Changing cilazapril to an alternative blood pressure medication in 2023

A 60-year-old physiotherapist with mild hypertension, diet-controlled type 2 diabetes and a previous coronary stent has been managed with cilazapril 5mg each morning for eight years, along with rosuvastatin 40mg and aspirin EC 100mg each morning.

He has also been encouraged to maintain good “lifestyle” habits to lower his blood pressure: exercise more, maintain a reasonable weight, eat salt in moderation, drink alcohol sensibly and not smoke (he has never smoked). He was also advised to eat a Mediterranean-style diet, with your general advice being “everything in moderation, but above all, do not put on weight”.

When he comes to see you, his BP is 135/85mmHg. His general examination is unremarkable, although his BMI is 29kg/m². You arrange for an electrocardiogram to be taken and discuss the current situation.

1. What does the ECG show?
2. Why is cilazapril being withdrawn by Pharmac?
3. Which ACE inhibitors and angiotensin receptor blockers (ARBs) are now funded in New Zealand?
4. Is ramipril a good option?
5. What unique opportunity is currently present for treating hypertension?
6. What are the potential benefits of ARBs over ACE inhibitors for the management of hypertension?
7. What is the BP treatment target in 2023?
8. How will you reach the BP treatment target for your patient?

Ramipril significantly reduced the rates of death, myocardial infarction or stroke

1. The ECG shows sinus rhythm, a normal axis and a rate of 63 beats per minute. It is normal, as for most patients with hypertension.

2. Most countries use ACE inhibitors other than cilazapril. In New Zealand, slightly more than half of the 500,000 annual ACE inhibitor prescriptions have been for cilazapril, due to Pharmac manoeuvres in 2002, which made cilazapril and quinapril the nation’s only funded ACE inhibitors.

Gradually, other ACE inhibitors have been funded. However, as most countries do not use cilazapril, the only manufacturer left making it will stop, and cilazapril will not be available in New Zealand by the end of 2023.

3. Current Pharmac funded ACE inhibitor drugs for adult patients with hypertension are cilazapril, quinapril, lisinopril, perindopril, enalapril, and from 1 December 2022, ramipril. Ramipril is available in capsules of 1.25mg, 2.5mg, 5mg and 10mg. These capsules cannot be cut in half. Losartan and candesartan are funded ARBs.

4. Ramipril is a very welcome addition to the funded ACE inhibitors and might be one of the best choices for hypertension treatment. It is widely used overseas, especially in Europe. The previous lack of funded ramipril in New Zealand has been disappointing. ACE inhibitors are thought to retard the progression of atherosclerosis.

Ramipril was used in the first Heart Outcomes Prevention Evaluation (HOPE) trial, published in 2000. In this study, 9300 high-risk patients (age 55 or older) who had evidence of vascular disease plus one other cardiovascular risk factor, and who were not known to have a low ejection fraction or heart failure, were randomly assigned to receive ramipril 10mg or placebo for a mean of five years. The cohort included 47 per cent with treated hypertension and 38 per cent with diabetes.¹

Ramipril significantly reduced the rates of death, myocardial infarction or stroke (14 per cent versus 17.8 per cent, p<0.0001). Treating 1000 patients for four years prevented 150 events in approximately 70 patients.¹

5. It is perfectly reasonable to simply change a patient from cilazapril to another funded ACE inhibitor. However, this could also be an opportunity to move to the equally efficacious, but generally better tolerated, ARB medications for hypertension management.

6. A 2018 comprehensive review of ACE inhibitors and ARBs used in hypertension management, published in the Journal of the American College of Cardiology, concluded that ARB medicines are a better and safer option than ACE inhibitors.²

The review article states: “Given the equal outcome efficacy but fewer adverse events with ARBs, risk-to-benefit analysis in aggregate indicates that at present there is little, if any, reason to use ACE inhibitors for the treatment of hypertension.”²

7. The 2023 BP target is an average of 130/80mmHg or below, without provoking recurrent postural hypotension.

8. You elect to change the cilazapril 5mg to ramipril 5mg, with a plan to reassess his BP at two and six weeks. If the BP is still high, you will increase to ramipril 7.5mg, then to 10mg. If still high, you will then add either chlorthalidone 12.5mg daily or indapamide 2.5mg each morning. This would be a good combination. Hence, your patient would then take two pills each morning.

You plan to check the creatinine and electrolytes at your two-week BP review and also two weeks after any dose increase, or after adding the diuretic, and then every three to six months in the first year. You then plan to check the creatinine and electrolytes on an annual basis.

You are aware that some patients have a significant fall in the serum sodium level, or develop a high potassium level, or have significant renal impairment with ACE inhibitors, ARBs or diuretic medicines.

Details have been changed to protect patient confidentiality

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