Clinical articles

The benefits of angiotensin-converting enzyme (ACE) inhibitors occur early in the treatment period and may be dose-dependent. The utilisation of ACE inhibitors in cardiovascular patients is often suboptimal. This current study evaluates the clinical use of a specific ACE inhibitor dose-escalation pack.
Fifty hospital in-patients with a definite indication for ACE inhibitor therapy were randomised to receive either a dose-escalation pack or ‘usual’ initiation and escalation of ramipril. Patients and general practitioners received an information sheet outlining the benefits and risks of ACE inhibitors and the need for monitoring of serum urea and electrolytes. The groups were matched for age, gender, deprivation score and blood pressure. One patient died in each group and one patient withdrew from the control group. More patients in the dose-escalation group reached target dose by six weeks (72% vs. 33%; p< 0.01) and three months (67% vs. 35%; p<0.05). At three months, there were no differences in serum creatinine, urea or potassium (all p>0.05). Cough was the most commonly reported side effect although there was no difference in its incidence between the dose-escalation and control groups (8% vs. 6%, p>0.05). This study demonstrates that the use of a specific dose-escalation pack for the ACE inhibitor ramipril is a simple, reliable and safe mechanism for reaching a target dose. This approach could find utility with other drug therapies.

Blockade of the renin-angiotensin system by angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) has been shown to be effective in treating hypertension and heart failure. There are currently seven ARBs in clinical practice, of which olmesartan medoxomil (Olmetec®) is the newest agent in the class. This article reviews the pharmacokinetics, pharmacodynamics, safety, efficacy, clinical use, dosing and cost of olmesartan medoxomil. This information is based on published data from human efficacy, safety and drug comparison studies. Olmesartan medoxomil (10–40 mg) has been shown consistently to achieve significant reductions in both systolic and diastolic blood pressures in human studies, which persist over the course of one year. There are limited, mainly experimental, data on its use in heart failure and atherosclerosis.
It is an effective and well-tolerated agent with a long duration of action, allowing once-daily dosage in the treatment of hypertension.

Diabetes is associated with both premature cardiovascular disease and renal disease. The presence of microalbuminuria is itself an independent risk factor for the development of cardiovascular disease. Angiotensin-converting enzyme (ACE) inhibitors were initially shown to slow the progression of established renal disease in patients with type 1 diabetes. Subsequent trials have demonstrated a similar benefit in patients with type 2 diabetes and with the use of angiotensin II receptor blockers (ARBs). The use of ACE inhibitors to prevent cardiovascular events in patients with established cardiovascular disease but not left ventricular dysfunction was established in two large randomised trials – HOPE and EUROPA. These benefits were maintained within the diabetic subgroups of these trials and appear to be independent of blood pressure lowering. The LIFE trial also provides evidence of the benefits of ARBs in reducing cardiovascular events in a high-risk population of diabetic patients with hypertension and left ventricular hypertrophy. Ideally, therefore, all diabetic patients with renal or cardiovascular disease should be treated with ACE inhibitors or ARBs.

Lowering elevated blood pressure reduces mortality and the risk of stroke, coronary heart disease and heart failure.
The presence of benign prostatic hyperplasia (BPH) is a compelling indication for the use of an alpha blocker in the treatment of hypertension. Alpha blockers are first-line therapy for men with lower urinary tract symptoms (LUTS) and prostatic hyperplasia. In men with prostates larger than 30 cm3 or prostate-specific antigen > 1.4 ng/ml, 5-alpha reductase inhibitors may also be added. Typically, alpha blockers improve LUTS by 30–40% and maximum urinary flow rates by 16–25%, with clinical improvement within two weeks. The 5-alpha antagonists are only effective in men with a large prostate and may take up to six months to achieve their full effect.
The Medical Treatment of Prostatic Symptoms (MTOPS) study assessed the long-term effects of doxazosin, finasteride and combination treatment on symptom scores, the clinical progression of BPH and the long-term risk of complications. Combination treatment reduced the risk of clinical progression by 66%, a significantly greater reduction than that induced by either agent alone. The improvement in the symptom score was also significantly greater in the combination treatment group.
Erectile dysfunction (ED) may be a marker for other diseases, such as hypertension. ED is both more prevalent and more severe among patients with hypertension than among the general population. The link may be related to nitric oxide/cyclic GMP pathways and endothelial function. Many prescription drugs are associated with ED, including antihypertensive agents. The alpha blockers and angiotensin receptor blockers are the drugs least likely to cause ED, and may even improve the situation. All currently licensed ED treatments are suitable for managing ED in the cardiovascular patient, when used according to the manufacturer’s instructions. PDE5 inhibitors and alpha blockers should be temporally separated, or selective alpha blockers may be preferable, in order to avoid postural hypotension.

There is extensive evidence of an increased risk of coronary heart disease (CHD) amongst South Asians (Indo-Asians) compared with Caucasians. This increased risk is not explained by conventional risk factors for CHD, such as smoking, hypertension and elevated total cholesterol levels. Studies have consistently demonstrated an increased prevalence of metabolic abnormalities including insulin resistance, diabetes, impaired glucose tolerance and dyslipidaemia, characterised by low plasma levels of high-density lipoprotein cholesterol (HDL-C) and high levels of triglycerides and lipoprotein a (Lp[a]), amongst South Asians. Together these factors predispose to accelerated atherosclerosis, and this is accentuated by adoption of a Western lifestyle. Nicotinic acid is the most potent lipid-modifying therapy for increasing HDL-C (by up to 30%), and is also effective in reducing triglycerides and Lp(a). Clinical studies in Caucasian patients have shown that nicotinic acid can also be safely used in patients with controlled type 2 diabetes. Long-term intervention studies have demonstrated the clinical benefits of nicotinic acid treatment, reducing cardiovascular morbidity and mortality in Caucasian patients with CHD. Nicotinic acid could potentially offer important therapeutic benefits in South Asians. Further clinical studies in this patient group are needed to substantiate this potentially useful treatment strategy and identify specific groups that would derive most benefit.

Amiodarone is used to prevent atrial and ventricular arrhythmias
in high-risk patients, such as after a myocardial infarction (MI)
and in congestive cardiac failure. Its use has increased since the mid-1990s
and, in 2001, around one million prescriptions were dispensed in primary care in England.

Many large studies have confirmed the importance of controlling hypertension in reducing cardiovascular morbidity and mortality. Prescribers are now faced with a wide choice of antihypertensives and a growing body of evidence about their effects.
This article reviews recent evidence about angiotensin II receptor blockers (ARBs). It concludes that they are effective in reducing blood pressure and cardiovascular disease. ARBs also have a renoprotective effect in diabetes. They are generally better tolerated than ACE inhibitors or beta blockers. Newer members of the class may be more effective than older ones at controlling hypertension, and combinations of ARBs with ACE inhibitors may be more effective than either drug alone. Many patients will require combinations of different classes of antihypertensive agents, and ARBs have an important place in providing therapy tailored to the needs of the individual patient.

We report a case of very early onset of
amiodarone-induced pulmonary toxicity,
which appeared 12 days after starting treatment.

Antiplatelet therapy plays a major role in the secondary prevention of ischaemic stroke. The antiplatelet agents that are most used in the clinic include aspirin, dipyridamole and clopidogrel. These agents inhibit platelet activation through different mechanisms of action. Aspirin is the first-line drug in the secondary prevention of stroke; a combination of aspirin with dipyridamole produces a synergistic antithrombotic effect. Clopidogrel is slightly more effective than aspirin at reducing the risk of ischaemic events. Trials comparing the combination of aspirin and clopidogrel versus aspirin are underway. Intravenous antiplatelet therapy with glycoprotein IIb/IIIa receptor inhibitors for acute stroke and as an adjunct to carotid artery stenting appears promising. However, oral GPIIb/IIIa receptor inhibitors appear hazardous.

Five case histories are described to illustrate the importance of patent foramen ovale and atrial septal aneurysm as risk factors in stroke aetiology. Diagnostic methods, and the current and future management of these atrial septal defects, are briefly discussed.