PSCK9 Inhibitors Research Articles

Efficacy and Safety of PSCK9 Inhibitors on Patients with Acute Coronary Syndrome: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

PCSK9 MaB (Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor) may reduce the occurrence of major adverse cardiovascular events (MACEs) in patients diagnosed with acute coronary syndrome (ACS). In this meta-analysis, we conducted a thorough compilation of evidence from established clinical studies to evaluate PCSK9 MaB's capacity to control blood lipid levels and prevent MACEs in ACS patients. We conducted searches on Pubmed, Embase, the Cochrane Library, and Web of Science to identify relevant articles. Data from ACS patients were extracted using a standardized format for aggregating data. We calculated the risk ratio (RR) for MACE and assessed changes in blood lipid parameters. All statistical analyses were performed using RevMan. 11 articles representing 5 trials were included in our systematic review and meta-analysis. When compared to a placebo, PCSK9 MaB significantly reduced the risk of MACEs ( = 0%, p = 0.63, RR [95% CI] = 0.88 [0.81, 0.97], p 0.01) and the recurrence rate of ACS ( = 45%, p = 0.18, RR [95% CI] = 0.89 [0.83, 0.95], p 0.01). Additionally, PCSK9 MaB notably reduced low-density lipoprotein cholesterol (LDL-C) levels (SMD [95% CI] = -2.12 [-2.32, -1.92], p 0.01) and Apolipoprotein B (ApoB) levels (SMD [95% CI] = -1.83 [-2.48, -1.18], p 0.01). Importantly, there were no significant differences in adverse reactions between the PCSK9 MaB group and the control group. PCSK9 MaB, whether used as a standalone treatment or in combination with other therapies, can effectively inhibit PCSK9. It substantially lowers key blood lipid parameters, including low-density lipoprotein (LDL), ApoB, and triglycerides, all without giving rise to notable safety concerns.

The benefits of PCSK9 inhibitors in patients with acute coronary syndrome: a systematic review and meta-analysis

Abstract Background Proprotein convertase subtilisin/kexin 9 (PSCK9) inhibitors have been beneficial for many patients with hyperlipidemia. The objective of this study was to investigate the benefit of PSCK9 inhibitors in patients with acute coronary syndrome (ACS). Methods We systematically searched PubMed, EMBASE, and Cochrane Clinical Trials (published before January 2023; no language restriction) to compare the treatment of patients with ACS using PCSK9 inhibitors and placebo. The primary end points were major adverse cardiovascular events, nonfatal myocardial infarction, cardiogenic death, stroke, hospitalization for recurrent ACS, and coronary revascularization. Fixed- or random-effects models were used to assess the aggregated data. Results Of the 1686 identified studies, 5 were eligible and included in our analysis (of a total of 38,005 participants, 18,609 cases were placed in the PCSK9 inhibitor treatment group and 19,396 cases in the placebo group). Compared with the placebo group, PCSK9 inhibitors significantly reduced the major adverse cardiovascular events (odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.77–0.88; P < 0.00001) for patients following ACS. The incidence of nonfatal myocardial infarction (relative risk: 0.80; 95% CI: 0.74–0.87; P < 0.00001), cardiovascular death (OR: 0.96; 95% CI: 0.83–1.10; P = 0.56), stroke (OR: 0.74; 95% CI: 0.63–0.88; P = 0.0007), hospitalization for recurrent ACS (OR: 0.57; 95% CI: 0.40–0.83; P = 0.003), or coronary revascularization (OR: 0.82; 95% CI: 0.76–0.88; P < 0.00001) all demonstrated a significant decrease in the comparison between the 2 groups. Conclusion This meta-analysis demonstrated that treatment with PCSK9 inhibitors in patients with ACS reduced the probability of multiple cardiovascular events and improved patient prognosis.

Effects of PCSK-9 inhibitors on arterial structure and function: preliminary results

Abstract Background One of the latest chapters in the research for new and stronger lipid lowering therapies has led to the development of PCSK9 inhibitors. In addition to the benefit on lipid profile, a limited number of studies have been published showing a possible improvement in vascular function and structure following their administration. Purpose To evaluate the effects of PCSK9 inhibitors on structural (via carotid Intima Media Thickness – IMT) and functional (carotid-femoral Pulse Wave Velocity – cf-PWV - and brachial artery Flow Mediated Dilatation - FMD) arterial properties. Methods Twenty-two dyslipidemic patients with a clinical indication to PSCK9 inhibitors were prospectively recruited at the cardiology rehabilitation of a hospital. Anthropometric, clinical and therapeutic data were recorded. Each patient underwent instrumental examinations to assess cf-PWV, IMT and FMD at T0 (before the start of therapy), T1 (after 6 months) and T2 (after 12 months). Results In the 22 patients who reached 6 months of follow up there was a significant reduction in LDL cholesterol (from 127.8±31.7 to 47.4±29.1 mg/dl, p<0. 0001) while there was no significant difference in arterial parameters (cf-PWV: from 10.5±3.5 to 9.4±2.3 m/s, p=0.092; FMD: from 11.4±8.1 to 9.8±8.3%, p=0.407; IMT: from 775.6±192.8 to 768.7±144.7, microm, p=0.854). Similar results were also obtained in the 12 patients who reached one year of follow-up: LDL from 129.4±29.1 to 48.8±21.9 mg/dl, p<0.0001; cf-PWV from 10.4±3.3 to 10.5±2.9, p=0.874; FMD from 12.0±9.1 to 11.0±5.6%, p=0.930; IMT from 745.1±203.9 to 770.0±127.3 microm, p=0.710. Conclusion Our study confirm the strong LDL reduction with PCSK9 inhibitors that are needed in order to reach the targets set by the ESC 2019 guidelines. In contrast, they do not show a significant effect on arterial function and structure in terms of cf-PWV, FMD and carotid IMT.

PSCK9 inhibitors (PCSK9i) (monoclonal antibodies and inclisiran) in clinical practice. 5 years’ experience of London tertiary lipid centre

PSCK9 inhibitors (PCSK9i) (monoclonal antibodies and inclisiran) in clinical practice. 5 years’ experience of London tertiary lipid centre

Smoking and diabetes attenuate beneficial effects of PSCK9 inhibitors on arterial wall properties in patients with high lipoprotein (a) levels

Smoking and diabetes attenuate beneficial effects of PSCK9 inhibitors on arterial wall properties in patients with high lipoprotein (a) levels

Impact of alirocumab/evolocumab on lipoprotein (a) concentrations in patients with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized controlled trials.

Familial hypercholesterolaemia (FH) is a common hereditary genetic disorder, characterized by elevated circulating low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] concentrations, leading to atherosclerotic cardiovascular disease (ASCVD). Two types of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors- alirocumab and evolocumab- are efficient drugs in the treatment of FH, which can effectively reduce Lp(a) levels. Embase, MEDLINE, and PubMed up to November 2022 were searched for randomized clinical trials (RCTs) evaluating the effect of alirocumab/evolocumab and placebo treatment on plasma Lp(a) levels in FH. Statistics were analysed by Review Manager (RevMan 5.3) and Stata 15.1. Eleven RCTs involved a total of 2408 participants. Alirocumab/evolocumab showed a significant efficacy in reducing Lp(a) [weighted mean difference (WMD): -20.10%, 95% confidence interval (CI): -25.59% to -14.61%] compared with placebo. In the drug type subgroup analyses, although the efficacy of evolocumab was slightly low (WMD: -19.98%, 95% CI: -25.23% to -14.73%), there was no difference with alirocumab (WMD: -20.54%, 95% CI: -30.07% to -11.02%). In the treatment duration subgroup analyses, the efficacy of the 12-week duration group (WMD: -17.61%, 95% CI: -23.84% to -11.38%) was lower than in the group of ≥ 24 weeks' duration (WMD: -22.81%, 95% CI: -31.56% to -14.07%). In the participants' characteristics subgroup analyses, the results showed that no differential effect of alirocumab/evolocumab therapy on plasma Lp(a) concentrations was observed (heterozygous FH [HeFH] WMD: -20.07%, 95% CI: -26.07% to -14.08%; homozygous FH [HoFH] WMD: -20.04%, 95% CI: -36.31% to -3.77%). Evaluation of all-cause adverse events (AEs) between alirocumab/evolocumab groups and placebo groups [relative risk (RR): 1.05, 95% CI: 0.98-1.12] implied no obvious difference between the 2 groups. Anti-PCSK9 drugs (alirocumab and evolocumab) may be effective as therapy for reducing serum Lp(a) levels in FH, and no differences were observed in treatment durations, participant characteristics, and other aspects of the 2 types of PCSk9 inhibitors. However, further experimental studies and RCTs are warranted to clarify the mechanism of PSCK9 inhibitors to lowering Lp(a) concentrations in FH.

EFFECTS OF PCSK-9 INHBITORS ON ARTERIAL STRUCTURE AND FUNCTION: PRELIMINARY RESULTS

Objective: One of the latest chapters in the research for new and stronger lipid lowering therapies has led to the development of PCSK9 inhibitors. In addition to the benefit on lipid profile, a limited number of studies have been published showing a possible improvement in vascular function and structure following their administration. To evaluate the effects of PCSK9 inhibitors on structural (via carotid Intima Media Thickness – IMT) and functional (carotid-femoral Pulse Wave Velocity – cf-PWV - and brachial artery Flow Mediated Dilatation - FMD) arterial properties. Design and method: Twenty-two dyslipidemic patients with a clinical indication to PSCK9 inhibitors were prospectively recruited at the Cardiology Rehabilitation of ASST Grande Ospedale Metropolitano Niguarda Hospital (Milan, Italy). Anthropometric, clinical and therapeutic data were recorded. Each patient underwent instrumental examinations to assess cf-PWV, IMT and FMD at T0 (before the start of therapy), T1 (after 6 months) and T2 (after 12 months). Results: In the 22 patients who reached 6 months of follow up there was a significant reduction in LDL cholesterol (from 127.8±31.7 to 47.4±29.1 mg/dl, p<0. 0001) while there was no significant difference in arterial parameters (cf-PWV: from 10.5±3.5 to 9.4±2.3 m/s, p = 0.092; FMD: from 11.4±8.1 to 9.8±8.3%, p = 0.407; IMT: from 775.6±192.8 to 768.7±144.7, microm, p = 0.854). Similar results were also obtained in the 12 patients who reached one year of follow-up: LDL from 129.4±29.1 to 48.8±21.9 mg/dl, p<0.0001; cf-PWV from 10.4±3.3 to 10.5±2.9, p = 0.874; FMD from 12.0±9.1 to 11.0±5.6%, p = 0.930; IMT from 745.1±203.9 to 770.0±127.3 microm, p = 0.710. Conclusions: Our study confirm the strong LDL reduction with PCSK9 inhibitors that are needed in order to reach the targets set by the ESC 2019 guidelines. In contrast, they do not show a significant effect on arterial function and structure in terms of cf-PWV, FMD and carotid IMT.

Differences in treatment strategies for LDL-cholesterol reduction in a university lipid clinic vs. standard care apart from the use of PCSK9 inhibitors

Lipid-lowering therapy (LLT) in patients with cardiovascular disease (CVD) is insufficient despite clear guideline recommendations. Lipid clinics have specialized in patients with dyslipidemia, but the magnitude and reduction of low-density lipoprotein cholesterol (LDL-C) in lipid clinics has not yet been studied in depth. To assess LDL-C reduction in very high-risk CVD patients achieved in a lipid clinic through different forms of LLT in comparison to standard care without the initiation of PSCK9 inhibitors. Data from 96 lipid clinic patients were analyzed retrospectively and compared to 84 standard care patients. Very high-risk patients were defined according to the European Society of Cardiology (ESC). Different combinations of LLT focusing on statins and ezetimibe were investigated. Achievement of LDL-C treatment goals according to ESC guidelines as well as LDL-C reduction were assessed. Baseline and follow-up data of 180 very high-risk CVD patients (mean age 67.7 (±9.8) y; 60.6% male) were used. Achievement of the LDL-C goal in lipid clinic patients increased significantly from 14.6% at baseline to 41.7% at the latest visit (p<0.001) while standard care patients improved from 21.4% to 33.3% (p=0.08). The largest relative LDL-C reduction via an adjustment in LLT was achieved by initiation of high-intensity statins (50.8 ± 4.9%, n=5, p < 0.05). Treatment in a lipid clinic leads to a superior LDL-C goal achievement in very high-risk CVD patients as compared to standard care with the highest reduction under LLT with high-intensity statins and ezetimibe. Referral algorithms have to be established for high-risk patients.

P197 EFFECTS OF PCSK–9 INHBITORS ON ARTERIAL STRUCTURE AND FUNCTION: PRELIMINARY RESULTS

Abstract Background One of the latest chapters in the research for new and stronger lipid lowering therapies has led to the development of PCSK9 inhibitors. In addition to the benefit on lipid profile, a limited number of studies have been published showing a possible improvement in vascular function and structure following their administration. Purpose: To evaluate the effects of PCSK9 inhibitors on structural (via carotid Intima Media Thickness – IMT) and functional (carotid–femoral Pulse Wave Velocity – cf–PWV – and brachial artery Flow Mediated Dilatation – FMD) arterial properties. Methods Twenty–two dyslipidemic patients with a clinical indication to PSCK9 inhibitors were prospectively recruited at the Cardiology Rehabilitation of ASST Grande Ospedale Metropolitano Niguarda Hospital (Milan, Italy). Anthropometric, clinical and therapeutic data were recorded. Each patient underwent instrumental examinations to assess cf–PWV, IMT and FMD at T0 (before the start of therapy), T1 (after 6 months) and T2 (after 12 months). Results In the 22 patients who reached 6 months of follow up there was a significant reduction in LDL cholesterol (from 127.8±31.7 to 47.4±29.1 mg/dl, p&amp;lt;0. 0001) while there was no significant difference in arterial parameters (cf–PWV: from 10.5±3.5 to 9.4±2.3 m/s, p=0.092; FMD: from 11.4±8.1 to 9.8±8.3%, p=0.407; IMT: from 775.6±192.8 to 768.7±144.7, microm, p=0.854). Similar results were also obtained in the 12 patients who reached one year of follow–up: LDL from 129.4±29.1 to 48.8±21.9 mg/dl, p&amp;lt;0.0001; cf–PWV from 10.4±3.3 to 10.5±2.9, p=0.874; FMD from 12.0±9.1 to 11.0±5.6%, p=0.930; IMT from 745.1±203.9 to 770.0±127.3 microm, p=0.710. Conclusion Our study confirm the strong LDL reduction with PCSK9 inhibitors that are needed in order to reach the targets set by the ESC 2019 guidelines. In contrast, they do not show a significant effect on arterial function and structure in terms of cf–PWV, FMD and carotid IMT.

Barriers to prescribing proprotein convertase subtilisin-kexin type 9 inhibitors after coronary revascularisation.

Guidelines advocate for intensive lipid-lowering in patients with atherosclerotic cardiovascular disease (ASCVD). In May 2020, evolocumab, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, became government subsidised in Australia for patients with ASCVD requiring further low-density lipoprotein cholesterol (LDL-C) lowering. To identify barriers to prescribing PCSK9 inhibitors in hospitalised patients with ASCVD. A retrospective 3-month, single-site, observational analysis was conducted in consecutive patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Lipid-lowering therapy prescriptions, including PSCK9 inhibitors, were assessed using electronic medical records, compared against the Australian Pharmaceutical Benefits eligibility criteria, and barriers to PCSK9 inhibitor use identified. Of 331 patients, 244 (73.7%) underwent PCI and 87 (26.3%) underwent CABG surgery. A lipid profile during or within 8 weeks of admission was measured for 202 (82.8%) patients undergoing PCI and 59 (67.8%) undergoing CABG surgery. In patients taking high-intensity statins on admission (n = 109), LDL-C ≥1.4, ≥1.8 and >2.6mmol/L was seen in 64 (58.7%), 44 (40.4%) and 19 (17.4%) patients respectively. High-intensity statin prescribing at discharge was high (>80%); however, ezetimibe was initiated in zero patients with LDL-C ≥1.4 mmol/L. There was variable advice given by clinicians for LDL-C targets. No patients met the criteria for subsidised PSCK9 inhibitor therapy, largely due to lack of qualifying lipid levels following combined statin and ezetimibe therapy. Prescribing of non-statin LDL-C-lowering therapies remains low in patients with ASCVD. Underprescribing of ezetimibe and suboptimal lipid testing rates are barriers to accessing subsidised PCSK9i therapy using current Australian eligibility criteria.

LDL as a therapeutic target

The incidence of atherosclerotic cardiovsacular disease (ASCVC) has increased in the developed countries. Dyslipidemia is a primary major risk factor for ASCVD and LDL lowering is one of the main objectives. Although treatment goals for dyslipidemias should be personalized in every patient, statins are cost-effective in primary and secondary prevention of ASCVD. New treatments with higher power and greater decreases in LDL, PSCK9 inhibitors, have made a new breakthrough in ASCVD treatment. The 2019 Guidelines for de Management of Dyslipidaemias: Lipid Modification to reduce Cardiovascular Risk (European Society of Cardiology/European Atherosclerosis Society) with the level of evidence and the strength of the recommendations can facilitate the best decisions and benefits to our patients in clinical practice.

Smoking and diabetes attenuate beneficial effects of PSCK9 inhibitors on arterial wall properties in patients with very high lipoprotein (a) levels

Background and aimsElevated lipoprotein (a) (Lp(a)) and low-density lipoprotein cholesterol levels (LDL-C) are significant residual risk factors for cardiovascular events. Treatment with protein convertase subtilisin kexin type 9 (PCSK9) inhibitors reduces the levels of both. Less is known about effects of PCSK9 inhibitors on functional and morphological properties of the arterial wall. The aim of the present study was to determine whether other factors besides decreased LDL-C and Lp(a) are associated with functional (flow-mediated dilation [FMD]) and morphological (carotid intima-media thickness [c-IMT], pulse-wave velocity [PWV]) changes of the arterial wall properties in patients with coronary artery disease (CAD) treated with alirocumab and evolocumab. MethodsOne hundred patients with CAD after myocardial infarction before 55 years and with high Lp(a) were randomised to lipid-lowering therapies without PCSK9 inhibitors (control; N = 31), or with alirocumab 150 mg SC (N = 35) or evolocumab 140 mg SC (N = 34), every 2 weeks. All patients underwent blood sampling for biochemical analyses and ultrasound measurements for FMD, c-IMT and PWV. ResultsThere were no significant changes in FMD for the control (10.7% ± 6.6%–11.1% ± 4.4%, p = 0.716) and alirocumab (10.7% ± 5.9%–11.2% ± 5.3%, p = 0.547) groups, while evolocumab promoted significant increase (11.2% ± 6.8%–14.1% ± 6.6%, p < 0.0001). Only in non-smokers and non-diabetics significant improvements in FMD (p < 0.0001) after treatment with PCSK9 inhibitors were observed. ConclusionThese data show that for patients with CAD and high Lp(a) levels, beneficial effects of PCSK9 inhibitors on the arterial wall properties can be attenuated by specific risk factors, such as smoking and diabetes.

Effectivity, safety and adherence with PCKS9 inhibitors

Background and Aims : The main purpose of the study is to evaluate the effectivity, safety and adherence in patients who undergoing treatment with PSCK9 inhibitors (iPCKS9), evolocumab and alirocumab, in our Lipid Unit of ALTHAIA. Xarxa assistencial universitarà de Manresa (Barcelona).

LDL como objetivo terapéutico

The incidence of atherosclerotic cardiovsacular disease (ASCVC) has increased in the developed countries. Dyslipidemia is a primary major risk factor for ASCVD and LDL lowering is one of the main objectives. Although treatment goals for dyslipidemias should be personalized in every patient, statins are cost-effective in primary and secondary prevention of ASCVD. New treatments with higher power and greater decreases in LDL, PSCK9 inhibitors, have made a new breakthrough in ASCVD treatment. The 2019 Guidelines for de Management of Dyslipidaemias: Lipid Modification to reduce Cardiovascular Risk (European Society of Cardiology/European Atherosclerosis Society) with the level of evidence and the strength of the recommendations can facilitate the best decisions and benefits to our patients in clinical practice.

Smoking and Diabetes Attenuate Beneficial Effects of PSCK9 Inhibitors on Arterial Wall Properties in Patients with Very High Lipoprotein (a) Levels

Smoking and Diabetes Attenuate Beneficial Effects of PSCK9 Inhibitors on Arterial Wall Properties in Patients with Very High Lipoprotein (a) Levels

PCSK-9 Inhibitors in a Real-World Setting and a Comparison Between Alirocumab and Evolocumab in Heterozygous FH Patients.

A real-world setting study of familial hypercholesterolemia (FH) patients who received Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in a specialized referral center in Mexico City. Ten patients between the ages of 18 and 70 years, with a diagnosis of FH according to Dutch Lipid Clinic Network (DLCN) criteria, with failure to achieve their Low-density lipoprotein Cholesterol (LDL-C) goals, and with standard therapy between 2016 and 2017 enrolled in a simple randomization in which a group of 5 participants received alirocumab (75 mg every 2 weeks) and the remaining 5 patients received evolocumab (140 mg every 2 weeks). Comparative analysis was made, analyzing the means of LDL at baseline at 4, 6, and 12 weeks. The evolocumab group had an average initial LDL-C of 277 mg/dL, which, after 12 weeks of treatment, was significantly reduced to 116 mg/dL; P = 0.04 (95% confidence interval [CI]: 11.5–310.9). The alirocumab group with a mean initial LDL-C of 229 mg/dL showed a reduction of LDL-C levels at 12 weeks of treatment to 80 mg/dL; P = 0.008 (95% CI: 63.8–233.7). In conclusion, PCSK9 inhibitors are an excellent treatment option in patients with FH who do not reach their LDL-C goals with standard therapy or due to intolerance to the standard therapy. There is no difference in the lipid-lowering effect between both PSCK9 inhibitors.

Reduction of epicardial adipose tissue thickness with PCSK9 inhibitors

Abstract Introduction Epicardial adipose tissue (EAT) is clinically related to atherosclerosis and increased cardiovascular risk. The proprotein convertase subtilisin/kexin type 9 inhibitors (IPCSK9) are a novel group of effective drugs for lowering LDL cholesterol and cardiovascular events, however their effect on EAT has not yet been determined. Objective To assess the effect of treatment with PCSK9 inhibitors on epicardial adipose tissue. Methods The study enrolled 41 patients under treatment with PCSK9 inhibitors. At the end of the study only 24 patients were included, who were measured thickness of epicardial adipose tissue (TEAT) by transthoracic echocargiogram (just an echocardiographer using Siemens Acuson SC 2000 Prime with two-dimensional 4V1c transducer in two projections: long parasternal axis in the pericardial space of the outer edge of the myocardium above the right ventricle and in a short parasternal axis at the height of papillary muscles on the right ventricle, in telesystole and averaging three measurements; It was measured in millimeters.) using in 2 times before and after 6 months of initiation of treatment. Results Of 24 patients, 16 patients recieved evolocumab and 8 alirocumab patients; the mean TEAT pre-treatment and post-treatment was 6.84 mm (1.97) and 5.41 mm (1.86), respectively (p=0.0001); The mean percentage of change of the TEAT after 6 months of treatment was −20.39 (17.20). The mean serum LDL cholesterol levels pre-treatment and post-treatment were 188.04 mg/dL (144.0) and 94.96 mg/dL (106.04), respectively (p=0.0001); The mean change in LDL cholesterol was −51.89 (22.81). Just one patient had myocardial infarction. There was no difference between the means of reducing the percentage of change in epicardial adipose thickness between evolocumab and alirocumab. There was no correlation between lipid decrease and TEAT. Conclusion There is a significant reduction after 6 months of treatment with PSCK9 inhibitors in thickness of epicardial adipose tissue. Effect of IPCSK9 in TEAT and Lipids Funding Acknowledgement Type of funding source: None

Utilization of PCSK-9 Inhibitors in Statin Intolerant Cardiac Transplant Patients

Background HMG CoA Reductase Inhibitors, commonly referred to as statins, are widely used in heart transplant patients as dyslipidemia is common after cardiac transplantation and increases the risk of cardiovascular adverse events including cardiac allograft vasculopathy (CAV). However, not all patients can tolerate statins or see an adequate lowering of the low density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors have been shown to be effective at lowering LDL with great tolerance and excellent safety profiles in the general population. Yet, there is limited data regarding effect of PCSK9 inhibitors in heart transplant patients. Objective To study the effect of PSCK-9 inhibitors in post-cardiac transplant patients. Method We reviewed post heart transplant patients who received PCSK9 inhibitors at our University Medical Center from 2017 to March 2020. We found four patients who were eligible. Results The mean age of the four patients was 65.75± 4.7 years (3 Females). Indication for PCSK9 inhibitors in three patients was statin intolerance due to myopathy; the fourth patient had familial hypercholesterolemia that required more aggressive therapy. Average time for initiation of the medication since heart transplant was 10.25 years. The average duration of treatment was 18.25 months. Two patients were on Evolocumab 140mg subcutaneously once every 2 weeks, and the other two were on Alirocumab 75mg every 2 weeks. All four patients continued the medicine with no side effects. Mean LDL-C prior to initiation of the drug was 125.75± 24.42 mg/dL. At 8-12 week follow up there was significant reduction in the LDL 35.75 ±13.74mg/dL (p=0.006).There was no significant dose changes to the immunosuppressive medications. None of the four patients experienced rejection of the transplanted heart. Only one patient with familial hypercholesterolemia had mild CAV on heart catheterization prior to initiation of the drug and there was no progression of the CAV at one year follow up. Conclusion PCSK9-inhibitors were effective in reducing low-density lipoprotein levels in post-cardiac transplant patients and were well tolerated without any rejection or modifications to the transplant medications in this small cohort of patients. The study findings are promising and highlight the need for larger, prospective, multicenter studies.

Estimation of the major cardiovascular events prevention with Inclisiran

Background and aimsThe ORION 10–11 trials have reported the efficacy of Inclisiran on low-density lipoprotein cholesterol (LDLc) reduction, and also suggested prevention of major cardiovascular events (MACE) incidence. MethodsWe have performed a meta-analysis of the available studies, involving PCSK9 inhibitors or Inclisiran for >6 months, that reported the incidence of MACE. The primary endpoint was MACE incidence, as reported in outcomes-based randomized clinical trials (OB-RCT) and non OB-RCT. Analyses were performed using fixed effect models and fractional polynomial regression. ResultsThe meta-analysis included a total of 57,431 patients, 1592 treated with Inclisiran and 28,259 with PSCK9 inhibitors (17,244 with evolocumab and 11,015 with alirocumab). Baseline mean LDLc was 104.1 (12.9) mg globally. On-treatment mean LDLc was 40.1 (7.8) mg/dl and mean absolute LDLc reduction was 60.6 (10.3) mg/dl. A total of 5389 MACE were reported, 2482 in patients receiving the study drug and 2907 in patients assigned to placebo. Treatment was associated with OB-RCT and no heterogeneity was observed. The estimation of MACE reduction associated with LDLc reduction, adjusted by age, diabetes, hypertension and baseline LDLc, provided a linear trend in the risk of MACE and LDLc reduction that was linear and all studies fitted properly. ConclusionsThe results of the ORION 10–11 trials are in concordance with results of trials involving treatment with PCSK9 inhibitors. The results of the ORION-4 trial will provide definite evidence on the effects of Inclisiran on MACE reduction.

Prevention of myocardial infarction and stroke with PCSK9 inhibitors treatment: a metanalysis of recent randomized clinical trials.

Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors treatment induce large reductions in low-density lipoprotein cholesterol (LDLc) and major cardiovascular events. Clinical trials might have been underpowered to test the effect of PSCK9 inhibitors treatment on myocardial infarction and stroke, two of the most relevant cardiovascular events, since all analyzed a combined endpoint. we performed a meta-analysis, with currently available studies involving PCSK9 inhibitors and event rate adjudication, with the aim of assessing treatment effects on myocardial infarction and stroke. We included 81,700 patients, 41,979 treated with a PSCK9 inhibitors: 17,244 with evolocumab; 13,720 with bococizumab and 11,015 with alirocumab. A total of 1,319 cases of myocardial infarctions were registered in the treatment group vs. 1,608 in controls, resulting in 19.0% reduction associated with PCSK9 treatment (RR: 0.81, 95% CI 0.76-0.87). Similarly, PCSK9 inhibitors treatment resulted in a 25% reduction of stroke (RR: 0.75, 95% CI 0.65-0.85) when all studies were analyzed together and the statistically significant heterogeneity was not observed in the analysis restricted to end-point based clinical trials. PCSK9 inhibitors treatment had no effect on mortality (RR: 0.95, 95% CI 0.86-1.04). PCSK9 inhibitors reduce the incidence of myocardial infarction by 19% and stroke by 25%.