease in high-risk subjects

2.P.77 Lipid-lowering therapy in secondary prevention by Swiss primary care physicians: How far are we from the target values?

2.P.77 Lipid-lowering therapy in secondary prevention by Swiss primary care physicians: How far are we from the target values?

Secondary prevention of heart disease amongst patients with lipid abnormalities: practice and trends in the United States.

Patients with established coronary disease and abnormalities of lipid metabolism represent a particularly important subgroup, since their mortality risk is typically 10 times greater than that amongst-subjects with comparable risk factors but no clinical history. Such patients are commonly treated initially with anti-anginal therapy; if ischaemic symptoms persist they often undergo revascularization (bypass or angioplasty). While invasive procedures restore blood flow and relieve ischemia, they do not, in most cases, reduce risk of subsequent MI or death, or alter the underlying atherogenic process(es). Despite this, there has been a progressive 54% decline in age-adjusted cardiac mortality over the period 1960-1995, which appears best attributable to US lifestyle changes. In particular, the past decade has provided compelling evidence for the merits of a fourth approach: comprehensive risk factor management. Clinical outcome studies have confirmed the substantial merit of aspirin prophyllaxis and of intensive lipid-lowering therapy in secondary prevention. Prospective angiographic trials and evidence from studies of vascular biology have provided insight into mechanisms of benefit. As a consequence, lipid therapy and aspirin use have increased greatly among middle aged and older US citizens, especially those with CAD. The growth of comprehensive medical management now rivals that of invasive revascularization in secondary prevention.

Trials of lipid-lowering therapy in secondary prevention of coronary heart disease.

The Scandinavian Simvastatin Survival Study showed that a 35% decrease in LDL-cholesterol was accompanied by a 42% reduction in coronary mortality. Even if the period of time is longer than 1 year for the divergence of survival curves in the simvastatin and placebo groups there are reasons to believe that the beneficial effect of lipid lowering is rapid. The effect may be mediated by stabilization of lipid-rich coronary lesions or by effects on endothelium. Lipid-lowering studies in the acute stage of coronary heart disease are suggested.

Clinical perspectives on primary and secondary prevention of coronary atherosclerosis

Several clinical trials have provided compelling evidence in support of the benefits of lipid-lowering therapy for primary and secondary prevention of atherosclerosis. The results of primary prevention trials have demonstrated that coronary morbidity can be reduced and survival improved with effective lipid-lowering regimens. There has been concern, however, regarding harmful effects (e.g., increased rate of suicide and increased risk of gastrointestinal cancer) of cholesterol-lowering therapies in primary prevention trials. These concerns are not well supported by strong evidence, and there has been lack of a dose-response relationship. It is generally believed that for 1% reduction in serum cholesterol, there is a 2% reduction in the risk of coronary events. The results of numerous secondary prevention trials have clearly demonstrated the benefit of lipid-lowering therapies in reducing the risk of future cardiac events and cardiac mortality in patients with preexistent coronary artery disease. Several studies have shown that treatment regimens effective in reducing LDL cholesterol levels lead to regression of atherosclerotic plaques as well as retard the progression of the disease process. Interestingly, some of these studies have also shown that when measured angiographically, the luminal diameter at the site of stenotic lesions might improve only by an average of 2% to 3%; however, this small degree of improvement is associated with a remarkable reduction by 35% to 25% in the risk of future coronary events. These findings further corroborate the hypothesis about the importance of a lipid-rich cap of the vulnerable plaques and suggest that the reduction in lipid levels is associated with the efflux of lipids from the plaque, thus converting it from a vulnerable to a stable state. The most recent data from the 4S trial have unequivocally demonstrated the benefits of treatment with HMG coenzyme-A reductase inhibitors in reducing the risk of future coronary events and improving the overall survival in patients with established CHD. Although there is still ongoing controversy regarding the precise course of action for primary prevention of CHD, the results of a large number of studies provide overwhelming evidence in support of aggressive lipid-lowering therapy for secondary prevention of CHD. Based on the findings of these studies, it seems prudent that clinicians become actively involved in the evaluation and management of lipid abnormalities and other risk factors in patients with CHD.