Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery disease patients with or without diabetes: a prospective, observational cohort study

Jia, Peng; Liu, Mingming; Jin, Jing‐Lu; Cao, Ye‐Xuan; Guo, Yuan‐Lin; Wu, Na‐Qiong; Zhu, Cheng‐Gang; Dong, Qian; Sun, Jing; Xu, Rui‐Xia; Li, Jianjun

doi:10.1186/s12933-020-01142-0

Cited by 29 publications

(33 citation statements)

References 51 publications

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“…The authors suggest to measure PCSK9 levels in patients with diabetes to identify the ones with particularly high cardiovascular risk, indicating that these patients might be the ones who might even profit from lower LDL-targets (e.g. < 40 mg/dl) established by therapeutic PCSK9 inhibition [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

Fischer

Hochfellner

Knoll

et al. 2021

Cardiovasc Diabetol

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Background The lipid-lowering and positive cardiovascular effect of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors was shown in several studies, hence, they are more widely used in the lipid-lowering management of individuals with high cardiovascular risk. As real-world data are still scarce, specifically in patients with type 2 diabetes (T2D), the aim of this retrospective analysis was to investigate the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol (LDL-C) in an outpatient clinic of a tertiary care center in routine care. Methods A retrospective analysis of data extracted from the electronic patient record was performed. Patients who were routinely prescribed with PCSK9 inhibitor therapy (alirocumab or evolocumab) during the years 2016 and 2019 were included in the analysis. Characteristics of the patient population, the effects on LDL-C and HbA1c levels as well as subsequent cardiovascular events were assessed over an observation period of 18 months. Results We identified 237 patients treated with PCSK9 inhibitors between January 2016 and September 2019. Almost all patients (97.5%) received PCSK9 inhibitors for secondary prevention. 26.2% of the population had a concomitant diabetes diagnosis. Intolerance to statins (83.1%), ezetimibe (44.7%) or both agents (42.6%) was reported frequently. Three months after initiation of PCSK9 inhibitor therapy, 61.2% of the patients achieved LDL-C levels < 70 mg/dl, and 44.1% LDL-C levels < 55 mg/dl. The median LDL-C was lowered from 141 mg/dl at baseline, to 60 mg/dl after 3 months and 66 mg/dl after 12 months indicating a reduction of LDL-C as follows: 57.5% after 3 months and 53.6% after 12 months. After 3 months of observation, target achievement of LDL-C was higher in patients with T2D compared to non-diabetes patients; < 55 mg/dl: 51% vs. 41.5%; < 70 mg/dl 69.4 vs. 58.5%. After 12 months even more pronounced target LDL achievement in T2D was demonstrated < 55 mg/dl: 58.8% vs. 30.1%; < 70 mg/dl 70.6 vs. 49.6%. Patients with insufficiently controlled T2D (HbA1c > 54 mmol/mol) had a higher reduction in LDL-C but still were more likely to subsequent cardiovascular events. Conclusions Significant reductions in LDL-C and a high percentage of patients achieving recommended treatment targets were observed. The percentage of patients with T2D meeting recommended LDL-C targets was higher than in those without T2D. Still some patients did not achieve LDL-C levels as recommended in current guidelines. Special attention to the characteristics of these patients is required in the future to enable achievement of treatment goals and avoid adverse cardiovascular outcomes.

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Section: Discussionmentioning

confidence: 99%

Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

Fischer

Hochfellner

Knoll

et al. 2021

Cardiovasc Diabetol

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“…(4) Both, the FOURIER trial on Evolocumab and the ODYSSEY OUTCOMES trial on Alirocumab showed that PCSK9 inhibitors were not only capable to signi cantly lower LDL-C levels, but also result in a substantial reduction of the cardiovascular event rate without relevant risk of adverse events. (5,6) Pathophysiologically elevated concentrations of circulating PCSK9 are adversely associated with cardiovascular metabolic markers and inferior cardiovascular outcome (7). As recommended in the guidelines for the management of dyslipidemias by the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) published in 2019, treatment with a PCSK9 inhibitor is indicated for secondary prevention to lower plasma LDL-C in very-high risk patients who do not achieve their target LDL-C or even for primary prevention in particular very-high risk patients as those with familial hypercholesterolemia (FH) who do not achieve their LDL-C goal despite maximal tolerated therapy with statins and ezetimibe.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Effects of PCSK9 Inhibitors in a Tertiary Care Center – Real World Data

Fischer

Hochfellner

Knoll

et al. 2021

Preprint

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BackgroundThe lipid-lowering and positive cardiovascular effect of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors was shown in several studies, hence, they are more widely used in the lipid-lowering management of patients with high cardiovascular risk. As real-world data are still scarce, the aim of this retrospective analysis was to investigate the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol (LDL-C) in an outpatient clinic of a tertiary care center in routine care.MethodsA retrospective analysis of data extracted from the electronic patient record was performed. Patients who were routinely prescribed with PCSK9 inhibitor therapy (Alirocumab or Evolocumab) during the years 2016 and 2019 were included in the analysis. Characteristics of the patient population, the effects on LDL-C and HbA1c levels were assessed over the course of treatment.ResultsWe identified 237 patients treated with PCSK9 inhibitors between January 2016 and September 2019. Almost all patients (97.5%) received PCSK9 inhibitors for secondary prevention. Comorbidities at baseline included: arterial hypertension (68.8%), diabetes mellitus (25.3%), smoking (5.9%). Vascular disease at baseline was present as follows: coronary heart disease (74.7%), history of stroke or transient ischemic attack (13.5%), carotid artery disease (30.8%), peripheral artery disease (18.1%), chronic kidney disease (9.7%), history of percutaneous coronary intervention (46.4%), history of coronary artery bypass surgery (16.0%).Intolerance to statins (83.1%), ezetimibe (44.7%), and both agents was reported frequently (42.6%).Six to nine months after initiation of PCSK9 inhibitor therapy, 61.7% of the patients achieved LDL-C levels ≤70 mg/dl, and 44.3% achieved LDL-C levels ≤55 mg/dl. The median LDL-C was lowered from 141 (IQR 117 - 188) mg/dl at baseline, to 60 (43 - 91) mg/dl (6 to 9 months) and 67 (44 - 89) mg/dl (12 to 18 months) indicating a reduction of LDL-C as follows: -54.9% (interquartile range (IQR) 44.4 – 57.3) after 6 to 9 months, -53.2% (IQR 42.6 – 67.1) after 12 to 18 months from baseline. ConclusionsSignificant reductions in LDL-C and a high percentage of patients achieving recommended treatment targets were observed. Still some patients did not achieve LDL-C levels recommended in current guidelines. Special attention to the characteristics of these patients is required in the future to enable achievement of treatment goals and avoid adverse cardiovascular outcomes.

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“…Thirdly, it is also worth noting that the individuals with pre-DM is considered to have higher risk of developing T2DM compared to subjects with normal glucose regulation (NGR) [ 5 ]. Furthermore, in analysis of our data published recently [ 3 ], all 1225 patients with stable CAD were further divided into three subgroups according to diabetic status (T2DM: n = 377, pre-DM: n = 489, NGR: n = 359) and an ascending increment of baseline levels of PCSK9 were observed [T2DM vs. pre-DM vs. NGR: 246.51 (199.43, 292.22) vs. 238.88 (198.53, 275.65) vs. 225.31 (185.95, 263.36) ng/mL, Fig. 1 ].…”

mentioning

confidence: 99%

“…Besides, the association between PCSK9 and T2DM has becoming an interesting issue since its discovery. It was previously showed that plasma PCSK9 levels were higher in patients with T2DM [ 3 ]. Moreover, the results available from epidemiology, preclinical and clinical studies suggested a positive correlation of circulating PCSK9 concentration with glycemic parameters and risks of T2DM [ 3 ].…”

mentioning

confidence: 99%

“…It was previously showed that plasma PCSK9 levels were higher in patients with T2DM [ 3 ]. Moreover, the results available from epidemiology, preclinical and clinical studies suggested a positive correlation of circulating PCSK9 concentration with glycemic parameters and risks of T2DM [ 3 ]. Meanwhile, a recent animal study has revealed that downregulating PCSK9 can ameliorate lipid and glucose metabolism [ 4 ].…”

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confidence: 99%

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The predictive utility of circulating PCSK9 levels on diabetes mellitus

Jia

Zhu

2021

Cardiovasc Diabetol

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Increasing data including ours have suggested that proprotein convertase subtilisin/kexin type 9 (PCSK9), a novel regulator of cholesterol metabolism, may also play an important role in the development of type 2 diabetes mellitus (T2DM) and is associated with clinical outcomes in diabetic patients. Previous studies revealed that elevated plasma PCSK9 levels had a higher incidence of new-onset T2DM. Moreover, the results of available epidemiological, preclinical, and clinical studies have indicated that plasma PCSK9 concentration is correlated with glycemic parameters and can predict the adverse cardiovascular events in diabetic patients with coronary artery disease. However, there is currently no general agreement about the association of PCSK9 with T2DM. The usefulness of the circulating PCSK9 concentration as a predictor for the risk of new-onset T2DM should be clinically prudential.

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Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery disease patients with or without diabetes: a prospective, observational cohort study

Cited by 29 publications

References 51 publications

Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

Metabolic Effects of PCSK9 Inhibitors in a Tertiary Care Center – Real World Data

The predictive utility of circulating PCSK9 levels on diabetes mellitus

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Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery disease patients with or without diabetes: a prospective, observational cohort study

Cited by 29 publications

References 51 publications

Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus

Metabolic Effects of PCSK9&nbsp;Inhibitors in a Tertiary Care Center – Real World Data

The predictive utility of circulating PCSK9 levels on diabetes mellitus

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Metabolic Effects of PCSK9 Inhibitors in a Tertiary Care Center – Real World Data