The association between compliance with antihypertensive drugs and modification of antihypertensive drug regimen

BACKGROUND: Non-compliance is an important factor in lack of control of blood pressure. Uncontrolled blood pressure, as well as patients' complaints about the prescribed medication, may lead to modification of the initially prescribed antihypertensive drug regimen. The objective of this study was to assess the association between non-compliance and change in medication regimen. METHODS: A nested case-control study within a cohort of new users of antihypertensive drugs between 1 January 1999 and 31 December 2002. We used data from the PHARMO database, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 subjects. Cases were subjects whose initial drug regimen was modified. Controls did not undergo such a modification. Conditional logistic regression was used to calculate odds ratios (OR) and their 95% confidence intervals (CI), and to adjust for confounders. RESULTS: In a cohort of 39,714 new users of antihypertensive drugs, we identified 11,937 cases and 11,937 matched controls. The percentage of non-compliant patients (compliance < 80%) among cases and controls was 5.1 and 3.6%, respectively [OR 1.39 (95% CI: 1.22-1.58)]. The association is stronger in females [OR 1.64 (95%CI: 1.37-1.94)] than in males [OR 1.14 (95% CI: 0.94-1.40)] and stronger if the duration of episode of use is longer than 6 months. CONCLUSION: Non-compliance is significantly associated with the occurrence of change in antihypertensive medication regimen. Pharmacists and physicians can use pharmacy data, although data tend to overestimate actual compliance, to assess and improve compliance with antihypertensive drugs, before modifying treatment regimens.     

The effect of antihypertensive drugs on vascular compliance

Measurement of vascular compliance has assumed increasing importance as a marker of early disease of the vascular wall, a predictor of future vascular disease, and a way to monitor the effects of vasoactive agents on arterial wall stiffness. Vascular compliance can be estimated by several methods: measurement of the pulse pressure, or pulse pressure-stroke volume ratio; analysis of the systolic pulse wave augmentation index and the diastolic pulse wave contour; ultrasonic echo-tracking; and MRI. Because few comparative studies have been done, the physiologic significance of the measures of compliance obtained by each method is uncertain. Antihypertensive drugs may improve vascular compliance by reducing blood pressure, relaxing vascular smooth muscle, or promoting long-term effects on vascular smooth muscle and cardiomyocyte growth and remodeling. Angiotensin converting enzyme (ACE) inhibitors have been reported to improve vascular compliance in nearly all studies, suggesting a beneficial class effect independent of blood pressure reduction. Favorable changes in the vascular wall-lumen ratio of small vessels from subcutaneous gluteal biopsy specimens after treatment with ACE inhibitors and the persistence of improved vascular compliance after withdrawal of therapy indicate that these agents may produce long-term vascular remodeling. Although few studies have been done, angiotensin II receptor antagonists improve vascular compliance, possibly by blocking angiotensin II-mediated cell proliferation and increasing apoptosis via unopposed AT1 receptor stimulation. In contrast, calcium antagonists and b-blockers have variable effects on vascular compliance, although b-blockers with intrinsic sympathomimetic activity improve vascular compliance. Diuretics have little effect on vascular compliance beyond their blood pressure-lowering actions, except for spironolactone, which by improving vascular compliance may have contributed to the reduction in heart failure mortality seen in the Randomized Aldactone Evaluation Study.     

696例高血压患者降压药物治疗效果分析

目的：了解原发性高血压（EH）患者的药物疗效,以便进一步提高高血压的控制率。方法：选择2009年12月至2011年12月连续2年来我院体检的4300人为对象,通过每年1次的健康体检和门诊治疗进行观察,并对696例高血压患者的降压药疗效进行统计分析。结果：4300例体检者中,确定为原发性高血压的患者810例（患病率18．8％）,其中696例（治疗率85．9％）患者使用口服降压药物治疗,单药治疗318例（45．7％）,联合用药治疗378例（54．3％）;高血压控制率90．8％（632／696）,其中单药控制率86．8％（276／318）,两药联用控制率94．70%（230／243）,三药联用控制率94．8％（55／58）,四药联用或固定复方制剂控制率92．2％（71／77）,联合用药组血压控制率显著高于单药治疗组（P〈0．05或〈0．01）。联合治疗中以钙拈抗剂使用率（57．9％）最高,其次为血管紧张素Ⅱ受体抑制剂使用率（42．2％）。结论：对于高血压患者联合用药血压控制率显著高于单药治疗。     

Microalbuminuria in patients with essential hypertension: effects of several antihypertensive drugs.

PURPOSE: Microalbuminuria can be present in 10% to 40% of patients with essential hypertension and is associated with an increased incidence of cardiovascular events. The effect of commonly used antihypertensive agents on urinary albumin excretion (UAE) has not been well established. The aim of this study was to evaluate the effects of a converting enzyme inhibitor, a calcium channel blocker, a beta blocker, and a diuretic on UAE and on creatinine clearance in patients with mild to moderate hypertension. PATIENTS AND METHODS: We prospectively measured UAE prior to and 4 and 8 weeks after treatment with enalapril, nitrendipine, atenolol, or a diuretic in 48 patients with essential hypertension and microalbuminuria. RESULTS: All these agents were equally effective in reducing arterial pressure. However, enalapril but not the other agents significantly decreased UAE. CONCLUSION: Eight weeks of therapy with enalapril may reduce UAE in patients with mild to moderate essential hypertension, whereas other agents, such as nitrendipine, atenolol, or diuretics, had no measurable effect on UAE. The clinical and prognostic significance of these observations remains to be established.     

Long-term compliance with antihypertensive therapy: another facet of chronotherapeutics in hypertension

Despite improvements in the management of hypertension in the past several years and the numerous efficacious antihypertensive agents available to today's physician, nearly 70% of patients do not have their hypertension adequately controlled. Noncompliance with prescribed regimens appears to be one of the primary contributors to the large numbers of patients with uncontrolled hypertension. A behaviour that can affect all patients, noncompliance is perplexing because it remains largely unrecognized in clinical practice. Several types of noncompliance exist, the 'drug holiday' being the most common. Good communication with the patient and the entire health care team is essential to improving patient compliance. Long-acting medications that provide good control of blood pressure beyond the 24 h dosing period should be considered as the drugs of choice in noncompliant hypertensive patients. This article discusses different types of compliance, methods of measuring compliance, and the clinical consequences of noncompliance in hypertension.     

Beneficial effect of combination therapy with antihypertensive drugs in patients with hypertension

BACKGROUND: Cardiac hypertrophy and failure are major complications of hypertension. OBJECTIVES: The beneficial effect of treatment with antihypertensive drugs on serum levels of brain natriuretic peptide (BNP) was examined in patients with essential hypertension. METHODS: Antihypertensive drugs were administered to 88 hypertensive patients (44 diabetic and 44 nondiabetic) whose systolic blood pressure was greater than 140 mmHg and/or diastolic blood pressure was greater than 90 mmHg. Other antihypertensive drugs were added every two months until the blood pressure fell below 130/85 mmHg. Candesartan, benidipine, bisoprolol or celiprolol, and bunazosin were administered in this order. RESULTS: The mean systolic blood pressure was reduced from 163.7+/-11.6 mmHg to 121.8+/-7.5 mmHg after 12 months in patients with diabetes and from 167.6+/-12.3 mmHg to 122.8+/-7.5 mmHg in patients without diabetes. The mean diastolic blood pressure was also significantly reduced in patients with and without diabetes. Serum BNP levels were reduced from 52.2+/-38.8 pg/mL to 38.8+/-30.9 pg/mL in patients with diabetes and from 47.1+/-34.2 pg/mL to 35.8+/-22.5 pg/mL in patients without diabetes. In patients older than 70 years of age, serum BNP levels were reduced from 56.3+/-39.3 pg/mL to 40.2+/-23.0 pg/mL in those with diabetes and from 54.6+/-32.9 pg/mL to 38.0+/-16.0 pg/mL in those without diabetes. CONCLUSIONS: These results indicate that combination therapy with antihypertensive drugs is usually necessary to reduce blood pressure to below 130/85 mmHg and to improve serum BNP levels.     

Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension.

The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin hypertension. (3) A volume factor may be operating in patients with low renin hypertension since a hypotensive effect is demonstrated after the addition of volume-depleting drugs. (4) Determination of plasma renin activity with adequate methods can predict the treatment response to hypotensive agents.     

妊娠期高血压治疗中降压药物的应用进展

妊娠期高血压(HDCP)是妊娠期的特发疾病,以妊娠20周后出现高血压、水肿、蛋白尿为主要表现的全身各器官和系统损害的一种妊娠期并发症,严重影响母婴健康,是孕产妇和围生儿患病及死亡的主要原因之一[1,2]。降压治疗是HDCP的重要治疗手段,目的是预防子痫、心脑血管意外和胎盘早剥等严重母胎并发症,保证母儿安全,有效改善妊娠结局。我国2015年HDP诊治指南[3]参考了国际指南并结合我国国情建议:收缩压≥160 mmHg和(或)舒张压≥110 mmHg(1 mmHg=0.133 kPa)给予降压药物治疗,目标血压控制在130~155/80~105 mmHg,合并器官功能损伤,应控制130~139/80~89 mmHg,降压过程应平稳,避免过度波动,且血压不应低于130/80 mmHg,以保证子宫-胎盘的血流灌注[4]。     

Efficacy and tolerability of felodipine based antihypertensive therapy in hospitalized patients with hypertension

AIM: To compare efficacy and tolerability of felodipine based antihypertensive therapy with those of standard hospital treatment of hypertension. MATERIAL: Inhospital patients were randomized 1:2 to standard antihypertensive therapy or to therapy which included felodipine (n=50 and 100, 36 and 35% men, mean age 66.0+/-8.4 and 64.3+/-8.1 years, initial blood pressure 162.4+/-9.3/99.3+/-6.4 and 163.2+/-10.3/98.2+/-6.5 mm Hg, respectively). Felodipine was used: (1) as first drug with subsequent addition of other drugs as required; (2) after cessation of previously ineffective therapy; (3) in cases of intolerance to previous therapy, (4) as supplementation to previously insufficiently effective therapy. Results. At discharge in felodipine group 6, 25, 29 and 40% of patients received mono- (felodipine 10 mg/day), 2, 3 and 4 component therapy, respectively. In standard treatment group all patients received combination therapy with 3 (48%) or 4 (52%) drugs. Felodipine group compared with group of standard therapy was characterized by less frequent correction of antihypertensive therapy (0.8+/-0.6 and 2.2+/-0.9, p<0.05), smaller number of drugs used (3.03+/-0.95 and 3.52+/-0.5, p<0.01), more frequently achievement of target blood pressure level (88 and 64%, p=0.0075), less pronounced difference between morning and evening self-measured blood pressure. CONCLUSION: The use of felodipine in hospitalized patients with hypertension allowed achieving target blood pressure with fewer drugs. Felodipine was safe and well tolerated.     

Comparative effectiveness of antihypertensive drugs in nondiabetic patients with hypertension: A population‐based study

The authors compared the effectiveness of thiazide diuretic (TD), angiotensin‐converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and calcium channel blocker (CCB) monotherapies for the treatment of nondiabetic hypertension using MarketScan Databases 2010–2014. Multivariable Cox regression models assessed whether the addition of a new antihypertensive drug, treatment discontinuation, or switch and major cardiovascular or cerebrovascular events varied across groups. A total of 565 009 patients started monotherapy with ACEIs (43.6%), CCBs (23.6%), TDs (18.8%), or ARBs (14.0%). Patients who took TDs had a higher risk for either drug addition or discontinuation than patients who took ACEIs (hazard ratio [HR], 0.69 [95% CI, 0.68–0.70] vs HR, 0.81 [95% CI, 0.80–0.81]), ARBs (HR, 0.67 [95% CI, 0.66–0.68] vs HR, 0.66 [95% CI, 0.65–0.67]), and CCBs (HR, 0.85 [95% CI, 0.84–0.87] vs HR, 0.94 [95% CI, 0.93–0.95]). Conversely, patients who took TDs experienced a lower risk of clinical events compared with patients who took ACEIs (HR, 1.24 [95% CI, 1.15–1.33]), ARBs (HR, 1.28 [95% CI, 1.18–1.39]), and CCBs (HR, 1.35 [95% CI, 1.25–1.46]). Our results provide a strong rationale for choosing TDs as first‐line monotherapy for the control of hypertension.     

Efficacy of intravenous verapamil in arterial hypertension refractory to three-step antihypertensive therapy.

Intravenous verapamil infusion reduced the arterial pressure (AP) in 13 out of 71 (76.5%) patients with severe arterial hypertension (AH) refractory to a two-week, three-step oral antihypertensive medication. Investigations including echo- and radio-cardiography were performed: in the control period before starting the three-step treatment; after two weeks before intravenous verapamil infusions; 10 days after stopping the verapamil administration, and before leaving the hospital during continued 3-4 weeks three-step therapy. The AP reduction was caused by decreased total peripheral resistance. Verapamil administration improved also intracardiac haemodynamics and left ventricular contraction. The AP was effectively controlled even after stopping the verapamil administration and continuing the three-step oral antihypertensive treatment. No manifest changes in the left ventricular function were registered.     

Relationship between home blood pressure measurement and medication compliance and name recognition of antihypertensive drugs.

This study examined the relationship of home blood pressure measurement to medication compliance and name recognition of antihypertensive drugs in outpatients with hypertension. A total of 1,452 consecutive outpatients (842 males, 610 females; mean age 65+/-11 yr) seeking care at our institute answered questions at our cardiovascular outpatient clinic such as whether they had a sphygmomanometer at home, how often they measured their blood pressure at home, and how often they missed taking their medication. Among a total of 777 patients on antihypertensive drugs who had a sphygmomanometer at home, 16 of the 242 patients (6.5%) who measured their home blood pressure every day occasionally missed taking their medication, whereas this number was 22 for the 216 patients (10.1%) who measured their home blood pressure several times a week, 16 for the 146 patients (11.0%) who measured their home blood pressure several times a month, and 25 for the 173 patients (14.5%) who never measured their home blood pressure (p< 0.01 between patients who measured their home blood pressure every day and those who did not measure their home blood pressure). Among a total of 271 patients taking one or two antihypertensive drugs, the number of patients who could name their antihypertensive drugs was 47 of the 86 patients (55%) who measured their home blood pressure every day, 43 of the 78 patients (55%) who measured their home blood pressure several times a week, 24 of the 41 patients (58%) who measured their home blood pressure several times a month, and 22 of the 66 patients (33%) who never measured their home blood pressure (p< 0.02). In conclusion, medication compliance and antihypertensive drug name recognition were better in patients who measured their home blood pressure than in patients who did not measure their home blood pressure. From these results, we conclude that physicians should recommend home blood pressure measurement to patients being treated with antihypertensive drugs, because there is a possibility that home blood pressure measurement might improve medication compliance.     

Minoxidil in severe hypertension with renal failure. Effect of its addition to conventional antihypertensive drugs

Minoxidil, a new vasodilator antihypertensive compound, was given to 9 uremic patients with severe hypertension uncontrollable with currently available drugs. Addition of minoxidil in doses of 5 to 10 mg twice daily to their prior therapy, resulted in satisfactory control of blood pressure in all patients. Supine blood pressure fell from a control value of 200 ± 6/124 ± 3 to 164 ± 5/91 ± 2 mm Hg (mean and standard error) after administration of minoxidil, and no patient experienced orthostatic hypotension. Tachyphylaxis has not been seen during a follow-up period averaging 26 weeks. Side effects resulting from minoxidil have been limited to mild hypertrichosis in 2 patients, nausea in another 2 and fluid retention, which was readily controlled by either hemodialysis or furosemide. Minoxidil appears, therefore, to provide a means for controlling blood pressure in patients with severe hypertension resistant to all other antihypertensive drugs.     

Leukocyte intracellular cations in hypertension: Effect of antihypertensive drugs

Leukocyte (WBC) cations were determined in 32 normotensive control subjects and in 47 agematched patients with uncomplicated hypertension. The intracellular concentration of sodium (Na⁺) which averaged 25.5 mEq./Kg. wet cell weight (wcw) in the hypertensive patients was significantly higher (P <.01) than in the control subjects (average 19.7 mEq./Kg. wcw). Elevated WBC Na⁺ was observed only in the hypertensive patients under age 50 years. WBC potassium, magnesium, and percentage water content were not significantly different in hypertensive patients as compared to the control subjects. The finding of an increased intracellular Na⁺ content in hypertensive patients is consistent with recent observations relating the extracellular/intracellular Na⁺ gradient to vascular smooth muscle tension and to the control of the peripheral vascular resistance.WBC cations also were determined after treatment with hydrochlorothiazide, hydralazine, reserpine, or alpha methyldopa. Hydrochlorothiazide was associated with a reduction in WBC sodium content (P < .01). Reserpine also was associated with a lesser fall in WBC sodium (P < .05). Cell water content decreased slightly after hydrochlorothiazide (P < .05), but increased slightly following reserpine (P < .05). Changes in WBC, sodium, or water were not significant following alpha methyldopa or hydralazine. None of the drugs were associated with changes in WBC potassium or magnesium, although serum potassium concentration decreased significantly (P < .05) with hydrochlorothiazide.     

The effect of antihypertensive drugs on in vivo platelet activity in essential hypertension.

OBJECTIVE: To investigate whether antihypertensive drugs have a beneficial effect upon the abnormal in vivo platelet function found in patients with essential hypertension. DESIGN: A cross-sectional study in which plasma beta-thromboglobulin, a marker of in vivo platelet activation, was measured in patients with essential hypertension on various antihypertensive drugs. All were free from any other diseases which might affect platelet function. METHODS: Plasma beta-thromboglobulin was measured in 24 patients with untreated essential hypertension, 21 normotensive control patients, 16 patients receiving angiotensin converting enzyme (ACE) inhibitors, 16 patients receiving a beta-adrenoceptor blocker, 12 patients receiving calcium antagonists and 12 patients receiving a diuretic alone. RESULTS: Untreated hypertensives had significantly elevated plasma beta-thromboglobulin levels compared with controls. Plasma beta-thromboglobulin levels in patients receiving beta-blockers and diuretics were not significantly different from untreated hypertensives. Treatment with calcium antagonists was associated with lower plasma beta-thromboglobulin levels, but this difference was not statistically significant. In contrast, treatment with ACE inhibitors was associated with significantly lower plasma beta-thromboglobulin levels compared with untreated hypertensives. CONCLUSION: These results suggest that antihypertensive drugs have different effects upon abnormal in vivo platelet function in patients with essential hypertension. The apparent beneficial effect of ACE inhibitors may mean that they have more impact than other drug groups in the prevention of coronary heart disease.     

药师干预对老年高血压患者用药依从性的影响

目的：探讨接受药师药物咨询对老年高血压患者用药依从性的影响。方法：随机抽取确诊的高血压患者曾接受药师药物咨询者（药物咨询组）和仅接受常规药物治疗者（常规治疗组）,各80例,在治疗前及治疗后1个月及3个月后用Morisky调查问卷评价用药依从性。结果：干预前药物咨询组和常规治疗组患者用药依从性佳者比例分别为20％和21．2％,两组无明显差异（P〉0．05）,1个月及3个月后药物咨询组依从性佳者比例分别上升至42．5％及57．6％,较常规治疗组的22．5％和23．7％显著升高（P〈0．01）。3个月后药物咨询组血压达标率明显高于常规治疗组（60．0％比42．5％,P〈0．05）。结论：药师药物咨询可显著提高病人用药依从性和疗效,药师在提高用药疗效方面能发挥重要作用。     

Randomized-controlled trial of a telephone and mail intervention for alcohol use disorders: three-month drinking outcomes

BACKGROUND: Alcohol screening, brief intervention, and referral to specialized treatment (ASBIR) reduce drinking and related harms. Unanswered questions are how to manage nondependent patients with poor response to brief interventions, how to manage dependent patients who do not obtain treatment, and how to ensure population-wide delivery of ASBIR. Telephone-administered counseling may provide answers. METHODS: We conducted a 12-month randomized controlled trial of a telephone and mail intervention for non-treatment-seeking primary care patients with alcohol use disorders. We enrolled 897 subjects after systematic screening in 18 primary care clinic waiting rooms in and around Madison and Milwaukee, Wisconsin, and subsequent telephone-administered diagnostic interviews. Experimental subjects received up to six sessions of protocol-driven telephone counseling based on principles of motivational interviewing and stages of readiness to change. Control subjects received a pamphlet on healthy lifestyles. The paper reports on 3-month drinking outcomes for men and women with alcohol abuse and dependence. RESULTS: Male experimental subjects (N=199) manifested a 30.6% decline in risky drinking days, compared with a 8.3% decline in controls (N=201, p<0.001). The total consumption declined by 17.3% compared with 12.9% by controls (p=0.001). Female experimental subjects (N=246) manifested a 17.2% decrease in risky drinking days compared with an 11.5% decrease by controls (N=251; p=NS) and a 13.9% decline in total consumption compared with 11.0% by controls (p=NS). Greater numbers of telephone counseling sessions were associated with greater declines in drinking. CONCLUSION: Following systematic screening, a six-session telephone and mail intervention is more effective than a pamphlet in reducing drinking at 3 months for non-treatment-seeking men with alcohol abuse and dependence. An intervention effect of the enrollment procedures may have obscured further intervention effectiveness. Telephone counseling shows promise for non-treatment-seeking primary care patients with alcohol use disorders.     

Prospective comparison of endoscopy patient satisfaction surveys: e-mail versus standard mail versus telephone

OBJECTIVES: The dramatic growth of the Internet holds potential for use in survey distribution. Comparisons of electronic mail (e-mail) to traditional survey techniques are lacking. We compared standard mail, telephone, and e-mail modes of endoscopy satisfaction survey administration with respect to response rate, timeliness of response, response content, and cost-efficiency of responses. METHODS: An endoscopy satisfaction questionnaire consisting of seven core items from the modified Group Health Association of America-9 survey was distributed to patients after routine outpatient endoscopy. Patients were randomized to receive the questionnaire by standard mail, telephone, or e-mail. Response rates and findings in the three groups were compared. The "nonresponders" to the standard mail and e-mail surveys were subsequently contacted by telephone to determine their level of satisfaction. RESULTS: The phone survey response rate (90%) was higher than e-mail (70%) or standard mail (85%), although e-mail was the most cost-efficient mode of survey delivery. There was no significant difference in satisfaction scores among the three groups. Nonresponders were significantly more satisfied than "responders." CONCLUSIONS: A survey technique utilizing e-mail with subsequent follow-up by telephone to nonresponders appears to be the most cost-efficient way to deliver a questionnaire. The satisfaction levels of the responders may underestimate the overall satisfaction of the population being surveyed.