Secondary Prevention Of Vascular Events Research Articles

A Study on the Effectiveness of Mono and Dual Antiplatelet Therapy in Secondary Prevention of Vascular Events

A Study on the Effectiveness of Mono and Dual Antiplatelet Therapy in Secondary Prevention of Vascular Events

Strategies to reduce out-of-pocket medication costs for Canadians with peripheral arterial disease.

Given that peripheral arterial disease (PAD) disproportionately affects people of lower socioeconomic status, out-of-pocket expenses for preventive medications are a major barrier to their use. We carried out a cost comparison of drug therapies for PAD to identify prescribing strategies that minimize out-of-pocket expenses for these medications. Between March and June 2019, we contacted outpatient pharmacies in Hamilton, Ontario, Canada, to assess pricing of pharmacologic therapies at dosages included in the 2016 American College of Cardiology/American Heart Association guideline for management of lower extremity PAD. We also gathered pricing information for supplementary charges, including delivery, pill splitting and blister packaging. We calculated prescription prices with and without dispensing fees for 30-day brand-name and generic prescriptions, and 90-day generic prescriptions. Twenty-four pharmacies, including hospital-based, independent and chain, were included in our sample. In the most extreme scenario, total 90-day medication costs could differ by up to $1377.26. Costs were affected by choice of agent within a drug class, generic versus brand-name drug, quantity dispensed, dispensing fee and delivery cost, if any. By opting for prescriptions for 90 days or as long as possible, selecting the lowest-cost generic drugs available in each drug class, and identifying dispensing locations with lower fees, prescribers can minimize out-of-pocket patient medication expenses. This may help improve adherence to guideline-recommended therapies for the secondary prevention of vascular events in patients with PAD.

Use of Lipid-Lowering Drugs After Intracerebral Hemorrhage.

Hyperlipidemia is common in patients with intracerebral hemorrhage (ICH). Accumulating evidence indicates that patients with ICH are at risk for future hemorrhage recurrence, cardiovascular disease, and ischemic stroke and highlights the importance of secondary prevention of vascular events after ICH. Although the benefits of intensive treatment of hyperlipidemia for reducing ischemic cardiac and vascular events in patients with ischemic stroke are well established, the benefit versus harm in patients with ICH are less clear. Epidemiological studies suggest that hyperlipidemia is protective against ICH and that intensive lowering of lipids is associated with increased risk for ICH. Similarly, although currently available lipid-lowering treatments have been thoroughly studied in patients with ischemic cardiac and vascular disease, only few randomized trials of these therapies included a very small number of patients with history of ICH. Thus, limiting any definitive conclusions regarding the safety and net benefit of these treatments in ICH populations. Currently, there is no consensus regarding the optimal strategy for management of hyperlipidemia after ICH. In this article, we review relevant literature to outline the competing risks and benefits of lipid-lowering treatments in this vulnerable patient population. We suggest a treatment paradigm based on available data but note that data from dedicated randomized trials are needed to build the necessary evidence to guide optimal lipid-lowering strategy in patients with a history of ICH.

Long-term mortality and recurrent vascular events in lacunar versus non-lacunar ischaemic stroke: A cohort study.

IntroductionStudies of differences in very long-term outcomes between people with lacunar/small vessel disease (SVD) versus other types of ischaemic stroke report mixed findings, with limited data on myocardial infarction (MI). We investigated whether long-term mortality, recurrent stroke and MI risks differ in people with versus without lacunar/SVD ischaemic stroke.Patients and methodsWe included first-ever strokes from a hospital-based stroke cohort study recruited in 2002–2005. We compared risks of death, recurrent stroke and MI during follow-up among lacunar/SVD versus other ischaemic stroke subtypes using Cox regression, adjusting for confounding factors.ResultsWe included 812 participants, 283 with lacunar/SVD ischaemic stroke and 529 with other stroke. During a median of 9.2 years (interquartile range 3.1–11.8), there were 519 deaths, 181 recurrent strokes and 79 MIs. Lacunar/SVD stroke was associated with lower mortality (adjusted HR 0.79, 95% CI 0.65 to 0.95), largely due to markedly lower all-cause mortality in the first year. From one year onwards this difference attenuated, with all-cause mortality only slightly and not statistically significantly lower in the lacunar/SVD group (0.86, 95% CI 0.70 to 1.05). There was no clear difference in risk of recurrent stroke (HR 0.84, 95% CI 0.61–1.15) or MI (HR 0.83, 95% CI 0.52–1.34).ConclusionLong-term risks of all-cause mortality, recurrent stroke and MI are similar, or only slightly lower, in patients with lacunar/SVD as compared to other ischaemic stroke. Patients and physicians should be as vigilant in optimising short- and long-term secondary prevention of vascular events in lacunar/SVD as for other stroke types.

Ischemic Stroke as a Clinical Form and Pathogenetic Model in the Structure of Сentral Nervous System Lesions in COVID-19

Models of pathogenetic effects of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the new coronavirus infection 2019 (COVID-19) on the brain indicate the possibility of both direct and indirect damage. Objective of the research. to study the features of the course of ischemic stroke in patients with COVID-19 disease. Methods. A retrospective analysis of 5 cases of acute ischaemic stroke in patients with COVID 19 who underwent inpatient treatment in march – April 2020 in one of the multi-specialty hospitals in Saint Petersburg, which was re-designated to receive patients with COVID-19 infection and has a primary vascular department. Results. Among 5 patients COVID-19 (3 men, 2 women; average age 76.8Ѓ}12.0 years), 3 registered in-hospital ischemic stroke (IHS), 2 patients were hospitalized with suspected cerebral stroke by ambulance. In vivo, COVID-19 was diagnosed in 3 patients; in 2 cases, the SARS-COV 2 virus was detected in the sectional material. All patients had high comorbidity: a history of stroke and/or myocardial infarction; 3 patients had diabetes mellitus; 2 had atrial fibrillation. Patients with IHS at the time of stroke development received secondary prevention of vascular events. The severity of ischemic stroke was 21.4Ѓ}4.3 on the NIHSS scale. According to the TOAST classification, the stroke was atherothrombotic (n=2), cardioembolic (n=1) and unspecified subtypes (n=2). Adverse outcome was registered in all cases on 5–11 day of stroke development (the average life expectancy after a stroke = 7,4 days). Conclusion. Experience in treating patients with COVID-19 indicates the need for monitoring the coagulation system and active prevention of thrombosis. Providing care to patients with ischemic stroke on the background of COVID-19 is associated with additional organizational difficulties associated with the need to comply with strict anti-epidemic measures, which affect the intra- hospital logistics and quality of care.

Follow-up after surgical treatment for intermittent claudication (FASTIC): a study protocol for a multicentre randomised controlled clinical trial

BackgroundIntermittent claudication (IC) is a classic symptom of peripheral arterial disease, and strongly associated with coronary heart disease and cerebrovascular disease. Treatment of IC and secondary prevention of vascular events include best medical treatment (BMT), changes in lifestyle, most importantly smoking cessation and increased physical exercise, and in appropriate cases surgery. A person-centred and health promotion approach might facilitate breaking barriers to lifestyle changes and increasing adherence to secondary prevention therapy. The FASTIC study aims to evaluate a nurse-led, person-centred, health-promoting follow-up programme compared with standard follow-up by a vascular surgeon after surgical treatment for IC.MethodsThe FASTIC-study is a multicentre randomised controlled clinical trial. Patients will be recruited from two hospitals in Stockholm, Sweden after surgical treatment of IC through open and/or endovascular revascularisation and will be randomly assigned into two groups. The intervention group is offered a nurse-led, person-centred, health-promoting programme, which includes two telephone calls and three visits to a vascular nurse the first year after surgical treatment. The control group is offered standard care, which consists of a visit to a vascular surgeon 4–8 weeks after surgery and a visit to the outpatient clinic 1 year after surgical treatment. The primary outcome is adherence to BMT 1 year after surgical treatment and will be measured using The Swedish Prescribed Drug Registry. Clinical assessments, biomarkers, and questionnaires will be used to evaluate several secondary outcomes, such as predicted 10-year risk of cardiovascular and cerebrovascular events, health-related quality of life, and patients’ perceptions of care quality.DiscussionThe FASTIC study will provide important information about interventions aimed at improving adherence to medication, which is an unexplored field among patients with IC. The study will also contribute to knowledge on how to implement person-centred care in a clinical context.Trial registrationClinicalTrials.govNCT03283358, registration date 06/13/2016.

Improving the diagnosis, treatment and secondary prevention of stroke using a unified online system: primary vascular department - regional vascular center - family doctor

The introduction of the Stroke Platform (SP) in the Belgorod Region to improve the efficiency of diagnosis and care for patients with stroke. Stroke platform is a unified information platform that unites all stages of treatment of a patient with stroke, from the first symptoms to dispensary observation by a family doctor and control of targeted provision of medicines for the secondary prevention of vascular events. The SP includes 6 modules: the Central Archive of Medical Images or the Picture Archiving and Communication System (PACS) and connection to a single circuit of all CT devices of the regional medical institutions; Stroke register; secondary prevention register; routing bureau; statistics and analytics; COVID platform. The SP, as it develops, can be supplemented with those modules that are necessary to improve the quality and availability of patient care. More than 100 consultations of CT images are carried out monthly through the SP, the average response time is less than 10 minutes, 52 platform participants are in constant contact, all medical institutions of the region are connected. Five hundred and forty patients were consulted for 6 months of 2020. The share of hospitalizations in specialized departments increased to 97.6% versus 86.3%. The availability of high-tech medical care for patients with stroke has increased due to timely transfer to the district vascular center. Endovascular interventions for aneurysms and arteriovenous malformations, stenting of extracerebral arteries during dissection, mechanical thrombectomy from large arteries are performed. Mortality decreased from 19.7% (2019) to 17.6%. At the stage of outpatient follow-up, it is possible to obtain information about the range of those drugs that are prescribed to the patient for prophylaxis and are delivered to the target. The main feature of the SP is the speed and efficiency of making medical decisions, ergonomics and ease of interaction, a single workspace.

Costs of bleeding on long-term antiplatelet treatment without routine co-prescription of proton-pump inhibitors.

Long-term antiplatelet treatment is associated with major bleeding. To determine the costs associated with major bleeding in patients treated with aspirin-based antiplatelet treatment for secondary prevention of vascular events without routine prescription of proton-pump inhibitors and to estimate the likely long-term savings from routine co-prescription. In a prospective population-based cohort study of TIA, ischemic stroke, and MI treated with antiplatelet drugs, we evaluated hospital care costs associated with bleed management during 10-year follow-up. Bleeding-associated costs were averaged across all patients. For upper GI-bleeds, mean costs were compared with the cost of routine co-prescription of proton-pump inhibitor. Among 3166 patients on antiplatelet therapy with 405 first bleeding events, the average cost of major bleeding was $13,093 (S.D. 20,501), with similar costs for upper GI bleeds and intracranial bleeds (p = 0.235). However, total costs among the 3166 patients were higher for upper GI bleeds ($1,158,385 vs. $740,123). Averaged across all patients, the 10-year cost of major bleeding was $838 (95%CI: 680-1007), $411 due to upper GI bleeding, the cost of which increased from $175 in those aged <75 years to $644 at age ≥75 years (p < 0.0001). The corresponding costs of routine life-long co-prescription of proton-pump inhibitor to those patients not on prior treatment were $85 (84-88) and $39 (38-42). In secondary prevention with aspirin-based antiplatelet treatment without routine proton-pump inhibitor use, the long-term costs of upper-GI bleeding at age ≥75 years are much higher than at younger age groups, and are at least 10-fold greater than the drug cost of routine co-prescription of proton-pump inhibitor.

John Adam Dormandy: championed new approaches to tackling peripheral arterial disease

John Dormandy was a consultant vascular surgeon, researcher, and medical educator best known for innovative work on the diagnosis and management of peripheral arterial disease. He had a leading role...

Use of Alternative Antiplatelet Agents for Clopidogrel Hypersensitivity.

Clopidogrel is a widely used agent for secondary prevention of vascular events and is a cornerstone of dual antiplatelet therapy in patients with acute coronary syndrome (ACS) post coronary stent implantation. Hypersensitivity reactions to clopidogrel are well documented and may range from localized to systemic in presentation. This can lead to discontinuation of therapy, thus increasing the risk of vascular events. The authors have developed recommendations for potential alternative agents for the management of clopidogrel hypersensitivity reactions. Proposed strategies include treatment with an alternative P2Y12 inhibitor, cilostazol or warfarin.

Clustering of ABCB1 and CYP2C19 Genetic Variants Predicts Risk of Major Bleeding and Thrombotic Events in Elderly Patients with Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy with Aspirin and Clopidogrel.

ObjectiveThe clinical efficacy of clopidogrel in secondary prevention of vascular events is hampered by marked inter-patient variability in drug response, which partially depends on genetic make-up. The aim of this pilot prospective study was to evaluate 12-month cardiovascular outcomes in elderly patients with acute coronary syndrome (ACS) receiving dual antiplatelet therapy (aspirin and clopidogrel) according to the clustering of CYP2C19 and ABCB1 genetic variants.MethodsParticipants were 100 consecutive ACS patients who were genotyped for CYP2C19 (G681A and C-806T) and ABCB1 (C3435T) polymorphisms, which affect clopidogrel metabolism and bioavailability, using PCR-restriction fragment length polymorphism. They were then grouped as poor, extensive and ultra-rapid metabolisers based on the combination of CYP2C19 loss-of-function (CYP2C19*2) and gain-of-function (CYP2C19*17) alleles and ABCB1 alleles. The predictive value of each phenotype for acute vascular events was estimated based on 12-month cardiovascular outcomes.ResultsThe poor metabolisers were at an increased risk of thrombotic events (OR 1.26; 95% CI 1.099–1.45; χ2 = 5.676; p = 0.027), whereas the ultra-rapid metabolisers had a 1.31-fold increased risk of bleeding events compared with the poor and extensive metabolisers (OR 1.31; 95% CI 1.033–1.67; χ2 = 5.676; p = 0.048). Logistic regression model, including age, sex, BMI and smoking habit, confirmed the differential risk of major events in low and ultra-rapid metabolisers.ConclusionsOur findings suggest that ACS patients classified as ‘poor or ultra-rapid’ metabolisers based on CYP2C19 and ABCB1 genotypes should receive alternative antiplatelet therapies to clopidogrel.Electronic supplementary materialThe online version of this article (10.1007/s40266-018-0555-1) contains supplementary material, which is available to authorized users.

Effects of a health promotion program on medication adherence to antiplatelet therapy among ischemic stroke patients in Hainan Province, China.

Survivors of ischemic stroke are still at a significant risk for recurrence. Antiplatelet agents are the treatment of first choice for long-term secondary prevention of vascular events. This study aims to assess a health promotion program on medication adherence to antiplatelet therapy among ischemic stroke patients in Hainan province, China. In five hospitals from the intervention group, four highly experienced physicians trained 62 neurologists, who in turn trained 613 stroke patients to improve their awareness and adherence to antiplatelet therapy. Physicians and patients of the control group received usual stroke management programs. After one-year follow-up, the proportion of patients who took the antiplatelet therapy increased significantly in the intervention group, reaching 73.2%, with a pre-post difference between two arms of 22.9% ( P < 0.01). There was also a significant net increase in the proportion of patients with awareness of antiplatelet therapy (24.4%, P < 0.01). Multivariate analysis illustrated health promotion program, higher education, annual household income, insurance, and medical status affected antiplatelet drug use in stroke patients. In conclusion, the health promotion program, based on a train-the-trainer approach, showed positive effects on awareness of and adherence to antiplatelet therapy, which has the potential to be scaled up to other resource-limited areas.

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.

Abstract 197: Statin Therapy Is Associated With Higher MTHFR Methylation Levels in a Stroke Cohort

Introduction: Epigenetics refers to changes in gene function that occur by gene methylation, histone modification or RNA mechanisms. Many of these are heritable, but can also be altered by lifestyle and medication. Genome-wide hypomethylation is associated with atherosclerosis and hyperhomocysteinemia, and specific genes can be hyper or hypomethylated in vascular disease. Statins have pleiotropic effects on the vasculature, and may affect DNA methylation. Hypothesis: The methylation levels of genes implicated in vascular disease are altered by treatment with common cardiovascular medications. Methods: 189 individuals from a well characterised stroke cohort and controls were included. 44 were established on statin therapy, 49 on aspirin and 28 on an ACE inhibitor. The following genes implicated in vascular disease were investigated: LINE1, SOD3, ALOX15, ERa, MTHFR , PITX2, IFNGR1, TNFa, IL10, and INS . Methylation status was assessed by bisulphite conversion of DNA followed by PCR and pyrosequencing. Each methylation site was analysed individually and mean methylation level across all sites within a gene calculated. Statistical analysis for the effect of drug therapy was based on logistic regression and ANOVA. Results: One significant association was found: subjects on statin therapy had higher MTHFR methylation levels than those not receiving statin (p=0.002). Statistical analysis adjusted for stroke effect (p=0.025) remained significant. Correction for multiple testing was not performed as the candidate genes are linked in pathways. There was no effect of aspirin or ACE inhibitor on methylation status of any of the genes tested. Discussion: MTHFR plays an important role in homocysteine and folate metabolism, providing methyl groups for DNA methylation. High levels of homocysteine are a risk factor for cardiovascular disease and there is published evidence that statin therapy results in lower plasma homocysteine levels. This finding requires further investigation in a larger cohort with a defined dose and duration of treatment. If this finding is replicated, there may be value in exploring the mechanisms linking statins, MTHFR methylation and homocysteine levels and the implications for primary and secondary prevention of vascular events.

Differential effect of B-vitamin therapy by antiplatelet use on risk of recurrent vascular events after stroke.

Although several randomized controlled trials failed to show a benefit of B vitamin therapy on composite outcomes of cardiovascular death, myocardial infarction, and stroke among individuals with elevated homocysteine, recent post hoc analyses have suggested that several factors may interact with the effects of vitamin treatment. One post hoc analysis revealed an interaction between B vitamin therapy and antiplatelet use; however, those results have not been replicated in other studies or populations. We conducted a post hoc analysis of the Vitamin Intervention for Stroke Prevention (VISP) trial, a randomized controlled trial evaluating treatment with high- versus low-dose B vitamin therapy for secondary prevention of vascular events among stroke survivors with elevated homocysteine. Cox regression models were used to assess primary (recurrent stroke) and secondary (stroke, myocardial infarction, or vascular death) outcomes among individuals on high- versus low-dose vitamin therapy, categorized by antiplatelet use, after adjusting for covariates. Among 3680 participants, 52% took antiplatelet medications. When compared with low-dose therapy, high-dose vitamin therapy was associated with higher stroke risk among individuals on antiplatelets (hazard ratio, 1.43; 95% confidence interval, 1.02-2.01), but trended toward lower risk among those not on antiplatelets (hazard ratio, 0.86; 95% confidence interval, 0.62-1.19). High-dose B vitamin therapy may be associated with a higher risk of recurrent stroke among stroke survivors taking antiplatelets, but does not have a significant effect on recurrent stroke risk in those who are not on antiplatelets. Future randomized controlled trials may consider evaluating the effect of homocysteine lowering among stroke survivors with elevated homocysteine who are not on antiplatelet therapy.

PTH-040 Using Nice Criteria To Assess The Management Of Acute Upper Gi Bleeds During Weekends – The Experience Of A District General Hospital

IntroductionThe management of acute upper GI bleeds (AUGIB) comes under greatest stress at weekends; this is a topical concern given the national drive towards a 7 day working week. We...

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Long-Term Effects of Secondary Prevention on Cognitive Function in Stroke Patients

Limited long-term follow-up data exist on the impact of appropriate secondary prevention therapies on cognitive function in patients after first-ever stroke. The aim of this study is to determine the effect of secondary prevention of vascular events on cognitive function after stroke. Data were collected between 1995 and 2011 (n=4413) from the community-based South London Stroke Register covering an inner-city multiethnic source population of 271 817 inhabitants. Modified Poisson regression models were constructed to adjust for cognitive function status at 3 months, demographic and socioeconomic characteristics, case mix, stroke subtype, vascular risk factors, disability, and stroke recurrence. In patients with ischemic strokes without a history of atrial fibrillation (AF), there was a reduced risk of cognitive impairment associated with the use of different prevention treatments: (1) antihypertensives (relative risk, 0.7 [95% confidence interval, 0.57-0.82] for diuretics; relative risk, 0.8 [95% confidence interval, 0.64-0.98] for angiotensin-converting enzyme inhibitors; and relative risk, 0.7 [95% confidence interval, 0.55-0.81] for their combination), (2) a combination of aspirin and dipyridamole (relative risk, 0.8 [95% confidence interval, 0.68-1.01]), and (3) statin (relative risk, 0.9 [95% confidence interval, 0.76-1.06]) when clinically indicated. Protective effects against cognitive impairment were also observed in patients on the combination of antihypertensives, antithrombotic agents, and lipid-lowering drugs (relative risk, 0.55 [95% confidence interval, 0.40-0.77]). No significant associations were noted between poststroke cognitive impairment and antihypertensives among hemorrhagic stroke patients. Appropriate vascular risk management was associated with a long-term reduced risk of cognitive impairment. Focus on optimal preventive drug therapy of vascular risk factors and management should be supported.

Trends in clinical laboratory homocysteine testing from 1997 to 2010: the impact of evidence on clinical practice at a single institution

During the past decade, several clinical trials investigating the potential benefits of homocysteine-lowering therapy for the secondary prevention of vascular events were completed and published. The objective of the study was to determine trends in clinical laboratory testing for homocysteine at a single institution over the time period from 1997 to 2010. A single-center, retrospective analysis was performed at a large, academic, tertiary care medical center in the USA. The database was searched for clinical laboratory measurements of plasma or serum homocysteine between January 1, 1997 and December 31, 2010. Individual medical records were reviewed for a subset of 221 unique patients in the 10-year period from 2001 to 2010 who had homocysteine values ≥20 μmol/L. From 1997 to 2003, there was a 16-fold increase in the annual number of homocysteine assays performed. Testing for homocysteine declined in 2004 and 2006, coinciding with the publication of intervention trials that failed to support a clinical benefit of homocysteine-lowering therapy for the secondary prevention of vascular events. Subgroup analysis suggested that homocysteine testing for the indication of suspected nutritional deficiency or hypercoagulability remained steady despite a decline in testing for the indication of cardiac risk assessment. The frequency of clinical laboratory testing for plasma or serum homocysteine changed bimodally over the time period from 1997 to 2010. These observations suggest that clinical practice was impacted by emerging evidence from association studies and intervention trials investigating homocysteine as a potentially treatable cardiac risk factor.