Secondary Prevention Of Atherosclerotic Disease Research Articles

Novel Aspects Targeting Platelets in Atherosclerotic Cardiovascular Disease—A Translational Perspective

Platelets are important cellular targets in cardiovascular disease. Based on insights from basic science, translational approaches and clinical studies, a distinguished anti-platelet drug treatment regimen for cardiovascular patients could be established. Furthermore, platelets are increasingly considered as cells mediating effects "beyond thrombosis", including vascular inflammation, tissue remodeling and healing of vascular and tissue lesions. This review has its focus on the functions and interactions of platelets with potential translational and clinical relevance. The role of platelets for the development of atherosclerosis and therapeutic modalities for primary and secondary prevention of atherosclerotic disease are addressed. Furthermore, novel therapeutic options for inhibiting platelet function and the use of platelets in regenerative medicine are considered.

All-cause and in-hospital mortality after aspirin use in patients hospitalized with COVID-19: a systematic review and meta-analysis.

With the results of the largest randomized controlled trial (RECOVERY) and the most extensive retrospective cohort study on coronavirus disease 2019 (COVID-19) recently published, we performed a meta-analysis on the association of aspirin with mortality of COVID-19. We aimed to investigate the role of aspirin in COVID-19 hospitalizations. We searched PubMed, EMBASE and Cochrane databases for studies from 1 January 2020 until 20 July 2022, that compared aspirin versus non-aspirin use in hospitalized COVID-19 patients. We excluded case reports, review articles and studies on non-hospitalized COVID-19 infections. We used the inverse variance method and random effects model to pool the individual studies. Ten observational studies and one randomized controlled trial met the criteria for inclusion. There were 136695 total patients, of which 27168 were in the aspirin group and 109527 were in the non-aspirin group. Aspirin use was associated with a 14% decrease in all-cause mortality compared with non-aspirin use in patients hospitalized with COVID-19 [relative risk (RR) 0.86, confidence interval (95% CI) 0.76-0.97; P = 0.002; I 2=64%]. Among subgroups of studies reporting in-hospital mortality in COVID-19 hospitalizations, aspirin use was associated with a 16% decrease in in-hospital mortality compared with non-aspirin use (RR 0.84, 95% CI 0.71-0.99; P = 0.007; I 2 =64%). Our study shows that aspirin decreases in-hospital mortality in patients hospitalized with COVID-19. Further studies are needed to assess which COVID-19 patient populations benefit most, such as patients on aspirin for primary versus secondary prevention of atherosclerotic disease. In addition, significant bleeding also needs to be considered when assessing the risk-benefit of aspirin use.

Aspirin in primary prevention of cardiovascular and cerebrovascular diseases

Acetylsalicylic acid (aspirin) is one of the most used medications worldwide. The antithrombotic agent acts mainly through inhibition of cyclooxygenase-1 and consequently thromboxane A2 synthesis, causing an irreversible suppression of platelet function. Despite of its proven benefit in the treatment and secondary prevention of atherosclerotic diseases, its use for the primary prevention remains controversial due to an unclear balance between the benefits and risks of aspirin. Moreover, the recent evidence indicates that the risk of major bleeding outweighs the potential to reduce ischemic events in patients without atherosclerotic diseases, thus, precluding the general use of aspirin for the primary prevention.

How to Use Statins in Secondary Prevention of Atherosclerotic Diseases: from the Beneficial Early Initiation to the Potentially Unfavorable Discontinuation.

Statins, a class of lipid-lowering drugs, reduce morbidity and mortality in patients with established atherosclerosis-related cardiovascular disease. Early initiation of statin therapy after admission for acute coronary syndromes (ACS), stroke, or transient ischemic attack (TIA) is associated with improved cardiovascular outcomes. Moreover, high-dose statin treatment prior to coronary or carotid revascularization has been shown to reduce cardiovascular events in these patients. However, many patients may be undertreated, and a residual cardiovascular risk remains in current clinical practice. Despite the beneficial role of statins, their discontinuation rate among patients is still elevated leading to severe adverse cardiovascular events due to atherosclerotic plaque destabilization. In this review, we summarized the impact of statin treatment among patients, focusing on the initiation time-points as well as the potential harm derived by their discontinuation.

Outreach and equity in patient centered outcomes research: Lessons from the adaptable study at Montefiore hospital

Background and Aims: ADAPTABLE is the first PCOR trial in US, comparing the effectiveness of two aspirin doses for secondary prevention of atherosclerotic disease. Novel features include patients’ representation as research partners, leveraging of electronic health records, participation via internet and low cost. Direct patient engagement can improve research impact and provide access to minority populations, often less represented in clinical research. We aim to analyze patient's data from Montefiore Hospital in Bronx, NY, serving a community of socioeconomically disadvantaged minorities.

Effect of Statins on Recurrent Venous Thromboembolism (from the COMMAND VTE Registry)

Statins, which are considered as essential for primary and secondary prevention of atherosclerotic diseases, were also reported to reduce first venous thromboembolism (VTE). However, the effect of statins on VTE recurrence remains conflicting. We aimed to examine the association between statin use and VTE recurrence in a large observational study in Japan. The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE in 29 centers in Japan between January 2010 and August 2014. In the current study, the entire cohort was divided into statin group (N = 437) and no-statin group (N = 2590) according to the status of statin use at baseline. The statin group as compared with the no-statin group was older (statin group 71.2 vs no-statin group 66.5 years, p <0.001), included more women (67% vs 60%, p = 0.008), and less frequently had active cancer (12% vs 25%, p <0.001). There was no significant difference in the clinical presentation of VTE (pulmonary embolism, 58% vs 56%, p = 0.44). The cumulative 3-year incidence of recurrent VTE was significantly lower in the statin group than the no-statin group (3.8% vs 8.8%, p <0.001). After adjusting for confounders including active cancer, statin use was associated with significantly lower risk for recurrent VTE (Hazard ratio 0.49, 95% confidence interval 0.29 to 0.78, p = 0.002). The results were consistent in a sensitivity sub-group analysis with and without active cancer. In conclusion, statin use was associated with significantly lower risk for the recurrent VTE in patients with VTE.

Disparities in Secondary Prevention of Atherosclerotic Heart Disease After Coronary Artery Bypass Grafting in Northern Plains American Indians.

Introduction: Cardiovascular disease has become the leading cause of death in American Indians (AIs). For patients with severe disease requiring coronary artery bypass grafting (CABG), AIs have been demonstrated to present with increased risk factors. Guideline-directed medical therapy after CABG effectively reduces mortality and recurrent ischemic events in all patients and is especially important in high-risk populations such as AIs.Methods: Isolated CABG patients between 2012 and 2017 were studied and 74 AI patients were identified. Propensity matching was performed and the resulting 148 patients were followed for a year after surgery. Guideline-directed medical therapy (GDMT) for secondary prevention of atherosclerotic disease after CABG was detailed in all patients.Results: GDMT was similar between groups (85% AI vs. 89% non-AI; p=NS), and the incidence of prescribed antiplatelet medications, beta-blockers, and statins was similar. AIs were more likely to receive insulin therapy (p=0.002) and opioids (p=0.03) at discharge, while non-AIs were more likely to receive anti-arrhythmic medications (p=0.002). One year after discharge, GDMT trended lower in AIs (75% AI vs. 85% non-AI; p=0.2) and AIs were less likely to be on a statin 1 year after surgery (81% AI vs. 93% non-AI; p=0.04). Opioid use trended higher after 1 year in AIs (28% AI vs. 18% non-AI; p=NS) and fewer AI patients participated in cardiac rehabilitation (CR) after CABG.Conclusions: Disparities in GDMT for secondary prevention of coronary artery disease after CABG exist, with fewer AI patients receiving statins and undergoing CR 1 year after surgery. Increased use of opioids in AIs is troubling and deserves further investigation. Improved adherence to GDMT would be expected to improve long-term outcomes after CABG in this high risk population.

Anti-thrombotic strategies in elderly patients receiving platelet inhibitors.

Acetyl-salicylic acid is the basic anti-thrombotic therapy used for single anti-platelet therapy in primary as well as secondary prevention of atherosclerotic disease. Dual anti-platelet therapy (DAPT) is the cornerstone of maintenance medication following elective percutaneous coronary intervention or acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). DAPT duration has been frequently discussed. Currently, guideline recommendations strengthen the importance of individualized treatment to reduce bleeding risk based on clinical predictors, of which older age is an important one. Patients aged ≥75 years are often underrepresented in randomized clinical trials, but present a patient cohort deemed both at heightened ischaemic as well as bleeding risk. We aimed to summarize the evidence or the lack of evidence for anti-platelet treatment strategies in patients aged ≥75 years including combinations with anticoagulants in secondary prevention or coronary interventions in elderly patients with atrial fibrillation. This review article represents the author's interpretation of available data and is not discussed by a formal task force; it is intended to point out missing evidence and to provide age-specific data for individualized decision making, which is currently encouraged by the guidelines.

Canakinumab for secondary prevention of atherosclerotic disease

ABSTRACTIntroduction: The widespread prevalence of cardiovascular disease (CVD) and its impact on morbidity and mortality requires effective secondary prevention measures. For years, inflammation has been advocated as a key mediator of atherosclerosis and its associated complications. Drugs for secondary prevention of CVD events include interventions aimed at risk factors control and antithrombotic management, but there is no drug currently recommended that specifically targets inflammation. Recently, the inflammatory hypothesis of atherosclerosis has been confirmed by a randomized clinical trial of canakinumab, a monoclonal antibody that blocks an inflammatory pathway mediated by interleukin-1β.Areas covered: This article reviews the pharmacology of canakinumab, its current clinical development status and upcoming regulatory perspectives.Expert opinion: In the CANTOS trial, canakinumab 150 mg met the pre-specified criteria of statistical significance, showing a reduction in combined cardiovascular events, myocardial infarction, re-hospitalization due to urgent revascularization and any coronary revascularization, but no impact on all-cause or cardiovascular death. There were more death attributed to sepsis or infection with canakinumab than placebo, but fewer reports of arthritis, gout, osteaoarthritis and cancer-related death. Because interleukin-1β is only one of the potential pro-inflammatory pathways that may serve as a target for atherothrombotic protection, other anti-inflammatory drugs may be the object of future investigations. If approved, the initial penetration of canakinumab will face hurdles in view of cost issues, but costs are likely to decrease if the drug loses its present status of orphan drug with the new indication.

Platelet inhibition in elderly patients

Single antiplatelet therapy (SAPT) using predominantly acetylsalicylic acid (ASA) is the baseline anti-thrombotic therapy in primary as well as secondary prevention of atherosclerotic disease. Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following elective percutaneous coronary interventions or acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction and unstable angina pectoris). In the past the duration of DAPT in particular has been frequently discussed. Current recommendations, such as the "Focused Update DAPT 2017" of the European Society of Cardiology (ESC) emphasize the importance of strategies aiming to reduce an increased risk of bleeding based on clinical predictors. In this case older age is an important factor relevant for bleeding. In this article, the evidence for SAPT or DAPT is summarized with aspecial focus on patients aged ≥75years.

Safety and efficacy of vorapaxar in secondary prevention of atherosclerotic disease: A meta-analysis of randomized control trials

ObjectiveTo study the cumulative evidence for vorapaxar use in patients with atherosclerotic cardiovascular disease. MethodsA systematic review of randomized control trials in MEDLINE, EMBASE, EBSCO, CINAHL, Web of Science and Cochrane databases comparing vorapaxar with placebo was performed. Pre-specified efficacy endpoints were all-cause mortality, CV mortality, myocardial infarction (MI), ischemic stroke and repeat revascularization. The pre-specified safety endpoint was intracranial hemorrhage (ICH) and a composite of TIMI major and minor bleeding. Risk ratios were used as the metric of choice by applying random effects models. ResultsFive randomized controlled trials with 40,630 patients were included in final analysis. Compared with placebo, vorapaxar led to a statistically non-significant reduction in risk of MI [RR 0.86; 95% CI 0.80–0.93, p=0.427] and ischemic stroke [RR 0.84; 95% CI 0.72–0.97, p=0.920]. No differences were observed between vorapaxar and placebo with respect to all-cause mortality [RR 0.99; 95% CI 0.90–1.08, p=0.620], cardiovascular mortality [RR 0.94; 95% CI 0.83–1.06, p=0.351], repeat revascularization [RR 0.97; 95% CI 0.82–1.15, p=0.236], and TIMI bleeding [RR 1.29; 95% CI 0.98–1.69, p=0.126]. Vorapaxar was associated with a statistically non-significant higher risk of ICH [RR 2.36; 95% CI 1.40–3.96, p=0.137] compared with placebo. ConclusionAddition of Vorapaxar to standard medical therapy in in patients with atherosclerotic disease led to a statistically non-significant reduction in the risk of MI and ischemic stroke at the cost of statistically non-significant increase in risk of ICH.

Abstract 18972: Safety and Efficacy of Vorapaxar in Secondary Prevention of Atherosclerotic Disease: A Meta-analysis of Randomized Control Trials

Background: A substantial risk of residual cardiovascular events remains despite the current standard antiplatelet therapy in patients with atherosclerotic disease. Protease activating receptor (PAR-1) antagonist Vorapaxar is a novel antiplatelet agent acting by inhibition of thrombin-induced platelet aggregation. Recently, FDA has approved vorapaxar for long term secondary prevention of vascular events in stable patients with a prior MI or PAD, and without history of stroke or transient ischemic attack. However, these recommendations are largely based on a single phase 3 randomized control trial (TRA 2P TIMI-50). Objective: To study the cumulative evidence for vorapaxar use in patients with atherosclerotic cardiovascular disease. Methods: A systematic review of randomized control trials in MEDLINE, EMBASE, EBSCO, CINAHL, Web of Science and Cochrane databases comparing vorapaxar with placebo was performed. Pre-specified efficacy endpoints were all-cause mortality, CV mortality, myocardial infarction, stroke and repeat revascularization. The pre-specified safety endpoint was the composite of TIMI major and minor bleeding. Risk ratios were used as the metric of choice by applying random effects models.. Results: A total of 5 RCTs with 40,630 patients were included. Compared with placebo, vorapaxar led to a significant risk reduction in terms of myocardial infarction [RR 0.93; 95% CI 0.80-0.92] and stroke [RR 0.84; 95% CI 0.72-0.97]. No differences were observed between vorapaxar and placebo with respect to all-cause mortality [RR 0.99; 95% CI 0.90-1.07], cardiovascular mortality [RR 0.93; 95% CI 0.84-1.02], and repeat revascularization [RR 0.96; 95% CI 0.85-1.08]. Vorapaxar was associated with a higher risk of TIMI major and minor bleeding [RR 1.30; 95% CI 1.02-1.65] compared with placebo. There was insignificant (I-squared) heterogeneity between studies. Conclusion: Vorapaxar reduces the risk of ischemic events in patients with atherosclerotic disease at the cost of an increased bleeding risk.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Therapie von Fettstoffwechselstörungen

Lipid disorders play an essential role in the pathogenesis of atherosclerotic diseases. An integral part of the clinical evaluation is the estimation of the individual cardiovascular risk using risk scores and patient history. Due to the long established prognostic relevance, reduction of low-density lipoproteins (LDL) using statins remains beyond doubt the central intervention both in primary and secondary prevention of atherosclerotic diseases. Indispensible components of treatment in all patients with elevated triglyceride levels are lifestyle changes contributing to a reduction of accompanying risk factors, in particular physical activity and smoking cessation.

Oral High-Dose Multivitamins and Minerals After Myocardial Infarction

Whether high-dose multivitamins are effective for secondary prevention of atherosclerotic disease is unknown. To assess whether oral multivitamins reduce cardiovascular events and are safe. Double-blind, placebo-controlled, 2 x 2 factorial, multicenter, randomized trial. (ClinicalTrials.gov: NCT00044213) SETTING: 134 U.S. and Canadian academic and clinical sites. 1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier and had serum creatinine levels of 176.8 mol/L (2.0 mg/dL) or less. Patients were randomly assigned to an oral, 28-component, high-dose multivitamin and multimineral mixture or placebo. The primary end point was time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. The median age was 65 years, and 18% of patients were women. The qualifying MI occurred a median of 4.6 years (interquartile range [IQR], 1.6 to 9.2 years) before enrollment. Median follow-up was 55 months (IQR, 26 to 60 months). Patients received vitamins for a median of 31 months (IQR, 13 to 59 months) in the vitamin group and 35 months (IQR, 13 to 60 months) in the placebo group (P = 0.65). Totals of 645 (76%) and 646 (76%) patients in the vitamin and placebo groups, respectively, completed at least 1 year of oral therapy (P = 0.98), and 400 (47%) and 426 (50%) patients, respectively, completed at least 3 years (P = 0.23). Totals of 394 (46%) and 390 (46%) patients in the vitamin and placebo groups, respectively, discontinued the vitamin regimen (P = 0.67), and 17% of patients withdrew from the study. The primary end point occurred in 230 (27%) patients in the vitamin group and 253 (30%) in the placebo group (hazard ratio, 0.89 [95% CI, 0.75 to 1.07]; P = 0.21). No evidence suggested harm from vitamin therapy in any category of adverse events. There was considerable nonadherence and withdrawal, limiting the ability to draw firm conclusions (particularly about safety). High-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications. However, this conclusion is tempered by the nonadherence rate. National Institutes of Health.

Effectiveness of antiplatelet therapy in atherosclerotic disease: comparing the ASA low-response prevalence in CVD, CAD and PAD

Although acetylsalicylic acid (ASA, aspirin) reduces the risk of ischemic events in patients with atherosclerosis, a substantial number of incidents continue to occur. As only limited data exist we evaluated the antiplatelet effectiveness of ASA in patients with different manifestations of atherosclerosis as in cerebrovascular, coronary artery and peripheral arterial disease (CVD, CAD, PAD). For the evaluation of the antiplatelet effectiveness of ASA we used whole blood aggregometry (Chrono-log Model 590). The patients in the different subgroups received ASA 100, 200 or 500mg daily. We analysed 737 consecutive patients: 47.5% with CVD, 33.6% with CAD, and 18.9% with PAD. We identified 28.0% of the CVD, 18.1% of the CAD and 21.6% of the PAD patients to be ASA low-responder (ALR). Comparing subgroups treated with 100mg ASA, 36.4% were ALR in the CVD group as were 13.1% of the CAD and 21.6% of the PAD patients. Multivariate regression analysis revealed an odds ratio for being ALR of 4.50 (95% confidence interval (CI) 1.70-11.9) when 100mg and of 2.97 (95% CI 1.58-5.60) when 200mg ASA was taken compared to a dose of 500mg. Despite the proven benefits of antiplatelet therapy in the secondary prevention of atherosclerotic disease, current antiplatelet management is suboptimal as up to 36% of patients failed to achieve an adequate platelet inhibitory effect. Our findings may explain, at least in part, the high rates of cardiovascular events observed in the course of atherothrombotic disease and support the need to improve antiplatelet therapy.

Effectiveness of generic rosuvastatin in patients with ischaemic cerebrovascular disease

Statin therapy is the cornerstone of anti-atherosclerotic treatment, and it considered obligatory in the secondary prevention of atherosclerotic diseases. Rosuvastatin is well-known and efficacious lipid-lowering agent. Generic drugs are more frequently used instead of its ancestors. Generic rosuvastatin forms have been approved recently to the Central European market, but their safety and efficacy have not been previously examined in cerebrovascular patient populations. 109 patients with documented ischaemic cerebrovascular events were included in our study. 20 mg generic rosuvastatin significantly decreased total cholesterol (5.47 vs. 3.88 mmol/l, p<0.01), low-density lipoprotein (3.16 vs. 1.84 mmol/l, p<0.01) and trigliceride levels (1.77 vs. 1.33 mmol/l, p<0.05, and there was a non-significant high-density lipoprotein increasing tendency (1.27 vs. 1.36 mmol/l, p = 0.08). There was also a significant decrease in high-sensitive C-reactive protein levels (3.73 vs. 2.82 mg/l, p<0.05). Overall, 30% decrease in total cholesterol, 42% decrease in low-density lipoprotein, 25% decrease in trigliceride and high-sensitive C-reactive protein and 9% increase in high-density lipoprotein levels were observed. The generic rosuvastatin studied by the authors proved to be safe and efficacious lipid-lowering agent. Based on these short term results, in daily practice, generic rosuvastatin treatment seems to be cost-effective for the treatment of patients with ischemic cerebrovascular disease.

Cilostazol in the Management of Atherosclerosis

The burden of atherosclerosis is particularly high in western countries in terms of mortality and disability. The cerebral arteries (stroke or transient ischemic attack [TIA]), coronary arteries (myocardial infarction [MI]) and peripheral arteries (intermittent claudication [IC], ischemic limb) can be affected. Atherosclerosis may involve different mechanisms such as inflammation, platelet activation, endothelial damage, balance between proliferation and apoptosis of smooth muscle cells and oxidative stress. Research is focused to counteract each of these aspects. Many antithrombotic drugs are currently available and most of them act as inhibitors of platelet function. Aspirin, ticlopidine, clopidogrel and the combination of aspirin plus dipyridamole are widely used for primary (in high-risk patients) and secondary prevention of atherosclerotic diseases. Research of new pharmacological strategies is driven by the need to reduce the risk of bleeding associated with the use of antiplatelet drugs. In this context cilostazol, a type III phosphodiesterase inhibitor, has demonstrated antiplatelet and vasodilator effects with low rate of bleeding complications. This review will focus on the pharmacological properties of cilostazol and its use in the management of atherothrombotic vascular diseases.

Inflammation-induced atherosclerosis as a target for prevention of cardiovascular diseases from early life.

Atherogenesis starts from the fetal life, and its natural course consists of interrelations between traditional risk factors and inflammatory, immune, and endothelial biomarkers. Even the early-stages of atherosclerotic lesions, i.e. fatty streaks present the features of chronic inflammation. Markers of inflammation are associated with insulin resistance and major atherosclerosis risk factors. Several studies have confirmed a relationship between surrogate markers of future cardiovascular disease with childhood obesity, notably abdominal obesity, as well as with the degree of obesity. Moreover, functional and structural changes are documented in arteries of children with a familial predisposition to atherosclerotic diseases; these changes are associated with clusters of inflammatory factors and markers of oxidation. In addition to the development of atheromatous plaques, inflammation also plays an essential role in the destabilization of artery plaques, and in turn in the occurrence of acute thrombo-embolic disorders. Markers of inflammation can provide predictive clinical information about outcomes of patients with acute coronary syndromes, independent of the extent of myocardial damage. Moreover, serum levels of the inflammatory markers might add prognostic information provided by traditional risk factors. Platelets have an important role in vascular inflammation and atherosclerosis and in the formation of mural thrombi. As lifestyle modification trials have been successful in decreasing endothelial dysfunction and the level of markers of inflammation among children and adolescents, it is suggested that in addition to expanding pharmacological therapies considered for secondary prevention of atherosclerotic diseases aiming to control the inflammatory process, the importance of primordial/primary prevention of atherosclerosis should be underscored.

The effects of time-released garlic powder tablets on multifunctional cardiovascular risk in patients with coronary artery disease

The double-blinded placebo-controlled randomized study has been performed in 51 coronary heart disease (CHD) patients to estimate the effects of time-released garlic powder tablets Allicor on the values of 10-year prognostic risk of acute myocardial infarction (fatal and non-fatal) and sudden death, with the respect of secondary CHD prevention. It has been demonstrated that 12-month treatment with Allicor results in the significant decrease of cardiovascular risk by 1.5-fold in men (p < 0.05), and by 1.3-fold in women. The above results were equitable also in terms of relative risks. The main effect that played a role in cardiovascular risk reduction was the decrease in LDL cholesterol by 32.9 mg/dl in men (p < 0.05), and by 27.3 mg/dl in women. Thus, the most significant effects were observed in men, while in women the decrease of cardiovascular risk appeared as a trend that might be due presumably to the insufficient sample size. Since Allicor is the remedy of natural origin, it is safe with the respect to adverse effects and allows even perpetual administration that may be crucial for the secondary prevention of atherosclerotic diseases in CHD patients.