This paper describes use of the prescription records of a large pharmaceutical benefits management organization to retrospectively analyze the refill behavior of patients who have recently started antihypertensive therapy in the outpatient setting. Using logistic regression analysis, the author identified class of antihypertensive medication, patient age, and dosing frequency as clinically important independent covariates that are predictive of persistence (defined as continuing therapy with the original antihypertensive drug as originally prescribed) at 12 months. At 12 months' follow-up, the percentage of patients continuing initial angiotensin II (A-II) antagonist therapy was substantially higher than the percentage continuing therapy with angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers, or thiazide diuretics (64% vs 58%, 50%, 43%, and 38%, respectively). Additional studies are needed to explain why more patients continued with the same A-II antagonist therapy at 12 months compared with the other classes of antihypertensive drugs; whether these findings are explained by drug tolerability, financial incentives, newness of the product, selection bias, or other factors; whether these differences will be maintained in the following years; and whether the differences are associated with better health outcomes.

Left ventricular hypertrophy (LVH), as assessed by ECG or echocardiography, is a powerful independent coronary risk factor. The present overview of 104 studies sets out to compare the ability of various forms of antihypertensive therapy to reverse LVH as assessed by echocardiography. Most observations involved four classes of treatment--combination therapy, ACE inhibitors, beta-blockers and calcium antagonists (mainly dihydropyridines). The former two therapies were significantly more effective than the latter two in reversing LV mass, independently of length of time on treatment and degree of fall in blood pressure. Possible reasons for these differences are discussed. The clinical significance of these results is unclear although preliminary data indicate that regressing LVH is associated with fewer cardiovascular events.

BACKGROUND Noncompliance with antihypertensive therapy is a major problem that hinders successful hypertension management. OBJECTIVE To study antihypertensive drug persistence for hypertensive patients in routine clinical settings. METHODS Hypertensive patients were retrospectively studied (1994 through 1998) using databases managed by Saskatchewan Health. The study population (46,458 people) included all patients with an International Classification of Diseases-9 code of 401, 402, 403 or 404, or any four-digit code included in these categories, who received at least one antihypertensive therapy prescription during the first 4.5 years of the study and received no antihypertensive therapy 12 months before the dispensing of the first therapy. Prescriptions were placed into the following drug classes: angiotensin II antagonists, angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers and diuretics. Persistence was determined for four intervals in the patient's therapy at 180, 360, 540 and 720 days. RESULTS Drug class had a statistically significant (P<0.001) effect on persistence. Angiotensin II antagonists had the highest persistence followed by angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers and diuretics. Persistence decreased as the time interval increased. Females were significantly more persistent than males (P<0.005), and elderly patients were significantly more persistent than younger patients (P<0.001) at each of the four time intervals. For angiotensin II antagonists, age and sex did not affect persistence. CONCLUSIONS The consistently higher persistence associated with the use of angiotensin II antagonists may improve the management of hypertension.

PURPOSE To synthesize and analyze new information on the epidemiology, pathophysiology, and management of hypertension in the elderly to guide physicians making treatment decisions. DATA IDENTIFICATION An English-language literature search using MEDLINE (1972-1988) and bibliographic reviews of textbooks and review articles. STUDY SELECTION Primary research articles on the epidemiology, pathophysiology, and management of hypertension in the elderly were reviewed. Particular emphasis was placed on large randomized clinical trials. DATA EXTRACTION Study design and quality were assessed, with particular attention to subject selection, sample size, definition of outcome variables, and applicability of the results to management of the elderly hypertensive patient. RESULTS OF DATA SYNTHESIS Epidemiologic studies confirm that elevated systolic blood pressure in the elderly is more highly correlated with subsequent cardiovascular morbidity and mortality than is elevation of diastolic blood pressure. Results of several large randomized trials of the treatment of diastolic hypertension in elderly patients indicate that treatment is beneficial, at least up to age 80. For instance, the European Working Party on Hypertension in the Elderly reported that drug treatment resulted in a significant relative reduction (27%) in overall cardiovascular mortality, or an absolute reduction of 29 fewer cardiovascular events per 1000 person-years of treatment. Data from well-designed studies are not available to make a definitive statement about the treatment of isolated systolic hypertension. CONCLUSION The cardiovascular risk reduction from treating mild to moderate diastolic hypertension in the elderly is significant, but the magnitude of absolute risk reduction is not so great that treatment should invariably be pursued if serious side effects cannot be avoided.

OBJECTIVE.- To compare long-term plasma lipid changes among 6 antihypertensive treatment interventions for stage I (mild) hypertension. DESIGN.- Multicenter, randomized, double-blind, parallel-group clinical trial. SETTING.- Four academic clinical research units in the United States. PARTICIPANTS.- A total of 902 men and women, aged 45 to 69 years, with stage I diastolic hypertension (diastolic blood pressure <100 mm Hg), recruited from 11914 persons screened in their communities. INTERVENTIONS.- Participants were randomized to 1 of 6 treatment groups:(1) placebo,(2) beta-blocker (acebutolol),(3) calcium antagonist (amlodipine),(4) diuretic (chlorthalidone),(5) alpha1-antagonist (doxazosin), and (6) angiotensin-converting enzyme inhibitor (enalapril). All groups received intensive lifestyle counseling to achieve weight loss, dietary sodium and alcohol reduction, and increased physical activity. MAIN OUTCOME MEASURES.- Changes in plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides from baseline to annual visits through 4 years. RESULTS.- Mean changes in all plasma lipids were favorable in all groups. The degree of weight loss with fat-modified diet and exercise was significantly related to favorable lipid changes. Significant differences (P<.01) among groups for average changes during follow-up in each lipid were observed. Decreases in plasma total cholesterol and LDL cholesterol were greater with doxazosin and acebutolol (for plasma total cholesterol, 0.36 and 0.30 mmol/L [13.8 and 11.7 mg/dL], respectively), less with chlorthalidone and placebo (0.12 and 0.13 mmol/L [4.5 and 5.1 mg/dL], respectively). Decreases in triglycerides were greater with doxazosin and enalapril, least with acebutolol. Increases in HDL cholesterol were greater with enalapril and doxazosin, least with acebutolol. Significant relative increases in plasma total cholesterol with chlorthalidone compared with placebo at 12 months were no longer present at 24 months and beyond, when mean plasma total cholesterol for the chlorthalidone group fell below baseline. Analyses of participants continuing to receive chlorthalidone throughout the 4 years of follow-up indicated this was not due solely to an increasing percentage of participants changing or discontinuing use of medication during follow-up. CONCLUSIONS.- Weight loss with a fat-modified diet plus increased exercise produces favorable long-term effects on blood pressure and all plasma lipid fractions of adults with stage I hypertension; blood pressure reduction is enhanced to a similar degree by addition of a drug from any one of 5 classes of antihypertensive medication. These drugs differ quantitatively in influencing the degree of long-term favorable effects on blood lipids obtained with nutritional-hygienic treatment.

Heterogeneity of response to antihypertensive therapy is a well-recognized clinical phenomenon. An agent that is antihypertensive in one patient may increase blood pressure in another or have no effect in a third. We believe that this variety of individual response to drug treatment can provide a new framework for the study of hypertensive subjects. Different patterns of response elicited by sequential trials of individual drugs with different mechanisms of action (diuretics, calcium channel blockers, alpha-blockers, beta-blockers, and converting enzyme inhibitors) should provide another means to classify hypertensive patients into biologically relevant groups. The documentation and analysis of this therapeutic heterogeneity in relation to renin profiling and to other physiological and demographic parameters may add a new dimension to the investigation of the pathophysiology of hypertension; it may serve as a basis for more appropriate stratification of participants in clinical trials and may ultimately contribute to a more rational approach to patient management.

OBJECTIVE: To provide Canadian physicians with evidence-based guidelines for the pharmacologic treatment of hypertensive disorders in pregnancy. OPTIONS: No medication, or treatment with antihypertensive or anticonvulsant drugs. OUTCOMES: Prevention of maternal complications, and prevention of perinatal complications and death. EVIDENCE: Pertinent articles published from 1962 to September 1996 retrieved from the Pregnancy and Childbirth Module of the Cochrane Database of Systematic Reviews and from MEDLINE; additional articles retrieved through a manual search of bibliographies; and expert opinion. Recommendations were graded according to levels of evidence. VALUES: Maternal and fetal well-being were equally valued, with the belief that treatment side effects should be minimized. BENEFITS, HARMS AND COSTS: Reduction in the rate of adverse perinatal outcomes, including death. Potential side effects of antihypertensive drugs include placental hypoperfusion, intrauterine growth retardation and long-term effects on the infant. RECOMMENDATIONS: A systolic blood pressure greater than 169 mm Hg or a diastolic pressure greater than 109 mm Hg in a pregnant woman should be considered an emergency and pharmacologic treatment with hydralazine, labetalol or nifedipine started. Otherwise, the thresholds at which to start antihypertensive treatment are a systolic pressure of 140 mm Hg or a diastolic pressure of 90 mm Hg in women with gestational hypertension without proteinuria or pre-existing hypertension before 28 weeks' gestation, those with gestational hypertension and proteinuria or symptoms at any time during the pregnancy, those with pre-existing hypertension and underlying conditions or target-organ damage, and those with pre-existing hypertension and superimposed gestational hypertension. The thresholds in other circumstances are a systolic pressure of 150 mm Hg or a diastolic pressure of 95 mm Hg. For nonsevere hypertension, methyldopa is the first-line drug; labetalol, pindolol, oxprenolol and nifedipine are second-line drugs. Fetal distress attributed to placental hypoperfusion is rare, and long-term effects on the infant are unknown. Magnesium sulfate is recommended for the prevention and treatment of seizures. VALIDATION: The guidelines are more precise but compatible with those from the US and Australia.

OBJECTIVE Hypertension guidelines recommend initial treatment with a beta-blocker or diuretic and adding the other drug where blood pressure is not controlled. We hypothesized that systematic rotation through the major classes of antihypertensive drugs would demonstrate substantial differences in the pattern of an individual patient's response, and suggest a more rational approach to choosing best treatment. DESIGN Thirty-four young hypertensives (age 28-55, median 47) rotated in a double-blind, Latin-square, crossover fashion through 6 weeks of treatment each with amlodipine, doxazosin, lisinopril, bisoprolol, bendrofluazide and placebo. Blood pressure was measured at each visit.'Best' drug, defined by efficacy and tolerability, was repeated at the end. RESULTS Rotation doubled the number of patients reaching target blood pressure (systolic < 140 mmHg) on one drug (P = 0.03). All five drugs were represented among the 'best' drugs. In six patients, the blood pressure on 'best' drug was at least 10 mmHg lower than on any other. Response to the 'best' drug was highly correlated (r = 0.79) with its previous administration. By contrast, there were only weak correlations between responses to pairs of drugs, except for angiotensin-converting enzyme (ACE) inhibitor (A) with beta-blocker (B), and calcium blocker (C) with diuretic (D)- each r = 0.71, P < 0.005). In these young patients, the majority of patients (23/34) responded best to a drug suppressing the renin system (A and B). CONCLUSIONS Patients vary reproducibly in their response to initial treatment, and switching among drugs can increase the efficacy of monotherapy. The results support an AB/CD scheme for choosing therapy, in which the first drug is taken from one of these pairs, and uncontrolled patients switch to one of the other pair.