Management Of Atherosclerotic Cardiovascular Disease Research Articles

Atherosclerotic cardiovascular disease landscape in Singapore.

Cardiovascular disease (CVD) is the leading cause of death worldwide, accounting for over one-third of all deaths in Singapore. An analysis of age-standardized mortality rates (ASMR) for CVD in Singapore revealed a deceleration in the initial rapid decline in ASMR. A decrease in smoking prevalence may have contributed to the initial rapid decline in ASMR. Furthermore, other major risk factors, such as diabetes mellitus, hypertension, elevated low-density lipoprotein levels, and obesity, are steadily rising. Singapore's CVD economic burden is estimated to be 8.1 billion USD (11.5 billion SGD). The burden of CVD can only be reduced using individual and population-based approaches. Prevention programs must also be developed based on an understanding of risk trends. Therefore, this article attempts to capture the burden of CVD, trends in risk factor control, preventive care, disparities, and current unmet needs, particularly in atherosclerotic cardiovascular disease management in Singapore.

Contemporary attitudes and beliefs on coronary artery calcium from social media using artificial intelligence

Coronary artery calcium (CAC) is a powerful tool to refine atherosclerotic cardiovascular disease (ASCVD) risk assessment. Despite its growing interest, contemporary public attitudes around CAC are not well-described in literature and have important implications for shared decision-making around cardiovascular prevention. We used an artificial intelligence (AI) pipeline consisting of a semi-supervised natural language processing model and unsupervised machine learning techniques to analyze 5,606 CAC-related discussions on Reddit. A total of 91 discussion topics were identified and were classified into 14 overarching thematic groups. These included the strong impact of CAC on therapeutic decision-making, ongoing non-evidence-based use of CAC testing, and the patient perceived downsides of CAC testing (e.g., radiation risk). Sentiment analysis also revealed that most discussions had a neutral (49.5%) or negative (48.4%) sentiment. The results of this study demonstrate the potential of an AI-based approach to analyze large, publicly available social media data to generate insights into public perceptions about CAC, which may help guide strategies to improve shared decision-making around ASCVD management and public health interventions.

Colchicine's Role in Cardiovascular Disease Management.

Colchicine-an anti-inflammatory alkaloid-has assumed an important role in the management of cardiovascular inflammation ≈3500 years after its first medicinal use in ancient Egypt. Primarily used in high doses for the treatment of acute gout flares during the 20th century, research in the early 21st century demonstrated that low-dose colchicine effectively treats acute gout attacks, lowers the risk of recurrent pericarditis, and can add to secondary prevention of major adverse cardiovascular events. As the first Food and Drug Administration-approved targeted anti-inflammatory cardiovascular therapy, colchicine currently has a unique role in the management of atherosclerotic cardiovascular disease. The safe use of colchicine requires careful monitoring for drug-drug interactions, changes in kidney and liver function, and counseling regarding gastrointestinal upset. Future research should elucidate the mechanisms of anti-inflammatory effects of colchicine relevant to atherosclerosis, the potential role of colchicine in primary prevention, in other cardiometabolic conditions, colchicine's safety in cardiovascular patients, and opportunities for individualizing colchicine therapy using clinical and molecular diagnostics.

Sports-Statin Interaction: Ensuring Safe and Smart Synergy

Both sports (physical activity) and statins are recommended for the prevention and management of atherosclerotic cardiovasculardisease. The synergy that they create in risk reduction, however, may turn dysfunctional at times. Statin usage is associated witha risk of muscle-related conditions including myalgia, myositis and rhabdomyolysis. This risk is exacerbated by unaccustomedphysical activity, exercise or sports. The communication shares practical and pragmatic suggestions regarding the preventionand management of the potential sports-statin interactions that may occur. It also highlights the need to consider drug-lifestyleinteractions, apart from conventional drug-drug interactions.

Unlocking the mysteries of VLDL: exploring its production, intracellular trafficking, and metabolism as therapeutic targets

Reducing circulating lipid levels is the centerpiece of strategies for preventing and treating atherosclerotic cardiovascular disease (ASCVD). Despite many available lipid-lowering medications, a substantial residual cardiovascular risk remains. Current clinical guidelines focus on plasma levels of low-density lipoprotein (LDL). Recent attention has been given to very low-density lipoprotein (VLDL), the precursor to LDL, and its role in the development of coronary atherosclerosis. Preclinical investigations have revealed that interventions targeting VLDL production or promoting VLDL metabolism, independent of the LDL receptor, can potentially decrease cholesterol levels and provide therapeutic benefits. Currently, methods, such as mipomersen, lomitapide, and ANGPTL3 inhibitors, are used to reduce plasma cholesterol and triglyceride levels by regulating the lipidation, secretion, and metabolism of VLDL. Targeting VLDL represents an avenue for new lipid-lowering strategies. Interventions aimed at reducing VLDL production or enhancing VLDL metabolism, independent of the LDL receptor, hold promise for lowering cholesterol levels and providing therapeutic benefits beyond LDL in the management of ASCVD.

Statins Ticagrelor and Rhabdomyolysis: A Coincidence or a Drug Interaction?

Statins play a key role in the management of atherosclerotic cardiovascular disease for both primary and secondary prevention. However, their increasing usage has correspondingly led to a higher incidence of adverse effects, with muscle symptoms being the most common. An intriguing drug interaction exists between ticagrelor and high-intensity statins, which may exacerbate the adverse effects of statin-induced rhabdomyolysis, leading to significant consequences. This study was conducted to examine the profile of patients who have experienced statin-induced rhabdomyolysis while undergoing percutaneous transluminal coronary angioplasty (PTCA). This was an observational study that included 1,862 patients who underwent PTCA at our institute over the course of 1 year. Over a 1-year period, we encountered four patients who were being treated with high-intensity statin therapy following acute coronary syndrome. These patients presented with muscle weakness and kidney injury. A notable commonality among all patients was the co-prescription of ticagrelor. Two patients died, while the other 2 were successfully managed through hydration, electrolyte balance, dialysis, and alternative lipid management drugs. The concomitant use of ticagrelor and high-intensity statins should be carefully considered due to the additional risk of rhabdomyolysis and kidney injury. Future pharmacokinetic studies are needed to establish a causal relationship and predict potential drug interactions, which, if not avoided, could be fatal.

Feasibility of an Integrated Digital and Pharmacological Approach Targeting Blood Lipids in Atherosclerotic Cardiovascular Disease Management

Objectives: Strong evidence supports the importance of lipid-lowering and exercise therapies in the long-term therapy of atherosclerotic cardiovascular disease (ASCVD). Establishing efficient comprehensive intervention programs that combine pharmacological and exercise prescription is crucial to investigate with the aid of digital technologies. Methods: A convenience sample of 25 ASCVD patients (57.8 ± 9.5 years, 76% males) was gathered. All participants were prescribed with 12-week home exercise program supervised by an app and bimonthly 75mg alirocumab subcutaneous injections. Follow up visits were scheduled at the end of 4th and 12th week. Results: Nineteen participants completed the program with a retention rate of 76%. Sixteen (84.2%) participants received all six doses of alirocumab. The total management time of the 12-week program added up to 65.47 minutes per patient. Satisfaction score was 4.2 ± 0.6 and the User Version of the Mobile Application Rating Scale (uMARS) overall objective quality score on the app was 3.4 ± 0.7. At the 4-week and 12-week follow-ups, LDL-C levels reduced compared to baseline (−1.5 ± 0.8 mmol/L, P < 0.001, −1.6 ± 0.8 mmol/L, P < 0.001, respectively), along with TC (−1.8 ± 1.2 mmol/L, P < 0.001, −1.6 ± 1.3 mmol/L, P < 0.001, respectively), but not TG, HDL-C, GAD-7 and PHQ-9. Conclusion: The integrated pharmaceutical and digital ERx intervention program was feasible and well accepted in ASCVD patients.

Low dose rivaroxaban for the management of atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease is characterized by some risk of major adverse events despite the availability of effective medical therapies for secondary prevention. There is emerging evidence suggesting that thrombin partly contributes to this residual risk. In fact, thrombin (i.e., activated coagulation factor II) triggers not only the conversion of fibrinogen to fibrin but also platelet activation and various pathways responsible for pro-atherogenic and/or pro-inflammatory effects through interaction with protease activated receptors. To reduce the risk associated with thrombin activation, oral anticoagulants antagonists of vitamin K showed promise, but were associated with unacceptable bleeding rates. Direct oral anticoagulants targeting the activated factors X and II carry a lower risk of bleeding than vitamin K antagonists. Rivaroxaban, a direct inhibitor of activated factor X approved at the dose of 20mg once daily for the prevention of thromboembolic events, has been also investigated at a reduced dose of 2.5mg twice daily in several alternative scenarios of atherosclerotic cardiovascular disease, in combination with standard of care. Current guidelines recommend that low-dose rivaroxaban is given in an adjunct to standard therapy to patients with stable atherosclerosis and acute coronary syndromes at low bleeding risk. Several studies are underway to evaluate its putative benefits in other clinical settings.

388 The current state of management of atherosclerotic cardiovascular disease in dermatomyositis patients

388 The current state of management of atherosclerotic cardiovascular disease in dermatomyositis patients

Prescribing of low-dose rivaroxaban in patients with atherosclerotic cardiovascular disease in the United Kingdom and the Netherlands.

Low-dose rivaroxaban has been indicated for the management of atherosclerotic cardiovascular disease (ASCVD) after recent (2019-2020) updates to European guidelines. We aimed to describe prescription trends of low-dose rivaroxaban in ASCVD patients over the period 2015-2022 in two European countries, to compare the trends before and after guideline changes, and to determine the characteristics of users. In a cross-sectional interrupted time series analysis, utilization of low-dose rivaroxaban (2.5 mg, twice daily) was measured in Clinical Practice Research Datalink Aurum (United Kingdom [UK]) and the PHARMO Database Network (the Netherlands) from 1 January 2015 to 28 February 2022 in patients with an ASCVD diagnosis. Incidence rates (IRs) and incidence rate ratios (IRRs) of new use (within 182 days) compared to the reference period, 2015-2018, were calculated. Age, sex and comorbidities of users were compared to those of nonusers. In the UK, from 721 271 eligible subjects the IR of new use of low-dose rivaroxaban in the period 2015-2018, before guideline changes, was 12.4 per 100 000 person-years and after guideline changes in 2020-2022 was 124.0 (IRR 10.0, 95% confidence interval [CI] 8.5, 11.8). In the Netherlands from 394 851 subjects, the IR in 2015-2018 was 2.4 per 100 000 person-years and in 2020 was 16.3 (IRR 6.7, 95% CI 4.0, 11.4). Users were younger (UK mean difference [MD] -6.1years, Netherlands -2.4years; P< .05) and more likely to be male (UK difference 11.5%, Netherlands 13.4%; P< .001) than nonusers. There was a statistically significant increase in the use of low-dose rivaroxaban for the management of ASCVD after guideline changes in the UK and the Netherlands. There were international differences, but low-dose rivaroxaban has not been put into widespread practice.

Evaluation of lipoprotein(a) in the prevention and management of atherosclerotic cardiovascular disease: A survey among the Lipid Clinics Network

Background and aimsThe European Atherosclerosis Society (EAS) Lipid Clinics Network promoted a survey in order to identify and understand how and when lipoprotein(a) [Lp(a)] is tested and clinically evaluated in lipid clinics throughout Europe, and the challenges that may prevent evaluation from being carried out. MethodsThis survey was divided into three areas of inquiry: background and clinical setting information of clinicians, questions for doctors who claimed not to measure Lp(a), in order to understand what were the reasons for not ordering the test, and questions for doctors who measure Lp(a), to investigate the use of this value in the management of patients. ResultsA total of 151 centres clinicians filled in the survey, out of 226 invited. The proportion of clinicians who declare to routinely measure Lp(a) in clinical practice was 75.5%. The most common reasons for not ordering the Lp(a) test were the lack of reimbursement or of treatment options, the non-availability of Lp(a) test, and the high cost of performing the laboratory test. The availability of therapies targeting this lipoprotein would result in a greater propensity of clinicians to start testing Lp(a). Among those who declared to routinely measure Lp(a), the Lp(a) measurement is mostly requested to further stratify patients' cardiovascular risk, and half of them recognized 50 mg/dL (approx. 110 nmol/L) as the threshold for increased cardiovascular risk due. ConclusionsThese results warrant for a great deal of effort from scientific societies to address the barriers that limit the routine use of the measurement of Lp(a) concentration and to recognise the importance of Lp(a) as a risk factor.

PS-P16-4: VALIDATION OF CHO ET AL FORMULA FOR APOLIPOPROTEIN B100 CALCULATION; A POTENTIAL ATHEROSCLEROTIC RISK TOOL IN LIMITED RESOURCES SETTINGS

Objectives: Increased atherogenic lipid molecules such as low-density lipoprotein cholesterol (LDL) concentration is associated with increased risk of atherosclerotic, but a substantial risk of cardiovascular disease often remains after LDL and other lipid parameters concentrations have been extensively treated to healthy level. Owning to the lack of assay procedure in the current research geographical area, this study aims to determine the sensitivity and specificity of Apolipoprotein B100 derived from Cho's formula in conjunction with existing routine lipid profile parameters. Method: The lipid profile parameters (TC, LDLC, HDLC, Apo B100, TG and non-HDL-C) in the fasting samples of 301 adult patients in the Chemical Pathology Laboratories of the Federal Medical Centre; Birnin Kudu Jigawa State, and Birnin Kebbi, Kebbi State Nigeria. The Apo B100 was calculated using Cho equation (Cho et al., 2012). Receiver Operating Curve (ROC) was employed to determine the sensitivity and reliability of lipid parameters in the assessment of atherosclerotic risk. Cho^’ s Equation: ApoB100 = -33.12 + 0.675*LDLc + 11.95*ln(Trig) Results: From the table 1, the areas under the curves represent the probability that the lipid assay for a randomly chosen atherosclerotic risk case (sensitivity) will exceed the result for a randomly chosen no risk case (specificity). The asymptotic significance for HDL-C, TC, LDL-C Apo B100 and non-HDL-C were less than 0.05, and AUC greater than 0.7. Furthermore, LDL-C, Apo B100, non-HDL-C, and TC have AUC of 1.00, 0.990, 0.976, and 0.885 respectively. In addition to their high AUC, the specificity of TC, HDL-C, LDL-C Apo B100 and non-HDL-C for ASCVD risk were 74.4, 37.2, 100.0, 94.8 and 88.4 percent respectfully, whereas TG has no significant influence (AUC) on risk of ASCVD. It is worthy to mention that the AUC of HDL-C was statistically significant, but lower than 0.70 (0.429). The serum TC, LDL-C, Apo B100, and non-HDL-C level of greater than 172.1mmg/dl, 106.3 mg/dl, 95.6 mg/dl, and 135.3 mg/dl respectively were associated with a high risk of atherosclerotic as indicated by their specificities and sensitivities. Conclusion: It can be concluded that using the TC, LDL-C, Apo B100 and non-HDL-C for atherosclerotic risk estimation guaranteed significant reliability. It can be concluded that Apo B100 derived using Cho formula showed a high sensitivity and specificity in predicting atherosclerotic risk at a serum level of approximately 96 mg/dl. Therefore, Apo B100 derived from Cho formula may be a useful tool in the management of atherosclerotic cardiovascular disease in limited resources settings.

Sustained usage of an app-based clinical-decision making aid for the management of atherosclerotic cardiovascular disease

Abstract Background Complexity of therapies for atherosclerotic cardiovascular disease (ASCVD) risk reduction represents a challenge for clinicians and may lead to poor uptake of these therapies. Purpose The goal of this project was to design an easy-to-use, point-of-care tool to risk stratify ASCVD patients and provide individualized guidance for clinicians to incorporate these agents. Methods Based on the REACH registry trial and predictive modeling (including 49,689 patients with ASCVD in 44 countries), we designed and implemented an app for secondary risk assessment. Using demographic and comorbidity profiles, this tool was used to calculate an individual's 20-month risk of cardiovascular events and mortality. It also provided graphical comparison to an age-matched control with optimized cardiovascular risk profile to illustrate the modifiable residual risk. The app then utilized the patient's risk profile to provide specific guidance for possible therapeutic interventions SGLT2-inhibitors, GLP1-agonists, PCSK9-inhibitors, Vascular-dose Rivaroxaban, and Icosapent Ethyl. Additionally, it identified individuals who qualified for cardiac rehabilitation or may benefit from smoking cessation interventions, including counselling or pharmacological therapies. We launched a pilot test of the “Residual Cardiovascular Risk: Assessment and Management Guide” app at a regional cardiac center. 240 referring physicians (including family doctors, emergency physicians, internists, and cardiologists) were invited by email or fax to utilize the app. Feedback was solicited from all users three months into the test period. Following this, no further marketing of the app was performed for all users. Usage data was recorded using Google Analytics over a 12-month period and analyzed in 4-month increments. Results From January to December 2021, our app was used to risk stratify 1576 patients. A total of 47 individual users utilized the app over this period. From January to April, the app was used on average 160 times monthly. From May to August, it was used 115 times monthly. From September to December, it was used 118 times monthly. Twenty-four physicians provided feedback; 100% affirmed the functionality, ease of use, and utility of the tool. The app was described as “useful for discussions with patients”, “helpful to optimize patients” and “similar to a mini-cardiology consult”. User suggestions resulted in further improvements to the app, including integration of reports into Electronic Medical Records. Conclusions The early success of this app demonstrates a need for simple, accessible, and individualized guidance for management of ASCVD patients to improve uptake of guideline-based medical therapies. This tool demonstrates sustained usage among clinicians, as well as subjective utility in aiding therapeutic decision making. Future clinical research will focus on the ability of this tool to impact physician prescribing patterns and clinical outcomes. Funding Acknowledgement Type of funding sources: None.

Management of statin intolerance in a pharmacy led cardiology innovative medicines optimisation lipid clinic

Abstract Background Statins are cornerstone in the management of atherosclerotic cardiovascular disease. If a patient has experienced clinically significant adverse drug reactions (ADRs), representing an unacceptable risk or may result in adherence issues, we would consider them intolerant. The prevalence is lower in randomised trials than cohort observational studies, 5% vs. 17%. Purpose To assess how many people we reviewed in clinic were able to be re-challenged and successfully continued on a statin, free from side effects. Methods Over 6 months we reviewed all patients referred to our innovative clinic for lipid optimisation labelled as “statin intolerant”. Initially, as per our protocol, we adopted a person-centred approach and explored this label (actual vs. potential concerns, any previous issues, symptoms experienced and timings, statins tried (if any), and patient's feelings on re-challenge). A statin re-challenge was offered if not contraindicated. If agreed, based on shared-decision making, we offered patients a once weekly statin (usually rosuvastatin 5mg) with a clear self-management plan to up/down-titrate frequency and dose, until they identify a tolerated regimen. We measured LDL-C at baseline and every 3 months thereafter until satisfactory. Results Of 207 patients referred 152 (73%) were labelled as “statin intolerant”. Average age was 62 (±11), 51% females. 78% for secondary prevention and 37% had familial hypercholesterolaemia. The average baseline LDL-C was 4.4mmol/L. 108 (71%) qualified for PCSK9 inhibitors therapy (PCSK9i) as per UK NICE guidance. The top 3 reported ADRs were musculoskeletal side effects (48%), GI upsets (13%) and deranged LFTs (7%). 25 (58%) of those “intolerant” who did not qualify for PCSK9i attempted a re-challenge with statins vs. 44 (41%) among those who qualified. Of the 69 patients, who accepted a re-challenge, 43 (62%) were successfully restarted on a statin. At an average of 14 months post re-challenge, LDL-C (available for &amp;gt;80% of the sample) was reduced by an average of 31% in those not on PCSK9i, compared to a 62% reduction (sustained over an average of 40 months) in those on combination therapy with PCSK9i. The top 3 rosuvastatin regimens established were 5mg OD (29%), 5mg weekly (24%) and 10mg OD (15%). Approximately 80% of patients were on rosuvastatin, and the rest accepted atorvastatin, pravastatin or simvastatin. There was no attempt to re-challenge in 77 (51%) patients, mostly due to choice (45%) or statins re-challenged prior to referral (44%). We stopped statins in 6 cases due to intolerable ADRs. Conclusion(s) By using a person-centred approach, and a variety of strategies to tackle “statin intolerance” we have successfully re-established over 60% of patients with very high CVD risk on statins. While patients who qualified for PCSK9i therapy were less likely to consider re-challenge with statins (41% v 58%), combination lipid-lowering therapies produced better reduction in LDL-C. Funding Acknowledgement Type of funding sources: None.

Sustained usage of an app-based clinical-decision making aid for the management of atherosclerotic cardiovascular disease

Abstract Background Complexity of therapies for atherosclerotic cardiovascular disease (ASCVD) risk reduction represents a challenge for clinicians and may lead to poor uptake of these therapies. Purpose The goal of this project was to design an easy-to-use, point-of-care tool to risk stratify ASCVD patients and provide individualized guidance for clinicians to incorporate these agents. Methods Based on the REACH registry trial and predictive modeling (including 49,689 patients with ASCVD in 44 countries), we designed and implemented an app for secondary risk assessment. Using demographic and comorbidity profiles, this tool was used to calculate an individual's 20-month risk of cardiovascular events and mortality. It also provided graphical comparison to an age-matched control with optimized cardiovascular risk profile to illustrate the modifiable residual risk. The app then utilized the patient's risk profile to provide specific guidance for possible therapeutic interventions SGLT2-inhibitors, GLP1-agonists, PCSK9-inhibitors, Vascular-dose Rivaroxaban, and Icosapent Ethyl. Additionally, it identified individuals who qualified for cardiac rehabilitation or may benefit from smoking cessation interventions, including counselling or pharmacological therapies. We launched a pilot test of the “Residual Cardiovascular Risk: Assessment and Management Guide” app at a regional cardiac center. 240 referring physicians (including family doctors, emergency physicians, internists, and cardiologists) were invited by email or fax to utilize the app. Feedback was solicited from all users three months into the test period. Following this, no further marketing of the app was performed for all users. Usage data was recorded using Google Analytics over a 12-month period and analyzed in 4-month increments. Results From January to December 2021, our app was used to risk stratify 1576 patients. A total of 47 individual users utilized the app over this period. From January to April, the app was used on average 160 times monthly. From May to August, it was used 115 times monthly. From September to December, it was used 118 times monthly. Twenty-four physicians provided feedback; 100% affirmed the functionality, ease of use, and utility of the tool. The app was described as “useful for discussions with patients”, “helpful to optimize patients” and “similar to a mini-cardiology consult”. User suggestions resulted in further improvements to the app, including integration of reports into Electronic Medical Records. Conclusions The early success of this app demonstrates a need for simple, accessible, and individualized guidance for management of ASCVD patients to improve uptake of guideline-based medical therapies. This tool demonstrates sustained usage among clinicians, as well as subjective utility in aiding therapeutic decision making. Future clinical research will focus on the ability of this tool to impact physician prescribing patterns and clinical outcomes. Funding Acknowledgement Type of funding sources: None.

Update in antilipidaemic management of atherosclerotic cardiovascular disease: emerging concepts, new risk assessment, and risk-related management

Update in antilipidaemic management of atherosclerotic cardiovascular disease: emerging concepts, new risk assessment, and risk-related management

Impact of Non-Pharmacological Interventions on the Mechanisms of Atherosclerosis.

Atherosclerosis remains the leading cause of mortality and morbidity worldwide characterized by the deposition of lipids and fibrous elements in the form of atheroma plaques in vascular areas which are hemodynamically overloaded. The global burden of atherosclerotic cardiovascular disease is steadily increasing and is considered the largest known non-infectious pandemic. The management of atherosclerotic cardiovascular disease is increasing the cost of health care worldwide, which is a concern for researchers and physicians and has caused them to strive to find effective long-term strategies to improve the efficiency of treatments by managing conventional risk factors. Primary prevention of atherosclerotic cardiovascular disease is the preferred method to reduce cardiovascular risk. Fasting, a Mediterranean diet, and caloric restriction can be considered useful clinical tools. The protective impact of physical exercise over the cardiovascular system has been studied in recent years with the intention of explaining the mechanisms involved; the increase in heat shock proteins, antioxidant enzymes and regulators of cardiac myocyte proliferation concentration seem to be the molecular and biochemical shifts that are involved. Developing new therapeutic strategies such as vagus nerve stimulation, either to prevent or slow the disease’s onset and progression, will surely have a profound effect on the lives of millions of people.

DOACs and Atherosclerotic Cardiovascular Disease Management: Can We Find the Right Balance Between Efficacy and Harm.

The balance between efficacy and harm remains a challenge in the adoption of non-vitamin K antagonist direct oral anticoagulants (DOACs) for secondary atherosclerotic disease prevention. We provide a comprehensive review of the evidence for and against the addition of DOACs to the current management of atherosclerotic cardiovascular disease, including stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD), and percutaneous coronary interventions (PCI). The DOAC class exerts pleiotropic effects on atherosclerotic progression through coagulation and inflammatory pathways. In ACS, low-dose DOAC provides no added efficacy in the setting of dual antiplatelet therapy; however, full-dose DOAC increases bleeding. Efficacy-safety profile favor use of low-dose rivaroxaban in select stable CAD or PAD patients. Atrial fibrillation patients undergoing PCI resort to dual therapy with DOAC due to prohibitory bleeding with triple anti-thrombotic therapy. Evidence favors DOAC use in CAD and PAD; however, careful individual considerations must be undertaken.

Cerebrovascular Disease and Statins.

Elevated low-density lipoprotein-cholesterol (LDL-C) is a causal factor for the development of atherosclerotic cardiovascular disease (ASCVD); accordingly, LDL-C lowering is associated with a decreased risk of progression of atherosclerotic plaques and development of complications. Currently, statins play a central role in any ASCVD management and prevention strategies, in relation to their lipid-lowering action and potentially to pleiotropic effects. After coronary artery disease, stroke is the most frequent cause of ASCVD mortality and the leading cause of acquired disability, a major public health problem. There is often a tendency to aggregate all types of stroke (atherothrombotic, cardioembolic, and haemorrhagic), which have, however, different causes and pathophysiology, what may lead to bias when interpreting the results of the studies. Survivors of a first atherothrombotic ischemic stroke are at high risk for coronary events, recurrent stroke, and vascular death. Although epidemiological studies show a weak relationship between cholesterol levels and cerebrovascular disease as a whole compared with other ASCVD types, statin intervention studies have demonstrated a decrease in the risk of stroke in patients with atherosclerosis of other territories and a decrease in all cardiovascular events in patients who have had a stroke. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial demonstrated the benefit of high doses of atorvastatin in the secondary prevention of ischemic stroke. In this review, we discuss the evidence, use and recommendations of statins in the primary and secondary prevention of stroke, and their role in other scenarios such as the acute phase of ischemic stroke, cerebral hemorrhage, cardioembolic stroke, small vessel disease, and cognitive impairment.

Synergistic actions between angiotensin-converting enzyme inhibitors and statins in atherosclerosis

AimsHypertension and hypercholesterolemia are independent risk factors for atherosclerotic cardiovascular disease (ASCVD) by acting directly on the endothelium and activating the renin-angiotensin aldosterone system (RAAS) and mevalonate pathways. This review examines how the severity and duration of these risk factors may influence the cardiovascular risk through a reciprocal interplay leading to oxidative stress and pro-inflammatory response. Data synthesisThe review highlights the clinical evidence supporting the benefits of statins and angiotensin-converting enzyme (ACE) inhibitors for hypertension, lipid disorders and ASCVD management, both individually and combined, at all stages of the cardiovascular continuum. ConclusionDrug strategies incorporating an ACE-inhibitor and a statin, and in particular perindopril and atorvastatin, have consistently demonstrated reductions in the rate of ASCVD events in patients with hypertension and lipid disorders, cementing their position as first-line therapies for the management of atherosclerosis complications.