Assessment of ‘once daily’ verapamil for the treatment of hypertension using ambulatory, intra-arterial blood pressure recording

Abstract

A new, slow release formulation of verapamil, "verapamil o.d." was administered to 12 patients with essential hypertension. Drug administration was started at a dose of 240 mg and increased to 480 mg after 2 weeks of treatment if the cuff blood pressure response was unsatisfactory. The drug reduced the daytime intra-arterial blood pressure significantly from 180.7/106.8 mm Hg to 157.3/89.4 mm Hg. The daytime heart rate fell from 88.1 to 71.8 beats/min. The night-time blood pressure decreased from 155.7/87.2 mm Hg to 140.5/75.3 mm Hg. The nocturnal heart rate decreased from 62.8 to 57 beats/min. Hourly plots of mean systolic and diastolic pressure showed a significant reduction of systolic pressure for 21 of 24 h and of diastolic pressure for all 24 h following a single morning dose. The drug modified the absolute blood pressure and heart-rate response during both forms of exercise, but did not alter the magnitude or rate of blood pressure change. The tilt-test produced no evidence of postural hypotension. Only one patient experienced any side effects whilst taking the drug. These results indicate good 24-h blood pressure control and reduced exercise blood pressure levels during treatment with this new formulation of verapamil. The reduced frequency of drug administration should improve patient compliance with treatment of hypertension.

CXL-1020, a Novel Nitroxyl (HNO) Prodrug, Is More Effective than Milrinone in Models of Diastolic Dysfunction—A Cardiovascular Therapeutic: An Efficacy and Safety Study in the Rat

“…The role of L-type Ca 2+ channel in mediating the effects of MIL vs. CXL-1020 was evaluated by selectively antagonizing that current in vivo with verapamil (VER) (see schematic of the experimental design with black block indicating data acquisition in Figure 6A ). VER alone had no effect on HR or Tau but decreased PRSW, consistent with its documented vasoactive and negative inotropic profile (Figures 6B–D , Table 9 , and Caruana et al, 1987 ). In the setting of L-type Ca 2+ blockade, the positive inotropic effect of CXL-1020 was preserved (minimally attenuated) while that of MIL was abolished (Table 9 and Figure 6D ).…”

24 h blood pressure control with the once daily calcium antagonist, amlodipine.

“…Our results indicate that amlodipine effectively reduced blood pressure over 24 h, with a mean daytime reduction of the same order of magnitude as other calcium channel antagonists such as verapamil (Caruana et al, 1987) and tiapamil (Caruana et al, 1985), although slightly less than that of nifedipine .…”

“…There is some evidence that the incidence of side-effects is reduced with long-acting or slowrelease preparations (Caruana et al, 1987), presumably because of a steadier plasma level without sudden peaks. Moreover, it has been suggested (Blackwell, 1973) that compliance is improved by once-daily therapies, especially in non-painful conditions such as hypertension (Kubacka & Juhl, 1985).…”

Fixed-combination of amlodipine and diuretic chronotherapy in the treatment of essential hypertension: improved blood pressure control with bedtime dosing—a multicenter, open-label randomized study

“…[17][18][19][20]31,32 The retrospective Syst-Eur 25 and HOPE 33 outcome trials show that evening administration of nitrendipine and ramipril impacts sleep-time blood pressure by converting the 24-h blood pressure pattern to a dipper pattern and decreasing CVD risk in the HOPE study. The CONVINCE trial 34,35 did not show a chronotherapy benefit, but the MAPEC trial 36 results suggest that night time dosing is beneficial.…”