Schmieder.qxp 4/7/08 12:18 pm Page 69
Hypertension
Cardiovascular Risk Management –
Efficacy of Manidipine in Hypertension and Beyond
a report by
Roland E Schmieder
Vice Chair, Department of Nephrology and Hypertension, University Hospital Erlangen
The primary goal in the treatment of hypertensive patients is to achieve the generation DHP that has sustained 24-hour antihypertensive activity
maximum possible reduction in the long-term total risk of cardiovascular and is well tolerated during once-daily dosing with the recommended
(CV) and renal morbidity and mortality. In addition to the lowering of blood doses (10 or 20mg/day).
20,21
Compared with the second-generation
pressure (BP) per se, successful realisation of the primary goal of treatment DHP amlodipine, which is one of the most extensively studied and
also requires appropriate consideration of co-morbidities.
1–3
Although there widely used DHPs, manidipine is at least as effective an
is some controversy surrounding the benefits of ancillary effects of different antihypertensive agent, but with more favourable tolerability, in
classes of antihypertensive agents on the underlying mechanisms of vascular patients with mild to moderate hypertension.
20–23
disease,
4,5
it is also acknowledged that specific drug classes may have
benefits that extend beyond their BP-lowering effects, and specific Manidipine in Isolated Systolic Hypertension Patients
antihypertensive drug classes are increasingly being recommended as Progressive increases in systolic BP (SBP) related to structural and
particularly beneficial in groups of patients with different CV risk factors.
1,3
functional modifications of the arterial tree during the ageing process
contribute to the high incidence of ISH in elderly patients.
24
In general,
Recent results from large randomised studies have shown reductions in CV landmark trials specifically addressing the treatment of ISH have used
mortality and morbidity in patients with hypertension treated with calcium DHPs with good effect.
6,25
The antihypertensive effect of manidipine
antagonists,
6–13
with overall CV benefits comparable to those seen with has recently been compared with that of amlodipine in a study in
older drug classes such as β-adrenoceptor antagonists (β-blockers) and elderly patients with ISH.
26
At the end of this three-month trial, a
diuretics, and potential additional benefit in terms of stroke prevention.
14
response (≥15% reduction in sitting SBP) was achieved in similar
The addition of a calcium antagonist (amlodipine) to an angiotensin- proportions of patients in the two treatment groups, as was
converting enzyme (ACE) inhibitor reduced the risk of combined major CV normalisation of sitting SBP to ≤140mmHg (see Figure 1). Relative to
events in patients with diabetes mellitus to a greater extent than the the significant 19.5 and 18.4mmHg reductions in SBP reported in
combination of a β-blocker with a thiazide diuretic (hazard ratio 0.87; association with manidipine and amlodipine, respectively (p<0.001),
p=0.0283) in the large Anglo-Scandinavian Cardiac Outcomes Trial- potentially harmful, clinically significant alterations in diastolic BP did
Blood Pressure Lowering Arm (ASCOT-BPLA) in 19,257 patients with not occur in either treatment group (reductions of approximately
hypertension.
8
Notably, in this context meta-analytical data are available to 5mmHg). Although both DHPs exhibited a good safety profile in these
show that newer antihypertensive agents, including calcium antagonists, elderly patients, the incidence of ankle oedema, which is typical of
have a greater beneficial effect on intima-media thickness (IMT) than older DHPs and, expectedly, the most common adverse event, was more
agents such as thiazide diuretics and β-adrenoceptor blockers.
15
than double in the amlodipine than in the manidipine group (9 versus
4%) (see Table 1).
Further analysis has yielded other information of interest: antihypertensive
therapy based on a second-generation long-acting calcium antagonist has Manidipine in Patients with Type 2 Diabetes and
been shown to be particularly beneficial in older patients with isolated Metabolic Syndrome
systolic hypertension (ISH) and diabetes mellitus.
16
Of 4,695 patients aged As shown by a retrospective analysis of the literature, the co-existence
60 years or over in the Systolic Hypertension in Europe (Syst-Eur) trial,
6
of diabetes mellitus with hypertension roughly doubles the risk of CV
492 (10.5%) had diabetes mellitus. Reductions in overall mortality,
mortality from CV disease and all CV events were significantly greater
Roland E Schmieder is a Professor of Internal Medicine,
among patients with diabetes mellitus than among those without.
Nephrology and Hypertension, Head of the Clinical Research
Centre and Vice Chair of the Department of Nephrology and
Dihydropyridine calcium antagonists (DHPs) are very effective
Hypertension at the University Hospital Erlangen, Germany. He
also directs the Institute of Preventative Medicine at the
antihypertensive agents that are widely used for the treatment of
University Erlangen-Nuremberg and the Community Hospital
hypertension, both as first-choice treatment and in combination with
Nuremberg. Professor Schmieder is a member of numerous
professional societies and committees, and is a Fellow of the
other antihypertensive drugs.
17–19
However, just as differences exist
American College of Physicians (ACP) and the American
between various classes of antihypertensive agents with regard to College of Cardiology (ACC). He is on the international Editorial Board of the American Journal of
ancillary effects, differences also exist within classes, including the
Hypertension, the Journal of Human Hypertension and the Journal of Nephrology, among other
scientific journals. Professor Schmieder received his post-graduate medical training in nephrology,
DHPs. Evolution of DHPs from relatively short-acting first-generation
cardiology and hypertension at the University Hospital of Bonn, and then at the Alton Ochsner
agents to slow-onset, long-acting latest-generation agents has been
Foundation, New Orleans. He graduated in medicine from the University of Tübingen, Germany.
aimed at maintaining antihypertensive efficacy while improving E: roland.schmieder@rzmail.uni-erlangen.de
tolerability.
18
Manidipine is a lipophilic, highly vasoselective third-
© TOUCH BRIEFINGS 2008 69
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