Pharmacological Basis Of Drug Therapy Biology Essay


This Report will consider Coronary Heart Disease(CHD) with particular focus on the underlying cause, diagnosis and management of a patient with stable angina that goes on to require heart surgery ,as this is relevant to the hospital case. CHD is described by the British Heart Foundation as "Scotlands biggest killer" with approximately 9,000 people dying in Scotland each year from CHD, affecting 1 in 5 males and 1 in 6 females. [1] Over the past ten years there have been reductions in the amount of heart related deaths, particularly in the over 65 age group. [2] Smoking is considered to be one of the biggest risk factors for heart disease and since the arrival of the smoking ban in Scotland in 2006, the number of people smoking has decreased resulting in less CHD related deaths. The improvements in risks factors as well as the improvement of primary and secondary preventative measures that are now at the disposal of healthcare professionals, contribute to the reduction in deaths that are attributed to heart disease. It is important to consider that smoking is not the only risk factor for CHD and measures have to be put in place to address all contributing factors for CHD to improve the health and wellbeing of people in the UK.

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The underlying cause of CHD is the development and progression of atherosclerosis. Atherosclerosis is a progressive condition that begins in youth and continues throughout life. As time passes, the extended deposits of fat, cholesterol and smooth muscle cells that line the walls of the coronary arteries, thicken and harden to form a mass, leading the formation of an atheroma. These deposits can develop into plaques and can rupture causing thrombosis which can lead to a clot. If there is a clot, blood flow to the heart becomes reduced and the extent of the clot or occlusion within the lumen of the coronary artery will determine the severity of heart disease. [3] Risk factors play a very important role in the development of this condition and have been well documented over the years, highlighting the importance of addressing lifestyle issues and ensuring that pharmacological intervention continues to improve. Patient`s should be treated with appropriate medication to delay the development of atherosclerosis and coronary heart disease.

A detailed clinical assessment should be carried out initially in patients who are potential candidates for angina. This includes: taking a thorough medical and family history check, blood pressure monitoring, fasting blood glucose testing for the possibility of Type 2 diabetes and a cholesterol test. [4] It is also important to establish the severity, location and duration of the chests pains to provide supporting evidence that CHD is the underlying cause and to help healthcare professionals provide appropriate medical treatment. [5] Other tests carried out routinely for the prognosis of stable angina are an ECG, exercise tolerance test and coronary angiogram. [6] These tests, together with the initial clinical assessment can provide enough evidence to confidently diagnose CHD.

The pharmacological management of a patient with stable angina aims to alleviate symptoms and this section of the report will only consider the mechanisms of action of the key drugs that this patient was on and supporting evidence justifying their use will be considered in the next section. As this patient also received heart surgery, this will also be covered in the next section. The key drugs were as follows:

Bisoprolol - Beta blockers play a pivotal role in the treatment of stable angina and function by reducing the workload of the heart, improving supply and demand of oxygen to the heart and by reducing blood pressure as a result of reducing cardiac output. Their action is due to their ability to competitively inhibit the binding of adrenaline and noradrenaline to the beta 1 receptors in the heart. [7] This group of drugs remains first line in the treatment of stable angina.

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Aspirin - Aspirin has many indications, some of which include: anti inflammatory, anti-pyrexia and as anti-platelet agent. The pharmacological effects of aspirin as an antiplatelet agent are down to its ability to inhibit the cyclo-oxygenase enzyme(COX) primarily COX 1. The COX 1 enzyme, once activated, leads to the production of Thromboxane A2, which promotes platelet aggregation and thrombus formation. This can lead to a reduction in blood flow and can sometimes lead to clot depending on the degree of occlusion. Thus by inhinbting the production of TxA2 , Aspirin produces an anti-platelet effect. [8] Aspirin is widely used in primary and secondary prevention of cardiovascular events.

GTN spray - GTN sprays are used to alleviate chest pain and work by dilating veins(reducing pre-load) and arteries(reducing after load) which leads to an increase in coronary blood flow and an increase in oxygen supply to the heart muscle. [9] 

Lisinopril - Lisinopril is an angiotensin -converting -enzyme (ACE) inhibitor that works by preventing the conversion of angiotensin 1 to angiotensin 2. Angiotensin 2 is a potent vasoconstrictor and thus by preventing its production causes a reduction in arteriolar resistance and an increase in venous capacity. These benefits result in a reduction in blood pressure. [10] 

Simvastatin- Simvastatin is an HMG-CoA reductase inhibitor. HMG- CoA reductase is an enzyme that is responsible for the synthesis of LDL cholesterol and so by inhibiting its production, reduces LDL cholesterol levels and delays the progression of atherosclerosis, which is a major contributing factor for CHD. Similarly to aspirin, statins are routinely prescribed in patients presenting with a cardiovascular risk of greater than 20% in a ten year period.


Before looking at the evidence to support or refute the drugs chosen to treat this patient, it is important to mention that in any published guidance document or formulary, the drugs chosen to treat a particular condition must provide enough supporting evidence and justify their inclusion, a term commonly known as evidence based medicine.

As mentioned earlier in this report, this patient had a 6 month history of worsening stable angina and as a result had to undergo surgery in the form of a coronary heart bypass graft due to the development of a 3 vessel coronary artery occlusion, which was confirmed after a coronary angiogram. This section will take each key drug used in turn an aim to provide supporting evidence for its use in treatment of this patient.

The first drug to consider is beta blockers and as mentioned in the last section of the report, they are considered to be first line treatment in patients presenting with chest pains as a consequence of CHD. Several studies have been carried to evaluate the use of beta blockers and in one meta-analysis that compared the efficacy and tolerability of beta blockers, calcium channel blockers and nitrates for the treatment of stable angina, it was found that patients assigned to beta blockers experienced 0.31(95% CI,0.00-0.62, P<0.05) fewer angina attacks per week than patients taking calcium channel blockers, namely nifedipine. As the P value was less than 0.05, it could be concluded these results are statistically significant. [11] This meta analysis also went on to demonstrate that beta blockers had a more favourable side effect profile than calcium channel antagonists as fewer patients assigned beta blockers withdrew from the trial due to adverse effects than those from the calcium antagonist arm. This study also concluded that not enough evidence was available to make a confident comparison between nitrates and beta blockers. Another trial involving more than 4000 patients, with an average age above 65, evaluated the effects of beta blockers in patients who had established CHD but without any previous medical history. The conclusions were that beta blockers were able to provide a reduction in death rates or an improvement in survival rate. [12] This group of patients were followed up for an average of 3 years. This supporting evidence justifies the use of Bisprolol in this patient and whilst the majority of trials carried out evaluate some of the older beta blockers such as propranolol and atenolol, there is compelling evidence to suggest that Bisoprolol is as effective as some of the more established beta blockers. [13] The dose that this patient is on also ties in with the recommendations in the BNF which states that in a patient with angina, the range of dose is 5-20mg depending on the patient themselves. [14] 

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This patient was also prescribed a sublingual GTN spray to alleviate symptoms of chest pain and this forms part of SIGN guidelines 96 as part of the treatment regime in patients with stable angina. Studies have shown that GTN spray via the sublingual route is effective at providing immediate relief from chest pains as a result of CHD. In one study, a group of patients who all had exercised induced stable angina were assigned either a sublingual GTN spray at doses of 0.2, 0.4 or 0.8 mg or placebo. The endpoints of this particular study were: the efficacy of the GTN spray prior to exercise and to identify if the effects were dose dependent. It was found that patients who took 0.4 or 0.8mg of GTN prior to exercise were able to prevent symptoms of angina occurring suggesting that sublingual GTN can be used not only at the onset of chest pain but also as a preventative measure in patients with exercise induced stable angina. [15] In patients with stable angina it is common practice to prescribe a nitrate for the immediate relief of symptoms and in this patient`s case, the decision is justified and is not in question.

There is good clinical evidence to support the use of triple therapy in patients who are not sufficiently controlled on combination therapy but as this patient had been adequately controlled on his beta blocker and GTN( at least before the decision to carry out surgery), this report will not consider the concept of triple therapy.

Due to the fact this patient had obstruction in 3 coronary arteries the decision was made by the hospital to perform a Coronary Artery Bypass Graft (CABG) after confirmation via a coronary angiogram. Briefly, CABG involves rerouting a section of narrowed or blocked coronary artery with a section of healthy vein or mammary artery. In this patient, the mammary artery had been used and there is strong clinical evidence to support using the mammary artery as opposed to a saphenous vein graft as this has been shown to reduce death in the long term, prevent the likelihood of further cardiovascular events and the need for further surgery. [16] Due to some of the concerns about the use of "on pump" surgery, where a pump and oxygenator perform the role of the heart and lungs, the decision was made to use" off pump" coronary bypass graft surgery. An incision to the chest is still made although this form off surgery does not produce some of the cognitive problems that are associated with "on pump surgery" and this surgery is performed when the heart is beating. The mortality rates in patients who receive revascularisation via CABG are very low with statistics published in 2003 indicating that mortality rates 30 days post surgery was 2.0%. [17] It should be borne in mind that there is no concrete evidence to support that surgery was the cause of death in this group of patients but in the same light, it cannot be proven that it wasn't. It is still essential to publish the figures to allow professionals to make their own judgements.

When a patient presents as a candidate for heart surgery, the surgeon has the decision to make as to whether the patient will get more benefit from CABG or PCI( Percutaneous Coronary Intervention) and many trials have been carried out to compare the effectiveness between the two in various types of patients. A study carried out in 2005 examined the long term outcomes of CABG versus PCI. There were approximately 60,000 patients with multi vessel disease and each patient was either allocated surgery via CABG or surgery via PCI stent implantation. The endpoints that this study was rates of death and rates of revascularisation within 3 years post surgery. The study demonstrated that the long term risk of death in patients after CABG compared to PCI was 0.64(p<0.05, CI 0.56-0.74) in patients with triple vessel blockage suggesting that patients in the CABG arm had a better survival rate. This particular study also demonstrated that the need for revascularisation was higher in the PCI stent group compared with CABG group over the 3 year follow up, with values of 7.8% versus 0.3% respectively. [18] 

It can therefore be concluded, in patients with triple vessel occlusion, CABG provides better long term survival rates and also reduces the need for revascularisation within 3 years when compared to PCI stent implants. This supports and justifies the decision to carry out a CABG rather than a PCI as this patient had triple vessel occlusion and from the evidence provided, this patient has a better long term survival likelihood and a reduced chance of needing revascularisation within the next 3 years. It has also been demonstrated to be more cost effective to carry out a CABG procedure in a patient with multiple occlusions in the coronary arteries when compared to PCI, which should be taken into consideration as each hospital will have a budget to conform to.

Following surgery, a patient with established CVD should always be initiated on secondary prevention medication to decrease the likelihood of further cardiovascular events occurring,. This patient was given Aspirin when he was diagnosed with stable angina and the Aspirin should continue post surgery. It is routine to begin Aspirin quickly after surgery and one particular study demonstrated that if Aspirin was initiated within 2 days from surgery, there was a significant reduction in the incidence of heart attack and stroke (48% and 50% respectively). This study also demonstrated a decrease in the number of patients dying in the aspirin group (1.3% death rate) when compared to placebo (4 % death rate). [19] It is also advised that a patient stop taking their aspirin 3-5 days prior to surgery due to the bleeding risk. This is the advice of the British Thoracic surgeons and is common practice in hospitals across the country. This patient did have his aspirin stopped prior to surgery and started quickly again post surgery, corresponding to the evidence based guidance that forms part of the sign 96 recommendations.

This patient is also on Simvastatin as a secondary preventative measure and this will also continue in a bid to prevent further cardiovascular problems. Similar to Aspirin, statins are routinely prescribed in patients at CVD risk and many studies have been published to highlight the long term benefits of statins in preventing/delaying the development of atherosclerosis which can lead to heart problems as mentioned earlier. Statin use has shown to have profounding benefits in patients with established stable angina and one particular report published in 2005, demonstrated that the use of statins can significantly reduce the number of coronary events, reperfusion and deaths by achieving only a modest reduction in LDL cholesterol levels. These findings were based over a 5 year period and it was also evident from the report, that these benefits were independent of a patients starting lipid profile suggesting that benefits could be seen in any patient presenting as high risk for a further cardiovascular event. [20]