To beta-blocker, or to ivabradine? To nitrate, or CCB? Best practice angina update - selecting agents that suit the patient. Case studies guide drug choices in the face of multiple comorbidities and precipitants.
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Case study 1
Patient: 60-year-old female with hypertension and ischaemic heart disease
- Patient presents with persistent stable angina (NYHA II), on optimal medical therapy in respect of secondary prevention
- She is on bisoprolol 5mg daily and sublingual nitrates as needed.
- Blood pressure: 110/75mmHg
- Pulse: 79bpm in sinus rhythm.
Question 1. Which of the following anti-anginal treatments would be appropriate, considering her clinical profile?
View Expert Comment »
Adding ivabradine would be the best next step in the treatment of this patient. Heart-rate-lowering agents, such as beta-blockers, non-dihydropyridine CCBs (diltiazem and verapamil) and ivabradine are the preferred drugs when the heart rate is >70bpm. Ivabradine can be safely and usefully added to beta-blockers when heart rate remains elevated (≥70bpm) but combining ivabradine with diltiazem or verapamil is clearly contraindicated. Vasodilators such as dihydropyridine CCBs and nitrates are less attractive in this patient, because they might increase heart rate. The other anti-anginal drugs can be co-administered, when necessary.
Combining beta-blockers with diltiazem or verapamil is, however, not recommended owing to the risk of the patient’s developing high-degree atrioventricular block. While no consensus exists on an optimal heart-rate target, the European Medicines Agency recommends that heart-rate-lowering agents should be administered when the heart rate is >70bpm, but that the dose should be decreased if it remains <50-55bpm.
Case study 2
Patient: 50-year-old female with established coronary artery disease
Patient with established coronary artery disease (previous coronary angioplasty and stents) and well-controlled type 2 diabetes mellitus presents with effort intolerance due to classic angina pectoris.
- Blood pressure: 127/70mmHg
- Pulse: 65bpm in sinus rhythm.
Question 2. Which of the following anti-anginal drugs would be preferred, based on the history of diabetes and established coronary artery disease?
View Expert Comment »
All of the listed drugs can be selected singly or in combination, as diabetes is often associated with coronary atherosclerosis and is considered an ischaemic equivalent. Patients with diabetes have a more severe ischaemic burden, both symptomatic and silent. Treatment of chronic stable angina in these patients requires drugs with a positive or neutral metabolic action.
Traditionally, beta-blockers were considered to facilitate new-onset diabetes and aggravate glycaemic control. For these reasons, beta-blockers are to be avoided in patients with diabetes and chronic stable angina. However, newer vasodilating beta-blockers, such as carvedilol and nebivolol, have been reported to improve insulin sensitivity, overcoming the metabolic limitations of traditional beta-blockers. All the other anti-anginal drugs can be used to ameliorate the ischaemic burden.
Case study 3
Patient: 55-year-old male with known ischaemic heart disease
- The patient has known ischaemic heart disease and presents with evidence of left ventricular dysfunction and heart failure (left ventricular ejection fraction 37%)
- He has a background of hypertension and was successfully revascularised by his cardiologist approximately 12 months previously
- His dominant symptom is angina pectoris on minimum effort.
Question 3. What would be the preferred anti-anginal therapy for this patient?
View Expert Comment »
The recommended approach is to introduce beta-blockers with ivabradine. When chronic stable angina is present in patients with left ventricular systolic dysfunction with or without overt heart failure, the overwhelming evidence-based indication is to use those beta-blockers which can reduce chronic stable angina and, at the same time, effectively reduce cardiovascular morbidity and mortality. These beneficial effects seem to be directly correlated with the heart-rate-lowering effect of some beta-blockers; therefore, beta-blockers with intrinsic sympathomimetic activity (pindolol, penbutolol sulphate and acebutolol hydrochloride) should be avoided.
If the heart rate remains elevated (>70bpm) despite optimal beta-blockade, ivabradine should be considered. This is based on the results of the SHIFT trial, which showed a further prognostic benefit of adding ivabradine to evidence-based optimal therapy in patients with overt heart failure and reduced ejection fraction. Similar benefits were also seen in the subgroup with chronic stable angina. Diltiazem and verapamil should be used with caution in this subset of patients because they can worsen left ventricular dysfunction.
Case study 4
Patient: 60-year-old male with known ischaemic heart disease
- Patient presents with new onset atrial fibrillation (AF) aggravating his anginal symptoms
- Patient’s other cardiovascular risk factors are controlled on treatment.
Question 4. Which of the following drugs/drug classes would be preferred in his case?
View Expert Comment »
The recommended approach is to add a beta-blocker and/or a non-dihydropyridine CCB.
AF might be aggravating anginal symptoms owing to an increased heart rate; therefore, agents such as beta-blockers and non-dihydropyridine CCBs should be preferred when this comorbidity is present. Conversely, because of its selectivity for I channels, ivabradine is ineffective in patients with AF and might even increase the incidence of the arrhythmia. Ivabradine is therefore contraindicated in patients with chronic stable angina and AF. Dihydropyridine CCBs and nitrates should be avoided because they can further increase heart rate, whereas the non-dihydropyridine CCBs can be added to beta-blockers to ensure improved control of the symptoms of chronic stable angina.
Question 5. In patients with angina, perception of the symptoms is:
Question 6. Which of the following statements is correct? The main cause of angina is:
Question 7. When deciding on initial anti-anginal therapy, which of the following comorbidities are important to consider before prescribing therapy?
Question 8. Current European guidelines categorically recommend anti-anginal therapies as first-line (beta-blockers, CCBs, short-acting nitrates) or second-line (long-acting nitrates, ivabradine), based on improved efficacy and cardiovascular outcomes associated with first-line therapy options.
Question 9. Ivabradine was shown in the SHIFT study to add further benefit to patients with overt heart failure and reduced ejection fraction already on evidence-based optimal therapy.
Question 10. The European Medicines Agency recommends that anti-anginal (heart rate lowering) agents should: