A Follow-Up Study of the Prevalence of Valvular Heart Abnormalities in Hyperprolactinemic Patients Treated With Cabergoline.

CONTEXT: Uncertainty exists whether the long-term use of ergot-derived dopamine agonist (DA) drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease and whether current regulatory authority guidelines for echocardiographic screening are clinically appropriate. OBJECTIVE: Our objective was to provide follow-up echocardiographic data on a previously described cohort of patients treated with DA for lactotrope pituitary tumors and to explore possible associations between structural and functional valve abnormalities with the cumulative dose of drug used. DESIGN: Follow-up echocardiographic data were collected from a proportion of our previously reported cohort of patients; all had received continuous DA therapy for at least 2 years in the intervening period. Studies were performed according to British Society of Echocardiography minimum standards for adult transthoracic echocardiography. Generalized estimating equations with backward selection were used to determine odds ratios of valvular heart abnormalities according to tertiles of cumulative cabergoline dose, using the lowest tertile as the reference group. SETTING: Thirteen centers of secondary/tertiary endocrine care across the United Kingdom were included. RESULTS: There were 192 patients (81 males; median age, 51 years; interquartile range [IQR], 42-62). Median (IQR) cumulative cabergoline doses at the first and second echocardiograms were 97 mg (20-377) and 232 mg (91-551), respectively. Median (IQR) duration of uninterrupted cabergoline therapy between echocardiograms was 34 months (24-42). No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. CONCLUSION: This large UK follow-up study does not support a clinically significant association between the use of DA for the treatment of hyperprolactinemia and cardiac valvulopathy.

Antihypertensive efficacy of indapamide SR in hypertensive patients uncontrolled with a background therapy: the NATIVE study.

OBJECTIVES: Antihypertensive monotherapy rarely achieves blood pressure (BP) control. NATIVE (NATrilix SR use in combInation antihypertensiVe thErapy) evaluated indapamide sustained release (SR) in hypertensive patients receiving background therapy. RESEARCH DESIGN AND METHODS: Patients remaining hypertensive (systolic BP [SBP], 145-180 mmHg; diastolic BP [DBP], 95-105 mmHg) while receiving an angiotensin-converting enzyme (ACE) inhibitor (n = 709), beta-blocker (n = 629), calcium-channel blocker (CCB; n = 493), angiotensin II type 1 receptor blocker (ARB; n = 75), alpha-blocker (n = 29) or other therapy (n = 6) were enrolled, recruited by physicians from 228 centres in Pakistan. Indapamide SR 1.5 mg was administered daily for 3 months with background therapy. BP was assessed every 2 weeks, and blood glucose and total cholesterol were evaluated at baseline and study end in a patient subgroup. Adverse events were also recorded. MAIN OUTCOME MEASURES AND RESULTS: Of 2073 enrolled patients (49% males; mean age 51 years), 1941 received indapamide SR and background therapy. SBP and DBP decreased significantly (SBP, 166 +/- 16 mmHg at baseline vs. 132 +/- 12 mmHg at 3 months; DBP, 102 +/- 8 mmHg vs. 83 +/- 6 mmHg; both p < 0.0001 vs. baseline). Patients uncontrolled with an ACE inhibitor, beta-blocker, CCB or ARB achieved an SBP/DBP decrease of 34 +/- 15/19 +/- 9, 33 +/- 17/19 +/- 10, 33 +/- 15/18 +/- 8 or 35 +/- 16/20 +/- 12 mmHg, respectively (all p < 0.0001). In all, 84% of patients achieved target SBP (< or = 140 mmHg) and 61% achieved BP normalisation (SBP < 140, DBP < 90 mmHg). The absence of placebo control may lead to an overestimation of the extent of the BP reduction achieved. Glucose and cholesterol levels were unaffected by indapamide SR. Four percent of patients experienced side-effects, which were mild-to-moderate in severity. CONCLUSIONS: In patients with hypertension despite antihypertensive therapy, indapamide SR significantly reduced BP with a good acceptability profile. Indapamide SR may represent an effective additional therapy for patients who do not achieve BP goals with other antihypertensive agents.