To assess the prevalence of LDL-C >1.8 mMol/L in a subgroup of very high risk patients with ASCVD, who remain at a very high-residual risk for ACS, despite treatment with high-intensity statins in combination with ezetimibe. This subgroup of very…
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Study endpoint:
- Proportion of patients with LDL-C >1.8 mMol/L during stepwise incremental
lipid modifying therapy with respectively a statin, statin + ezetimibe.
Secondary outcome
Study parameters:
- Medical history: ASCVD; T2DM; developing allergies or intolerances to
alirocumab, ezetimibe or statins
- LDL-C plasma levels at each consecutive step
- Optional: non-HDL plasma levels at each consecutive step
- Prescription preference for atorvastatin or rosuvastatin to achieve "high
intensity statin therapy" (HIST)
- % of patients that tolerates sustained HIST on atorvastatin or on rosuvastatin
- % of patients that does NOT tolerate HIST with atorvastatin, but does
tolerate HIST when switching to rosuvastatin
- % of patients that does NOT tolerate HIST with rosuvastatin, but does
tolerate HIST when switching to atorvastatin
- % of patients that reaches target LDL <=1.8 mMol/l while NOT on HIST
- % of patients that compared to baseline achieves 50% LDL reduction ([1]
patients not on HIST; [2] patients on HIST; [3] patients on HIST + ezetimibe;
[4] patients on HIST + ezetimibe + alirocumab)
- % of patients that compared to baseline achieves 50% LDL reduction AND LDL
>1.8 OR LDL <=1.8 (patient-groups 1-4)
- non-HDL-C levels in patients with LDL <=1.8 mMol/l and in patients with LDL
>1.8 mMol/l, with or without alirocumab
- Non-HDL-C levels in patients with LDL <=1.8 mMol/l ánd triglycerides >2
mMol/l, with or without alirocumab
- Prescription preference when atorvastatin 1dd40mg does not meet the LDL-target
- Creatinine kinase in patients with statin intolerance
- % of patients with an LDL <=1.8 mMol/l after one year on HIST
- % of patients with an LDL <=1.8 mMol/l after one year on HIST + ezetimibe
- % of patients with an LDL <=1.8 mMol/l after one year on HIST + ezetimibe +
alirocumab
Components of the TIMI Risk Score for Secondary Prevention (TRS 2_P):
- CHF, hypertension, age (>=75 yr), diabetes, prior stroke, prior CABG,
peripheral artery disease, eGFR <60, smoking [12]
Background summary
Hyperlipidaemia is one of the important risk factors in developing
cardiovascular disease. LDL-C of <1.8 mMol/L or a reduction of at least 50% is
recommended for very high risk patients. Different classes of lipid- modifying
drugs are available. In patients with hypercholesterolaemia or combined
hyperlipidaemia, statin mono-therapy is first choice therapy. In a large
proportion of patients on statin mono-therapy, however, therapeutical target
LDL-C levels are not reached, and ezetimibe should be added. If target LDL-C
levels are unmet despite statin-ezetimibe combination therapy, a PCSK9
inhibitor (PCSK9-i) may be added.
In real world care, the proportion of patients with atherosclerotic
cardiovascular disease (ASCVD) not reaching target LDL-C levels despite
consecutive therapy with statin mono-therapy, statin + ezetimibe or statin +
ezetimibe + PCSK9-i is unknown.
In the Netherlands and many other European countries, reimbursement of the
PCSK9-i is restricted to a subgroup of *very high risk patients* not reaching
target LDL-C levels despite statin-ezetimibe combi-therapy.
In the present study, the prevalence of very high risk patients with ASCVD who
remain at very high-residual risk for an acute coronary syndrome (ACS), defined
as an LDL-C >1.8 mmMol/L (or non-HDL >2.6 mMol/l) will be analysed by a
prospective, stepwise implementation of high intensity statin mono-therapy,
followed by high intensity statin + ezetimibe combination-therapy if LDL-C
still >1.8 mMol/L after 4 weeks of statin mono-therapy. Lipid levels will be
measured 4 weeks after initiation of each step. A subset of patients whose
LDL-C remains >1.8 mMol/L despite this intervention, will be treated with the
PCSK9 inhibitor Alirocumab, 75 or 150 mg, and the efficacy of this therapy will
be measured by lipid levels after 4 weeks of therapy.
Study objective
To assess the prevalence of LDL-C >1.8 mMol/L in a subgroup of very high risk
patients with ASCVD, who remain at a very high-residual risk for ACS, despite
treatment with high-intensity statins in combination with ezetimibe. This
subgroup of very high risk patients is defined as patients with a history of
ASCVD and/or diabetes mellitus type II (T2DM), and a new type I ST elevation or
non-ST elevation myocardial infarction ([N]STEMI).
Study design
A prospective, open label, stepwise cohort study of consecutive patients
admitted for type I STEMI or NSTEMI, characterized by a rise and/or fall of
troponin with at least one value above the 99th percentile upper reference
limit, and a history of ASCVD and/ or T2DM.
Patients with an LDL-C<=1.8 mMol/L at baseline will be registered, but not
included in the study. All patients with an LDL-C>1.8 mMol/L, with or without
therapy with statins and/or ezetimibe at baseline, will be treated with
high-intensity statin therapy (i.e., atorvastatin >=40 mg or rosuvastatin >=20 mg
or the maximum tolerated dose of a statin) for a period of 4 weeks. Lower
statin doses are acceptable for patients with a valid reason for not using high
intensity doses (advanced age and high frailty score, low body weight,
drug-drug interaction). Patients with known statin-attributed muscle symptoms
or who develop statin-attributed muscle symptoms during the study will be
treated following the therapeutic flow-chart for management of patients with
statin-associated muscle symptoms of the EAS Consensus Panel.
After 4 weeks, lipids are measured. If LDL-C >1.8 mMol/L, ezetimibe 10 mg is
added on top of statin therapy. Patients with documented statin intolerance to
at least three different statins, as defined by the EAS Consensus Panel, will
be treated with 10 mg ezetimibe mono-therapy. Four weeks later lipids are
measured, and if LDL-C >1.8 mMol/L, alirocumab will be added on top of current
treatment with a statin and ezetimibe, in accordance with the following
dosing-schedule:
• if 1.8alirocumab 75 mg, or alirocumab 150 mg will be added
• if 2.6<=LDL-C<3.6 mMol/L, at the investigator*s discretion alirocumab 75 mg or
alirocumab 150 mg will be added
• if LDL-C>=3.6 mMol/L, alirocumab 150 mg will be added
Two weeks after the second dose of alirocumab, lipids are measured.
Intervention
Patients are treated according to cholesterol treatment guidelines. The choice
of PCSK-9 inhibitor is directed by the protocol. When a PCSK-9 inhibitor needs
to be prescribted, alicobumab is the drug of choice.
There are no other interventions in this study,
Study burden and risks
There are no additional risks or burden for study participants.
The burden for the patient is limited to the drawing of blood samples (at 4, 8
and 12 weeks and 12 months), all of which are standard of care. For this study
no extra visits or physical examinations are required.
Moreelsepark 1
Utrecht 3511 EP
NL
Moreelsepark 1
Utrecht 3511 EP
NL
Listed location countries
Age
Inclusion criteria
- Admission because of type I (N)STEMI, and
- History of ASCVD (i.e., cerebrovascular disease (Transient ischemic attack,
cerebral infarction, amaurosis fugax, retinal infarction), Coronary artery
disease (unstable Angina pectoris, MI, ACS, coronary revascularization
(coronary angioplasty or surgical procedure for coronary bypass)), Peripheral
artery disease (Symptomatic and documented obstruction of an distal extremity
artery or surgical operation (percutaneous transluminal angioplasty, bypass or
amputation), and/or a history of T2DM.
Exclusion criteria
- Age <18 years
- Age >70 years ánd a Clinical Frailty Score >3.
o To measure the frailty score, the validated Dutch translation of the Canadian
Study of Health and Aging (CSHA) Clinical Frailty Scale will be used (table 2)
- Pregnancy and lactating women
- Known intolerance for alirocumab
- Active PCSK9-i therapy
- Participation in lipid modifying drug trials
- Life expectancy <1 yr.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL66879.100.18 |