The calcium edge
Lercanidipine offers sustained 24-hour blood-pressure control, improved tolerability
Whether as initial therapy or as add-on maintenance medication, calcium antagonists remain a powerful and effective treatment for hypertension, especially in the elderly and those with high systolic blood pressure.
This, according to Prof. Alberto Zanchetti, scientific director of the Instituto Auxologico Italiano in Milano, Italy, had been proved in many randomized clinical trials in the last 10 years and reinforced by the development of the long-acting, high-lipophilic versions of dihydropyridines like lercanidipine (Zanidip).
Zanchetti, who spoke at the joint convention of the Philippine Society of Hypertension and the Philippine Lipid Society, said calcium antagonists can help fill the gap between expert recommendations and actual clinical practice in treating hypertension.
Zanchetti said the emphasis on which drug to use as first-line therapy has been rendered "outdated by the need to use two or more drugs to achieve the BP-reduction target" of lower than 140/90 mm Hg. "In most patients, it is difficult to achieve this target using only one drug," he stressed.
In choosing an antihypertensive agent, the following should be considered:
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previous experience of the patient with an antihypertensive agent,
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effect on target-organ damage,
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onset of action
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duration of action or ability of the drug to maintain blood pressure over 24
hours,
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tolerability, and
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cost of the drug (secondary to efficacy and tolerability).
Long duration of action
He said dihydropyridines are favored for use in elderly patients and those with systolic hypertension. They are also indicated for those with angina pectoris, peripheral vascular disease, and carotid atherosclerosis.
Dihydropyridines should be used with caution in certain individuals, particularly those with congestive heart failure.
Long duration of action and high lipophilicity are also among the advantages of calcium antagonists, according to Zanchetti, saying both make sustained 24-hour BP-control possible.
Among the long-acting dihydropy-ridines, lercanidipine is the most lipophilic, being "10 times more lipophilic than amlodipine, 20 times more than other dihydropyridines," Zanchetti noted. This strong capacity of binding to the active membranes of the smooth muscle cells accounts for its direct diffusion to the calcium channels, making its concentration constant and stable over a longer period of time, he explained.
Sustained effect at trough is one of the advantages seen in studies with lercanidipine, according to Zanchetti. Studies showed that BP levels with 10-mg lercanidipine remained consistent over a 24-hour period, making once-a-day dosing possible.
Lercanidipine also helps prevent target-organ damage, according to Grassi et al., which looked at forearm blood flow, forearm vascular resistance, calf blood flow, and vascular resistance. The study confirmed that being a vasodilator, lercanidipine increased forearm blood flow and lowered resistance, an effect not seen with a diuretic. After 12 months of treatment, lercanidipine showed a 50-percent reduction in forearm vascular resistance and 40 percent in the calf, indicating, according to Zanchetti, "a regression of vascular hypertrophy."
The COHORT study analyzed 828 elderly patients who were randomized into lercanidipine 10 mg (420), amlodipine 5 mg (200), and lacidipine 2 mg (208). Target BP was =140/90.
There was significant mean reduction (p < 0.01) in sitting systolic- and diastolic-blood-pressure levels from baseline after six months, whether in lercanidipine (29.6 ± 0.7/14.3 ± 0.4 mm Hg), amlodipine (29.7 ± 1.0/14.5 ± 0.6 mm Hg), or lacidipine (29.4 ± 1.0/14.0 ± 0.6 mm Hg). Those patients who were observed at 12, 18, and 24 months continued to show similar changes. Also, the reduction in standing BP was the same in the three groups.
Also at six months, all study arms achieved similar responder rates (about 80 percent), normalized rates (50 to 55 percent), and ratio of patients who needed combination therapy (20 to 25 percent). The authors added that the "same percentage was displayed by the groups of patients entering in the analysis at 12, 18, and 24 months of treatment."
At the end of the two-year follow-up period, 16 percent of patients on amlodipine dropped out due to adverse events-higher than lercanidipine (11 percent) and lacidipine (eight percent). The incidence of single adverse events (dizziness, vertigo, flushing, headache, palpitations, tachycardia, and asthenia) was hardly different in all groups. Edema, however, was reported twice more frequently in the amlodipine group (19 percent) than in the lercanidipine (9.3 percent) and lacidipine (4.3 percent) groups.
They concluded: "Lercanidipine and lacidipine have an antihypertensive effect comparable to amlodipine but a better tolerability profile."
Zanchetti stressed that, at a time when effectively controlling hypertension requires combination therapy, "calcium antagonists offer a distinct advantage because they can easily be combined with practically all other classes of antihypertensive agents."
And with higher lipophilicity and longer duration of action that allow once-daily dosing, lercanidipine not only offers better tolerability but also enhances patient compliance, leading to success of treatment, he summed up.
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