Skip to main content
Download PDF
Download ePub

Personalized management of dyslipidemias in patients with diabetes—it is time for a new approach (2022)

Cardiovascular Diabetology volume 21, Article number: 263 (2022) Cite this article

Abstract

Dyslipidemia in patients with type 2 diabetes (DMT2) is one of the worst controlled worldwide, with only about 1/4 of patients being on the low-density lipoprotein cholesterol (LDL-C) target. There are many reasons of this, including physicians’ inertia, including diabetologists and cardiologists, therapy nonadherence, but also underusage and underdosing of lipid lowering drugs due to unsuitable cardiovascular (CV) risk stratification. In the last several years there is a big debate on the risk stratification of DMT2 patients, with the strong indications that all patients with diabetes should be at least at high cardiovascular disease (CVD) risk. Moreover, we have finally lipid lowering drugs, that not only allow for the effective reduction of LDL-C and do not increase the risk of new onset diabetes (NOD), and/or glucose impairment; in the opposite, some of them might effectively improve glucose control. One of the most interesting is pitavastatin, which is now available in Europe, with the best metabolic profile within statins (no risk of NOD, improvement of fasting blood glucose, HOMA-IR, HbA1c), bempedoic acid (with the potential for the reduction of NOD risk), innovative therapies—PCSK9 inhibitors and inclisiran with no DMT2 risk increase, and new forthcoming therapies, including apabetalone and obicetrapib—for the latter one with the possibility of even decreasing the number of patients diagnosed with prediabetes and DMT2. Altogether, nowadays we have possibility to individualize lipid lowering therapy in DMT2 patients and increase the number of patients on LDL-C goal without any risk of new onset diabetes and/or diabetes control worsening, and in consequence to reduce the risk of CVD complications due to progression of atherosclerosis in this patients’ group.

Introduction

Type 2 diabetes (DMT2) has been recognized as one of the major risk factors for cardiovascular diseases (CVDs). In 1990, the worldwide prevalence of diabetes was 211.2 million individuals, and in 2021 patients with a diagnosis of DMT2 increased to 536.6 million, while it is projected to reach 783.2 million people globally in 2045 [1, 2]. Thus, type II diabetes is an ever-increasing issue of epic proportions in modern medicine.

Patients with diabetes should be classified as having high CV risk

Adults with diabetes have a four times higher atherosclerotic cardiovascular disease (ASCVD) risk compared with non-diabetic adults, and this cardiovascular (CV) risk rises with worsening glycaemic control. Diabetes has been associated with a 75% increase in all-cause mortality in adults, and CVD accounts for a large part of the excess mortality [3]. Despite intense debate, the recent recommendations of the European Society of Cardiology (ESC) 2021 on prevention indicated that DMT2 patients may be classified as being at moderate CV risk (patients with well controlled diabetes of recent onset [e.g. < 10 years], no evidence of target organ damage [TOD] and no additional ASCVD risk factors) [4]. However, we may very seldom observe such patients in clinical practice—as almost all our DMT2 patients exhibit other risk factors and/or subclinical organ damage, when carefully assessed. Thus, for this group the ASCVD risk is often underestimated and consequently undertreated [5]. Moreover, this ASCVD risk increases sharply many years before the diabetes is diagnosed.

At the time of diagnosis, macro- and microvascular changes are already present in a significant proportion of patients, as Gerstein et al. reported in 1997 [6]. A subsequent meta-analysis by Cai et al. showed that prediabetes was associated with an increased risk of all-cause mortality (relative risk [RR] = 1.13, 95% CI: 1.10–1.17), CVDs (RR = 1.15, 95% CI: 1.11–1.18), coronary heart disease (RR = 1.16; 95% CI: 1.11–1.21), and stroke (RR = 1.14; 95% CI: 1.08–1.20) after a median follow-up time of 9.8 years [7]. Moreover, the meta-analysis of Gujral et al. which included 1.85 million subjects, showed that impaired glucose tolerance and elevated fasting glucose significantly increased the risk of macrovascular and microvascular complications [8]. De Simone et al. also reported that end-organ damage such as left ventricular hypertrophy, left atrial dilatation and high urinary albumin/creatinine ratio occurred in large proportion of patients before the clinical diagnosis of type 2 diabetes. [9]

Moreover, at the DMT2 diagnosis, other CV risk factors typically coexist, such as abdominal obesity, dyslipidemia, arterial hypertension, and metabolic sydnrome [10, 11]. The 2021 ESC prevention guidelines [4] are too complex for practitioners to stratify the risk of diabetic patients and this may result in inappropriate treatment of some patients [12]. Taking this into account, the authors strongly suggest a change in the approach to risk stratification among diabetic patients e.g. according to the guidelines of the Polish Lipid Association (PoLA) and 5 other major Polish scientific societies from 2021. Hence, in the PoLA guidelines, patients with diabetes are immediately classified as having either high, very high or extreme CV risk (Fig. 1) [13].

Fig. 1
figure 1

Cardiovascular risk categories in patients with diabetes mellitus according to the Polish Lipid Association 2021 (with permission). [1, 13] 1Target organ damage is defined as the presence of microalbuminuria, retinopathy, neuropathy, and/or left ventricular myocardial damage; 2“Other” means 2 or more; 3Major risk factors include: age ≥ 65 years, hypertension, dyslipidaemia, smoking, obesity; 4Not applicable to young adults (< 35 years of age) with type 1 diabetes lasting < 10 years. Lp(a) lipoprotein(a), hsCRP high-sensitivity C-reactive protein, eGFR estimated glomerular filtration rate

Full size image

Goals and rules of lipid-lowering treatment in patients with diabetes and dyslipidemia

More than 1/3 of diabetic patients have atherogenic dyslipidemia, which further increases the risk of atherosclerotic CVD [14]. As shown in the AHEAD (Action for Health in Diabetes) study, the presence of dyslipidemia in patients with type 2 diabetes significantly increased the risk of ASCVD (hazard ratio [HR] = 1.30; 95% CI: 1.03–1.63) and coronary artery disease (HR = 1.48; 95% CI: 1.14–1.93) [15]. In patients with diabetes and coexistence of lipid disorders, it is recommended to reduce low density lipoprotein cholesterol (LDL-C) levels to < 1.8 mmol/l (< 70 mg/dl) and to achieve at least a reduction of 50% of the baseline value (Fig. 2) [13].

Fig. 2
figure 2

Recommendations by Polish Lipid Association 2021 on treatment of lipid disorders in patients with diabetes (with permission). [13] LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, Lp(a) lipoprotein a, hsCRP high-sensitivity C-reactive protein, eGFR estimated glomerular filtration rate

Full size image

In the case of lipid disorders in diabetic patients, practitioners should follow the principle: "the lower, the better", but also to strive for “the earlier, the better” as soon as possible and maintain it as long as possible, preferably throughout the patient’s lifetime “the longer, the better”. Such an approach will significantly reduce the risk of CVD in these patients [13]. The paradigm of “the lower, the better” has been confirmed in hundreds of trials and meta-analyses, therefore we would like to explain the importance of the two additional rules.

Paradigm II: the earlier, the better

Increased LDL-C is associated with a significant increase in the risk of ASCVD. A 16% (HR = 1.16; 95% CI: 1.12–1.21) increase in risk is observed for every additional 1 mmol/l of LDL-C. Among subject aged 20–49 this relationship is much stronger, and here a 47% (HR = 1.47; 95% CI: 1.32–1.64) increase in risk is observed for every additional 1 mmol/l of LDL-C [16]. A study by Navar-Boggan et al. showed that the incidence of moderate dyslipidemia in young adults who were not treated with statins increased the risk of coronary artery disease by 67% (HR = 1.67; 95% CI: 1.06–2.64) over 15 years of follow-up [17]. The atherogenic effect of LDL-C appears to be dependent on both the concentration of circulating LDL-C and the duration of exposure to this concentration [18]. Therefore, it is especially important for very high and extremely high risk patients to achieve LDL-C targets through the use of intensive lipid lowering therapy to significantly reduce atheroma plaque volume and to stabilize plaques. For many patients, this will require immediate (upfront) combination therapy, as the extent of lipid-lowering required to reach targets would not be achievable with monotherapy [13, 19,20,21]

Paradigm III: the longer, the better

The consequences of statin discontinuation on the risk of major CV events were assessed by Thompson et al. in a study involving 67,418 older, long-term statin users. It was shown that patients who discontinued statin therapy exhibited an approximately 30% higher risk of major adverse CV events during the 6-year follow-up [22]. In a study by Rannanheimo et al. covering 97,575 new statin users aged 45 to 75 years followed for 3 years, it was shown that those with better adherence had a significantly better prognosis (25% lower risk of any CV event or death) than those with low-adherence. Good adherers also had a lower incidence of acute coronary syndrome (ACS) (HR = 0.56; 95% CI: 0.49–0.65) and acute cerebrovascular events (HR = 0.67; 95% CI: 0.60–0.76) compared to poor adherers [23]. A meta-analysis by Martin-Ruiz et al. found that patients with best adherence to statin therapy showed a significant reduction in risk of ischemic heart disease (IHD) by 18%, CVD by 47%, cerebrovascular disease by 26% and death by 49% compared to patients with the worst adherence [24]. In the study by Giral et al. it was found that stopping statin use led to a significant increase in the risk of any CV event (HR = 1.33; 95% CI: 1.18–1.50), coronary event (HR = 1.46; 95% CI: 1.21- 1.75), and cerebrovascular event (HR = 1.26; 95% CI: 1.05–1.51) [25]. Finally, Ference et al. showed that those adherent patients being on LDL-C target for at least 5 years may expect at least a 25% ASCVD risk reduction, and those having lifetime adherence (40 years or longer) even a 55% ASCVD risk reduction [26].

Optimization of lipid-lowering treatment in patients with diabetes and dyslipidemia

In our opinion, the stepwise approach to intensification of lipid-lowering treatment in patients with diabetes (as recommended by ESC) (Fig. 3) [4] should be replaced with a one-step intensive lipid lowering treatment strategy to follow the abovementioned paradigms and to really prevent first and recurring CVD events.

Fig. 3
figure 3

2021 European Society of Cardiology recommendation on low-density lipoprotein cholesterol goals. [4] CVD cardiovascular risk, ASCVD atherosclerotic cardiovascular disease, DM diabetes mellitus

Full size image

Moreover, with the advent of novel therapies and those expected to be available soon, we now have the potential to offer effective individualized treatment of dyslipidemia in patients with diabetes. The main rules to remember to be effective with lipid lowering therapy (LLT) are: (1) correctly assess the ASCVD risk of the diabetic patient; (2) determine the baseline LDL-C level to be able to calculate the expected absolute LDL-C reduction needed for your patient to reach their target; (3) explore the full lipid and lipoprotein profile to tailor the therapy to the specific dyslipidemia.

Pitavastatin

Pitavastatin, which is finally available on European market, seems to be an excellent choice for patients at high risk of diabetes (the elderly, with metabolic disorders, obesity, metabolic syndrome, insulin resistance in the course of various diseases), pre-diabetes and finally diabetes with concomitant metabolic disorders [13, 27]. Pitavastatin is the third most potent statin. At a dose of 4 mg, daily it reduces LDL-C by approximately 44% (range: 43–47%) [28]. A meta-analysis by Seo et al. that included 10,238 new pitavastatin users (15,998 person-years of follow-up) and 18,605 atorvastatin and rosuvastatin users showed that pitavastatin use was associated with a significantly lower risk of new-onset diabetes (NOD) in comparison to the atorvastatin and rosuvastatin (HR = 0.72; 95% CI: 0.59–0.87) [29]. It is also worth emphasizing that administration of highest-dose pitavastatin (4 mg) did not increase the risk of NOD in patients at high risk of developing diabetes during 3-years of follow-up [30]. Pitavastatin has also been shown to reduce HbA1C levels in patients with poorly controlled type 2 diabetes [31]. Moreover, it is the most effective statin for improving the atherogenic profile of patients with diabetes, and has the most potent high density lipoprotein cholesterol (HDL-C)-raising effect (increases above 20% may occur) [32], and significantly reduces triglycerides (TG) (− 18–25%) [33, 34]. An randomized controlled trial by Moroi et al. which included 664 patients, including 76% with diabetes, showed that pitavastatin therapy compared with atorvastatin may more effectively prevent CV events in hypercholesterolemic patients with one or more risk factors for ASCVD despite having similar effects on LDL-C concentration [35].

Pitavastatin monotherapy could be recommended for patients with diabetes who are required to reduce their LDL-C by 40 to 50% from baseline.

Ezetimibe

When the target LDL-C reduction exceeds 50%, the combination of pitavastatin, or rosuva- and atorvastatin, bearing in mind that these latter drugs increase the NOD risk, with ezetimibe might be considered [36]. In the randomized HIJ-PROPER study involving 1734 ACS patients with dyslipidemia, it was shown that the addition of ezetimibe to pitavastatin resulted in an additional reduction of LDL-C by 14%, enabling a 52% reduction in LDL-C which was associated with a significant 23% reduction of event rate and other outcomes—with 23% reduction of stroke risk and 55% reduction of all-cause mortality [37]. The addition of ezetimibe to statin therapy is associated with greater efficacy than statin monotherapy in reducing the incidence of CVD and stroke among diabetic patients (RR = 0.69; 95% CI: 0.67–0.73 and RR = 0.74; 95% CI: 0.56–0.98, respectively), as shown in the meta-analysis of 136,893 subjects carried out by Miao et al. [38]. It was also confirmed in the recent randomised, open-label, non-inferiority trial on the long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in ASCVD patients (the RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases [RACING] study) (37% patients with DMT2). The authors showed that moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL-C concentrations of < 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction [39]. In a meta-analysis of 48 RCTs by Wang et al. ezetimibe did not influence the risk of NOD (RR = 0.88; 95% CI: 0.61–1.28) [39]. Despite inconsistent data, it is worth mentioning, that ezetimibe may reverse insulin resistance, reduce lipid dysmetabolism after a meal and improve endothelial function in patients with metabolic syndrome and coronary artery disease [40].

The addition of ezetimibe to statin therapy (preferably as a fixed-dose combination [FDC]) should be recommended for patients with diabetes who are required a reduction of LDL-C by 50–65% from baseline.

Bempedoic acid

In the clinical scenario of patients with diabetes where the required reduction of LDL-C exceeds 60%, the use of a triple therapy may be beneficial: statin plus ezetimibe plus bempedoic acid. Bempedoic acid reduces LDL-C by up to 25% and in combination with ezetimibe by as much as 40% [41,42,43]. Triple therapy, including a moderate dose of statin is associated with up to 70% LDL-C reduction [44]. In a study by Leiter et al. which included 3621 subjects who were randomized 2:1 to monotherapy oral bempedoic acid 180 mg or placebo once daily for 12 to 52 weeks, it was shown that bempedoic acid significantly lowered LDL-C (up to approximately 30%) and HbA1C by -0.12% and did not worsen fasting glucose vs. placebo. Moreover, bempedoic acid was found to not increase the incidence of NOD vs. placebo over a median follow-up of 1 year [45]. A meta-analysis of 11 studies by Wang et al. showed that bempedoic acid reduced the risk of CV events by 25% (RR = 0.75; 95% CI: 0.56–0.99) and the risk of NOD by 35% in patients with hypercholesterolaemia (RR = 0.65; 95% CI: 0.44–0.96) [46]. An even greater reduction of NOD (41%) was observed in the meta-analysis of 10 RCTs with 3788 patients comprising 26 arms (active arm [n = 2460]; control arm [n = 1328]) by Cicero et al. [47]. Based on the data from phase 3 trials adverse events (AEs) related to bempedoic acid lead to slightly higher discontinuation in comparison to placebo (13.4/100 and 8.9/100 person-years, respectively). Bempedoic acid might be also associated with mild increases (clinically irrelevant) in creatinine (by mean 0.048 mg/dL), and uric acid (by mean 0.82 mg/dL) and mild reversible decreases in hemoglobin (reductions of ≥ 2 g/dL in 4.9/100 vs 2.0/100 person-years, respectively). Gout incidence was 1.6/100 vs 0.5/100 PY in the bempedoic acid vs placebo groups, especially in those with the previous history of gout or high baseline levels of uric acid [48, 49].

The addition of bempedoic acid plus ezetimibe (preferably as an FDC) to statin therapy should be recommended for patients with diabetes who are required to reduce LDL-C by 65–80% from baseline.

PCSK9 inhibitors and inclisiran

When the required reduction of LDL-C exceeds 80%, a proprotein convertase subtilisin/kexin 9 (PCSK9) modulator (alirocumab, evolocumab or inclisiran) should be added to the current LLT.

Alirocumab and evolocumab reduce LDL-C by about 60% in patients with diabetes and dyslipidemia, and also have a very positive effect on other lipid fractions in patients with diabetes: TG (− 15–30%), apolipoprotein B (− 35%) and Lp(a) (− 20–30%) [50, 51]. Next, inclisiran enables the reduction of LDL-C by 50–55%, non-HDL-C by 45%, apolipoprotein B by 41% and TG by 10% [52, 53]. PCSK9 modulators significantly reduce the risk of CV and CV death among patients with CVD (RR = 0.80; 95% CI: 0.73–0.87) and this effect might be even greater in those with pre- and diabetes [54,55,56]. Therapies with alirocumab, evolocumab, and inclisiran were not associated with an increased incidence of NOD [57]. The recently published FOURIER-OLE (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk-Open-Label Extension) study with 6635 patients (with about 34% patients with diabetes) and the follow-up of over 8 years confirmed both paradigms—the earlier on LDL-C goal, the better but also the longer the better, as evolocumab led to further reductions in cardiovascular events compared with delayed treatment initiation (15% lower risk of CV death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization, 20% lower risk of CV death, myocardial infarction, or stroke, and 23% lower risk of CV death. Incidences of AEs, including new-onset diabetes did not increase over time [58].

The addition of a PCSK9 targeted approach therapy to statin plus ezetimibe (preferably as an FDC) should be recommended in patients with diabetes who are required to reduce LDL-C by more than 80% from baseline.

Effective reduction of triglyceride rich lipoproteins

In patients who still have an elevated TG concentration (and/or non-HDL-C, which is now an equivalent goal to LDL-C), despite intensive LDL-C lowering treatment (using the drugs described above), the use of fenofibrate (in diabetic patients without ASCVD to reduce the risk of micro- and macrovascular complications) or icosapent-ethyl (in diabetic patients with ASCVD) is recommended [13, 59]. The ACCORDION study showed that the addition of fenofibrate to a statin in T2DM patients and dyslipidemia (baseline TG: 327.2 ± 125.3 mg/dl) led to a reduction in the risk of all-cause death in the long term—9.7 years follow-up from time of randomization—(HR: 0.68; 95% CI: 0.52–0.88), death from CVD (0.63; 95% CI: 0.42–0.95) and severe coronary heart disease (0.66; 95% CI: 0.51–0.86) [60]. The beneficial effect of fenofibrate on the prognosis of DMT2 patients and dyslipidemia was also confirmed by Koopal et al. In a study involving 17,142 patients from the FIELD (the Fenofibrate Intervention and Event Lowering in Diabetes), ACCORD (the Action to Control Cardiovascular Risk in Diabetes), and SMART (Second Manifestations of ARTerial disease) studies [61]. Unfortunately, the Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabeTes (PROMINENT) phase 3 study with pemafibrate was prematurely discontinued (April 2022) due to the unlikely achievement of the primary endpoint [62,63,64]. The REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial) showed that the use of icosapent ethyl (IPE) in patients with high TG and diabetes type 2 led to a reduction risk of CV death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina by 25% (HR = 0.77; 95% CI: 0.68–0.87). It should be emphasized, however, that IPE increased the risk of atrial fibrillation/flutter: 3.1 vs. 2.1%, P = 0.004) [65]. In addition, based on the JELIS study, it is recommended to use EPA at a dose of 1.8 g/day (and more), because it was shown that such therapy reduced the risk of major CV events in secondary prevention by 19% (HR = 0.81; 95% CI: 0.657–0.998) [66]. Based on the Polish guidelines, general recommendations for omega-3 acids applications were suggested as following: “In at least high-risk patients with TG ≥ 2.3 mmol/l (≥ 200 mg/dl) despite statin therapy, omega-3 acids (polyunsaturated fatty acids [PUFA] in a dose of 2 to 4 g/day) in combination with a statin may be considered (IIbC) [13, 67].

The personalized recommendations of management in patients with diabetes and dyslipidemia to reduce the risk associated with atherogenic dyslipidemia and improve (do not worsen) glucometabolic status is presented in Fig. 4.

Fig. 4
figure 4

Proposed therapy scheme for patients with diabetes and dyslipidemia. CV cardiovascular, LDL-C low density lipoprotein cholesterol, LLT lipid lowering therapy, FDC fixed dose combination, PCSK9 proprotein convertase subtilisin/kexin 9, TG triglyceride, ASCVD atherosclerotic cardiovascular disease. LLT in maximum, tolerated doses. *Patients at the risk of diabetes (with metabolic disorders, obesity, metabolic syndrome, insulin resistance in the course of various diseases), pre-diabetes and finally diabetes with concomitant metabolic disorders. 1Pitavastatin is preferable; 2In case of other statin—rosuvastatin or atorvastatin—always consider fixed dose combination with ezetimibe; 3FDC of statin and ezetimibe plus BA might also be an option; 4In most of the countries, reimbursement criteria does not allow the upfront triple combination therapy with PCSK9 inhibitors; Inclisiran is still not reimbursed in many countries; 5IPE is still not available in Europe

Full size image

Conclusions

The above recommendations aim to optimize LLT in high-risk patients with diabetes (which should also refer to those with prediabetes/metabolic disturbances), where ASCVD risk is often underestimated and undertreated. In fact, fewer than 30% of type II diabetes patients reach their LDL-C targets, irrespective of CVD risk. Due to the concise and practical form of this guidance paper, we have decided to mainly focus on the largest unmet need in diabetic patients—LDL-C goal achievement to clearly show that with the currently available LLTs and suitable approach we can easily be on the LDL-C target in this group of patients at high CVD risk. Thus, we do not discuss the role of non-HDL-C, which is now an equivalent lipid biomarker to LDL-C [13, 67], the remnants—and their important role in CV risk prediction in patients with atherogenic dyslipidemia [68], as well as apolipoprotein B (ApoB)—which has the largest predictive power, but it is still measured definitely too rarely [4, 13, 67]. We are also aware that for some of the above suggested recommendations, additional outcome data is required. It is undoubtedly true for pitavastatin, which has been much less extensively investigated in comparison to rosuvastatin and atorvastatin, for which we still need real-world data. Further evidence is required for the use of early combination therapy, as well for the novel compounds, inclisiran and bempedoic acid. Further investigations and new data are also required for the approach suggested to promote the reduction of TG associated ASCVD residual risk with omega-3 acids. In this context, we are also awaiting new therapies that may further improve the suggested therapeutic paradigms, including evinacumab [69, 70], apabetalone [71], and obicetrapib [72].

Overall, patients with diabetes should be carefully examined in terms of CV risk stratification (e.g., taking into consideration TOD, renal function, subclinical atherosclerosis, etc.), to define their lipid goals. We strongly suggest that, for such high-risk patients, LDL-C target should be achieved as early as possible to maximize CVD prevention.

Availability of data and materials

Not applicable.

Abbreviations

ACCORD:

The Action to Control Cardiovascular Risk in Diabetes study

ACS:

Acute coronary syndrome

AE:

Adverse event

AHEAD:

The Action for Health in Diabetes study

ApoB:

Apolipoprotein B

ASCVD:

Atherosclerotic cardiovascular disease

CV:

Cardiovascular

CVD:

Cardiovascular disease

DMT2:

Type 2 diabetes

ESC:

European Society of Cardiology

FDC:

Fixed-dose combination

FIELD:

The Fenofibrate Intervention and Event Lowering in Diabetes trial

HDL-C:

High density lipoprotein cholesterol

HR:

Hazard ratio

IHD:

Ischemic heart disease

LDL-C:

Low density lipoprotein cholesterol

LLT:

Lipid lowering therapy

NOD:

New-onset diabetes

PCSK9:

Proprotein convertase subtilisin/kexin 9

PoLA:

Polish Lipid Association

PROMINENT:

The Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabeTes study

PUFA:

Polyunsaturated fatty acids

RACING:

The RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases study

REDUCE-IT:

The Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial

RR:

Relative risk

SMART:

Second Manifestations of ARTerial disease study

TG:

Triglycerides

TOD:

Target organ damage

References

  1. Lin X, Xu Y, Pan X, Xu J, Ding Y, Sun X, et al. Global, regional, and national burden and trend of diabetes in 195 countries and territories: an analysis from 1990 to 2025. Sci Rep. 2020;10:14790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183: 109119.

    Article  PubMed  Google Scholar 

  3. Dal Canto E, Ceriello A, Rydén L, Ferrini M, Hansen TB, Schnell O, et al. Diabetes as a cardiovascular risk factor: An overview of global trends of macro and micro vascular complications. Eur J Prev Cardiol. 2019;26:25–32.

    Article  Google Scholar 

  4. Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42:3227–337.

    Article  PubMed  Google Scholar 

  5. Spannella F, Giulietti F, Di Pentima C, Sarzani R. Prevalence and control of dyslipidemia in patients referred for high blood pressure: the disregarded “double-trouble” lipid profile in overweight/obese. Adv Ther. 2019;36:1426–37.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gerstein HC. Glucose: a continuous risk factor for cardiovascular disease. Diabet Med. 1997;14:25–31.

    Article  Google Scholar 

  7. Cai X, Zhang Y, Li M, Wu JH, Mai L, Li J, et al. Association between prediabetes and risk of all cause mortality and cardiovascular disease: updated meta-analysis. BMJ. 2020;370: m2297.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gujral UP, Jagannathan R, He S, Huang M, Staimez LR, Wei J, et al. Association between varying cut-points of intermediate hyperglycemia and risk of mortality, cardiovascular events and chronic kidney disease: a systematic review and meta-analysis. BMJ Open Diabetes Res Care. 2021;9: e001776.

    Article  PubMed  PubMed Central  Google Scholar 

  9. de Simone G, Wang W, Best LG, Yeh F, Izzo R, Mancusi C, et al. Target organ damage and incident type 2 diabetes mellitus: the Strong Heart Study. Cardiovasc Diabetol. 2017;16:64.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Rawshani A, Rawshani A, Franzén S, Eliasson B, Svensson AM, Miftaraj M, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med. 2017;376:1407–18.

    Article  PubMed  Google Scholar 

  11. Olesen KKW, Madsen M, Egholm G, Thim T, Jensen LO, Raungaard B, et al. Patients with diabetes without significant angiographic coronary artery disease have the same risk of myocardial infarction as patients without diabetes in a real-world population receiving appropriate prophylactic treatment. Diabetes Care. 2017;40:1103–10.

    Article  CAS  PubMed  Google Scholar 

  12. Katsiki N, Banach M, Mikhailidis DP. Is type 2 diabetes mellitus a coronary heart disease equivalent or not? Do not just enjoy the debate and forget the patient! Arch Med Sci. 2019;15:1357–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Banach M, Burchardt P, Chlebus K, Dobrowolski P, Dudek D, Dyrbuś K, et al. PoLA/CFPiP/PCS/PSLD/PSD/PSH guidelines on diagnosis and therapy of lipid disorders in Poland 2021. Arch Med Sci. 2021;17:1447–547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Plana N, Ibarretxe D, Cabré A, Ruiz E, Masana L. Prevalence of atherogenic dyslipidemia in primary care patients at moderate-very high risk of cardiovascular disease. Cardiovascular risk perception. Clin Investig Arterioscler. 2014;26:274–84.

    PubMed  Google Scholar 

  15. Kaze AD, Santhanam P, Musani SK, Ahima R, Echouffo-Tcheugui JB. Metabolic dyslipidemia and cardiovascular outcomes in type 2 diabetes mellitus: findings from the look AHEAD study. J Am Heart Assoc. 2021;10: e016947.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mortensen MB, Nordestgaard BG. Elevated LDL cholesterol and increased risk of myocardial infarction and atherosclerotic cardiovascular disease in individuals aged 70–100 years: a contemporary primary prevention cohort. Lancet. 2020;396:1644–52.

    Article  CAS  PubMed  Google Scholar 

  17. Navar-Boggan AM, Peterson ED, D’Agostino RB Sr, Neely B, Sniderman AD, Pencina MJ. Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease. Circulation. 2015;131:451–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Braunwald E. How to live to 100 before developing clinical coronary artery disease: a suggestion. Eur Heart J. 2022;43:249–50.

    Article  PubMed  Google Scholar 

  19. Ray KK, Reeskamp LF, Laufs U, Banach M, Mach F, Tokgözoğlu LS, et al. Combination lipid-lowering therapy as first-line strategy in very high-risk patients. Eur Heart J. 2022;43:830–3.

    Article  CAS  PubMed  Google Scholar 

  20. Banach M, Penson PE, Vrablik M, Bunc M, Dyrbus K, Fedacko J, et al. ACS EuroPath Central & South European Countries Project. Optimal use of lipid-lowering therapy after acute coronary syndromes: A Position Paper endorsed by the International Lipid Expert Panel (ILEP). Pharmacol Res. 2021;166:105499.

    Article  CAS  PubMed  Google Scholar 

  21. Ostadal P, Steg PG, Poulouin Y, Bhatt DL, Bittner VA, Chua T, ODYSSEY OUTCOMES Investigators, et al. Metabolic risk factors and effect of alirocumab on cardiovascular events after acute coronary syndrome: a post-hoc analysis of the ODYSSEY OUTCOMES randomised controlled trial. Lancet Diabetes Endocrinol. 2022;10:330–40.

    Article  CAS  PubMed  Google Scholar 

  22. Thompson W, Morin L, Jarbøl DE, Andersen JH, Ernst MT, Nielsen JB, et al. Statin discontinuation and cardiovascular events among older people in Denmark. JAMA Netw Open. 2021;4: e2136802.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rannanheimo PK, Tiittanen P, Hartikainen J, Helin-Salmivaara A, Huupponen R, Vahtera J, Korhonen MJ. Impact of statin adherence on cardiovascular morbidity and all-cause mortality in the primary prevention of cardiovascular disease: a population-based cohort study in Finland. Value Health. 2015;18:896–905.

    Article  PubMed  Google Scholar 

  24. Martin-Ruiz E, Olry-de-Labry-Lima A, Ocaña-Riola R, Epstein D. Systematic review of the effect of adherence to statin treatment on critical cardiovascular events and mortality in primary prevention. J Cardiovasc Pharmacol Ther. 2018;23:200–15.

    Article  CAS  PubMed  Google Scholar 

  25. Giral P, Neumann A, Weill A, Coste J. Cardiovascular effect of discontinuing statins for primary prevention at the age of 75 years: a nationwide population-based cohort study in France. Eur Heart J. 2019;40:3516–25.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38:2459–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sahebkar A, Kiaie N, Gorabi AM, Mannarino MR, Bianconi V, Jamialahmadi T, et al. A comprehensive review on the lipid and pleiotropic effects of pitavastatin. Prog Lipid Res. 2021;84: 101127.

    Article  CAS  PubMed  Google Scholar 

  28. Zhang X, Xing L, Jia X, Pang X, Xiang Q, Zhao X, et al. Comparative lipid-lowering/increasing efficacy of 7 statins in patients with dyslipidemia, cardiovascular diseases, or diabetes mellitus: systematic review and network meta-analyses of 50 randomized controlled trials. Cardiovasc Ther. 2020;2020:3987065.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Seo WW, Seo SI, Kim Y, Yoo JJ, Shin WG, Kim J, et al. Impact of pitavastatin on new-onset diabetes mellitus compared to atorvastatin and rosuvastatin: a distributed network analysis of 10 real-world databases. Cardiovasc Diabetol. 2022;21:82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jeong HS, Hong SJ, Son S, An H, Kook H, Joo HJ, et al. Incidence of new-onset diabetes with 1 mg versus 4 mg pitavastatin in patients at high risk of developing diabetes during a 3-year follow-up. Cardiovasc Diabetol. 2019;18:162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Huang CH, Huang YY, Hsu BR. Pitavastatin improves glycated hemoglobin in patients with poorly controlled type 2 diabetes. J Diabetes Investig. 2016;7:769–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Teramoto T, Shimano H, Yokote K, Urashima M. Effects of pitavastatin (LIVALO Tablet) on high density lipoprotein cholesterol (HDL-C) in hypercholesterolemia. J Atheroscler Thromb. 2009;16:654–61.

    Article  CAS  PubMed  Google Scholar 

  33. Adams SP, Alaeiilkhchi N, Wright JM. Pitavastatin for lowering lipids. Cochrane Database Syst Rev. 2020;6:CD012735.

    PubMed  Google Scholar 

  34. Yokote K, Bujo H, Hanaoka H, Shinomiya M, Mikami K, Miyashita Y, et al. Multicenter collaborative randomized parallel group comparative study of pitavastatin and atorvastatin in Japanese hypercholesterolemic patients: collaborative study on hypercholesterolemia drug intervention and their benefits for atherosclerosis prevention (CHIBA study). Atherosclerosis. 2008;201:345–52.

    Article  CAS  PubMed  Google Scholar 

  35. Moroi M, Nagayama D, Hara F, Saiki A, Shimizu K, Takahashi M, et al. Outcome of pitavastatin versus atorvastatin therapy in patients with hypercholesterolemia at high risk for atherosclerotic cardiovascular disease. Int J Cardiol. 2020;305:139–46.

    Article  PubMed  Google Scholar 

  36. Casula M, Mozzanica F, Scotti L, Tragni E, Pirillo A, Corrao G, Catapano AL. Statin use and risk of new-onset diabetes: a meta-analysis of observational studies. Nutr Metab Cardiovasc Dis. 2017;27:396–406.

    Article  CAS  PubMed  Google Scholar 

  37. Hagiwara N, Kawada-Watanabe E, Koyanagi R, Arashi H, Yamaguchi J, Nakao K, et al. Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial. Eur Heart J. 2017;38:2264–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Miao XY, Liu HZ, Jin MM, Sun BR, Tian H, Li J, et al. A comparative meta-analysis of the efficacy of statin-ezetimibe co-therapy versus statin monotherapy in reducing cardiovascular and cerebrovascular adverse events in patients with type 2 diabetes mellitus. Eur Rev Med Pharmacol Sci. 2019;23:2302–10.

    PubMed  Google Scholar 

  39. Kim BK, Hong SJ, Lee YJ, Hong SJ, Yun KH, Hong BK, RACING investigators, et al. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. Lancet. 2022;400(10349):380–90.

    Article  CAS  PubMed  Google Scholar 

  40. Wang Y, Zhan S, Du H, Li J, Khan SU, Aertgeerts B, et al. Safety of ezetimibe in lipid-lowering treatment: systematic review and meta-analysis of randomised controlled trials and cohort studies. BMJMED. 2022. https://doi.org/10.1136/bmjmed-2022-000134.

    Article  Google Scholar 

  41. Nakamura A, Sato K, Kanazawa M, Kondo M, Endo H, Takahashi T, Nozaki E. Impact of decreased insulin resistance by ezetimibe on postprandial lipid profiles and endothelial functions in obese, non-diabetic-metabolic syndrome patients with coronary artery disease. Heart Vessels. 2019;34:916–25.

    Article  PubMed  Google Scholar 

  42. Banach M, Duell PB, Gotto AM Jr, Laufs U, Leiter LA, Mancini GBJ, et al. Association of bempedoic acid administration with atherogenic lipid levels in phase 3 randomized clinical trials of patients with hypercholesterolemia. JAMA Cardiol. 2020;5:1124–35.

    Article  PubMed  Google Scholar 

  43. Ballantyne CM, Laufs U, Ray KK, Leiter LA, Bays HE, Goldberg AC, et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol. 2020;27:593–603.

    Article  PubMed  Google Scholar 

  44. Rubino J, MacDougall DE, Sterling LR, Hanselman JC, Nicholls SJ. Combination of bempedoic acid, ezetimibe, and atorvastatin in patients with hypercholesterolemia: a randomized clinical trial. Atherosclerosis. 2021;320:122–8.

    Article  CAS  PubMed  Google Scholar 

  45. Leiter LA, Banach M, Catapano AL, Duell PB, Gotto AM Jr, Laufs U, et al. Bempedoic acid in patients with type 2 diabetes mellitus, prediabetes, and normoglycaemia: a post hoc analysis of efficacy and glycaemic control using pooled data from phase 3 clinical trials. Diabetes Obes Metab. 2022;24:868–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wang X, Zhang Y, Tan H, Wang P, Zha X, Chong W, et al. Efficacy and safety of bempedoic acid for prevention of cardiovascular events and diabetes: a systematic review and meta-analysis. Cardiovasc Diabetol. 2020;19:128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Cicero AFG, Fogacci F, Hernandez AV, Banach M. Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group and the International Lipid Expert Panel (ILEP). Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: a systematic review and meta-analysis. PLoS Med. 2020;17:e1003121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bays HE, Banach M, Catapano AL, Duell PB, Gotto AM Jr, Laufs U, et al. Bempedoic acid safety analysis: Pooled data from four phase 3 clinical trials. J Clin Lipidol. 2020;14:649-659.e6.

    Article  PubMed  Google Scholar 

  49. Laufs U, Ballantyne CM, Banach M, Bays H, Catapano AL, Duell PB, et al. Efficacy and safety of bempedoic acid in patients not receiving statins in phase 3 clinical trials. J Clin Lipidol. 2022;16:286–97.

    Article  PubMed  Google Scholar 

  50. Zhang J, Tecson KM, Rocha NA, McCullough PA. Usefulness of alirocumab and evolocumab for the treatment of patients with diabetic dyslipidemia. Proc (Bayl Univ Med Cent). 2018;31:180–4.

    PubMed  Google Scholar 

  51. Colhoun HM, Leiter LA, Müller-Wieland D, Cariou B, Ray KK, Tinahones FJ, et al. Effect of alirocumab on individuals with type 2 diabetes, high triglycerides, and low high-density lipoprotein cholesterol. Cardiovasc Diabetol. 2020;19:14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Khan SA, Naz A, Qamar Masood M, Shah R. Meta-analysis of inclisiran for the treatment of hypercholesterolemia. Am J Cardiol. 2020;134:69–73.

    Article  CAS  PubMed  Google Scholar 

  53. Leiter LA, Kallend DG, Koenig W, Landmesser U, Ray KK, Schwartz GG, et al. Efficacy and safety of inclisiran by baseline body mass index: a post hoc pooled analysis of the ORION-9, ORION-10 and ORION-11 phase III randomized controlled trials. Circulation. 2021;144:A11143.

    Google Scholar 

  54. Talasaz AH, Ho AJ, Bhatty F, Koenig RA, Dixon DL, Baker WL, Van Tassell BW. Meta-analysis of clinical outcomes of PCSK9 modulators in patients with established ASCVD. Pharmacotherapy. 2021;41:1009–23.

    Article  CAS  PubMed  Google Scholar 

  55. Sabatine MS, Leiter LA, Wiviott SD, Giugliano RP, Deedwania P, De Ferrari GM, et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017;5:941–50.

    Article  CAS  PubMed  Google Scholar 

  56. Ray KK, Colhoun HM, Szarek M, Baccara-Dinet M, Bhatt DL, Bittner VA, ODYSSEY OUTCOMES Committees and Investigators, et al. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial. Lancet Diabetes Endocrinol. 2019;7:618–28.

    Article  CAS  PubMed  Google Scholar 

  57. Wang X, Wen D, Chen Y, Ma L, You C. PCSK9 inhibitors for secondary prevention in patients with cardiovascular diseases: a bayesian network meta-analysis. Cardiovasc Diabetol. 2022;21:107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. O’Donoghue ML, Giugliano RP, Wiviott SD, Atar D, Keech A, Kuder JF, et al. Long-term evolocumab in patients with established atherosclerotic cardiovascular disease. Circulation. 2022;146:1109–19.

    Article  CAS  PubMed  Google Scholar 

  59. Averna M, Banach M, Bruckert E, Drexel H, Farnier M, Gaita D, et al. Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients: a statement from a European Atherosclerosis Society Task Force. Atherosclerosis. 2021;325:99–109.

    Article  CAS  PubMed  Google Scholar 

  60. Zhu L, Hayen A, Bell KJL. Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study. Cardiovasc Diabetol. 2020;19:28.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Koopal C, Visseren FLJ, Westerink J, van der Graaf Y, Ginsberg HN, Keech AC. Predicting the effect of fenofibrate on cardiovascular risk for individual patients with type 2 diabetes. Diabetes Care. 2018;41:1244–50.

    Article  CAS  PubMed  Google Scholar 

  62. Yokote K, Yamashita S, Arai H, Araki E, Matsushita M, Nojima T, et al. Effects of pemafibrate on glucose metabolism markers and liver function tests in patients with hypertriglyceridemia: a pooled analysis of six phase 2 and phase 3 randomized double-blind placebo-controlled clinical trials. Cardiovasc Diabetol. 2021;20(1):96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Yoshida M, Nakamura K, Miyoshi T, Yoshida M, Kondo M, Akazawa K, et al. Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet. Cardiovasc Diabetol. 2020;19(1):149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. KOWA to Discontinue K-877 (Pemafibrate) "PROMINENT" cardiovascular outcomes study. https://www.prnewswire.com/. Accessed 8 Apr 2022.

  65. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11–22.

    Article  CAS  PubMed  Google Scholar 

  66. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369:1090–8.

    Article  CAS  PubMed  Google Scholar 

  67. Solnica B, Sygitowicz G, Sitkiewicz D, Cybulska B, Jóźwiak J, Odrowąż-Sypniewska G, Banach M. 2020 Guidelines of the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA) on laboratory diagnostics of lipid metabolism disorders. Arch Med Sci. 2020;16(2):237–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lorenzatti AJ, Monsalvo ML, López JAG, Wang H, Rosenson RS. Effects of evolocumab in individuals with type 2 diabetes with and without atherogenic dyslipidemia: An analysis from BANTING and BERSON. Cardiovasc Diabetol. 2021;20(1):94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Surma S, Romańczyk M, Filipiak KJ. Evinacumab—the new kid on the block. Is it important for cardiovascular prevention? Int J Cardiol Cardiovasc Risk Prev. 2021;11:200107.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Surma S, Romańczyk M, Filipiak KJ. Angiopoietin-like proteins inhibitors: new horizons in the treatment of atherogenic dyslipidemia and familial hypercholesterolemia. Cardiol J. 2021. https://doi.org/10.5603/CJ.a2021.0006.

    Article  PubMed  Google Scholar 

  71. Kalantar-Zadeh K, Schwartz GG, Nicholls SJ, Buhr KA, Ginsberg HN, Johansson JO, et al. Effect of apabetalone on cardiovascular events in diabetes, CKD, and recent acute coronary syndrome: results from the BETonMACE randomized controlled trial. Clin J Am Soc Nephrol. 2021;16:705–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Nurmohamed NS, Ditmarsch M, Kastelein JJP. CETP-inhibitors: from HDL-C to LDL-C lowering agents? Cardiovasc Res. 2021. https://doi.org/10.1093/cvr/cvab350.

    Article  PubMed Central  Google Scholar 

Download references

Acknowledgements

None of the above-mentioned pharmaceutical companies had any role in this article, which has been written independently, without any financial or professional help, and reflects only the opinion of the authors, without any role of the industry.

This Expert Opinion paper has been officially endorsed by the International Lipid Expert Panel (ILEP).

Funding

None.

Author information

Author notes

  1. Maciej Banach and Stanisław Surma equally contributed to this work

Authors and Affiliations

  1. Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Rzgowska 281/289, 93-338, Lodz, Poland

    Maciej Banach

  2. Department of Cardiology and Congenital Heart Diseases of Adults, Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland

    Maciej Banach

  3. Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland

    Maciej Banach

  4. Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, Katowice, Poland

    Stanisław Surma

  5. Club of Young Hypertensiologists, Polish Society of Hypertension, Gdansk, Poland

    Stanisław Surma

  6. Department of Internal Diseases, University Hospital Center Zagreb School of Medicine, Zagreb University, Zagreb, Croatia

    Zeljko Reiner

  7. Department of Nutritional Sciences and Dietetics, International Hellenic University, Thessaloniki, Greece

    Niki Katsiki

  8. School of Medicine, European University of Cyprus, Nicosia, Cyprus

    Niki Katsiki

  9. Clinical Pharmacy and Therapeutics Research Group, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK

    Peter E. Penson

  10. Liverpool Centre for Cardiovascular Science, Liverpool, UK

    Peter E. Penson

  11. Department of Vascular Disease, University Medical Center Ljubljana, Ljubljana, Slovenia

    Zlatko Fras

  12. Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

    Zlatko Fras

  13. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  14. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  15. University Heart Center, Department of Cardiology, University Hospital Zurich, Zurich, Switzerland

    Francesco Paneni

  16. Center for Translational and Experimental Cardiology (CTEC), University Hospital Zurich and University of Zurich, Zurich, Switzerland

    Francesco Paneni

  17. Promise Department, School of Medicine, University of Palermo, Palermo, Italy

    Manfredi Rizzo

  18. College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE

    Manfredi Rizzo

  19. Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    John Kastelein

Authors
  1. Maciej Banach
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stanisław Surma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zeljko Reiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Niki Katsiki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter E. Penson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zlatko Fras
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Amirhossein Sahebkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Francesco Paneni
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Manfredi Rizzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. John Kastelein
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MB: designed the content of the paper and figures, revised the draft version of the paper, and prepared its final version based on the co-authors’ comments, submitted the paper to the journal; SS: prepared the draft version of the paper and figures, all other authors—made the critical comments on the draft version of the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Maciej Banach.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

All authors agreed and approved the final version of the publication.

Competing interests

MB: speakers bureau: Amgen, Herbapol, Kogen, KRKA, Polpharma, Mylan/Viatris, Novartis, Novo-Nordisk, Sanofi-Aventis, Teva, Zentiva; consultant to Abbott Vascular, Amgen, Daichii Sankyo, Esperion, Freia Pharmaceuticals, NewAmsterdam, Novartis, Polfarmex, Sanofi-Aventis; Grants from Amgen, Mylan/Viatris, Sanofi and Valeant; CMO at the Nomi Biotech Corporation; NK: has given talks, attended conferences and participated in trials sponsored by Amgen, Astra Zeneca, Boehringer Ingelheim, Elpen, Novartis, Novo Nordisk, Sanofi, Servier, Viatris, Vianex and WinMedica; PEP: owns four shares in AstraZeneca PLC and has received honoraria and/or travel reimbursement for events sponsored by AKCEA, Amgen, AMRYT, Link Medical, Mylan, Napp, Sanofi; ZR has received honoraria and participated in trials sponsored by Novartis, Arrowhead; MR: has given lectures, received honoraria, and research support, and participated in conferences, advisory boards, and clinical trials sponsored by Amgen, Astra Zeneca, Boehringer Ingelheim, Kowa, Eli Lilly, Meda, Mediately, Mylan, Merck Sharp and Dohme, Novo Nordisk, Novartis, Roche Diagnostics, Sanofi, and Servier. All other authors have nothing to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Banach, M., Surma, S., Reiner, Z. et al. Personalized management of dyslipidemias in patients with diabetes—it is time for a new approach (2022). Cardiovasc Diabetol 21, 263 (2022). https://doi.org/10.1186/s12933-022-01684-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12933-022-01684-5

Keywords

  • Cardiovascular risk
  • Diabetes
  • Individual therapy approach
  • Lipid lowering therapy
  • Statins

Cardiovascular Diabetology

ISSN: 1475-2840