Vigorous LDL cholesterol targets now set for secondary prevention of CVD

A 48-year-old dairy owner comes in for review. He has been under significant stress over the past two years as he continued to operate his corner dairy during the COVID-19 lockdowns. He has felt increasingly worried since his first heart attack, which occurred two months ago.

He was admitted to the local hospital with a non-ST-elevation myocardial infarction (non-STEMI), where he was managed with a cardiac angiogram and stent to a severe proximal left anterior descending artery stenosis. Significant calcification was seen within his coronary arteries. Fortunately, his peak troponin T level was only 410ng/L, and his echocardiogram showed no left ventricular impairment.

He had been discharged on tablets to be taken each morning: aspirin EC 100mg, bisoprolol 1.25mg, perindopril 4mg and atorvastatin 80mg. In addition, ticagrelor 90mg was to be taken twice daily for one year.

He is attending the rehabilitation classes, which are of help, but he is really concerned about the potential for him to die and leave his wife and four daughters with little local family support. He and his wife emigrated from New Delhi some 14 years before, to give more opportunities to their children, all of whom were born in New Zealand.

Before his heart attack, he had been well – he jogged three days a week and did not smoke or take any medications. He is slender, with a normal HBA1c level. His family are strict vegetarians. He has no past history, except for a mild sinusitis in the winter months, and he has no known allergies.

However, his family history is of his father having died from a heart attack at age 61, and his paternal grandfather also died from a heart attack at age 63.

Interestingly, his own cardiovascular risk had been calculated six months before his non-STEMI at 1.6 per cent over five years, as assessed by the NZ Primary Prevention Equations from the PREDICT study. Then, he had a systolic blood pressure of 115mmHg, a cholesterol level of 5.0mmol/L, a high-density lipoprotein cholesterol level of 1.5mmol/L, a low-density lipoprotein cholesterol level of 3.0mmol/L and triglycerides level of 1.1mmol/L.

You had wanted him to start statin medication, particularly in view of his family history. However, he had not wanted to take medications.

His current blood tests show a cholesterol level of 3.4mmol/L and an LDL cholesterol level of 1.9mmol/L. An electrocardiogram is performed by your practice nurse.

1. What does the ECG show?

2. Which patients are now eligible for funded rosuvastatin?

3. What very major change has occurred with Pharmac’s recent funding of rosuvastatin for some patients?

4. How might you improve your patient’s cardiovascular outcome?

5. Subsequent tests show a cholesterol level of 3.2mmol/L with an LDL cholesterol level of 1.7mmol/L. What further medication change might you make?

6. Which guidelines set these low targets for LDL cholesterol in the secondary prevention of vascular disease?

For the secondary prevention of vascular disease…there are two options for funding

1. The ECG shows sinus rhythm, a normal axis and a rate of 72 beats per minute. It is within normal limits. This is often the situation after a non-STEMI presentation.

2. In 2005, rosuvastatin was not funded when first considered by Pharmac, but it was still fairly widely used by patients who could pay for it, at about $60 per month. Many patients find rosuvastatin causes less myalgia, possibly due to it being hydrophilic, with less tissue absorption and, hence, fewer adverse effects than the lipophilic atorvastatin.

Now, some 16 years later, from 1 December 2021, Pharmac has designed Special Authority criteria to fund rosuvastatin. Arguably, the most important feature of this change has been the recognition that a lower LDL cholesterol target should be achieved in New Zealand patients than has previously been funded by Pharmac.

For the primary prevention of vascular disease, there are two options for funding of patients: some patients with “cardiovascular disease risk” (defined) and some patients with “familial hypercholesterolaemia” (defined) are now eligible. Discussion of this is outside the scope of this article.

For the secondary prevention of vascular disease, such as your patient, there are also two options for funding:

• The first option is for patients with “established cardiovascular disease”, which is defined as one of three groups – patients with proven coronary artery disease, proven peripheral artery disease, or who have experienced an ischaemic stroke. However, in addition, patients must have an LDL cholesterol which “has not reduced to less than 1.4mmol/L with treatment with the maximum tolerated dose of atorvastatin and/or simvastatin”.
• The second option is for patients who have experienced “recurrent major cardiovascular events”, which is defined as one of four groups: myocardial infarction, ischaemic stroke, coronary revascularisation or hospitalisation for unstable angina in the last two years. In addition, patients must have an LDL cholesterol which “has not reduced to less than 1.0mmol/L with treatment with the maximum tolerated dose of atorvastatin and/or simvastatin”.

3. With the funding of rosuvastatin, there is a recognition that patients will benefit from lower LDL cholesterol levels than were previously funded. In fact, it has been known for many years that lowering LDL cholesterol reduces the risk of atherosclerotic cardiovascular disease proportional to the reduction in LDL cholesterol.

Reduction in LDL cholesterol can be achieved with several medicines: statins and ezetimibe, bile-acid resins and fibrates (both rarely used and of limited benefit), as well as newer agents, such as bempedoic acid (not available or funded in New Zealand) or the PCSK9 inhibitors (eg, alirocumab, which is available but not funded in New Zealand).

The new Special Authority form accepts the funding of an LDL cholesterol target of <1.4mmol/L for all patients with established vascular disease, and an LDL cholesterol target of <1.0mmol/L for those at the very highest risk, with a recurrent vascular event within two years of the prior event.

4. Your patient now qualifies for a change from atorvastatin to rosuvastatin. The highest rosuvastatin dose (40mg) should lower the LDL cholesterol level by approximately 63 per cent, which is an extra 8 per cent compared with the top atorvastatin dose (80mg), which will lower the LDL cholesterol level by about 55 per cent.

5. His LDL cholesterol is now 1.7mmol/L. Unfortunately, he does not qualify for funding for the addition of ezetimibe, which would further lower the LDL cholesterol by approximately 20 per cent. For ezetimibe funding, Pharmac requires the LDL cholesterol level to be ≥2mmol/L on the highest tolerated dose of atorvastatin. Some patients now pay for ezetimibe treatment at about $45 dollars per month. However, your patient is unable to afford this.

6. The 2019 European guidelines for the management of dyslipidaemias set these vigorous targets,¹ which are now used by Pharmac. This is a very significant, and welcome, change in approach for New Zealand patients.

Details have been changed to protect patient confidentiality

Chris Ellis is a consultant cardiologist at The Heart Group and Mercy Hospital, Auckland