Change in Trajectories of Adherence to Lipid-Lowering Drugs Following Non-Fatal Acute Coronary Syndrome or Stroke.
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SUBMITTER: Zongo A
PROVIDER: S-EPMC6912969 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:Thresholds defining medication adherence are rarely evidence-based. A threshold of 0.8 is typically presumed to achieve improved outcomes. We aimed to assess the optimal threshold of adherence to lipid-lowering drugs (LLD) in predicting cardiovascular-related (CV) outcomes in patients with hypertension. DESIGN:Cohort study of new users of LLDs. SETTING:Comprehensive healthcare administrative databases of the province of Alberta (Canada) from 2008 to 2016. PARTICIPANTS:Patients with hypertension, who were new users of LLDs. Patients who had the outcomes prior to the initiation of LLD were excluded. MAIN OUTCOMES MEASURES:Hospitalization for acute coronary syndrome (ACS)/stroke, CV-related mortality and all-cause mortality. STATISTICAL ANALYSIS:Adherence to LLDs was assessed as the proportion of days covered (PDC) by any LLD, from drug initiation to censoring, outcome, or study end. Three methods were used to assess the threshold: Contal and O'Quigley method, minimum distance method, and Youden's J index. Cox regressions were used to assess the risk associated with each method-specific threshold and Akaike information criteria were used to retain the optimal threshold after adjustment. RESULTS:52229 patients were included; 4.0% were hospitalized for ACS/stroke, 3.4% died, and 1.3% died from CV-related cause. In predicting ACS/stroke, CV-related and all-cause mortality, the optimal adherence threshold was 0.52 (range: 0.51-0.54), 0.79 (0.45-0.87), and 0.84 (0.79-0.89), respectively. These results were consistent among patients aged ? 65 years (n = 19804). However, the results varied among those aged < 65 years, where the incidence rates of outcomes were low. CONCLUSION:In new-users of LLDs with hypertension, approximately 50% days covered by LLDs may be enough to prevent long-term occurrence of ACS, or stroke. However, a threshold near 0.80 may be needed to prevent or reduce the risk of all-cause or CV-related mortality.
| S-EPMC6760888 | biostudies-literature
Project description:There are several established lipid-modifying agents, including statins, fibrates, niacin, and ezetimibe, that have been shown in randomized clinical outcome trials to reduce the risk of having an atherosclerotic cardiovascular event. However, in many people, the risk of having an event remains unacceptably high despite treatment with these established agents. This has stimulated the search for new therapies designed to reduce residual cardiovascular risk. New approaches that target atherogenic lipoproteins include: 1) inhibition of proprotein convertase subtilisin/kexin type 9 to increase removal of atherogenic lipoproteins from plasma; 2) inhibition of the synthesis of apolipoprotein (apo) B, the main protein component of atherogenic lipoproteins; 3) inhibition of microsomal triglyceride transfer protein to block the formation of atherogenic lipoproteins; 4) inhibition of adenosine triphosphate citrate lyase to inhibit the synthesis of cholesterol; 5) inhibition of the synthesis of lipoprotein(a), a factor known to cause atherosclerosis; 6) inhibition of apoC-III to reduce triglyceride-rich lipoproteins and to enhance high-density lipoprotein (HDL) functionality; and 7) inhibition of cholesteryl ester transfer protein, which not only reduces the concentration of atherogenic lipoproteins but also increases the level and function of the potentially antiatherogenic HDL fraction. Other new therapies that specifically target HDLs include infusions of reconstituted HDLs, HDL delipidation, and infusions of apoA-I mimetic peptides that mimic some of the functions of HDLs. This review describes the scientific basis and rationale for developing these new therapies and provides a brief summary of established therapies.
| S-EPMC4813424 | biostudies-literature
Project description:BackgroundStroke is a leading cause of death worldwide, but it is unclear whether circulating lipids and lipid-lowering drugs are causally associated with stroke and its subtypes.MethodsWe used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-lowering drugs on stroke and its subtypes.ResultsThe inverse variance weighted Mendelian randomization (IVW-MR) revealed the low-density lipoprotein cholesterol (LDL-C) (OR, 1.46; 95% CI, 1.17-1.83; p = 0.0008) and apolipoprotein B (apoB) (OR, 1.46; 95% CI, 1.21-1.77; p = 0.0001) was positively correlated with large artery stroke (LAS). However, no causal effect was found in LDL-C and apoB on LAS risk when we conducted mvMR. The IVW-MR also found a suggestive evidence that decreased LDL-C levels mediated by the PCSK9 (proprotein convertase subtilisin-kexin type 9) gene were associated with a reduced risk of any stroke (AS) (OR, 1.31; 95% CI, 1.13-1.52; p = 0.0003), any ischemic stroke (AIS) (OR, 1.29; 95% CI, 1.10-1.51; p = 0.001), and LAS (OR, 1.73; 95% CI, 1.15-2.59; p = 0.008), while NPC1L1 (Niemann-Pick C1-like protein)-mediated LDL-C levels were associated with a higher risk of small vessel stroke (SVS) (OR, 6.10; 95% CI, 2.13-17.43; p = 0.0008). The SMR revealed that expression of PCSK9 was associated with risk of AS (OR, 1.15; 95% CI, 1.03-1.28; p = 0.01), AIS (OR, 1.02; 95% CI, 1.14-1.29; p = 0.03), cardioembolic stroke (CES) (OR, 1.28; 95% CI, 1.01-1.61; p = 0.04). And, a significant association was found between the expression of NPC1L1 and the risk of SVS (OR, 1.15; 95% CI, 1.00-1.32; p = 0.04).ConclusionWe cautiously find that LDL-C and apoB was positively correlated with LAS. These findings suggest that the reducing LDL-C levels could be an effective prevention strategy for reducing the risk of stroke.
| S-EPMC10390065 | biostudies-literature
Project description:Stroke events increase the risk of developing dementia, 10% for a first-ever stroke and 30% for recurrent strokes. However, the effects of stroke on global cognition, leading up to dementia, remain poorly understood. We investigated: (i) post-stroke trajectories of cognitive change, (ii) trajectories of cognitive decline in those who develop dementia over periods of follow-up length and (iii) risk factors precipitating the onset of dementia. Prospective cohort of hospital-based stroke survivors in North-East England was followed for up to 12 years. In this study, we included 355 stroke survivors of ≥75 years of age, not demented 3 months post-stroke, who had had annual assessments during follow-up. Global cognition was measured annually and characterized using standardized tests: Cambridge Cognition Examination-Revised and Mini-Mental State Examination. Demographic data and risk factors were recorded at baseline. Mixed-effects models were used to study trajectories in global cognition, and logistic models to test associations between the onset of dementia and key risk factors, adjusted for age and sex. Of the 355 participants, 91 (25.6%) developed dementia during follow-up. The dementia group had a sharper decline in Cambridge Cognition Examination-Revised (coeff. = -1.91, 95% confidence interval = -2.23 to -1.59, P < 0.01) and Mini-Mental State Examination (coeff. = -0.46, 95% confidence interval = -0.58 to -0.34, P < 0.01) scores during follow-up. Stroke survivors who developed dementia within 3 years after stroke showed a steep decline in global cognition. However, a period of cognitive stability after stroke lasting 3 years was identified for individuals diagnosed with dementia in 4-6 years (coeff. = 0.28, 95% confidence interval = -3.28 to 3.8, P = 0.88) of 4 years when diagnosed at 7-9 years (coeff. = -3.00, 95% confidence interval = -6.45 to 0.45, P = 0.09); and of 6 years when diagnosed at 10-12 years (coeff. = -6.50, 95% confidence interval = -13.27 to 0.27, P = 0.06). These groups then showed a steep decline in Cambridge Cognition Examination-Revised in the 3 years prior to diagnosis of dementia. Risk factors for dementia within 3 years include recurrent stroke (odds ratio = 3.99, 95% confidence interval = 1.30-12.25, P = 0.016) and previous disabling stroke, total number of risk factors for dementia (odds ratio = 2.02, 95% confidence interval = 1.26-3.25, P = 0.004) and a Cambridge Cognition Examination-Revised score below 80 at baseline (odds ratio = 3.50, 95% confidence interval = 1.29-9.49, P = 0.014). Our unique longitudinal study showed cognitive decline following stroke occurs in two stages, a period of cognitive stability followed by rapid decline before a diagnosis of dementia. This pattern suggests stroke may predispose survivors for dementia by diminishing cognitive reserve but with a smaller impact on cognitive function, where cognitive decline may be precipitated by subsequent events, e.g. another cerebrovascular event. This supports the assertion that the development of vascular dementia can be stepwise even when patients have small stroke lesions.
| S-EPMC9161377 | biostudies-literature
Project description:BackgroundLipid-lowering drugs are widely underused, despite strong evidence indicating they improve cardiovascular end points. Poor patient adherence to a medication regimen can affect the success of lipid-lowering treatment.ObjectivesTo assess the effects of interventions aimed at improving adherence to lipid-lowering drugs, focusing on measures of adherence and clinical outcomes.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and CINAHL up to 3 February 2016, and clinical trials registers (ANZCTR and ClinicalTrials.gov) up to 27 July 2016. We applied no language restrictions.Selection criteriaWe evaluated randomised controlled trials of adherence-enhancing interventions for lipid-lowering medication in adults in an ambulatory setting with a variety of measurable outcomes, such as adherence to treatment and changes to serum lipid levels. Two teams of review authors independently selected the studies.Data collection and analysisThree review authors extracted and assessed data, following criteria outlined by the Cochrane Handbook for Systematic Reviews of Interventions. We assessed the quality of the evidence using GRADEPro.Main resultsFor this updated review, we added 24 new studies meeting the eligibility criteria to the 11 studies from prior updates. We have therefore included 35 studies, randomising 925,171 participants. Seven studies including 11,204 individuals compared adherence rates of those in an intensification of a patient care intervention (e.g. electronic reminders, pharmacist-led interventions, healthcare professional education of patients) versus usual care over the short term (six months or less), and were pooled in a meta-analysis. Participants in the intervention group had better adherence than those receiving usual care (odds ratio (OR) 1.93, 95% confidence interval (CI) 1.29 to 2.88; 7 studies; 11,204 participants; moderate-quality evidence). A separate analysis also showed improvements in long-term adherence rates (more than six months) using intensification of care (OR 2.87, 95% CI 1.91 to 4.29; 3 studies; 663 participants; high-quality evidence). Analyses of the effect on total cholesterol and LDL-cholesterol levels also showed a positive effect of intensified interventions over both short- and long-term follow-up. Over the short term, total cholesterol decreased by a mean of 17.15 mg/dL (95% CI 1.17 to 33.14; 4 studies; 430 participants; low-quality evidence) and LDL-cholesterol decreased by a mean of 19.51 mg/dL (95% CI 8.51 to 30.51; 3 studies; 333 participants; moderate-quality evidence). Over the long term (more than six months) total cholesterol decreased by a mean of 17.57 mg/dL (95% CI 14.95 to 20.19; 2 studies; 127 participants; high-quality evidence). Included studies did not report usable data for health outcome indications, adverse effects or costs/resource use, so we could not pool these outcomes. We assessed each included study for bias using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. In general, the risk of bias assessment revealed a low risk of selection bias, attrition bias, and reporting bias. There was unclear risk of bias relating to blinding for most studies.Authors' conclusionsThe evidence in our review demonstrates that intensification of patient care interventions improves short- and long-term medication adherence, as well as total cholesterol and LDL-cholesterol levels. Healthcare systems which can implement team-based intensification of patient care interventions may be successful in improving patient adherence rates to lipid-lowering medicines.
| S-EPMC6464006 | biostudies-literature
Project description:Although technological and procedural advances have resulted in substantial improvements in clinical outcomes following percutaneous coronary interventions (PCI), recurrent coronary events may occur despite achieving optimal procedural results. Beyond myocardial revascularisation failure related to anatomical or stent-related factors, adverse cardiovascular events post PCI often arise from non-culprit lesions not treated during index interventions. While stenting treats a focal manifestation of a systemic, progressive disease, the residual risk following an acute coronary syndrome (ACS) or elective PCI is largely related to the systemic pro-atherogenic effects of suboptimally controlled cardiovascular risk factors. Lowering atherogenic lipid levels, in particular low-density lipoprotein cholesterol (LDL-C), can halt the progression of coronary atherosclerosis and improve cardiovascular outcomes to an extent that is proportional to the magnitude of LDL-C reduction. Early (in-hospital) initiation of intensive statin therapy leads to a very early clinical benefit following ACS, and prolonged adherence to optimised lipid-lowering treatment effectively reduces longer-term cardiovascular events following PCI. Therefore, achieving guideline-recommended treatment goals for LDL-C with statins and, if indicated, with the addition of non-statin lipid-lowering drugs should become a priority for all physicians involved in the treatment of patients with coronary heart disease, including comprehensive strategies initiated during the in-hospital care of patients undergoing coronary interventions. This review article summarises current evidence on the role of LDL-C in the development and progression of coronary atherosclerosis, discusses the clinical benefits of intensive lipid-lowering treatments, and presents current guideline recommendations, with emphasis on patients undergoing PCI.
| S-EPMC9890584 | biostudies-literature
Project description:BACKGROUND:Evidence that continuous positive airway pressure (CPAP) reduces cardiovascular morbidity comes largely from observational studies. This association may be confounded if CPAP adherents are healthier in ways not measured by investigators. We assessed whether patients adhering to lipid-lowering medications were more adherent to CPAP. METHODS:This was a retrospective cohort study undertaken at the Philadelphia Veterans Affairs (VA) Medical Center (2005-2006) of consecutive patients on lipid-lowering therapy newly initiating CPAP for obstructive sleep apnea. Adherence to medications dispensed via the VA closed-pharmacy system was measured as the proportion of days covered (>/=80% vs < 80%) in the year prior to CPAP initiation. CPAP adherence was defined as >/= 4 h/d of "mask-on" time, measured electronically daily during the first week of CPAP. We examined the association between medication adherence and CPAP adherence using multivariable logistic regression. RESULTS:Complete data were available for 117 of 142 (81.5%) subjects. After adjustment for age, race, medical comorbidity, and sleep apnea-related clinical factors, subjects with low medication adherence demonstrated a 40.1% (95% CI, 30.0-51.0) probability of using CPAP >/= 4 h/d compared with 55.2% (95% CI, 46.9-63.1) for subjects with adequate (>/=80%) medication adherence (adjusted for comparison, odds ratio (OR) = 1.8 [95% CI, 1.0-3.3], P = .04). Married patients were more adherent to medications and CPAP; inclusion of this factor reduced to nonsignificance the association of medication and CPAP adherence (OR = 1.6 [95% CI, 0.9-2.8], P = .12). CONCLUSION:Patients consistently refilling lipid-lowering medications were more adherent to CPAP, suggesting that differences in medication adherence or other health-promoting behaviors should be investigated in future nonrandomized, observational studies linking CPAP adherence and cardiovascular outcomes.
| S-EPMC2803121 | biostudies-literature
Project description: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.
| S-EPMC9248990 | biostudies-literature
Project description:Purpose of reviewBased on the recent data of the DA VINCI study, it is clear that, besides utilization of statins, there is a need to increase non-statin lipid lowering approaches to reduce the cardiovascular burden in patients at highest risk.Recent findingsFor hypercholesterolemia, the small synthetic molecule bempedoic acid has the added benefit of selective liver activation, whereas inclisiran, a hepatic inhibitor of the PCSK9 synthesis, has comparable effects with PCSK9 monoclonal antibodies. For hypertriglyceridemia, cardiovascular benefit has been achieved by the use of icosapent ethyl, whereas results with pemafibrate, a selective agonist of PPAR-α, are eagerly awaited. In the era of RNA-based therapies, new options are offered to dramatically reduce levels of lipoprotein(a) (APO(a)LRX) and of triglycerides (ANGPTL3LRX and APOCIII-LRx). Despite the demonstrated benefits of statins, a large number of patients still remain at significant risk because of inadequate LDL-C reduction or elevated blood triglyceride-rich lipoproteins or lipoprotein(a). The area of lipid modulating agents is still ripe with ideas and major novelties are to be awaited in the next few years.
| S-EPMC7946696 | biostudies-literature
Project description:OBJECTIVE:To summarise the effect of primary prevention with lipid lowering drugs on coronary heart disease events, coronary heart disease mortality, and all cause mortality. DESIGN:Meta-analysis. IDENTIFICATION:Systematic search of the Medline database from January 1994 to June 1999 for English language studies examining drug treatment for lipid disorders (use of the MeSH terms "hyperlipidemia" and "anticholesteremic agents," keyword searches for individual drug names, and a search strategy for identifying randomised trials to capture relevant articles); identification of older studies through systematic reviews and hand search of bibliographies. INCLUSION CRITERIA:All randomised trials of at least one year's duration that examined drug treatment for patients with no known coronary heart disease, cerebrovascular disease, or peripheral vascular disease and that measured clinical end points, including all cause mortality, coronary heart disease mortality, and non-fatal myocardial infarctions. DATA EXTRACTION:Review of the articles and extracted relevant data by two authors separately, with disagreements resolved by consensus. RESULTS:Four studies met eligibility criteria. Drug treatment reduced the odds of a coronary heart disease event by 30% (summary odds ratio 0.70, 95% confidence interval 0.62 to 0.79) but not the odds of all cause mortality (0.94, 0.81 to 1.09). When statin drugs were considered alone, no substantial differences in results were found. CONCLUSIONS:Treatment with lipid lowering drugs lasting five to seven years reduces coronary heart disease events but not all cause mortality in people with no known cardiovascular disease.
| S-EPMC27504 | biostudies-literature