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Calcium ions are intimately involved in many aspects of cardiovascular function. Modification of calcium homeostasis therefore represents a key target for pharmacological intervention to achieve therapeutic control of hypertension. The calcium channel blockers (CCBs) act by blocking calcium influx through voltage-dependent L (long-acting) channels without affecting calcium release from the sarcoplasmic reticulum. The effect of blocking these channels is a decrease in the intracellular calcium concentration, which reduces vascular smooth muscle tone. The subsequent decrease in peripheral resistance causes a decrease in systemic blood pressure. The CCBs also decrease myocardial contractility, which decreases myocardial oxygen consumption. Overall, the CCBs at therapeutic doses improve the efficiency of ventricular function. They also have a number of other beneficial effects, including an antiprolifera-tive effect. The CCBs in clinical use vary according to their relative selectivi-ties for vascular and cardiac tissue and their applicability to the treatment of hypertension or ischaemic heart disease. The first-generation CCBs (verapam-il, nifedipine and diltiazem) are associated with a relatively short duration of action and unwanted cardiovascular effects that were related to poor vascular selectivity. In addition, nifedipine was associated with a very rapid onset of action that caused a sudden vasodilation and reflex tachycardia in some patients. The newer second-generation CCBs, for example the dihydropyrid-ines, amlodipine, felodipine and nisoldipine, show greatly improved vascular selectivity and longer durations of action, achieved in part by novel con-trolled-release dosage forms. They bind to target receptors in a slow and sustained fashion, producing a smooth onset of action and 24-hour control of blood pressure. Once-daily dosing of these longer-acting agents improves patient compliance and is associated with a good side-effect profile. The second-generation CCBs are suitable antihypertensive agents for a wide range of patients, including the elderly and black patients, and those with concomitant diseases that preclude the use of other antihypertensives.

Imidapril in once-daily doses of up to 20mg was shown to be at least as effective as candesartan cilexetil given in once-daily doses of up to 16 mg in reducing BP throughout the entire 24-hour dosing interval. Both drugs were well tolerated.

SUMMARYThe unique findings from the HOPE (Heart Outcomes Prevention Evaluation) study strongly support extending the use of the angiotensin‐converting enzyme (ACE) inhibitor ramipril as a preventive agent for patients at high risk of cardiovascular events with normal left ventricular function. In addition, ramipril provides significant benefit in diabetic patients. These findings will impact on how ramipril is used in primary care, where ACE inhibitors are currently underprescribed. Patients reflecting the inclusion criteria of the HOPE study should be considered as suitable candidates for long‐term ramipril therapy as an addition to their existing drug regimen. Screening should include control of kidney function (by serum creatinine), particularly within the first two weeks of treatment, in addition to regular monitoring of serum potassium. However, the HOPE study shows that ramipril is well tolerated at high doses and over a long treatment period. The effectiveness of therapy should also be regularly reviewed and dose adjustments made where necessary. If concern remains, referral to a specialist – a cardiologist or a diabetologist – may ultimately be necessary.

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