Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure.

OBJECTIVES: The purpose of this research was to evaluate the therapeutic value of initiating a beta-blocker before an angiotensin-converting enzyme inhibitor (ACEI) in the treatment of heart failure. BACKGROUND: Although ACEI and carvedilol produce benefits in heart failure, whether the order of initiation of therapy determines the impact on left ventricular (LV) function and New York Heart Association functional class (NYHA FC) has not been determined. METHODS: A single-center, prospective, randomized, open-label study was performed. We evaluated whether initiation of therapy with carvedilol either before (n = 38) or after (n = 40) perindopril therapy in newly diagnosed patients in NYHA FC II to III heart failure with idiopathic dilated cardiomyopathy, with the addition of the alternative agent after six months, determined subsequent changes in NYHA FC and LV function (echocardiography and radionuclide ventriculography). Study drugs were titrated to maximum tolerable doses. RESULTS: There were no differences in baseline characteristics between the study groups. After 12 months 11 patients died (6 in the group where the ACEI was initiated). At 12 months the group receiving carvedilol as initial therapy achieved a higher tolerable dose of carvedilol (43 +/- 17 mg vs. 33 +/- 18 mg, p = 0.03); a lower dose of furosemide (p < 0.05); and better improvements in symptoms (NYHA FC, p < 0.002), LV ejection fraction (radionuclide: 15 +/- 16% vs. 6 +/- 13%, p < 0.05; echocardiographic, p < 0.01), and plasma N-terminal pro-brain natriuretic peptide concentrations (p < 0.02). CONCLUSIONS: As opposed to the conventional sequence of drug use in the treatment of heart failure, initiation of therapy with carvedilol before an ACEI results in higher tolerable doses of carvedilol and better improvements in FC and LV function.

Outcome of subsequent pregnancy in patients with documented peripartum cardiomyopathy.

Subsequent pregnancy in 6 patients with previous peripartum cardiomyopathy resulted in reduction of ejection fraction by >10% in 5 patients at 1 month postpartum. Two patients with impaired ejection fraction at onset of subsequent pregnancy died 3 months postpartum due to heart failure despite optimal medical therapy. Deterioration of left ventricular function occurred uniformly postpartum and was accompanied by elevation of tumor necrosis factor-alpha plasma levels from 2.4 +/- 1.1 pg/ml at onset of subsequent pregnancy to 6.2 +/- 2.4 pg/ml at 1 month postpartum.

Effect of slow-release indapamide and perindopril compared with amlodipine on 24-hour blood pressure and left ventricular mass in hypertensive patients of African ancestry.

BACKGROUND: In the treatment of hypertension in subjects of African origins, although hydrochlorothiazide (HCTZ) is not as effective as calcium channel blockers, indapamide is superior to HCTZ. In the present study we therefore compared the effects of slow release (SR) indapamide with the calcium channel blocker amlodipine, when used as initial therapy, on blood pressure (BP) and left ventricular mass (LVM) during 6 months of treatment in this group. METHODS: Patients with a mean daytime ambulatory diastolic BP > or =90 mm Hg and < or =110 mm Hg (n = 125, aged 53 +/- 11 years, 68% women) were randomized to receive open-label 1.5 mg of indapamide SR or 5 mg of amlodipine. If daytime ambulatory diastolic BP at 1 month was >/=90 mm Hg, 4 mg of perindopril was added to indapamide SR or the dose of amlodipine was increased to 10 mg. RESULTS: After 1 month of therapy, there was an equivalent decline in systolic and diastolic BP in both groups (P <.0001). In the indapamide-treated group (n = 62) the daytime BP decreased from 153 +/- 12/101 +/- 6 mm Hg to 138 +/- 15/92 +/- 10 mm Hg and for amlodipine (n = 58), it decreased from 152 +/- 13/99 +/- 5 mm Hg to 138 +/- 12/91 +/- 8 mm Hg. At 6 months daytime ambulatory BP decreased to 130 +/- 15/86 +/- 8 mm Hg and to 129 +/- 11/85 +/- 5 mm Hg for the indapamide SR (n = 42) and amlodipine (n = 44) treatment groups, respectively. Both groups showed equivalent regression of LVM index and relative wall thickness. CONCLUSIONS: These data suggest that in hypertensive patients of African ancestry initiating therapy with 1.5 mg of indapamide SR and then adding 4 mg of perindopril is equally as effective as amlodipine therapy at reducing BP, and modifying target organ damage.