Effect of evolocumab on acute arterial events across all vascular territories : results from the FOURIER trial

2021 ◽  
Author(s):  
Kazuma Oyama ◽  
Robert P Giugliano ◽  
Minao Tang ◽  
Marc P Bonaca ◽  
Jeffrey L Saver ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Limb Ischaemia ◽  
Lipid Lowering Therapy ◽  
Peripheral Vascular ◽  
Pcsk9 Inhibitor ◽  
Acute Limb Ischaemia ◽  
The Impact ◽  
Over Time

Abstract Aims We assessed the impact of the proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitor evolocumab on acute arterial events across all vascular territories, including coronary, cerebrovascular, and peripheral vascular beds, in patients with established atherosclerotic cardiovascular disease (ASCVD). Methods and results In the FOURIER trial, 27 564 patients with stable ASCVD on statin therapy were randomly assigned to evolocumab or placebo. Acute arterial events were a composite of acute coronary (coronary heart disease death, myocardial infarction, or urgent coronary revascularization), cerebrovascular (ischaemic stroke, transient ischaemic attack, or urgent cerebral revascularization), or peripheral vascular (acute limb ischaemia, major amputation, or urgent peripheral revascularization) events. Of the 2210 first acute arterial events, 74% were coronary, 22% were cerebrovascular, and 4% were peripheral vascular. Evolocumab reduced first acute arterial events by 19% (hazard ratio [HR] 0.81 [95% confidence interval 0.74–0.88]; P < 0.001), with significant individual reductions in acute coronary (HR 0.83 [0.75–0.91]), cerebrovascular (HR 0.77 [0.65–0.92]), and peripheral vascular (HR 0.58 [0.38–0.88]) events. There were 3437 total events (first plus recurrent), with evolocumab reducing total events by 24% (incidence rate ratio 0.76 [0.69–0.85]). The magnitude of reduction in acute arterial events with evolocumab numerically increased over time, with a 16% reduction (HR 0.84 [0.75–0.95]) in the first year followed by a 24% reduction (HR 0.76 [0.67–0.85]) thereafter. Conclusion The addition of the PCSK9 inhibitor evolocumab to statin therapy reduced acute arterial events across all vascular territories with a robust effect over time, indicating a pan-vascular impact of aggressive lipid-lowering therapy on these acute and clinically meaningful events. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633.

scholarly journals Acute arterial events across all vascular territories in the FOURIER trial

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K Oyama ◽  
R Giugliano ◽  
M Tang ◽  
M Bonaca ◽  
J Saver ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Lipid Lowering ◽  
Acute Limb Ischemia ◽  
Lipid Lowering Therapy ◽  
Peripheral Vascular ◽  
Private Company ◽  
Pcsk9 Inhibitor ◽  
Vascular Beds ◽  
Pcsk9 Inhibition ◽  
Over Time

Abstract Background In the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trial, adding the PCSK9 inhibitor evolocumab to statin therapy reduced low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk. Although atherosclerotic coronary, cerebrovascular, and peripheral vascular events share a related pathobiology, the effect of aggressive LDL-C lowering with PCSK9 inhibition on the risk of acute arterial events across all three vascular beds is not well-described. Purpose To assess the efficacy of evolocumab on acute arterial events in all vascular territories including coronary, cerebral, and peripheral vascular beds. Methods In the FOURIER trial, patients (n=27,564) with stable atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on a statin were randomly assigned to evolocumab versus placebo and followed for a median of 2.2 years (1.8–2.5). Acute arterial events were defined as a composite of coronary (coronary heart disease [CHD] death, myocardial infarction [MI], or urgent coronary revascularization), cerebrovascular (ischemic stroke, transient ischemic attack [TIA], or urgent cerebral revascularization), or peripheral vascular (acute limb ischemia, major amputation, or urgent peripheral revascularization) events. Cox proportional-hazard models were used to assess the efficacy of evolocumab on these outcomes. Landmark and total event analyses were also done. Results Of the 2,210 first acute arterial events occurring during follow-up, 74% were coronary, 22% were cerebrovascular, and 4% were peripheral vascular. Evolocumab reduced the risk of a first acute arterial event by 19% (HR 0.81, 95% CI 0.74–0.88; P<0.001), with significant individual reductions in acute coronary (HR 0.83; 95% CI 0.75–0.91; P<0.001), acute cerebrovascular (HR 0.77; 95% CI 0.65–0.92; P=0.004), and acute peripheral vascular (HR 0.58; 95% CI 0.38–0.88; P=0.01) events (Figure, top). The magnitude of the risk reduction with evolocumab tended to increase over time, with a 16% reduction (HR 0.84; 95% CI 0.75–0.96) in the first year followed by a 24% reduction (HR 0.76; 95% CI 0.67–0.85) thereafter (Figure, bottom). There were 3,780 total acute arterial events (first plus recurrent), with a 22% reduction with evolocumab (incidence rate ratio [RR] 0.78; 95% CI 0.70–0.87). Evolocumab prevented 496 total acute arterial events as compared to 222 first events. Conclusions The addition of the PCSK9 inhibitor evolocumab to statin therapy reduced the risk of acute arterial events across all vascular territories with a robust effect over time. These findings indicate a pan-vascular impact of aggressive lipid-lowering therapy on these acute and clinically meaningful events. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): The FOURIER trial was supported by Amgen.

scholarly journals The impact of the revised ESC Dyslipidaemia Guidelines on lipid-lowering therapy: simulating the need for PCSK9 inhibition in a contemporary ASCVD cohort

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Blaum ◽  
F.J Brunner ◽  
F Kroeger ◽  
J Braetz ◽  
B Bay ◽  
...  
Keyword(s):  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Treatment Target ◽  
Pcsk9 Inhibitor ◽  
Lowering Therapy ◽  
Artery Disease ◽  
Pcsk9 Inhibition ◽  
The Impact

Abstract Introduction The recently updated ESC guidelines on the management of dyslipidaemias recommend a more intense LDL-cholesterol (LDL-C) reduction. For patients with atherosclerotic cardiovascular disease (ASCVD) the LDL-C goal has been revised to ≤55 mg/dl with a concomitant class IA upgrade for cost intensive PCSK9 inhibitors. Purpose We aim to quantify the need for PCSK9 inhibitors to achieve the revised LDL-C target compared to former ESC recommendations in ASCVD patients Methods We included all patients with ASCVD (angiographically documented coronary artery disease, history of peripheral artery disease or stroke) from an observational cohort study ongoing since 2015. A simulation treatment algorithm adding sequentially a high intensity statin, ezetimibe and a PCSK9 inhibitor in case of a missed treatment target was applied with consideration of both partial and total statin intolerance. The need for PCSK9 inhibitors was calculated for 3 recommendations: 1. LDL-C treatment target ≤55 mg/dl (ESC 2019 Guidelines), 2. LDL-C treatment target ≤70 mg/dl (ESC 2016 Guidelines) and 3. risk-based use of PCSK9 inhibitors restricted to patients with a residual LDL-C >140 mg/dl or >100 mg/dl with clinical/angiographic risk factors (ESC consensus update 2017). Results We included 1936 patients (mean age 69 years, 74% male). Median LDL-C at inclusion was 86 mg/dl, with 60% of patients taking lipid lowering medication (55% statin only, 4% statin + ezetimibe, 1% ezetimibe only). Table 1 shows the distribution of medications required to meet recommendations 1–3. After simulated stepwise intensification of lipid lowering therapy 99% of patients achieved the revised LDL-C target of ≤55 mg/dl, with a need of 23.5% for a PCSK9 inhibitor. For the former LDL-C target of ≤70 mg/dl the need for PCSK9 inhibitors was 10.5%. Restricting the use of PCSK9 inhibitors to the highest risk patients according to the ESC 2017 consensus statement reduced the need for PCSK9 inhibition to only 1.4% with slightly fewer patients achieving their LDL-C target (78% for ≤55 mg/dl and 91% for ≤70 mg/dl respectively). Conclusion The revised LDL-C treatment goals substantially increase the projected need for PCSK9 inhibitors with an unclear health economic impact. Identification of ASCVD patients with a reasonable benefit/cost-ratio of PCSK9 inhibition remains to be investigated urgently. Funding Acknowledgement Type of funding source: None

Abstract 15913: Two-year Results of the Getting to an Improved Understanding of Low-density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) Registry of Patients With Atherosclerotic Cardiovascular Disease (ASCVD)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Christopher P Cannon ◽  
James A De Lemos ◽  
Christie M Ballantyne ◽  
Robert S Rosenson ◽  
Shushama Alam ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Statin Therapy ◽  
Treatment Guidelines ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitor ◽  
Statin Dose

Background: Atherosclerotic cardiovascular disease (ASCVD) treatment guidelines recommend intensive statin therapy and adding non-statin therapy if LDL-C ≥70 mg/dL. Methods: We designed the GOULD registry to assess lipid-lowering therapy (LLT) over time: At 120 U.S. centers, 5006 ASCVD patients on any (LLT) were enrolled in 1 of 3 cohorts: 1) currently on PCSK9 inhibitor (PCSK9i), 2) no PCSK9i and LDL-C ≥100 mg/dL, and 3) no PCSK9i and LDL-C 70-99 mg/dL. Results: Over the two years, only 16.8% had some type of LLT intensification, In the cohorts of patients with baseline LDL-C ≥ 100 and 70-99 mg/dL, LLT intensification was present in 21.9% and 14.3% respectively: statin dose was intensified in 6.1% and 6.1%, ezetimibe was added in 6.8% and 4.3% and PCSK9i was added in 6.3% and 2.2% respectively. Conversely, out of the total population, statins were discontinued in 246/4275 (5.8%), ezetimibe in 81/535 (15.1%), and PCSK9i in 47/544 (8.6%). At 24 months, 83.7% were on statin (43.4% high-intensity), with 14.2% on ezetimibe. Lipid panels were measured in 73% by 1 year and 84% by 2 years. Among Pts in the LDL-C ≥100 and 70-99 mg/dL cohorts, 18.6% and 30.4% achieved an LDL-C <70 mg/dL by 1 year, with little further change by 2 years: 21.3% and 33.5% respectively. In the PCSK9 cohort, 53.2% had LDL-C<70 mg/dl. Overall, only 31.7% had LDL-C <70 mg/dL at 2 years (an increase from 6.7% at baseline), while 25.0% had LDL-C >100 mg/dL. Conclusion: Of ASCVD patients with suboptimal LDL-C at baseline, even after 2 years of follow up, strikingly only 16% had LLT intensification, and thus most remained uncontrolled. Further intensive efforts are needed to achieve optimal LDL management in patients with ASCVD.

scholarly journals Lower is better: ezetimibe and PCSK9 inhibition join the mainstream of lipid‑lowering therapy

2016 ◽  
Vol 7 (1) ◽  
pp. 17-25
Author(s):  
Cezary Wójcik
Keyword(s):  
Statin Therapy ◽  
Heart Association ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Level Of Evidence ◽  
Cholesterol Guidelines ◽  
Pcsk9 Inhibition ◽  
Current Guidelines

The focus of 2013 cholesterol guidelines to prevent atherosclerotic cardiovascular disease (ASCVD) released by American College of Cardiology (ACC) and American Heart Association (AHA) is the administration of high intensity statin therapy to specific four groups of patients, which were found to benefit the most from such therapy. They no longer promote achieving specific LDL-C goals with a combination therapy involving statins and other drugs, as advocated by the former ATP-III guidelines as well as current guidelines of European Atherosclerosis Society, International Atherosclerosis Society or National Lipid Association. Such approach has been dictated by the strict reliance on randomized controlled trials as the only acceptable level of evidence. However, since publication of the 2013 ACC/AHA guidelines, cardiovascular benefits of ezetimibe added to statin therapy have been established. Moreover, the advent of PCSK9 inhibitors, providing a powerful supplement and/or alternative to statin therapy, further complicates the therapeutic horizon in dyslipdiemias. It is very likely that a new set of ACC/AHA guidelines will be published in 2016, with a return of specific LDL-C and Non-HDL-C goals of therapy as well as integration of drugs other than statins. As the treatment of dyslipidemias becomes more complex, the need for the subspecialty of clinical lipidology to be officially recognized becomes more evident.

scholarly journals PCSK9 inhibitors for in-hospital treatment of patients with acute coronary syndrome and severe lipid metabolism disorders

2020 ◽  
Vol 25 (8) ◽  
pp. 4010
Author(s):  
O. L. Barbarash ◽  
N. V. Fedorova ◽  
D. Yu. Sedykh ◽  
O. V. Gruzdeva ◽  
O. N. Khryachkova ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Statin Therapy ◽  
Lipid Lowering ◽  
High Density Lipoproteins ◽  
Hospital Treatment ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitor ◽  
Coronary Syndrome ◽  
Lowering Therapy ◽  
Baseline Values

Aim. To assess the efficacy and safety of PCSK9 inhibitor alirocumab as part of a combination lipid-lowering therapy in patients with acute coronary syndrome (ACS).Material and methods. This prospective, open-label, single-center activetreatment study included 13 patients hospitalized due to ACS. The main inclusion criterion was nonachievement of target low-density lipoprotein cholesterol (LDL-C) values (<1,4 mmol/L) with high-intensity statin therapy prior to ACS. During the first 30 days after ACS, all patients received therapy with atorvastatin 40-80 mg/day or rosuvastatin 20-40 mg/day in combination with alirocumab 150 mg/ml (Praluent) administered by subcutaneous injection. Lipid and biochemical profiles were monitored. The first injection of the PCSK9 inhibitor was performed on days 3-5 of hospitalization, the second — after 2 weeks.Results. On admission, the median LDL-C was 4,3 [3,5;5,3] mmol/L. A day after administration, there was a decrease in LDL-C by 41,9% (median 2,5 [1,8;3,2] mmol/L; p=0,001) without a negative effect on high-density lipoproteins (HDL-C) (median 1,2 [0,8;1,4] mmol/L; p=0,270). Before the next injection, LDL-C decreased by another 8% (median 2,3 [1,1;4,1] mmol/L). A day after the second injection, a decrease in LDL-C from the baseline values was 69,8% (median 1,3 [0,7;1,5] mmol/L; p=0,010). Strengthening lipid-lowering therapy with a PCSK9 inhibitor within 30 days after ACS did not lead to clinical and biochemical deterioration.Conclusion. The use of subcutaneous 150-mg injections of alirocumab 2 times a week 30 days after ACS in patients who did not reach target LDL-C values with statin therapy, leads to a 69% decrease in LDL-C from baseline values and is safe.

scholarly journals Non-statin lipid-lowering therapy over time in very-high-risk patients: effectiveness of fixed-dose statin/ezetimibe compared to separate pill combination on LDL-C

2020 ◽  
Author(s):  
Julius L. Katzmann ◽  
Francesc Sorio-Vilela ◽  
Eugen Dornstauder ◽  
Uwe Fraas ◽  
Timo Smieszek ◽  
...  
Keyword(s):  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Lipid Lowering ◽  
Fixed Dose ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
High Potency ◽  
Atherosclerotic Cardiovascular Disease Risk ◽  
Very High ◽  
Over Time

Abstract Background Many patients at very-high atherosclerotic cardiovascular disease risk do not reach guideline-recommended targets for LDL-C. There is a lack of data on real-world use of non-statin lipid-lowering therapies (LLT) and little is known on the effectiveness of fixed-dose combinations (FDC). We therefore studied prescription trends in oral non-statin LLT and their effects on LDL-C. Methods A retrospective analysis was conducted of electronic medical records of outpatients at very-high cardiovascular risk treated by general practitioners (GPs) and cardiologists, and prescribed LLT in Germany between 2013 and 2018. Results Data from 311,242 patients were analysed. Prescriptions for high-potency statins (atorvastatin and rosuvastatin) increased from 10.4% and 25.8% of patients treated by GPs and cardiologists, respectively, in 2013, to 34.7% and 58.3% in 2018. Prescription for non-statin LLT remained stable throughout the period and low especially for GPs. Ezetimibe was the most prescribed non-statin LLT in 2018 (GPs, 76.1%; cardiologists, 92.8%). Addition of ezetimibe in patients already prescribed a statin reduced LDL-C by an additional 23.8% (32.3 ± 38.4 mg/dL), with a greater reduction with FDC [reduction 28.4% (40.0 ± 39.1 mg/dL)] as compared to separate pills [19.4% (27.5 ± 33.8 mg/dL)]; p < 0.0001. However, only a small proportion of patients reached the recommended LDL-C level of < 70 mg/dL (31.5% with FDC and 21.0% with separate pills). Conclusions Prescription for high-potency statins increased over time. Non-statin LLT were infrequently prescribed by GPs. The reduction in LDL-C when statin and ezetimibe were prescribed in combination was considerably larger for FDC; however, a large proportion of patients still remained with uncontrolled LDL-C levels. Graphic abstract

Preoperative cardiovascular assessment as an opportunity to (re)affirm the 2019 ESC/EAS guidelines recommended LDL-C goal

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
A Ioannidis ◽  
V Giakoumi ◽  
A Pechlevanis ◽  
M Paraskelidou
Keyword(s):  
Lipid Lowering ◽  
Risk Category ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
City Hospital ◽  
The Novel ◽  
Observation Study ◽  
Pcsk9 Inhibitor ◽  
Cardiovascular Assessment ◽  
Risk Categories

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The novel 2019 ESC/EAS Guidelines on lipids recommend a more intensive reduction on LDL-C across CV risk categories in comparison with the 2016 edition. Purpose This cross-sectional observation study aimed to assess whether patients on lipid lowering therapy were aware of the new set LDL-C goals and if they achieved them. Methods Patients, taking at the time any statin, attending the preoperative CV assessment outpatient clinic at a city hospital in northern Greece were invited to participate. Results In total 625 eligible patients (45.1% female) were enrolled during 2020 (mean age 67 ± 9 years old). Mean duration of statin prescription was about 10 years (9.7 ± 7 years). About two thirds of the patients (402, 64.3%) had established atherosclerotic cardiovascular disease (ASCVD) and the rest were allocated into CV risk categories: low (24, 10.8%), medium (135, 60.5%), high (59, 26.5%) and very high (5, 2.2%). The estimated 10-year risk of CV death was calculated using SCORE. The majority (552, 88.3%) of the patients reported lab tests at least biannually. The majority of the participants (556, 89.0%) were taking a statin as monotherapy of either low (17, 2.7%), medium (237, 37.9%) or high (302, 48.3%) potency. One tenth (65, 10.4%) were prescribed a combination of ezetimibe with a medium or high potency statin. Lastly, only four patients (0.6%) were prescribed a PCSK9 inhibitor. Less than a quarter of the participants (143, 22.9%) had achieved the recommended LDL-C levels. Approximately, one out of six patients with established ASCVD had a LDL-C lower than 55mg/dL (68, 16.9%), while only one out of three primary prevention patients (75, 33.6%) had reached the LDL-C levels recommended for their allocated risk category. As expected, the higher the potency of the statin, the higher the percentage of patients reaching the goal. Moreover, twelve out of the sixty five the patients (18.5%) on ezetimibe combination therapy achieved the LDL-C goal. Lastly, three of the four patients (75.0%) on a PCSK9 inhibitor had attained the desired LDL-C level. No information could be collected regarding why patients not reaching the goal were not offered a statin of higher potency and/or dosing, a combination with ezetimibe or a PCSK9 inhibitor, accordingly. Disturbingly enough, none of the patient was aware that the LDL-C goals recommended by scientific societies had been lowered in 2019, although 94 patients (15.0%) could recall discussing LDL-C goals with their physician. The majority of the patients (427, 93.0%) reported that they would like to know the recommended (personal) LDL-C goals. Conclusions Greek patients taking statins were overall unaware of the novel set LDL-C goals. Hardly acceptable attainment of the LDL-C goal was observed. The preoperative assessment visit can be used to monitor the guidelines implementation. Further research is warranted to assess the barriers that obstruct a satisfactory goal achievement. Abstract Figure. Patients achieving LDL-C goal

Abstract P195: Combination Therapy not the Intensity of Statin Therapy Improves LDL Goal Attainment in Clinical Practice

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Brett Victor ◽  
Lilian Ahedor ◽  
Longjian Liu ◽  
Dean G Karalis
Keyword(s):  
Clinical Practice ◽  
Combination Therapy ◽  
Statin Therapy ◽  
Goal Attainment ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
High Potency ◽  
Lipid Lowering Drug ◽  
Lowering Drug ◽  
The Impact

Background: In clinical practice most coronary heart disease (CHD) patients (pts) are not achieving their recommend LDL goal of < 70 mg/dL. We assessed the impact of statin dose and combination therapy in achieving optimal LDL levels in CHD pts. Methods: We conducted a retrospective analysis of outpatient electronic health records (EHR) from a large cardiology practice from September 2008 to September 2009. The most recent lipid profile, lipid-lowering medications and doses were extracted from the EHR. Statin potency was assessed based on the brand and dose of statin. Results: We identified 9,950 CHD pts; 59% were on a statin alone (SA), 27% on a statin + another lipid-lowering drug, 4% on no statin but on another lipid-lowering drug and 10% were on no lipid-lowering drugs. Only 37% of SA pts achieved an LDL < 70 mg/dL, but did so more often than pts on no statin but on another lipid-lowering drug (37 vs. 18%; p < 0.0001). Among SA pts, 70% were on moderate to high potency statins. The intensity of statin therapy did not improve LDL goal attainment. Among pts on combination therapy, 41% on statin + ezetimibe (S+E) and 46% on statin + niacin (S+N) achieved an LDL < 70 mg/dL (p = 0.01 and < 0.0001 vs. SA). Only 14% of pts were on S+E and 9% on S+N. Statin plus fibrate did not improve LDL goal attainment compared to SA (35 vs. 37%; p = 0.23). Few pts were taking bile acid sequestrants (< 0.5%). If pts were switched to a high potency statin LDL goal attainment of < 70 mg/dL would increase to 46% and would increase further to 65% with combination therapy. Conclusions: Most CHD pts in clinical practice do not attain an LDL < 70 mg/dL, even among pts on high potency statins. The number of CHD pts on no statin is high. The combination of statin plus either ezetimibe or niacin is the most effective regimen to achieve an LDL < 70 mg/dL; however these drug combinations are used infrequently in clinical practice. Combination lipid-lowering therapy is needed to improve LDL goal attainment in CHD pts.

Genetic testing for familial hypercholesterolemia: Impact on diagnosis, treatment and cardiovascular risk

2019 ◽  
Vol 26 (12) ◽  
pp. 1262-1270 ◽  
Author(s):  
Seohyuk Lee ◽  
Leo E Akioyamen ◽  
Sumayah Aljenedil ◽  
Jean-Baptiste Rivière ◽  
Isabelle Ruel ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Confidence Interval ◽  
Familial Hypercholesterolemia ◽  
Odds Ratio ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Increased Risk ◽  
The Impact

Aims Familial hypercholesterolemia (FH) is the most common genetic disorder in medicine, with a prevalence of 1/250. Affected individuals have elevated low-density lipoprotein cholesterol (LDL-C) and an increased lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The diagnosis of FH is based on algorithms that include LDL-C levels, physical manifestations, family history of high LDL-C and premature ASCVD, and, more recently, genetic testing. We sought to determine the impact of genetic testing on the: 1) diagnosis of ‘definite familial hypercholesterolemia’, 2) initiation and adherence of lipid-lowering therapy and 3) risk of ASCVD. Methods We performed a systematic review and meta-analysis, pooling odds ratios and 95% confidence intervals for ASCVD from studies comparing risk estimates in individuals harboring FH-causing variants and unaffected individuals. Results After screening 3304 unique publications, 56 studies were included in the analysis. 1) Genetic testing provided confirmation of FH in 28–80%, over clinical criteria alone, depending on the diagnostic algorithm and the method of analysis. In two large population-based studies comprising 76,751 individuals, an FH-causing variant was identified in only 1.7–2.5% of subjects with an LDL-C > 4.9 mmol/L (190 mg/dL). 2) A confirmed molecular diagnosis increased lipid-lowering therapy adherence (five studies, n = 4181 definite FH). 3) Loss-of-function variant of the LDLR were at a markedly increased risk of myocardial infarction (odds ratio 6.77, 95% confidence interval 4.75–9.66), and patients with a milder (hypomorphic) pathogenic LDLR change had a 4.4-fold increase in risk (odds ratio 4.4, 95% confidence interval 2.34–8.26), compared with controls. Conclusion DNA sequencing confirms the diagnosis of FH but has a poor yield in unselected patients whose sole criterion is an elevated LDL-C. Initiation and adherence to treatment is improved. The risk of ASCVD is 4.4- to 6.8-fold increased in patients with an FH-causing variant compared with controls, depending on the severity of the DNA change.

Sign in / Sign up

Export Citation Format

Share Document