Evaluating the treatment of hypertension in diabetes mellitus: a need for better control?

Objectives To determine how well and to what extent blood pressure (BP) is controlled in diabetic hypertensive patients treated by primary care doctors, and to evaluate drug therapy in the backdrop of risk factors and laboratory findings. Methods A therapeutic audit of the medical records of diabetic hypertensives from nine primary care health centres in Bahrain. Results In 266 diabetic hypertensives (82 males and 184 females), the recommended target BP < 130/< 85 mmHg (WHO/ISH guidelines, 1999) was achieved in 20 (9.8%) with a BP of 119 ± 4/76 ± 5 mmHg. Among those who did not achieve target BP, 70 (34.5%) lacked systolic BP control (BP = 153 ± 17/79 ± 3 mmHg), four (2%) lacked diastolic BP control (BP = 123 ± 3/86 ± 3 mmHg) and 109 (53.7%) lacked both systolic and diastolic BP control (BP = 158 ± 20/94 ± 7 mmHg). The mean age of the group achieving target BP was significantly lower than the group which lacked systolic BP control (51.6 ± 9 vs. 63.5 ± 9 years; P < 0.0001). While there were no significant differences in fasting blood glucose, glycosylated haemoglobin, triglycerides, urea, creatinine, uric acid and serum electrolytes between the group achieving target BP vs. groups without target BP, a significant difference in total cholesterol was seen. Patients with ischaemic heart disease and/or isolated systolic hypertension did not achieve the target BP. Antihypertensive monotherapy was prescribed in 145 (54.5%) patients, whereas two‐ and three‐drug combinations were prescribed in 32.3 and 8.2% of patients, respectively. As monotherapy, angiotensin‐converting enzyme (ACE) inhibitors were the most frequently prescribed drugs followed by β‐blockers, calcium channel blockers (CCBs) and diuretics. As two‐drug combinations, an ACE inhibitor with a β‐blocker/diuretic and a β‐blocker with a CCB/diuretic were usually prescribed. Conclusions According to the WHO/ISH 1999 guidelines, approximately one out of 10 diabetic hypertensives achieved target BP control. In many instances, the drug therapy prescribed was inappropriate considering the comorbidity in patients and their laboratory findings. Improved BP control is needed in treating high‐risk groups such as patients with diabetes mellitus, and efforts should be made to improve the treatment of hypertension in the primary care setting.     

Results of a pilot pharmacotherapy quality improvement program using fixed-dose,combination amlodipine/benazepril antihypertensive therapy in a long-term care setting

BACKGROUND: Hypertension is common in older adults (aged > or =65 years). Treatment frequently requires multiple medications and can be expensive. OBJECTIVE: This study measured the impact of substituting low-dose, fixed-combination therapy using the calcium channel blocker (CCB) amlodipine and the angiotensin-converting enzyme (ACE) inhibitor benazepril for high-dose CCB monotherapy or dual therapy with a CCB and an ACE inhibitor on antihypertensive drug costs, the incidence of adverse events, and blood-pressure control. METHODS: A multicenter, pilot pharmacotherapy quality improvement program was undertaken in a long-term care facility setting. Consultant pharmacists reviewed pharmacy records and medical charts from long-term care facilities, identifying older patients with a diagnosis of hypertension who either took CCB concomitantly with an ACE inhibitor or experienced adverse events on high-dose CCB therapy. Eligible patients were identified and their physicians contacted regarding switching them to fixed-dose combination therapy. RESULTS: A total of 51 patients at 17 facilities were switched to fixed-dose amlodipine/benazepril combination therapy; 94.1% were women and 5.9% were men (mean age, 85.1 years; range, 64-99 years). The mean number of comorbidities was 1.6. During the subsequent 2 months, mean blood pressure remained at levels similar to those at baseline. The number of patients reporting at least 1 drug-related adverse event decreased by 81.8% (P < 0.05), and the incidence of edema decreased by 75.0%. The mean per-patient cost of antihypertensive drugs decreased by 33.1% (P < 0.001), a mean per-patient savings of 19.21 US dollars per month. CONCLUSION: In patients aged > or =65 years with hypertension in long-term care facilities, a change from high-dose CCB monotherapy or CCB/ACE-inhibitor dual therapy to fixed-dose combination amlodipine/benazepril therapy significantly reduced drug costs and the incidence of adverse events and maintained blood-pressure control.     

Rational pharmacotherapy of hypertension in the elderly: analysis of the choice and dosage of drugs

OBJECTIVES: To determine in older people with uncomplicated hypertension: (a) the pattern of prescribing of antihypertensives; (b) the extent of physicians' adherence to recommendations on dosage for antihypertensive combinations; (c) whether prescribing practice conforms with recommended therapeutic guidelines; and (d) the frequency of prescribing of other drugs which have the potential to alter the efficacy of antihypertensive agents. METHODS: A survey of prescribing in older patients with uncomplicated hypertension in primary care setting of Bahrain was conducted. RESULTS: Of the 432 (56.5%) patients on monotherapy, 192 (44.4%) were treated with beta-blockers, 87 (20.1%) with calcium channel blockers (CCBs), 53 (12.3%) with alpha-methyldopa, 47 (10.9%) with diuretics, 46 (10.6%) with angiotensin converting enzyme (ACE) inhibitors, and 7 (1.6%) with hydralazine. Of the 1146 patients on mono- or combination therapies, 434 (56.8%) were treated with beta-blockers, 244 (31.9%) with diuretics, 211 (27.6%) with CCBs, 139 (18.2%) with ACE inhibitors, 103 (13.5%) with alpha-methyldopa 8 (1.0%) with brinerdine and 7 (0.9%) with hydralazine. In the 332 (43.5%) patients on combination therapy, 15 different two- and three-antihypertensive drug combinations were prescribed: a diuretic with a beta-blocker (37.2%) and a beta-blocker with either a CCB (20.9%) or an ACE inhibitor (12.4%) were the most popular two-drug regimens. The most commonly prescribed triple drug regimens were a diuretic and a beta-blocker plus either a CCB (26.1%) or an ACE inhibitor (17.4%) and diuretic plus an ACE inhibitor and a CCB (15.2%). Daily dosage of beta-blockers, ACE inhibitors and alpha-methyldopa were somewhat high in a considerable proportion of patients on both mono- and combined therapies. A substantial proportion (9.7%) of patients on monotherapy were treated with immediate release nifedipine. CONCLUSION: The pharmacotherapy of hypertension in elderly patients was found in some instances not to conform to recommended guidelines. For certain classes of antihypertensive agent such as beta-blockers, ACE inhibitors and alpha-methyldopa, neither the principles of geriatric pharmacology nor of antihypertensive combination therapy, and in particular, the need to reduce daily dosage, were followed. The use of immediate release nifedipine in the elderly is irrational, and instead, the use of long-acting dihydropyridine CCBs should be considered. The results of long-term randomized clinical trials published during the last decade have had a minimal impact on clinical practice of primary care physicians in Bahrain.     

β‐Blocker in Post‐Myocardial Infarct Survivors with Preserved Left Ventricular Systolic Function

Background: Long‐term β‐blockade therapy is beneficial in post‐myocardial infarct (MI) patients with left ventricular (LV) dysfunction; nevertheless, its benefit in post‐MI patients with preserved LV function remains unclear. The objective of this study is to investigate the effects of long‐term β‐blockade therapy on the clinical outcomes in post‐MI patients with preserved LV function. Hypothesis: The beneficial effects of long‐term β‐blockade therapy in post‐MI patients with impaired LV function may extend to those with preserved LV function. Methods: Of 617 consecutive post‐MI patients referred for cardiac rehabilitation program, 208 patients (age: 62.7 ± 0.8 years; male: 76%) with preserved LV function (ejection fraction ≥ 50%), negative exercise stress test, and on angiotensin‐converting enzyme inhibition were studied. Results: Baseline characteristics were comparable between patients on β‐blocker (n = 154) and not on β‐blocker (n = 54). After a mean follow‐up of 58.5 ± 2.7 months, 14 patients not on β‐blocker (26%) and 14 patients on β‐blocker (9%) died with hazard ratio (HR) of 2.5 (95% confidence interval [CI]: 1.25–6.42, P = 0.01). Likewise, patients not on β‐blocker had a higher incidence of cardiac death (HR: 3.0, 95% CI: 1.07–12.10, P = 0.04), and non‐sudden cardiac death (HR: 10.1, 95% CI: 1.82–89.65, P = 0.01), but not sudden cardiac death compared with patients on β‐blocker (HR: 1.6, 95% CI: 0.34–7.61, P = 0.54). A Cox regression analysis revealed that only advanced age (≥75 years; HR: 2.55, 95% CI: 1.18–5.49, P = 0.02) and the absence of β‐blocker (HR: 2.41, 95% CI: 1.14–5.09, P = 0.02) were independent predictors for mortality. Conclusion: β‐blocker use was associated with a decrease in overall mortality and cardiac death in post‐MI patients with preserved LV function. (PACE 2010; 33:675–680)     

When antihypertensive monotherapy fails: fixed-dose combination therapy

BACKGROUND: Antihypertensive monotherapy fails to control blood pressure in many patients. METHODS: Data on the efficacy and tolerance of fixed dose angiotensin-converting enzyme (ACE) inhibitor/calcium antagonist combinations were reviewed, since they are the most widely prescribed medications for hypertension. RESULTS: A fixed-dose combination of two drug classes is an option for hypertension treatment. Four fixed-dose ACE inhibitor/calcium antagonist combinations are available. They achieve superior blood pressure control with no increase in adverse events compared with their monotherapy components. In addition, they antagonize some class-specific adverse effects and may exhibit beneficial effects on target organ disease, such as renal dysfunction and left ventricular hypertrophy. CONCLUSIONS: Fixed-dose combination therapy is an attractive option when reasonable doses of initial antihypertensive monotherapy fail. Use of such combinations could increase patient compliance, by virtue of better tolerance compared with increased-dose monotherapy and simplicity of administration.     

The dilemma of monotherapy or combination therapy in community‐acquired pneumonia

Scope

To study the factors associated with mortality in hospitalized patients with community‐acquired pneumonia treated with monotherapy or combination therapy.

Methods

PubMed and Scopus were searched. Patients receiving macrolides, β‐lactams and fluoroquinolones, as monotherapy or in combination, were included. Meta‐analyses and meta‐regressions were performed.

Results

Fifty studies were included. Overall, monotherapy was not associated with higher mortality than combination (RR 1.14, 95% CI 0.99‐1.32, I² 84%). Monotherapy was associated with higher mortality than combination in North American and retrospective studies. β‐lactam monotherapy was associated with higher mortality than β‐lactam/macrolide combination in the primary (1.32, 1.12‐1.56, I² 85%) and most sensitivity analyses. There was no difference in mortality between fluoroquinolone monotherapy and β‐lactam/macrolide combination (0.98, 0.78‐1.23, I² 73%). In meta‐regressions, the moderators that could partially explain the observed statistical heterogeneity were the frequency of cancer patients (P = .03) and Pneumonia Severity Index score IV (P = .008).

Conclusion

Due to the considerable heterogeneity and inclusion of unadjusted data, it is difficult to recommend a specific antibiotic regimen over another. Specific antibiotic regimens, study design and the characteristics of the population under study seem to influence the reported outcomes.     

Combination therapy with ACE inhibitors/angiotensin II receptor antagonists and diuretics in hypertension

Essential hypertension is a very heterogeneous disease and different pressor mechanisms might interact to increase blood pressure. It is therefore not surprising that antihypertensive drugs, given as monotherapy, normalize blood pressure in only a fraction of hypertensive patients. This is, for instance, the case for diuretics, angiotensin converting enzyme (ACE) inhibitors and angiotensin II (AT₁) receptor antagonists administered as single agents. The rationale for combining antihypertensive agents relates in part to the concept that the blood pressure-lowering effect may be enhanced when two classes are coadministered. Also, combination therapy serves to counteract counter-regulatory mechanisms that are triggered whenever pharmacologic intervention is initiated and that act to limit the efficacy of the antihypertensive medication. For example, the compensatory rise in renin secretion induced by sodium depletion may become the predominant factor sustaining high blood pressure. Simultaneous blockade of the renin–angiotensin system, with either an ACE inhibitor or an AT₁receptor blocker, makes this compensatory hyper-reninemia ineffective and allows maximum benefit from sodium depletion. The combination of a blocker of the renin–angiotensin system and a low dose of a diuretic increases the effectiveness, but not at the expense of tolerability compared with the individual components administered alone. Fixed-dose combinations containing an ACE inhibitor or an AT₁receptor blocker and a diuretic are therefore likely to become increasingly used not only as second-line therapy but also as first-line treatment.     

How infectious disease outbreaks affect community-based primary care physicians: Comparing the SARS and H1N1 epidemics

Objective

To compare how the infectious disease outbreaks H1N1 and severe acute respiratory syndrome (SARS) affected community-based GPs and FPs.

Design

A mailed survey sent after the H1N1 outbreak compared with the results of similar survey completed after the SARS outbreak.

Setting

Greater Toronto area in Ontario.

Participants

A total of 183 randomly selected GPs and FPs who provided office-based care.

Main outcome measures

The perceptions of GPs and FPs on how serious infectious disease outbreaks affected their clinical work and personal lives; their preparedness for a serious infectious disease outbreak; and the types of information they want to receive and the sources they wanted to receive information from during a serious infectious disease outbreak. The responses from this survey were compared with the responses of GPs and FPs in the greater Toronto area who completed a similar survey in 2003 after the SARS outbreak.

Results

After the H1N1 outbreak, GPs and FPs still had substantial concerns about the effects of serious infectious disease outbreaks on the health of their family members. Physicians made changes to various office practices in order to manage and deal with patients with serious infectious diseases. They expressed concerns about the effects of an infectious disease on the provision of health care services. Also, physicians wanted to quickly receive accurate information from the provincial government and their medical associations.

Conclusion

Serious community-based infectious diseases are a personal concern for GPs and FPs, and have considerable effects on their clinical practice. Further work examining the timely flow of relevant information through different health care sectors and government agencies still needs to be undertaken.     

Effectiveness of the fixed-dose combination of olmesartan/amlodipine/hydrochlorothiazide for the treatment of hypertension in patients stratified by age,race and diabetes,CKD and chronic CVD

The prevalence of hypertension is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and chronic cardiovascular disease (CVD), as well as in black and elderly subjects. In addition, these subjects have the lowest control of blood pressure (BP) among the hypertensive population, and also the risk of having a morbid or fatal cardiovascular event >20% in 10 years. For these reasons, aggressive control of BP to <130/80 mm Hg for these subjects is strongly recommended by National and International guidelines. To accomplish this goal, combination therapy with two or more antihypertensive drugs with a complementary mechanism of action is necessary. Drugs that block the renin–angiotensin system (RAS) in combination with a calcium channel blocker (CCB) and a diuretic have been shown to be the most effective combinations to accomplish this goal. However, this will require the administration of multiple drugs given separately, which will decrease the patient compliance and adherence to treatment. Poor patient compliance and adherence to treatment is a major factor for poor BP control. Several studies have shown that patient compliance is inversely related to the number of drugs being administered. To overcome this problem, several dual and triple-drug, fixed-dose combinations with a RAS blocker, a CCB and a diuretic have been developed and marketed, which are easier to administer, and have been shown to increase patient compliance and adherence to treatment. In this concise review, the effectiveness and safety of the fixed-dose, triple-combination of the RAS blocker olmesartan medoxomil, the CCB amlodipine besylate and the diuretic hydrochlorothiazide, as well as other similar combinations for the treatment of hypertension, will be discussed. These drug combinations have been shown to be effective, safe and well tolerated by most patients.     

Patterns of visits to physicians' offices, 1980 to 2003

In the past quarter century, the number of office visits to physicians in the United States increased from 581 million per year to 838 million per year, with slightly more than one half of total visits since 1980 being made to primary care physicians. Most visits to primary care physicians were made to family physicians (FPs) and general practitioners (GPs) until the mid 1990s, when visits to general internists and general pediatricians exceeded visits to FPs and GPs.     

Effect on the development of ankle edema of adding delapril to manidipine in patients with mild to moderate essential hypertension: a three-way crossover study

BACKGROUND: Use of the combination of an angiotensin-converting enzyme inhibitor (ACEI) and a calcium channel blocker (CCB) is considered a rational approach in patients whose hypertension is not controlled by monotherapy, providing better blood pressure (BP) control than the individual components with a lower incidence of adverse effects. In particular, such combinations have been found to reduce the incidence of ankle edema, the most common adverse effect of dihydropyridine annhypertensives. OBJECTIVE: The present study was undertaken to evaluate the effect on the development of ankle edema of adding the ACEI delapril to the CCB manidipine in patients with mild to moderate essential hypertension. METHODS: Patients between the ages of 30 and 70 years who had mild to moderate hypertension (diastolic BP [DBP] >90 and <110 mm Hg) were included in the study. After a 4-week placebo run-in period, eligible patients were randomized to receive 6 weeks each of manidipine 10 mg/d, delapril 30 mg/d, and both in a crossover fashion. There was a 2-week washout period between treatments. Ankle edema was assessed based on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP). Sitting BP, AFV, and PSTP were measured at the end of the placebo run-in period and the end of each active-treatment period. RESULTS: The study enrolled 40 patients with previously untreated hypertension (21 women, 19 men). Both manidipine and delapril monotherapy were associated with significant reductions from baseline in systolic BP (SBP) (mean [SD], -17.3 [4] and -14.8 [4] mm Hg, respectively; both, P<0.01) and DBP (-14.6 [3] and -12.9 [3] mm Hg; both, P<0.01). Compared with monotherapy, the combination of manidipine and delapril was associated with greater reductions from baseline in SBP (-21.8 [5] mm Hg; P<0.001) and DBP (-18.6 [4] mm Hg; P<0.001). Manidipme monotherapy was associated with significant increases from baseline in both AFV (7.9%; P<0.001) and PSTP (36.6%; P<0.01). Compared with manidipine alone, the combination of manidipine and delapril was associated with less pronounced increases in AFV (3.3%; P<0.05) and PSTP (10.4%; P<0.05). Ankle edema was clinically evident in 3 patients after receipt of manidipine monotherapy and in 1 patient after receipt of combination treatment. CONCLUSION: In these patients with mild to moderate essential hypertension, the addition of delapril to manidipine partially counteracted the manidipine-induced microcirculatory changes responsible for ankle edema.     

Use of antimigraine treatments by general practitioners

(Headache 2011;51:1122‐1131) Objectives.— To assess headache treatment patterns in 2 groups: general practitioners (GPs) who suffered from migraine themselves (GP‐M) and GPs having a close family member with migraine (GP‐CFM). The secondary objective was to assess the impact of migraine on activities of daily living in these 2 groups. Background.— Personal experience of migraine may influence prescribing practices of physicians treating patients with migraine. Little data are available on perceptions of migraine by GPs. Methods.— This was an observational, cross‐sectional, pharmacoepidemiological survey conducted in primary care in France. Most GPs completed 1 of 2 questionnaires, and GPs belonging to both groups could complete both. Data were collected on headache treatments used (GP‐M) or prescribed (GP‐CFM), and on self‐reported (GP‐M) or described (GP‐CFM) migraine features and impact on daily activities. Results.— The most frequently reported acute headache treatments in both groups were triptans and non‐steroidal anti‐inflammatory drugs (>75% of GPs); >81% of GPs in both groups were satisfied with acute headache treatments. Only 6.9% of the GP‐M group used and 17.2% of the GP‐CFM group prescribed a prophylactic treatment, which was considered satisfactory by 46.2% and 56.1%, respectively. In the preceding 3 months, 79.4% of the GP‐M group reported handicap in daily activities due to migraine, 23.6% interruption of extraprofessional activities and 7.6% interruption of work. In the GP‐CFM group, 32.6% described interruption of extraprofessional activities and 57.3% interference with daily activities or work. Conclusions.— Acute headache treatment prescribed by French GPs for their own migraines or those of their relatives respect practice guidelines and is considered as effective and satisfactory. Use of prophylactic medication is low and its effectiveness perceived as limited. Better use of prophylactic treatments may attenuate the impact of migraine on daily activities.     

Long-term blood pressure control: what can we do?

There are unique problems associated with the long-term control of blood pressure (BP) in patients with hypertension. Many of these problems warrant specific discussion for the primary care physician. Up to one-third of high-risk patients are estimated to have uncontrolled hypertension. Although long-term control is essential to avoid complications of cardiovascular disease, such as myocardial infarction, stroke, heart failure, and kidney disease, it can become troublesome because of challenges with patient compliance and adherence to medication regimens. This may be due to low tolerability profiles, complicated regimens, or prohibitive costs. Trials have shown that a combination approach may reduce side effects with complementary therapies such as a calcium channel blocker (CCB)/angiotensin receptor blocker (ARB) combination. Combination therapy can be used in any patient group not responsive to monotherapy, or who remain 20 mm Hg higher than their BP goal. This method may achieve the goal of reaching target BP sooner as a first-line approach and, in a fixed-dose combination, may be a more economic choice as well as a simpler regimen for the patient. Together with supportive measures, CCB/ARB combinations are a compelling alternative for the long-term treatment of hypertension.     

Heart rate recovery improvement in patients following acute myocardial infarction: exercise training, β‐blocker therapy or both

Heart rate recovery (HRR) is a strong mortality predictor. Exercise training (ET) and β‐blocker therapy have significant impact on the HRR of patients following myocardial infarction (MI). However, the combination of ET and β‐blocker therapy, as well as its effectiveness in patients with a more compromised HRR (≤12 bpm), has been under‐studied. Male patients (n = 64) post‐MI were divided: Training + β‐blocker (n = 19), Training (n = 15), β‐blocker (n = 11) and Control (n = 19). Participants performed an ergometric test before and after 3 months of intervention. HRR was obtained during 5 min of recovery and corrected by the cardiac reserve (HRR_corrCR). Compared to pre‐intervention, HRR_corrCR was significantly increased during the 1st and 2nd minutes of recovery in the Training + β‐blocker group (70·5% and 37·5%, respectively; P<0·05). A significant improvement, lasting from the 1st to the 4th minute of recovery, was also observed in the Training group (47%, 50%, 25% and 8·7%, respectively; P<0·05). In contrast, the β‐blocker group showed a reduction in HRR_corrCR during the 2nd and 3rd minutes of recovery (?21·2% and ?16·3%, respectively; P<0·05). In addition, interventions involving ET (Training + βb, Training) were significantly more effective in patients with a pre‐intervention HRR ≤ 12 bpm than for patients with HRR > 12 bpm. Combination of β‐blocker therapy with ET does not compromise the effect of training and instead promotes HRR and aerobic capacity improvement. In addition, this combination is particularly beneficial for individuals presenting with a more compromised HRR. However, chronic administration of β‐blocker therapy alone did not promote improvement in HRR or aerobic capacity.     

Evaluation of drug therapy and risk factors in diabetic hypertensives: a study of the quality of care provided in diabetic clinics in Bahrain

OBJECTIVE: To evaluate control of blood pressure (BP) and diabetes and the associated risk factors in diabetic hypertensives treated by diabetic clinic primary care physicians. METHODS: A retrospective analysis of the medical records of diabetic hypertensives from six primary care diabetic clinics in Bahrain. RESULTS: The recommended BP target <130/<85 mmHg and of glycosylated haemoglobin (HbA1C) <7% were achieved in 7.5% and 14.5%, respectively. Most of the patients with uncontrolled BP and HbA(1C) were at high cardiovascular risk. More patients were on antihypertensive monotherapy than on combination therapy (60.6% vs. 36.7%; P<0.0001). The recommended two- and three-antihypertensive drug combinations were less often prescribed. In high-risk patients glycaemic control achieved was poor: antidiabetic combination therapy vs. monotherapy did not significantly differ. Inappropriate prescribing practices, such as the use of immediate-release nifedipine monotherapy, use of sulphonylurea instead of metformin in obese patients, and a trend towards prescribing of glyburide rather than a gliclazide in the elderly, were observed. Lipid-lowering (13.5%) and antiplatelet (12.8%) drugs were infrequently prescribed. CONCLUSIONS: Hypertension and diabetes in patients treated at the primary care diabetic clinics were inadequately controlled. In several instances, mono- and combination antihypertensives prescribed were irrational. Lipid-lowering and platelet aggregation inhibition strategies have received little attention. Intensive antihypertensive and antidiabetic complementary combination therapy should be encouraged. Continuous professional education of diabetic clinic physicians and expert-supervised diabetic clinics are desirable.