Initiation Of Drug Therapy Research Articles

Choice of initial antihypertensive drugs and persistence of drug use—a 4-year follow-up of 78,453 incident users

To investigate patterns of initial drug therapy for the treatment of hypertension and to evaluate treatment persistence and change of treatment during a 4-year period in patients receiving thiazides (TZs) and/or angiotensin II-receptor blockers (ARBs) as first-line treatment. All initial users of antihypertensive drugs in 2005 and 2009 registered in the Norwegian Prescription Database were included. Treatment on five index dates at 1-year intervals was recorded. A patient was considered to be under treatment on an index date if a drug had been dispensed within the previous 180 days and to have maintained treatment persistence if he/she was on any antihypertensive treatment on the index date and all previous index dates. Among 78,453 new users of antihypertensives in 2005, women started more often with TZs than men (30 vs. 25 %) and less often with ARBs (22 vs. 25 %). In men, the hazard of non-persistence with antihypertensive treatment was significantly lower among initial ARB users than among TZ users (hazard ratio 0.87, 95 % confidence interval 0.81-0.94); in women no significant difference was found. After 4 years, 49 % of the men and 51 % of the women who had started with plain TZs were still using TZs, whereas 65 % of the male ARB users and 60 % of the female ARB users were still using ARBs. TZs and ARBs were the most widely used first-line antihypertensives. Among the men enrolled in the study, ARB users had a somewhat better persistence with antihypertensive treatment than TZ users. Among both genders, continuation on ARBs was more common than continuation on TZs.

Pre-hospital treatment of STEMI patients. A scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the eff ectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

Crescendo in Depolarization and Repolarization Heterogeneity Heralds Development of Ventricular Tachycardia in Hospitalized Patients With Decompensated Heart Failure

A critical need exists for reliable warning markers of in-hospital life-threatening arrhythmias. We used a new quantitative method to track interlead heterogeneity of depolarization and repolarization to detect premonitory changes before ventricular tachycardia (VT) in hospitalized patients with acute decompensated heart failure. Ambulatory ECGs (leads V(1), V(5), and aVF) recorded before initiation of drug therapy from patients enrolled in the PRECEDENT (Prospective Randomized Evaluation of Cardiac Ectopy with Dobutamine or Nesiritide Therapy) trial were analyzed. R-wave heterogeneity (RWH) and T-wave heterogeneity (TWH) were assessed by second central moment analysis and T-wave alternans (TWA) by modified moving average analysis. Of 44 patients studied, 22 had experienced episodes of VT (≥4 beats at heart rates >100 beats/min) following ≥120 minutes of stable sinus rhythm, and 22 were age- and sex-matched patients without VT. TWA increased from 18.6±2.1 μV (baseline, mean±SEM) to 27.9±4.6 μV in lead V(5) at 15 to 30 minutes before VT (P<0.05) and remained elevated until the arrhythmia occurred. TWA results in leads V(1) and aVF were similar. RWH and TWH were elevated from 164.1±33.1 and 134.5±20.6 μV (baseline) to 299.8±54.5 and 239.2±37.0 μV at 30 to 45 minutes before VT (P<0.05), respectively, preceding the crescendo in TWA by 15 minutes. Matched patients without VT did not display elevated RWH (185.5±29.4 μV) or TWH (157.1±27.2 μV) during the 24-hour period. This investigation is the first clinical demonstration of the potential utility of tracking depolarization and repolarization heterogeneity to detect crescendos in electrical instability that could forewarn of impending nonsustained VT. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00270400.

Time to discontinuation among the three second‐generation antidepressants in a naturalistic outpatient setting of depression

This study compared the discontinuation time among the three second-generation antidepressants (paroxetine, venlafaxine, and mirtazapine) in a naturalistic setting for outpatient treatment of depression. This study used data from retrospectively reviewed medical records of patients admitted to an outpatient psychiatric clinic between January 2003 and December 2005. Patient groups (paroxetine-, venlafaxine-, and mirtazapine-treated) were compared with each other with regard to their discontinuation times for a 6-month period after treatment initiation. The data were analyzed, using a Kaplan-Meier survival analysis, and a Cox proportional hazards regression model. There were no significant differences in discontinuation times among the three second-generation antidepressants during the 6-month period after initiation of drug therapy. In a naturalistic setting for the care of depression, it seems that there are no differences in discontinuation times among these three second-generation antidepressants.

Tratamiento prehospitalario de los pacientes con IAMCEST. Una declaración científica del Working Group Acute Cardiac Care de la European Society of Cardiology

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the eff ectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

Dermatophytid in Tinea Capitis: Rarely Reported Common Phenomenon With Clinical Implications

Tinea capitis may be associated with a dermatophytid, which appears as a disseminated eczematous eruption. This phenomenon may occur before or after initiation of systemic antifungal drug therapy and is not an indication for stopping medication. We present here a series of cases that involve 5 children with tinea capitis who developed a dermatophytid before or during the course of their management. In each child, the eruption resolved despite continuation of oral antifungal therapy. Our experience suggests that dermatophytid secondary to tinea capitis is much more common than reported. Furthermore, parents and clinicians frequently mistake dermatophytid for drug allergy. Recognition of this phenomenon, distinction of dermatophytid from drug allergy, and continuation of systemic treatment is essential for clearing the infection and dermatophytid.

Psychiatric Pharmacist and Primary Care Collaboration at a Skid-Row Safety-Net Clinic

There is limited access to psychiatric medication follow-up services at safety-net clinics serving the largely homeless minority population of Los Angeles' skid-row district. This paper describes the process of establishing a pharmacist-run psychiatric medication management service, the types of interventions provided by the psychiatric pharmacist, and patient and provider satisfaction with the service. The establishment of a collaborative practice agreement between primary care physicians and psychiatric pharmacists is described along with the patient demographics and types of pharmacist interventions. Primary care physicians were surveyed regarding their comfort level with managing psychiatric illness and prescribing psychotropic medications. They were also asked about their opinion of psychiatric pharmacist medication management services. An anonymous patient satisfaction survey was also administered. The development of psychiatric pharmacy services is described. The types of interventions included initiating drug therapy, adjusting dosages, discontinuing drug therapy, and providing medication education. Primary care providers were not comfortable in providing psychiatric medication follow-up for patients beyond uncomplicated depression and anxiety disorders. They expressed an overall positive view of psychiatric pharmacist services for their patients with established psychiatric diagnoses. Patient satisfaction ratings were high. A psychiatric pharmacist-run medication management service in collaboration with primary care providers can improve access to mental health services in safety-net clinics with good provider and patient satisfaction.

Dofetilide Dose Calculation Errors in Elderly Associated with Use of the Modification of Diet in Renal Disease Equation

To report 2 cases of drug dosage calculation errors that occurred when the Modification of Diet in Renal Disease (MDRD) equation was used for initiating drug therapy with dofetilide in elderly patients with chronic kidney disease. An 83-year-old woman and a 92-year-old man were admitted for dofetilide treatment initiation and cardioversion for atrial fibrillation. The estimated glomerular filtration rate (eGFR) determined with use of the MDRD equation was significantly higher than the estimated creatinine clearance (eCrCl) determined with use of the Cockcroft-Gault equation for both cases (85 vs 43 mL/min for the man and 40 vs 24 mL/min for the woman). Initial dofetilide dosages calculated by the MDRD equation were 2-fold higher than those calculated by eCrCl in both cases. Initiation of dose based on the MDRD in the first patient led to a 32% increase in the QTc interval from baseline. Dofetilide therapy was adjusted for QTc interval prolongation based on eCrCl and reinitiated at a lower dose, and the patient did not develop further significant increases in the QTc interval. In the second patient, the lower dose based on eCrCl was initiated and the QTc interval remained within an acceptable range. The initial dosing of dofetilide is based on eCrCl as specified by the drug manufacturer. Recent widespread use and automated reporting of the eGFR by clinical laboratories has tempted some clinicians to consider using eGFR for calculating drug doses. However, recent data suggest that the eGFR, calculated by the MDRD equation, consistently overestimates eCrCl, leading to dose discrepancies, particularly in the elderly. The cases reported here illustrate the drug dose calculation errors that may occur when using the MDRD equation for initiating doses of dofetilide. Use of the eGFR or MDRD equation for calculation of doses in renal dysfunction has not been validated, and significant drug dose errors have been reported. The use of eGFR to calculate doses of dofetilide should be avoided.

Free the Pharmacist!

The complexity and diversity of drug therapy for medical conditions continue to expand, resulting in a need for increased sophistication on the part of all care providers. If pharmacists are to be relevant in contemporary practice, they must possess the knowledge and skills to identify and resolve a great variety of drug-related problems. The requirement for pharmacists to have a range of knowledge and skills has resulted in changes to the curricula of pharmacy schools and has also led to the establishment of training programs and formal roles for advanced practitioners. However, such efforts will be unsuccessful in maximizing the benefit of pharmacists in patient care if these health care providers are encumbered with tasks and roles that do not require their specific skills. As individual professionals, and collectively as pharmacy departments striving to maximize pharmacists’ input, we need to identify and eliminate activities and tasks not requiring our skills. In other words, it is time to “free the pharmacist” from inappropriate roles and responsibilities. In practical terms, this means that we must either stop performing specific functions or find someone or something else to do them. Although it would be most efficient to stop doing things that have no benefit, I hope that our current practice is already focused on essential activities and that there are few opportunities for this type of liberation. Therefore, we must look for ways to “outsource” our work to others or to machines. An obvious group for assuming a greater role in the noncognitive work of the pharmacist would be pharmacy technicians. In this issue of the CJHP, the Point Counterpoint column presents a discussion about pharmacy technicians having greater roles in the planning and administration of drug distribution systems within institutions. The authors elaborate on some of the benefits of and concerns about this transfer of responsibility. I encourage all readers to review both opinions and consider whether developing this role for technicians would help in freeing them or their colleagues from participation in drug distribution systems. In addition to this potential role that technicians could fulfill to liberate pharmacists for more direct patient care, the CJHP has previously published numerous papers describing other innovative roles for technicians, including working with pharmacists to support direct patient care activities. For example, the authors of a previous Point Counterpoint column discussed the merits of having technicians obtain medication histories and provide discharge counselling. Others have described a role for technicians in medication reconciliation, whereby they obtain best possible medication histories. Collection of the data necessary for optimum drug dosing, with warfarin as the prototype medication, has also been successfully transferred to technicians. Collection of data by a technician on behalf of a pharmacist in a variety of clinical scenarios (e.g., adverse drug reactions, compliance with drug utilization guidelines, duplicate therapies) has been successfully implemented. The development of these roles for technicians has allowed pharmacists to better utilize their time and to focus their attention on patient care activities that require a pharmacist’s expertise and skills. Similarly, the use of technology (predominantly electronic) can reduce the time and effort involved in obtaining the information needed to identify and resolve drug-related problems. Much like prescribers who need specific information to initiate drug therapy, pharmacists need information to evaluate the patient’s clinical problem, determine the desired outcome, compare therapeutic alternatives, determine a monitoring plan, and educate the patient about drug-related problems encountered. Each one of these steps can be timeconsuming if manual searches and extraction of data are required. Imagine the time that would be saved if the pharmacist could simply access the institution’s clinical database to obtain all of the information in the patient’s medical record, including laboratory data, physical monitoring parameters, outpatient drug therapy (best possible medication history), and current therapy. Although the technology to do this exists today, most Canadian institutions cannot afford the costs. Therefore, until this capability is widely available, Canadian pharmacists must explore ways of utilizing electronic devices that could assist in some of these steps. For example, Fox and Felkey have published a series of columns in Hospital Pharmacy describing new electronic devices that facilitate data retrieval for pharmacists.

Comparative Efficacy and Safety of Combination Aliskiren/Amlodipine and Amlodipine Monotherapy in African Americans With Stage 2 Hypertension

Initial multiple drug therapy for hypertension achieves greater and quicker reductions and higher blood pressure (BP) control rates than monotherapy. This 8-week, prospective, multicenter, randomized, double-blind study compared the efficacy and safety of the initial combination of aliskiren/amlodipine with amlodipine monotherapy in African Americans with stage 2 hypertension. After a 1- to 4-week washout, patients received aliskiren/amlodipine 150/5 mg or amlodipine 5 mg for 1 week and then were force-titrated to aliskiren/amlodipine 300/10 mg or amlodipine 10 mg for 7 weeks. At week 8, greater reductions in mean sitting systolic BP were obtained with aliskiren/amlodipine (n = 220) than with amlodipine (n = 223) (least squares mean change [standard error of the mean], -34.1 [1.14] mm Hg vs -28.9 [1.12] mm Hg; P<.001). Ambulatory and central BP measures were consistent with clinic BP findings, although these were conducted in a small subset of patients (n = 94 in ambulatory BP monitoring substudy and n = 136 for central BP). More patients achieved goal BP (<140/90 mm Hg) with aliskiren/amlodipine than with amlodipine at week 8 (57.3% vs 48.0%; P = .051). Both treatment groups had similar adverse event rates (35.0% and 32.7%, respectively). The most common adverse events were peripheral edema (7.7% with aliskiren/amlodipine and 9.0% with amlodipine), headache, fatigue, and nausea. The combination of aliskiren/amlodipine reduced peripheral, ambulatory, and central BP more than amlodipine alone with similar tolerability in African Americans with stage 2 hypertension.

Akuter M. Wilson

Wilson disease is an autosomal recessive inherited disorder of human copper metabolism clinically associated with hepatic damage and/or neurological symptoms of varying degree. Copper accumulation and toxicity result in direct injury to hepatocytes followed by inflammation and irreversible impairment of neurons, mainly in the extrapyramidal system. A not insignificant number of cases begin with fulminant liver failure or acute appearance of neurological symptoms. If left untreated or in the case of delayed diagnosis and treatment, both acute manifestations may result in irreversible symptoms or even death. Rapid and exact diagnosis by means of clinical, biochemical and genetic analysis and the immediate initiation of drug therapy with copper chelators or, in the case of fulminant liver failure, orthotopic liver transplantation are essential for a favourable outcome in patients with acute Wilson disease.

The negative impact of rebate contracts on the health care of patients with depression in Germany

Aim of this study was to show the negative consequences of rebate contracts on health care of patients with depression. Negative consequences were defined as therapy withdrawal, increased resource utilization and the frequency of switch-back to initial pharmaceutical product in patients with conversion to a rebate pharmaceutical. This retrospective analysis was performed combining the information of 3 databases including information about 20 millions patients and 80% of all prescriptions in Germany. The time period of observation started 1 year before the initiation of rebate contracts. Observation time was 2 years. This study included adults (> 18 years) with an antidepressive drug therapy and who had a statutory health insurance with rebate contracts on antidepressive pharmaceuticals. The mean persistence was 329 days for patients, who were switched to a rebate product compared to 365 days for patients who stayed on the initial drug therapy (p < 0.0001). 29.9% of the patients who were converted to a rebate product switched back to the initial antidepressive drug therapy within 1 year. 1,871 additional patients would be hospitalized due to the conversion to a rebate pharmaceutical that caused direct inpatient costs amounting to 19.9 million EUR per year in Germany. Despite the above limitations this analysis presents a clear association between the initiation of rebate contracts and a negative impact on health care of patients with an antidepressive drug therapy.

Pre-hospital treatment of STEMI patients. A scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the effectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

The pharmacist's contribution to clinicians' ward rounds: analysis by the stages in the drug use process

Abstract Hospital pharmacists are increasingly becoming an integral part of the clinical team, with many pharmacists now attending clinicians' ward rounds. This exploratory study observed five pharmacists attending ward rounds in hospitals in South East England, each on two or three occasions. The pharmacists volunteered to take part in the study and consent was obtained from the clinicians in charge. Each round was observed, tape recorded and transcribed. The verbal contributions of each member of the team to the discussions of drugs were analysed and categorised using the stages of the drug use process. The rounds involved 109 patients and there were 269 separate conversations involving medication. Of these, 135 were patient-specific drug discussions where therapy was reviewed; the pharmacists made proposals to start, stop or alter therapy in nearly half of these discussions. There was no review of therapy in 38 per cent of patients in the study, ranging from 0 per cent on a medical round, to 75 per cent on a surgical round. The pharmacists were particularly involved in selecting the most appropriate dose, stopping drug therapy, and monitoring drugs. The clinicians were more involved in initiating drug therapy. All doctors questioned expressed their satisfaction with the pharmacists and their contribution to the ward rounds.

Anakinra as first‐line disease‐modifying therapy in systemic juvenile idiopathic arthritis: Report of forty‐six patients from an international multicenter series

To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA). Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome. Among 46 patients meeting inclusion criteria, anakinra monotherapy was used in 10 patients (22%), while 67% received corticosteroids and 33% received additional DMARDs. Outcomes were evaluated at a median followup interval of 14.5 months. Fever and rash resolved within 1 month in >95% of patients, while C-reactive protein and ferritin normalized within this interval in >80% of patients. Active arthritis persisted at 1 month in 39% of patients, at 3 months in 27%, and at >6 months of followup in 11%. Approximately 60% of patients, including 8 of 10 receiving anakinra monotherapy, attained a complete response without escalation of therapy. Disease characteristics and treatment were similar in partial and complete responders, except that partial responders were markedly younger at onset (median age 5.2 years versus 10.2 years; P = 0.004). Associated adverse events included documented bacterial infection in 2 patients and hepatitis in 1 patient. Tachyphylaxis was not observed. Anakinra as first-line therapy for systemic JIA was associated with rapid resolution of systemic symptoms and prevention of refractory arthritis in almost 90% of patients during the interval examined. These results justify further study of IL-1 inhibition as first-line, rather than rescue, therapy in systemic JIA.

Clinical Cardiology

Erectile dysfunction (ED) is a powerful predictor of coronary artery disease (CAD), especially in men <60 years of age.1 Conversely, a high percentage of men with chronic stable CAD have ED.2 ED usually precedes the onset of angina by 2 to 3 years and adverse cardiovascular events by 3 to 5 years, thus allowing time for risk factor modification to delay or prevent major adverse cardiovascular events.3 Despite the abundance of evidence linking these vascular diseases, application of this knowledge to clinical practice has been limited.3 Here, 2 theoretical cases are described with the goal of illustrating clinical practice guidelines to improve the management of patients with ED and CAD. A 44-year-old previously healthy man presented to primary care complaining that “I haven't had sex in 3 months because I can't get an erection.” The patient did not report any cardiovascular symptoms with exercise but admitted to a sedentary lifestyle. The patient's father suffered his first myocardial infarction at 53 years of age. The patient's blood pressure was 128/84 mm Hg. The patient denied any other cardiovascular symptoms or risk factors. The patient is diagnosed with ED, defined as the persistent inability to achieve and maintain an erection adequate for satisfactory sexual intercourse. ED is a cardiac risk factor and independently predicts mortality, primarily as a result of increased cardiovascular mortality (hazard ratio, 1.43).4 ED usually precedes angina by 2 to 3 years and adverse cardiovascular events by 3 to 5 years. A cardiovascular assessment is initiated to define the patient's risk of future cardiovascular events and to guide therapy. Cardiac risk factors are investigated, and risk factor modification is initiated. This patient's body mass index is 24 kg/m2, fasting glucose is 95 mg/dL, and fasting low-density lipoprotein cholesterol is 150 mg/dL. A …

Psychosis in Parkinson's disease: Therapeutic options

This publication offers a review of the pharmacological interventions studied for Parkinson's disease psychosis. Before initiating drug therapy for psychosis, possible contribution of antiparkinsonian medications to psychosis must be minimized by reducing their dose and completely switching them to levodopa if indicated. As a group, second- generation antipsychotics have been studied the most for Parkinson's disease psychosis. Evidence of efficacy for psychosis and safety for motor side effects is strongest for clozapine but routine use of clozapine is limited by its potential to cause agranulocytosis and the stringent monitoring requirements. Based on several open-label studies, quetiapine appeared to be a reasonable alternative, but recent double-blind studies create uncertainty about its efficacy. Olanzapine and aripiprazole have limited efficacy and are associated with worsening of motor symptoms. Literature is limited and lacks clarity about the utility of risperidone and ziprasidone in this scenario. Recently, encouraging literature has emerged on the use of donepezil and rivastigmine in patients with Parkinson's disease dementia and psychosis. There is a considerable need to further study the existing drugs and explore other pharmacotherapies in Parkinson's disease psychosis. Future research should ensure sound methodological quality and control for confounding variables to provide results that could be used reliably in clinical practice.

Long term patterns of use after initiation of oral antidiabetic drug therapy

The benefits of intensive and continuous antihyperglycemic drug therapy have been extensively described. Data on long-term patterns and modifications of antihyperglycemic drug use are scarce however. Moreover randomized controlled studies may not reflect actual drug use in daily clinical practice. The aim of this study is to describe the longitudinal patterns of antidiabetic drug modifications after initiation of oral antidiabetic therapy in a large cohort of type 2 diabetes patients. The study will focus specifically on differences between patients who initiate treatment with metformin compared to patients who initiate treatment with sulfonylureas. An observational study of longitudinal patterns of use and modification of oral antidiabetic drug therapy in 3323 patients who started with oral antidiabetic treatment between 1999 and 2007. Drug dispensing data were extracted from pharmacy information systems. This study shows that changes in international guidelines recommending metformin as first choice initial drug therapy in all patients were rapidly followed by prescribers. Patients starting diabetes treatment with metformin showed fewer modifications to treatment compared to patients initiating treatment with sulfonylureas. After correction for duration of follow-up, Cox regression analysis showed a hazard ratio of 0.84 for any modification in the metformin group compared to the sulfonylureas group. This study shows that adherence to type 2 diabetes treatment guidelines for initial treatment is implemented on a large scale. Longitudinal patterns show that the majority of patients receive a small number of modifications to their drug regimen. Discontinuation rates were relatively low.

Global cardiovascular risk profiles of untreated hypertensives in an urban, developing community in Africa

Blood pressure (BPR) control in people of African descent is poor, largely because of a lack of treatment. Although the requirements for immediate initiation of antihypertensive drug therapy are defined by global cardiovascular risk, the global cardiovascular risk profiles of untreated hypertensives at a community level are uncertain. To identify the distribution of global cardiovascular risk profiles of untreated hypertensives in an urban, developing community of African descent in South Africa. As part of the African Programme on Genes in Hypertension, we assessed nurse-derived clinic BP (the mean of five standardised BP values obtained according to guidelines), current antihypertensive therapy, and total cardiovascular risk in 1 029 participants older than 16 years of age from randomly selected nuclear families from the South West Township of Gauteng (SOWETO). Approximately 46% of participants had systolic/ diastolic BP values ≥ 140/90 mmHg and ∼23% of participants were hypertensives not receiving antihypertensive medication. Approximately 12% of untreated hypertensives had a high added risk and ∼18% a very high added risk (6.7% of the total sample). In untreated hypertensives, in contrast to the absence of severe hypertension and diabetes mellitus in those with lower risk profiles, a high cardiovascular risk profile in this group was characterised by severe hypertension in ∼52% and diabetes mellitus in ∼33%. Based on a high added risk carrying at least a 20% chance and a very high added risk at least a 30% chance of a cardiovascular event in 10 years, this translates into 1 740 events per 100 000 of the population within 10 years, events that could be prevented through antihypertensive drug therapy. In an urban, developing community of African ancestry, a significant proportion (6.7%) of people may have untreated hypertension and a global cardiovascular risk profile that suggests a need for antihypertensive drug therapy. Cardiovascular risk in this group is driven largely by the presence of severe hypertension or diabetes mellitus.

Combination Therapy in Hypertension

The goal of antihypertensive therapy is to abolish the risks associated with blood pressure (BP) elevation without adversely affecting quality of life. Drug selection is based on efficacy in lowering BP and in reducing cardiovascular (CV) end points, including stroke, myocardial infarction, and heart failure. Although the choice of initial drug therapy exerts some effect on long-term outcomes, it is evident that BP reduction per se is the primary determinant of CV risk reduction. Available data suggest that at least 75% of patients will require combination therapy to achieve contemporary BP targets, and increasing emphasis is being placed on the practical tasks involved in consistently achieving and maintaining goal BP in clinical practice. It is within this context that the American Society of Hypertension presents this Position Paper on Combination Therapy for Hypertension. It will address the scientific basis of combination therapy, present the pharmacologic rationale for choosing specific drug combinations, and review patient selection criteria for initial and secondary use. The advantages and disadvantages of single-pill (fixed) drug combinations and the implications of recent clinical trials involving specific combination strategies will also be discussed.