Sixty-three studies, with a total of 1,252 participants, were included. Twenty-eight studies (n=343) reported the acute effects of SA calcium antagonists, 46 studies (n=631) reported the long-term effects of SA calcium antagonists, and 20 studies (n=278) reported the effects of long-term treatment with LA calcium antagonists. The duration of treatment ranged from 1 week to 12 months.
Acute effect of SA calcium antagonists (28 studies, 343 participants).
Three studies used verapamil, one study used diltiazem, and 24 studies used dihydropyridines. The mean arterial pressure decreased in all studies by 13.7% (plus or minus, +/- 1.1; range: 3.5 to 30.7); the decrease was similar for dihydropyridines and non-dihydropyridines. Heart rate increased in all studies by 13.7% (+/-1.4; range: 0 to 29.5); the increase was similar for dihydropyridines and non-dihydropyridines. NE levels increased in all studies except in the one that used diltiazem. The increase in NE levels was more pronounced after dihydropyridine (31.9 +/- 2.1%) than after non-dihydropyridine administration (9.2 +/- 6%), (p<0.05). In the studies using dihydropyridines, the change in NE levels was related to the change in heart rate (r=0.59, p<0.01), and was inversely related to the change in mean arterial pressure (r=0.46, p<0.05).
Long-term effects of SA calcium antagonists (46 studies, 631 participants).
Three studies used verapamil, 6 studies used diltiazem, and 37 studies used dihydropyridines. The mean arterial pressure decreased in all studies by 14.7% (+/- 0.6; range: 4.4 to 27.0); the decrease was similar for dihydropyridines and non-dihydropyridines. Heart rate increased by 3.4% (+/-0.9) after dihydropyridine administration, and decreased by 5% (+/- 1.2) after non-dihydropyridine administration (p<0.001). NE levels increased by a similar extent after dihydropyridine or non-dihydropyridine administration. The change in NE levels was not related to either the change in heart rate or the change in mean arterial pressure.
Comparison between acute and long-term effects of SA calcium antagonists.
The mean arterial pressures decreased similarly during acute and long-term treatment. However, while acutely-administered calcium antagonists increased the heart rate, long-term treatment with calcium antagonists resulted in little change in heart rate (p<0.001). The increase in NE levels was less pronounced after long-term treatment with SA agents than during acute treatment (p=0.09).
LA calcium antagonists (20 studies, 278 participants).
Five studies used verapamil, 2 studies used diltiazem, and 13 studies used dihydropyridines. The mean arterial pressure decreased similarly after dihydropyridine (16.8 +/- 2.9%) and after non-dihydropyridine (11.2 +/- 1.2%) administration. Heart rate remained unchanged after dihydropyridine administration, but decreased by 7.1% (+/-1.8) after non-dihydropyridine administration (p<0.001 between the groups). NE levels increased by 14.5% (+/- 5) after dihydropyridine administration, but decreased by 20.7% (+/- 9.8) after non-dihydropyridine administration (p<0.001 between the groups).
Comparison between SA and LA calcium antagonists.
LA and SA agents decreased arterial blood-pressure by the same magnitude (14.8%). SA agents increased heart rate slightly (1.7%), whereas LA agents had little effect on NE levels (+2.1 +/- 6.1%). Unlike the SA drug, LA verapamil decreased NE levels (p<0.001). LA verapamil (GIST formulation) decreased blood-pressure more than the SA drug (p<0.05), without affecting the heart rate and NE levels (p<0.05).