Preventing Cardiovascular Disease : A Case Study

By: Pharma Tips | Views: 4114 | Date: 17-Dec-2011

A 51 year old Caucasian man is reviewed for the management of hypertension. His body mass index is 26kg/m2, he has never smoked, and does not have diabetes. He has a history of asthma and takes Qvar by inhalation. His brother had a ST-segment elevation myocardial infarction at the age of 53 years.

case study: preventing cardiovascular disease

A 51 year old Caucasian man is reviewed for the management of hypertension. His body mass index is 26kg/m2, he has never smoked, and does not have diabetes. He has a history of asthma and takes Qvar by inhalation. His brother had a ST-segment elevation myocardial infarction at the age of 53 years.


Fasting lipid profile: total cholesterol 6.8mmol/litre, HDL cholesterol 1.2mmol/litre, LDL cholesterol 4mmol/litre, triglycerides 3.5mmol/litre.

Despite appropriate modifications to diet, alcohol intake, and exercise, his blood pressure (after repeat measurement over 8 weeks) is raised at 174/102mmHg. There is no evidence of end organ damage or left ventricular hypertrophy. His U + Es, renal and liver function are normal.

What is this patient's 10-year risk of cardiovascular disease?
The Cardiovascular Risk Prediction Charts in the glossy pages at the back of the print version of BNF 57 predict that his cardiovascular disease (CVD) risk is >20% over the next 10 years. This risk will be increased by a factor of 1.3-1.5 because he has a male first-degree relative who developed premature coronary heart disease before the age of 55 years. The raised triglyceride concentration (>1.7mmol/litre) may increase his risk further.

How should this patient's hypertension be treated?
When blood pressure is persistently above 160/100mmHg, the Cardiovascular Risk Prediction Charts recommend antihypertensive treatment regardless of the CVD risk. The prescribing notes on Hypertension in section 2.5, BNF 57, state that response to drug treatment for hypertension may be affected by the patient's age and ethnic background. Either an ACE inhibitor or an angiotensin-II receptor antagonist is the most appropriate initial treatment in this patient under 55 years of age. A target systolic blood pressure <140mmHg and diastolic blood pressure <90mmHg is suggested. If a single antihypertensive drug is inadequate, then a thiazide diuretic or a calcium channel blocker can be added.

What other measures should be taken to reduce his CVD risk?
Despite the family history, his total cholesterol and LDL cholesterol are not high enough to suggest familial hypercholesterolaemia. Secondary causes of hyperlipidaemia should be excluded by checking the fasting blood glucose and thyroid function tests, even if there are no relevant symptoms.

The prescribing notes on Hypertension in section 2.5, BNF 57, recommend aspirin 75mg daily in those with a 10-year CVD risk of 20% or more and aged over 50 years. Unduly high blood pressure must be controlled before aspirin is given to avoid the risk of intracranial haemorrhage. A statin is also recommended in those with a 10-year CVD risk of 20% or more. If this patient without familial hypercholesterolaemia is started on an appropriate dose of a statin (e.g.simvastatin 40mg daily), there is no specific target for serum cholesterol and no need to measure the cholesterol concentration again for the primary prevention of CVD, unless indicated clinically.
The patient agrees to start ramipril 1.25mg daily and simvastatin 40mg daily.

Which fruit juice should this patient be advised to avoid?
Drug Interactions in Appendix 1, BNF 57, states that the plasma-simvastatin concentration is increased by grapefruit juice and that concomitant use should be avoided. This is classified as a hazardous drug interaction because there is an increased risk of myopathy.
2 months later, the patient develops uncomplicated community-acquired pneumonia. He has a history of immediate hypersensitivity to penicillin.

Which antibiotic should be started?
Table 1, section 5.1, BNF 57, recommends erythromycin, clarithromycin, or azithromycin for the treatment of uncomplicated community-acquired pneumonia in patients with penicillin allergy. Drug Interactions in Appendix 1, BNF 57, shows that there is an increased risk of myopathy when either clarithromycin or erythromycin is given with simvastatin, and concomitant use should be avoided. Azithromycin is not expected to interact with simvastatin and can be used. If it is necessary to use clarithromycin or erythromycin, simvastatin should be stopped temporarily until the course of antibiotic is completed.

His liver function tests are measured 3 months after starting simvastatin, and the alanine aminotransferase (ALT) concentration is 80 international units/litre (5-40).

Should simvastatin be discontinued?
The ALT may rise as a result of the lipid lowering effect of the statin. Statins can rarely cause hepatitis and jaundice. The prescribing notes on Statins in section 2.12, BNF 57, recommend that simvastatin should be discontinued if the ALT increases to more than 3 times the upper limit of the reference range. This patient's ALT concentration is not a cause for concern. However, his liver function tests should be checked earlier than usual, in 3-6 months time.

At a subsequent visit, the patient complains of mild muscle pain that is not interfering with his daily activities. His creatine kinase is 390 international units/litre (24-195).

What action should be taken?
Muscle aches and pain can occur without any rise in creatine kinase, and may start several weeks after commencing treatment. The prescribing notes on Statins in section 2.12, BNF 57, advise that it is not necessary to stop the statin unless the symptoms are severe or the creatine kinase is more than 5 times the upper limit of normal. The patient should be reviewed again after 4 weeks to enquire about his symptoms and his creatine kinase should be rechecked to see if it is rising. Further monitoring is then guided by the outcome of that visit.
1 year later the patient is admitted to hospital with unstable angina. He stopped taking simvastatin 6 months earlier because his brother's statin was discontinued after his brother became depressed and suffered sleeping problems.

The patient is discharged from hospital taking:
simvastatin 40mg daily, diltiazem modified-release 180mg daily, aspirin 75 mg daily, clopidogrel 75mg daily, ramipril 5mg once daily, Qvar 100 micrograms twice daily by inhalation
Today his total cholesterol concentration is 5.3mmol/litre. He is taking his medication.

 What adjustments can be made to his lipid-regulating drug therapy?
Doses of lipid-regulating drugs may be adjusted for the secondary prevention of cardiovascular events if a total cholesterol concentration of less than 4mmol/litre is not achieved or a LDL-cholesterol concentration of less than 2mmol/litre is not achieved with initial treatment. There is a possible increased risk of myopathy when simvastatin is given with diltiazem. The monograph for Simvastatin, BNF 57, advises that the dose of simvastatin should not exceed 40mg daily when it is used with diltiazem. In order to achieve target cholesterol concentrations, the use of an additional lipid-regulating drug such as ezetimibe or colestyramine should be considered under specialist advice. There is an increased risk of rhabdomyolysis when ezetimibe is used with a statin.


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