Michael P. Caruana

Effects of chronic congestive heart failure secondary to coronary artery disease on the circadian rhythm of blood pressure and heart rate

In 20 subjects with chronic congestive heart failure due to coronary artery disease, the 24-hour variability of ambulatory intraarterial blood pressure (BP) was studied using an improved Oxford Medilog system, and correlated with left ventricular function at rest. The mean radionuclide ejection fraction was 27% (range 10 to 42), the mean pulmonary arterial wedge pressure was 18 mm Hg (5 to 37) and the mean cardiac index was 2.8 liters/min/m2 (2 to 3.8). The 24-hour systolic BP and heart rate (HR) variability indexes were less than those of 22 normal volunteers (p less than 0.05) and were strongly correlated (p less than 0.05) with ejection fraction at rest and pulmonary arterial wedge pressure. Stepwise regression showed that a combination of the mean nocturnal HR and the standard deviation of the hourly mean systolic BP values accounted for 67% of the variability in ejection fraction between patients. Similarly, 73% of the variation in pulmonary wedge pressure was explained by combining the 24-hour mean HR and the mean nocturnal HR.

Carvedilol for systemic hypertension

Twenty-four hour profiles of intraarterial ambulatory blood pressure (BP) and heart rate were significantly reduced by administration of carvedilol, a new beta-blocker with vasodilating properties. Twelve patients were given carvedilol, 25 mg twice daily for 2 weeks; the dose was then increased to 50 mg twice daily if the target BP was not achieved. After 4 weeks of therapy, mean daytime reduction in BP was 25 +/- 3 mm Hg systolic and 19 +/- 3 mm Hg diastolic, and mean reduction in heart rate was 22 +/- 3 beats/min. BP at the peak of isometric exercise and during dynamic exercise was also significantly reduced. Radionuclide measurements showed that left ventricular ejection fraction was not affected by treatment, but there was a significant reduction in systolic and diastolic volumes. The drug was well tolerated. This clinical trial suggests that carvedilol will be a useful first-line drug for treatment of essential hypertension, and its vasodilating action may have a more favorable effect on left ventricular function than conventional beta-blocking drugs.

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

SummaryA 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 nighttime 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 complicance with treatment of hypertension.

First dose response and 24-hour antihypertensive efficacy of the new once-daily angiotensin converting enzyme inhibitor, ramipril.

The reduction in blood pressure (BP) after the first dose and after 8 weeks of treatment with a new once-daily angiotensin converting enzyme (ACE) inhibitor, ramipril, was examined in 12 untreated hypertensive patients, using ambulatory intraarterial BP monitoring. The first period of monitoring began 24 hours before the first dose was given, and continued for 24 hours afterwards. A second 24-hour period of monitoring was carried out after 8 weeks of treatment, commencing immediately after the morning dose. Angiotensin II levels and serum drug levels were measured at 0, 2, 6 and 24 hours after the acute dose. BP decreased progressively from the first hour after the first dose, reached a maximum in the fifth hour (p less than 0.001) and then the effect diminished. The maximum reduction of systolic BP in any patient was 64 mm Hg, the minimum 4 mm Hg. Blood pressure was significantly (p less than 0.05) reduced throughout the 24 hours after dosing, with a mean daytime reduction of 13/12 mm Hg, and a mean nighttime reduction of 15/7 mm Hg. Angiotensin II levels were significantly (p less than 0.02) and maximally reduced by 2 hours after administration, but the reduction was no longer significant after 24 hours. Serum drug levels were also maximal 2 hours after administration. The trial population could be clearly divided into groups of good and poor responders on the basis of BP reduction. The angiotensin II levels were higher before treatment, and decreased further, in all patients with a good response than in those with a poor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Carvedilol for systemic hypertension.

Summary: Twenty‐four hour profiles of intraarterial ambulatory blood pressure (BP) and heart rate were significantly reduced by administration of carvedilol, a new &bgr;‐blocker with vasodilating properties. Twelve patients were given carvedilol, 25 mg twice daily for 2 weeks; the dose was then increased to 50 mg twice daily if the target BP was not achieved. After 4 weeks of therapy, mean daytime reduction in BP was 25 ± 3 mm Hg systolic and 19 ± 3 mm Hg diastolic, and mean reduction in heart rate was 22 ± 3 beats/min. BP at the peak of isometric exercise and during dynamic exercise was also significantly reduced. Radionuclide measurements showed that left ventricular ejection fraction was not affected by treatment, but there was a significant reduction in systolic and diastolic volumes. The drug was well tolerated. This clinical trial suggests that carvedilol will be a useful first‐line drug for treatment of essential hypertension, and its vasodilating action may have a more favorable effect on left ventricular function than conventional &bgr;‐blocking drugs.

Once-and twice-daily bevantolol for systemic hypertension using 24-hour ambulatory intraarterial blood pressure recording

The antihypertensive efficacy of bevantolol, a selective beta 1-adrenoreceptor antagonist, was evaluated in 17 patients with essential hypertension, using continuous ambulatory intraarterial blood pressure (BP) monitoring. The study compared a twice-daily regimen (titrated dose of 200 to 600 mg/day) with the same amount given in a single daily dose. Within-patient comparisons of mean hourly systolic and diastolic BPs and heart rate showed a highly significant effect with twice-daily therapy (p less than 0.001) for all of the 24 hours. Similar significant results were obtained with a single morning dose. There was no difference between the pattern or extent of BP reduction with the 2 regimens. The decrease in BP after bevantolol persisted during the physiologic tests (rest, tilt, isometric and dynamic exercise). Four patients developed minor side effects with the single morning dose, and only 1 patient with the twice-daily regimen. These effects included tiredness, fatigue and dizziness. Unlike pure beta-blocking agents, bevantolol controlled the early morning increase in BP, lending support to the belief that it possesses vasodilatory properties in addition to beta blockade. These results suggest that bevantolol may be useful as first-line therapy in a once-daily dosage for the treatment of essential hypertension.

Effects of tiapamil, a new calcium channel blocker, on ambulatory intraarterial blood pressure and exercise-induced changes in blood pressure

Summary: The duration and magnitude of effect of a new calcium-channel blocker, tiapamil, given twice daily, was studied in 17 hypertensive patients using ambulatory intraarterial blood pressure recording. The drug produced moderate reductions of blood pressure throughout the 24-h cycle with slight reduction of effect before each dose. Ten patients reported side effects, and one withdrew as a result of these. Tiapamil attenuated the blood pressure rise during dynamic cycle ergometry but had no effect on the increase during isometric hand grip. We conclude that tiapamil is similar to existing calcium-channel blocking agents in lowering the blood pressure, but it does not appear to influence the response to isometric exercise in this dose.