Rates and determinants of reinitiating antihypertensive therapy after prolonged stoppage: a population-based study

OBJECTIVE: To assess patterns of restarting antihypertensive drugs after a prolonged period of discontinuation. METHODS: We conducted a retrospective cohort study among new users of blood pressure-lowering medication in the PHARMO database in The Netherlands, who had a period of at least 180 days without such medication. A multivariable Cox proportional hazard analysis was used to explore the baseline variables associated with reinitiating treatment. Case-crossover analysis was used to evaluate determinants of reinitiating treatment. RESULTS: We identified 35,714 patients as initiating blood pressure-lowering treatment during the period 1 January 1999 to 30 June 2004. Of the 18,357 (51.4%) patients who discontinued blood pressure-lowering treatment, 19.3% restarted treatment within 1 year and 60.7% restarted within 6 years. With every additional year they had been on therapy, patients were more likely to restart [odds ratio (OR) = 1.38; 95% confidence interval (CI) = 1.34-1.42]. The case-crossover analysis revealed that hospitalization for cardiovascular disease (OR = 2.20; 95% CI = 1.84-2.63), as well as refilling of another cardiovascular medication (OR = 1.25; 95% CI = 1.11-1.40), were each independently associated with reinitiating treatment. Refilling non-cardiovascular medications was not associated with reinitiating treatment (OR = 1.03; 95% CI = 0.97-1.10). CONCLUSION: Physicians should be aware that many patients have prolonged periods of discontinuation during the use of blood pressure-lowering medication, and that most of these patients will eventually resume therapy. Ongoing refilling other medications is not associated with reinitiating treatment. This suggests that, for some patients, the decision to discontinue may be drug specific rather than a behavioural characteristic applicable to all chronic treatments.     

Left ventricular dysfunction after acute myocardial infarction: results of a prospective multicenter study

In a multicenter prospective study of 866 patients who survived the coronary care unit phase of an acute myocardial infarction, variables reflecting left ventricular function were examined to assess their impact on 2 year survival. Single variables that reflected left ventricular dysfunction before infarction and in the acute and recovery phases were, respectively, history of prior myocardial infarction, rales in the coronary care unit dichotomized at greater than bibasilar and predischarge radionuclide ejection fraction dichotomized at less than 0.40. When combined in a stepwise fashion, patients lacking these three risk characteristics had a 2 year 4.2% mortality rate, whereas patients possessing all three characteristics had a 45% mortality rate. Rales in the coronary care unit and predischarge ejection fraction act independently, and each contributes to mortality. Fifty-two patients with advanced rales but an ejection fraction of 0.40 or greater had a 21% mortality rate. Similarly, 208 patients with few rales but an ejection fraction of less than 0.40 had a 15% mortality rate. These data suggest that the mortality risk imposed by those factors that assess permanent left ventricular damage is independent of and additive to the mortality risk contributed by dynamic, acute phase dysfunction. These data fit the hypothesis that acute phase dysfunction is, in part, due to transient ischemia that, on reversal, can restore function toward normal. The results suggest 1) that assessment of left ventricular function during the acute and recovery phases of myocardial infarction is necessary to define prognostic characteristics of an individual patient, and 2) that of particular importance is the identification of patients whose postinfarction course is consistent with reversible ischemia.     

Assessment of arterial ventricular coupling changes in patients under therapy with various antihypertensive agents by a non-invasive echocardiographic method

BACKGROUND: The integration between arterial and ventricular function has been studied by mostly invasive techniques. We considered assessing the influence of various antihypertensive medications on arterial-ventricular coupling (AVC) with the use of a non-invasive echocardiographic method. METHODS: A total of 9037 patients, who had been under treatment for essential arterial hypertension were studied echocardiographically at baseline prior to therapy and after 6 months of antihypertensive monotherapy (diuretics, beta-blockers without intrinsic sympathomimetic activity (ISA), beta-blockers with ISA, a-blockers, angiotensin converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (AIIRA), non-dihydropyridine calcium antagonists, and dihydropyridine calcium antagonists). The AVC was calculated by echocardiographic measurements based on the equation: AVC=ESV/SV (ESV, end systolic volume; SV, stroke volume). RESULTS: ACEI, AIIRA, and dihydropyridine calcium antagonists decreased (P<0.0001 for all) while diuretics, alpha-blockers, both beta-blocker groups, and non-dihydropyridines increased significantly the AVC values compared to baseline measurements (P<0.0001 for all, except P=0.02 for alpha-blockers). Changes in AVC were the most highly correlated with changes in EF (r=-0.979, P<0.0001). CONCLUSION: Various antihypertensive drugs have a differential effect on AVC with ACEI, AIIRA, and dihydropyridine calcium antagonists having the most favorable effect on this index. AVC provides a meaningful index of cardiovascular performance in hypertension and offers the possibility of wide employment and serial follow-up in large numbers of patients because of its completely non-invasive nature.     

Prolonged antihypertensive effect of amlodipine: a prospective double-blind randomized study.

Amlodipine is a calcium antagonist with a long elimination half-life (35 to 50 h) allowing a once daily dosing in the treatment of hypertension. This randomized, double-blind study was performed to assess the residual antihypertensive effect of amlodipine 5 mg O.D. 3 days after discontinuing therapy in previously well-controlled mild to moderate hypertensive patients. Blood pressure (BP) was evaluated by conventional (OBP) and by ambulatory blood pressure monitoring (ABPM). Amlodipine 5 mg OD administered during a 6-week period, significantly reduced both OBP and ABPM mean values (p < 0.05), whereas no change in heart rate was observed. At the end of the active treatment period, adequately controlled patients were randomized either to amlodipine 5 mg OD (group A) or amlodipine for 12 days followed by a 3-day period on placebo. After this double-blind treatment phase, group P exhibited no significant increase in BP (assessed by OBP or ABPM) when compared to group A. In conclusion, the duration of action of amlodipine extends largely beyond the 24-h span, and when patients omit their treatment for 3 days BP does not significantly increase.     

Current-based versus energy-based ventricular defibrillation: a prospective study

Defibrillation is thought to be mediated by a depolarizing current; however, the present method of defibrillation is based on delivering an empiric dose of energy to all patients. The hypothesis of this study was that for equivalent efficacy rates, a current-based defibrillation method would result in delivering less energy and peak current than would the standard energy-based method. In a group of 86 consecutive patients with ventricular fibrillation, every other patient was prospectively assigned to receive shocks according to method 1 or method 2. Method 1 was current based and delivered successive shocks of 25, 25 and a maximum of 40 A; method 2 was energy based and delivered shocks of 200, 200 and 360 joules. Patients in both groups were similar with respect to age, gender, weight, cardiac diagnosis, ejection fraction, antiarrhythmic therapy, chest circumference, chest depth and transthoracic impedance. Each method had statistically equivalent first shock (79% current-based versus 81% energy-based) and cumulative shock success rates. The mean first shock energy was 120 +/- 30 joules for patients receiving the current-based method and 200 joules for patients receiving energy-based shocks (p = 0.0001). The mean peak current was 24 +/- 2.3 and 33 +/- 5.0 A, respectively (p = 0.0001). Therefore, for equivalent first shock success rates, the energy-based method delivered 67% more energy and 38% more current than the current-based method. High transthoracic impedance (greater than or equal to 90 omega) predicted first shock failure only in patients undergoing defibrillation by the energy-based method (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Tetrahydrobiopterin: a novel antihypertensive therapy

Tetrahydrobiopterin (BH(4)) is a cofactor for the nitric oxide (NO) synthase enzymes, such that its insufficiency results in uncoupling of the enzyme, leading to release of superoxide rather than NO in disease states, including hypertension. We hypothesized that oral BH(4) will reduce arterial blood pressure (BP) and improve endothelial function in hypertensive subjects. Oral BH(4) was given to subjects with poorly controlled hypertension (BP >135/85 mm Hg) and weekly measurements of BP and endothelial function made. In Study 1, 5 or 10 mg kg(-1) day(-1) of BH(4) (n=8) was administered orally for 8 weeks, and in Study 2, 200 and 400 mg of BH(4) (n=16) was given in divided doses for 4 weeks. Study 1: significant reductions in systolic (P=0.005) and mean BP (P=0.01) were observed with both doses of BH(4). Systolic BP was 15+/-15 mm Hg (P=0.04) lower after 5 weeks and persisted for the 8-week study period. Study 2: subjects given 400 mg BH(4) had decreased systolic (P=0.03) and mean BP (P=0.04), with a peak decline of 16+/-19 mm Hg (P=0.04) at 3 weeks. BP returned to baseline 4 weeks after discontinuation. Significant improvement in endothelial function was observed in Study 1 subjects and those receiving 400 mg BH(4). There was no significant change in subjects given the 200 mg dose. This pilot investigation indicates that oral BH(4) at a daily dose of 400 mg or higher has a significant and sustained antihypertensive effect in subjects with poorly controlled hypertension, an effect that is associated with improved endothelial NO bioavailability.     

Predictors of self-reported noncompliance with antihypertensive drug treatment: a prospective cohort study

BACKGROUND: Persistence and compliance are different aspects of the broader concept of adherence to drug treatment. In a prior study, determinants of nonpersistence in a group of patients newly prescribed antihypertensive medications were examined. OBJECTIVE: To determine noncompliance among those who were persistent with therapy. METHODS: A prospective cohort study was conducted, in which individuals prescribed a new antihypertensive monotherapy were identified through a network of 173 pharmacies. Participants were interviewed by telephone twice during a three-month period. At the end of this period, individuals who reported still taking the medication initially prescribed were included in the analysis. Self-reported noncompliance was measured at three months. Data were analyzed using a multivariate logistic regression model. RESULTS: Of 509 eligible participants, 118 (23.2%) reported noncompliance with their drug treatment. Noncompliance was significantly associated with the use of angiotensin-converting enzyme inhibitors (adjusted OR [AOR] 3.0; 95% CI 1.17 to 7.92) compared with the angiotensin II receptor blocker losartan, and with the belief that hypertension is not a risk factor for cardiovascular diseases (AOR 2.0; 95% CI 1.21 to 3.33). On the other hand, noncompliance was inversely associated with the use of more than four pills of medication per day (AOR 0.3; 95% CI 0.15 to 0.64). CONCLUSIONS: Compliance with drug treatment could be improved by proper selection of medication, and by attempts to correct the false perceptions patients may have about hypertension. Further research is needed to better understand the clinical significance of a higher number of pills as a predictor of good compliance. Further research is also needed using different means of measuring noncompliance.     

Spa therapy for gonarthrosis: a prospective study

The objective of this study was to evaluate the effect of spa therapy on clinical parameters of patients with gonarthrosis. Patients with gonarthrosis (n=33) underwent a 2-week spa therapy using three treatment regimes and a 20-week follow-up as follows: group I (n=11) had mineral water baths and hot native mineral mud packs, group II (n=12) had mineral water baths and rinsed mineral-free mud packs and group III (n=10) had tap water baths and mineral-free mud packs. The patients and the assessing rheumatologist were blinded to the difference in the treatment protocols. A significant improvement in the index of severity of the knee (ISK), as well as night pain scores, was achieved in group I. Improvement in physical findings and a reduction in pain ratings on a visual analogue scale (VAS) did not reach statistical significance. Analgesic consumption was significantly decreased in both groups I and III for up to 12 weeks. Global improvement assessed by patients and physician was observed in all three groups up to 16 weeks but persisted to the end of the follow-up period in group I only. Patients with gonarthrosis seemed to benefit from spa therapy under all three regimes. However, for two parameters (night pain and ISK) the combination of mineral water baths and mud packs (group I) appeared to be superior.     

Relationship between left ventricular mechanics and low free triiodothyronine levels after myocardial infarction: a prospective study

Low free triiodothyronine (fT3) levels following acute myocardial infarction (AMI) are associated with greater impairment in cardiac mechanics compared with patients with AMI who have normal values of thyroid hormones. The objectives are to investigate left ventricular (LV) function and mechanics during a 6-month follow-up after myocardial infarction and to evaluate their prognostic implication using two-dimensional (2D) echocardiography and 2D speckle-tracking echocardiography in patients with low fT3 levels. The study design is prospective cohort study. One hundred forty patients with first-onset AMI were grouped according to serum fT3 levels: low fT3 group (fT3 <3.2 pmol/L; n = 44) and control group (fT3 >3.2 pmol/L; n = 96). Low levels of fT3 were associated with greater LV diameters and LV end-diastolic volume, and decreased systolic LV function. Systolic apical and basal rotation, peak systolic global longitudinal strain and strain rate, and LV twist and torsion were significantly decreased in the low fT3 group. The prognostic implication for predicting low fT3 levels was evaluated using ROC analysis. LV end-diastolic diameter index is the most sensitive (94.12 %), but has low specificity (37.93 %; area = 0.659, p = 0.01). By contrast, LV end-systolic volume is the most specific (94.03 %), but has low sensitivity (26.32 %; area = 0.594, p = 0.04). Low fT3 levels are significantly associated with worse LV mechanics. Low fT3 levels are important for prediction of LV structure, function, rotation, and deformation parameters during the late post-myocardial infarction period.     

Drug therapy of ventricular tachycardia: a cost comparison of randomized noninvasive and invasive approaches.

OBJECTIVE: Economic evaluation of noninvasive (suppression of ventricular arrhythmias detected by ambulatory monitoring) and invasive (suppression of arrhythmias induced by programmed stimulation) approaches to antiarrhythmic drug selection for ventricular tachyarrhythmias. DESIGN/SETTING: Randomized clinical trial/tertiary-care hospital. PATIENTS: Of 124 consecutive patients referred for treatment of symptomatic ventricular tachyarrhythmias, 57 consenting patients were eligible to have drug therapy selected by either noninvasive or invasive approaches. MEASUREMENTS: Costs of initial and follow-up (26 +/- 15 months) admissions for the two groups were compared. This economic evaluation also considered relative efficacies of the approaches using the primary outcome variable of symptomatic, sustained ventricular tachyarrhythmia recurrence (including sudden death). RESULTS: Initial hospitalization for therapy selection was less costly by the noninvasive approach ($6,869 +/- 4,019) than by the invasive approach ($13,164 +/- 6,740) (P less than 0.001). However, the noninvasive approach generated higher follow-up hospital costs ($9,204 +/- 9,217) than the invasive approach ($3,784 +/- 4,944) (P = 0.01). Thus, total hospital costs of the noninvasive ($16,073 +/- 9,423) and invasive approaches ($16,949 +/- 7,174) were equivalent. The two-year actuarial probability of a recurrent, sustained, symptomatic ventricular tachyarrhythmia was greater in noninvasive (0.50 +/- 0.10) than in invasive (0.20 +/- 0.08) approach patients (P = 0.02). CONCLUSIONS: The lower initial hospital costs of the noninvasive approach are offset by greater follow-up costs. Within two years the costs of the two approaches are equivalent. Thus, greater antiarrhythmic efficacy can be achieved by the invasive approach to drug selection without increasing total hospital costs.     

Left ventricular mass and function before and after antihypertensive treatment

We have studied the effect of blood pressure control upon left ventricular mass and function. Twenty hypertensive patients without clinical or electrocardiographic signs of cardiac involvement were given sequentially: placebo for two weeks; captopril (250 mg/day) for eight weeks; and captopril (125 mg/day), alone or combined with chlorthalidone (25 mg/day), for eight weeks. M-mode echocardiography was performed at the end of placebo period, after eight and after 16 weeks active treatment. Blood pressure was significantly reduced (p less than 0.01) by therapy, the maximum decrease being observed at the end of the study. Similarly, interventricular septal thickness, posterior wall thickness and left ventricular mass index showed a significant reduction (P less than 0.01 at the eighth and P less than 0.001 at the 16th week), while no changes were detected in left ventricular function. Furthermore, both wall stress index at end-diastole and end-systolic stress were significantly lowered by treatment (at the 16th week P less than 0.01 and P less than 0.001, respectively). Baseline systolic blood pressure was inversely correlated with the ratio of the left ventricular radius to posterior wall thickness (r = -0.97, P less than 0.001) but no relation was found between post-treatment fall in either systolic or diastolic blood pressure and left ventricular mass index. After treatment more patients showed normal left ventricular wall thickness in relation to systolic blood pressure. We conclude that in uncomplicated hypertensive patients captopril, either alone or combined with chlorthalidone, can reverse left ventricular hypertrophy by decreasing both septal and posterior wall thickness.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropsychiatric manifestations after mefloquine therapy for Plasmodium falciparum malaria: comparing a retrospective and a prospective study

Mefloquine has been increasingly used for treatment of chloroquine-resistant malaria since its introduction in the late 1970s. In 1987 the first case of toxic encephalopathy was published, and in 1989 the WHO initiated reporting and investigation of neuropsychiatric adverse reactions of mefloquine. Neuropsychiatric adverse drug reactions are now well documented. We compared an open prospective 3 year study including all patients with P. falciparum treated with mefloquine with an earlier published, retrospective study on a comparable population from our department covering the period up to 1989.dollar;>In the retrospective study neuropsychiatric adverse effects were not specifically asked for, while in the prospective study possible adverse reactions were registered daily according to a specified questionnaire. No case of neuropsychiatric adverse reaction was registered in the retrospective study. In the prospective study, 28% had one or more neuropsychiatric adverse reactions, although severity was mostly mild to moderate. Other adverse reactions occurred in 96% in the retrospective study compared to 81% in the prospective study. In conclusion: one often finds only what one looks for, e.g adverse events may be overlooked for a decade, if relatively uncommon. This report also shows that retro- and prospective studies may give very different results.