Dataset Information

Cardiovascular risk and response to lipid lowering therapy in patients with HIV infection according to different recommendations.

ABSTRACT:

Background

HIV patients are at increased cardiovascular risk while available European cardiovascular recommendations are ambiguous.

Methods

Retrospective analysis of 389 HIV-patients was conducted. Cardiovascular risk was determined by D:A:D, Framingham and SCORE scales. Patients were divided into risk groups as recommended by EACS 2019, PTN AIDS 2019 and ESC/EAS 2019 Guidelines and hypolipemic treatment was evaluated.

Results

In total, 389 HIV-positive patients took part in the study, most of whom were men (n = 312, 80.4%), mean age 41.69±10years. Mean lipid levels among all HIV patients: Tch:177.2±36mg/dl, HDL:48.9±18mg/dl, LDL:103.8±31mg/dl, TG:143.3±81mg/dl, AIP:0.45±0.3, non-HDL:129.2±36 mg/dl. Most of the participants (n = 360, 92.5%) were assigned to the high cardiovascular risk group according to ESC/EAS and PTN AIDS guidelines. The achievement of therapeutic LDLs according to ESC/EAS was 10.3% for those at very high cardiovascular risk (8.7% on lipid lowering treatment vs. 16.7% without hypolipemic drugs) and 12.0% (5.8% treated vs. 13.6% untreated) at high cardiovascular risk; according to PTN AIDS,17.2% achievement was noted by the very high-risk group (13% treated vs. 33.3% untreated), and 45.9% for the high-risk group (37.7% treated vs. 48.0% untreated); according to EACS Guidelines, 2.5% achievement in secondary prevention (3.8% treatedvs. 0% untreated) and 24.7% in primary prevention (22.2% treated vs. 26.1% untreated). Mean doses of statins were 8.75mg±6mg (Rosuvastatin) and 22.35±19mg (Atorvastatin).

Conclusions

The achievement of therapeutic LDLs by all recommendations is unsatisfactory, and generally worse in patients on lipid lowering therapy. Hypolipemic treatment of our HIV patients is based on low doses of statins, even in secondary prevention.

SUBMITTER: Pawlos A

PROVIDER: S-EPMC7771861 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Cardiovascular risk and response to lipid lowering therapy in patients with HIV infection according to different recommendations.

Pawlos Agnieszka A Broncel Marlena M Wlazłowska Ewelina E Jabłonowska Elżbieta E Gorzelak-Pabiś Paulina P

PloS one 20201229 12

<h4>Background</h4>HIV patients are at increased cardiovascular risk while available European cardiovascular recommendations are ambiguous.<h4>Methods</h4>Retrospective analysis of 389 HIV-patients was conducted. Cardiovascular risk was determined by D:A:D, Framingham and SCORE scales. Patients were divided into risk groups as recommended by EACS 2019, PTN AIDS 2019 and ESC/EAS 2019 Guidelines and hypolipemic treatment was evaluated.<h4>Results</h4>In total, 389 HIV-positive patients took part i ...[more]

PMID: 33373417

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Project description:BackgroundIn people living with HIV (PLWH), statins may be disproportionately effective but remain underutilized. A large prospective trial in patients with low to moderate cardiovascular (ASCVD) risk will reveal whether they should be considered in all PLWH. But its effect size may not apply to real-world PLWH with higher ASCVD and mortality risk. Also, the clinical role of non-statin lipid-lowering therapy (LLT) and LLT adherence in this population is unknown.MethodsComparative multi-level marginal structural model for all-cause mortality examining four time-updated exposure levels to LLT, antihypertensives, and aspirin in a virtual cohort of older PLWH. Incident coronary, cerebrovascular, and overall ASCVD events, serious infections, and new cancer diagnoses served as explanatory outcomes.ResultsIn 23,276 HIV-infected US-veterans who were followed for a median of 5.2 years after virologic suppression overall mortality was 33/1000 patient years: > 3 times higher than in the US population. Use of antihypertensives or aspirin was associated with increased mortality. Past LLT use (> 1 year ago) had no effect on mortality. LLT exposure in the past year was associated with a reduced hazard ratio (HR) of death: 0.59, 95% confidence interval (CI) 0.51-0.69, p < 0.0001 for statin containing LLT and 0.71 (CI: 0.54-0.93), p = 0.03 for statin-free LLT. For consistent LLT use (> 11/12 past months) the HR of death was 0.48 (CI: 0.35-0.66) for statin-only LLT, 0.34 (CI: 0.23-0.52) for combination LLT, and 0.27 (CI: 0.15-0.48) for statin-free LLT (p < 0.0001 for all). The ASCVD risk in these patients was reduced in similar fashion. Use of statin containing LLT was also associated with reduced infection and cancer risk. Multiple contrasting subgroup analyses yielded comparable results. Confounding is unlikely to be a major contributor to our findings.ConclusionsIn PLWH, ongoing LLT use may lead to substantially lower mortality, but consistent long-term adherence may be required to reduce ASCVD risk. Consistent non-statin LLT may be highly effective and should be studied prospectively.

Project description:BackgroundLipid-lowering therapy (LLT) is one of the key strategies for reducing the atherosclerotic cardiovascular disease (ASCVD) burden. However, little is known about the percentage of people in need of different LLT regimens to achieve optimal targets of low-density lipoprotein cholesterol (LDL-C), and the corresponding cost and benefit.MethodsWe conducted a simulation study based on the data from the nationwide China PEACE MPP population cohort (2015-2020), from which we included 2,904,914 participants aged 35-75 years from all the 31 provinces in mainland China. Participants were grouped based on their 10-year ASCVD risks, then entered into a Monte Carlo model which was used to perform LLT intensification simulation scenarios to achieve corresponding LDL-C goals in each risk stratification.ResultsAfter standardizing age and sex, the proportions of participants included at low, moderate, high, and very-high risk were 70.8%, 15.6%, 11.5%, and 2.1%, respectively. People who failed to achieve the corresponding LDL-C goals -8.1% at low risk, 19.6% at moderate risk, 53.2% at high risk, and 93.6% at very-high risk (either not achieving the goal or not receiving LLT)-would be in need of the LLT intensification simulation. After the use of atorvastatin 20 mg was simulated, over 99% of the population at low or moderate risk could achieve the LDL-C goals; while 11.3% at high and 24.5% at very-high risk would still require additional non-statin therapy. After the additional use of ezetimibe, there were still 4.8% at high risk and 11.3% at very-high risk in need of evolocumab; and 99% of these two groups could achieve the LDL-C goals after the use of evolocumab. Such LLT intensification with statin, ezetimibe, and evolocumab would annually cost $2.4 billion, $4.2 billion, and $24.5 billion, respectively, and prevent 264,170, 18,390, and 17,045 cardiovascular events, respectively.ConclusionsModerate-intensity statin therapy is pivotal for the attainment of optimal LDL-C goals in China, and around 10-25% of high- or very-high-risk patients would require additional non-statin agents. There is an opportunity to reduce the rising ASCVD burden in China by optimizing LLT.

Project description:ImportanceIn patients with atherosclerotic cardiovascular disease (ASCVD), guidelines recommend optimizing statin treatment, and consensus pathways suggest use of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with persistently elevated low-density lipoprotein cholesterol (LDL-C) levels despite use of statins. Recent trials have provided evidence of benefit in reduction of cardiovascular events with these agents.ObjectiveTo estimate the percentage of patients with ASCVD who would require a PCSK9 inhibitor when oral lipid-lowering therapy (LLT) is intensified first.Design, setting, and participantsThis simulation model study used a large administrative database of US medical and pharmacy claims to identify a cohort of 105 269 patients with ASCVD enrolled from January 1, 2012, through December 31, 2013, who met the inclusion criteria (database cohort). Patients were sampled with replacement (bootstrapping) to match the US epidemiologic distribution and entered into a Monte Carlo simulation (simulation cohort) that applied stepwise treatment intensification algorithms in those with LDL-C levels of at least 70 mg/dL. All patients not initially receiving a statin were given atorvastatin, 20 mg, and the following LLT intensification steps were applied: uptitration to atorvastatin, 80 mg; add-on ezetimibe therapy; add-on alirocumab therapy, 75 mg (a PCSK9 inhibitor); and uptitration to alirocumab, 150 mg. Sensitivity analyses included evolocumab as a PCSK9 inhibitor. Efficacy was estimated from published studies and incorporated patient-level variation. Data were analyzed from December 2015 to May 2017.ExposuresTreatment intensification strategies with LLT.Main outcomes and measuresUse of LLT among the population with ASCVD and distributions of LDL-C levels under various treatment intensification scenarios.ResultsInclusion criteria were met by 105 269 individuals in the database cohort (57.2% male and 42.8% female; mean [SD] age, 65.1 [12.1] years). In the simulation cohort (1 million patients; 54.8% male and 45.2% female; mean [SD] age, 66.4 [12.2] years), before treatment intensification, 51.5% used statin monotherapy and 1.7% used statins plus ezetimibe. Only 25.2% achieved an LDL-C level of less than 70 mg/dL. After treatment intensification, 99.3% could achieve an LDL-C level of less than 70 mg/dL, including 67.3% with statin monotherapy, 18.7% with statins plus ezetimibe, and 14% with add-on PCSK9 inhibitor.Conclusions and relevanceLarge gaps exist between recommendations and current practice regarding LLT in the population with ASCVD. In our model that assumes no LLT intolerance and full adherence, intensification of oral LLT could achieve an LDL-C level of less than 70 mg/dL in most patients, with only a modest percentage requiring a PCSK9 inhibitor.

Project description:The management of low-density lipoprotein cholesterol (LDL-C) levels is a central strategy for the prevention of atherosclerotic cardiovascular disease. Current United States (2018 American Heart Association/American College of Cardiology/Multisociety) and European (2019 European Society of Cardiology/European Atherosclerosis Society) guidelines endorse statin therapy as the first-line therapy for pharmacologic LDL-C lowering. However, in clinical practice up to 30% of patients report partial or complete intolerance to statin therapy. While the nocebo effect with statins is well described, perceived statin intolerance prevents many patients from achieving LDL-C thresholds associated with clinical benefit. Bempedoic acid is a novel, oral, non-statin lipid-l owering therapy that works by inhibiting adenosine triphosphate-citrate lyase, an enzymatic reaction upstream of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the hepatic cholesterol synthesis pathway. Bempedoic acid confers reduction in LDL-C of ~18% on background statin therapy,~21% in patients with statin intolerance, and ~38% when given in fixed-dose combination with ezetimibe. The CLEAR Outcomes trial, which enrolled high-risk primary and secondary prevention patients with reported statin intolerance and LDL-C levels ≥100 mg/dL, showed that bempedoic acid compared with placebo reduced 4-component major adverse cardiovascular events (MACE) by 13% (hazard ratio 0.87, 95% confidence interval 0.79-0.96). Bempedoic acid also reduced 3-component MACE by 15%, myocardial infarction by 23% and coronary revascularization by 19%. The benefit was even greater in the primary prevention cohort (hazard ratio 0.70, 95% confidence interval 0.55-0.89) for 4-component MACE. Bempedoic acid was associated with increases in uric acid levels and cholelithiasis, but numerically fewer events of myalgia and new-onset diabetes. These findings confirm that bempedoic acid is an effective approach to reduce cardiovascular outcomes in high-risk patients with statin intolerance who require further reduction in LDL-C.

Project description:BackgroundCardiovascular disease is the leading cause of morbidity and mortality with incidence rates of 5-10 per 1000 person-years, according to primary prevention studies. To control hyperlipidemia-a major risk factor of cardiovascular disease-initiation of lipid-lowering therapy with therapeutic lifestyle modification or lipid-lowering agent is recommended. Few systematic reviews and meta-analyses are available on lipid-lowering therapy for the primary prevention of cardiovascular diseases. In addition, the operational definitions of intensive lipid-lowering therapies are heterogeneous. The aim of our study was to investigate whether intensive lipid-lowering therapies reduce greater cardiovascular disease risks in primary prevention settings.MethodsMEDLINE, EMBASE, and Cochrane Library databases were searched from inception to March 2019 for randomized controlled trials. We used random effects model for overall pooled risk ratio (RR) estimation with cardiovascular events of interest and all-cause mortality rate for the intensive lipid-lowering group using the standard lipid-lowering group as the reference. The Cochrane Risk of Bias Tool was used for quality assessment.ResultsA total of 18 randomized controlled trials were included. The risk reductions in cardiovascular outcomes and all-cause mortality associated with more intensive vs. standard lipid-lowering therapy across all trials were 24 and 10%, respectively (RR 0.76, 95% confidence interval 0.68-0.85; RR 0.90, 95% confidence interval 0.83-0.97); however, the risk reduction varied by baseline LDL-C level in the trial. A greater risk reduction was noted with higher LDL-C level. Intensive lipid-lowering for coronary heart disease protection was more pronounced in the non-diabetic populations than in the diabetic populations.ConclusionsMore intensive LDL-C lowering was associated with a greater reduction in risk of total and cardiovascular mortality in trials of patients with higher baseline LDL-C levels than less intensive LDL-C lowering. Intensive lipid-lowering was associated with a significant risk reduction of coronary heart disease and must be considered even in the non-diabetic populations.

Dataset Information

Cardiovascular risk and response to lipid lowering therapy in patients with HIV infection according to different recommendations.

Background

Methods

Results

Conclusions

Publications

Cardiovascular risk and response to lipid lowering therapy in patients with HIV infection according to different recommendations.

Similar Datasets

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