Effectiveness of Levoamlodipine Maleate for Hypertension Compared with Amlodipine Besylate: a Pragmatic Comparative Effectiveness Study.

PURPOSE: Antihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting. METHODS: This was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness. RESULTS: Among the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient. CONCLUSION: In conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate. TRIAL REGISTRATION: Clinicaltrials.gov NCT01844570 registered at May 1, 2013.

Fixed-dose vs free-dose combinations for the management of hypertension-An analysis of 81 958 patients.

Fixed-dose combinations (FDC) have been developed to reduce the pill burden for hypertensive patients. Data on fixed-dose or free-dose (freeDC) ramipril/amlodipine (R/A) or candesartan/amlodipine (C/A) combination treatment initiation were assessed. 71 463 patients were prescribed R/A and 10 495 C/A. For both R/A and C/A, FDC patients were younger (both P < .001) and less comorbid. Prior MI (OR: 0.61 and 0.60), prior stroke (OR: 0.68 and 0.70) and CHD (OR: 0.68 and 0.64) were negatively associated with FDC use, whereas hyperlipidemia was positively associated (OR: 1.26 and 1.19). Use of antihypertensive comedication (OR: 0.78; OR: 0.55) and treatment discontinuation within 12 months (HR: 0.65 and 0.82) were less likely in FDC patients, who also showed superior adherence (mean MPR; both P < .001). Cost of the combination was higher for FDCs (both P < .001). FDCs improve persistence and adherence, although they are more commonly prescribed in patients with less cardiovascular disease.

Efficacy and Safety Assessment of Hypertension Management with Coveram (Perindopril/Amlodipine Fixed Combination) in Patients with Previous Angiotensin Receptor Blocker (ARB) Treatment: Arabian Gulf STRONG Study.

OBJECTIVE: We evaluated the safety and efficacy of hypertension management with Coveram (perindopril/amlodipine combination) in patients with uncontrolled blood pressure (BP). All patients were on previous angiotensin receptor blocker (ARB) treatment. METHODS: This was a 3 country, multi-centre (7 cities), open-label, observational study in the Arabian Gulf. Patients (≥18 years) were recruited between October 2012 and November 2013 and followed-up for 3 months after enrolment. Outcomes included changes in BP from baseline and BP goal attainment rates as per Joint National Committee- 8 (<140/90 mmHg for diabetics and those <60 years of age and <150/90 mmHg for those ≥60 years of age without diabetes). Medication tolerance was also assessed from both patient and physician perspectives. RESULTS: Hypertensive patients (n=760; mean age: 51±10 years; 67% were males) were included. A total of 178 patients (23%) were lost to follow-up. The perindopril/amlodipine combination was associated with an overall reduction in systolic BP (SBP) (31 mmHg; p<0.001) and diastolic BP (DBP) (18 mmHg; p<0.001) from baseline. An overall BP control rate was achieved in 87% (n=507) of the participants. There were significant incremental BP reductions with dose up-titration, especially SBP (p<0.001). Those with high SBP (>180 mmHg) at baseline were associated with a mean reduction of 59 mmHg (p<0.001). The perindopril/amlodipine combination had excellent tolerance levels over the study period from both patient and physician perspectives (at 99% and 98%, respectively; p<0.001). CONCLUSIONS: The perindopril/amlodipine combination is an effective and well tolerated anti-hypertensive option in patients on previous ARB treatment.

Evaluation of potential drug- drug interactions among Palestinian hemodialysis patients.

BACKGROUND: The aims of this study are to find the prevalence of potential drug-drug interactions (DDIs) in patients with Hemodialysis and identify factors associated with these interactions if present. METHODS: The study was an observational- retrospective cohort study that was conducted in ten hemodialysis units in the West bank, Palestine, between June and August 2015. The data collection form was completed by interviewing the patients in addition to reviewing their medical records. Potential DDIs were reviewed. SPSS program was used for data analysis. RESULTS: The study included 275 patients, a total of 930 potential interactions were identified in 245 (89.1 %) patients. Patients were prescribed 1-15 drugs with a mean (± SD) of 7.87 ± 2.44, calcium carbonate was the most common drug prescribed. The most common potential interaction in 114 (41.5 %) patients was Calcium Carbonate/Amlodipine followed by Calcium Carbonate/Aspirin in 76 (27.6 %) cases. Most patients (89.9 %) of the patients had one or more comorbid diseases; hypertension, diabetes and gout were the most common. Univariate analysis showed that the number of potential DDIs were related to the number of diseases, the number of prescribed drugs (P value <0.0001) and the age of the patient (P value = 0.015). The results of multiple linear regression showed a significant positive association between number of potential DDIs with the total number of medications (r = 0.242; p < 0.001). CONCLUSION: The prevalence of potential drug- drug interactions among hemodialysis patients is very common; they are highly expected and depend on the number of drugs taken by the patients. Many of these potential interactions are considered as preventable drug- related problems, so screening for potential interactions and monitoring regularly is highly needed.

Assessment of glomerular filtration rate based on alterations of serum brain-derived neurotrophic factor in type 2 diabetic subjects treated with amlodipine/benazepril or valsartan/hydrochlorothiazide.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is associated with sympathetic activation. However, the effects of BDNF on diabetic nephropathy are unknown. The aim of this study was to assess the estimated glomerular filtration rates (eGFRs) and changes in serum BDNF levels in type 2 diabetic subjects treated with antihypertensive medications. METHODS: In this randomized, double-blind clinical trial, type 2 diabetic subjects with hypertension were assigned to either the benazepril/amlodipine or valsartan/hydrochlorothiazide treatment groups for a 16-week period. The post hoc analyses were based on increased or decreased serum BDNF levels. RESULTS: Of the 153 enrolled subjects, the changes in eGFR were significantly and inversely correlated with those in BDNF in the 76 subjects treated with valsartan/hydrochlorothiazide (r = -0.264, P = 0.021) but not in the 77 subjects treated with benazepril/amlodipine (r = -0.025, P = 0.862). The 45 subjects with increased BDNF following valsartan/hydrochlorothiazide treatment exhibited a significantly reduced eGFR (-8.8 ± 14.9 mL/min/1.73 m(2); P < 0.001). Multivariate regression analysis revealed that increased serum BDNF represents an independent factor for reduced eGFR (95% confidence interval between -0.887 and -0.076, P = 0.020). CONCLUSIONS: Increased serum BDNF is associated with reduced eGFR in type 2 diabetic subjects treated with valsartan/hydrochlorothiazide but not with amlodipine/benazepril.

Pharmacokinetic drug-drug interaction assessment between LCZ696, an angiotensin receptor neprilysin inhibitor, and hydrochlorothiazide, amlodipine, or carvedilol.

LCZ696 is a first-in-class angiotensin receptor neprilysin inhibitor in development for treatments of hypertension and heart failure indications. In 3 separate studies, pharmacokinetic drug-drug interactions (DDIs) potential was assessed when LCZ696 was coadministered with hydrochlorothiazide (HCTZ), amlodipine, or carvedilol. The studies used a open-label, single-sequence, 3-period, crossover design in healthy subjects. Blood samples were collected to determine the pharmacokinetic parameters of LCZ696 analytes (AHU377, LBQ657, and valsartan), HCTZ, amlodipine, or carvedilol (R[+]- and S[-]-carvedilol) for statistical analysis. When coadministered LCZ696 with HCTZ, the 90% CIs of the geometric mean ratios of AUCtau,ss of HCTZ and that of LBQ657 were within a 0.80-1.25 interval, whereas HCTZ Cmax,ss decreased by 26%, LBQ657 Cmax,ss increased by 19%, and the AUCtau,ss and Cmax,ss of valsartan increased by 14% and 16%, respectively. Pharmacokinetics of amlodipine, R(+)- and S(-)-carvedilol, or LBQ657 were not altered after coadministration of LCZ696 with amlodipine or carvedilol. Coadministration of LCZ696 400 mg once daily (qd) with HCTZ 25 mg qd, amlodipine 10 mg qd, or carvedilol 25 mg twice a day (bid) had no clinically relevant pharmacokinetic drug-drug interactions. LCZ696, HCTZ, amlodipine, and carvedilol were safe and well tolerated when given alone or concomitantly in the investigated studies.

Simvastatin prescribing patterns before and after FDA dosing restrictions: a retrospective analysis of a large healthcare claims database.

BACKGROUND: Muscle-related events, or myopathies, are a commonly reported adverse event associated with statin use. In June 2011, the US FDA released a Drug Safety Communication that provided updated product labeling with dosing restrictions for simvastatin to minimize the risk of myopathies. OBJECTIVE: Our objective was to describe prescribing patterns of simvastatin in combination with medications known to increase the risk of myopathies following updated product labeling dosing restrictions in June 2011. METHODS: A retrospective observational analysis was carried out, in which administrative claims data were utilized to identify prescribing patterns of simvastatin in combination with calcium channel blockers (CCBs) and other pre-specified drug therapies. Prescribing patterns were analyzed on a monthly basis 24 months prior to and 9 months following product label changes. Incidence of muscle-related events was also analyzed. RESULTS: In June 2011, a total of 60% of patients with overlapping simvastatin-CCB claims and 94% of patients with overlapping simvastatin-non-CCB claims were prescribed an against-label combination. As of March 2012, a total of 41% and 93% of patients continued to be prescribed against-label simvastatin-CCB and simvastatin-non-CCB combinations, respectively. The most commonly prescribed dose of simvastatin was 20 mg (39%). Against-label combinations were most commonly prescribed at a simvastatin dose of 40 mg (56%). Amlodipine was the most commonly prescribed CCB in combination with simvastatin (70%) and the most common CCB prescribed against-label (67%). CONCLUSIONS: Despite improvements in prescribing practices, many patients are still exposed to potentially harmful simvastatin combinations. Aggressive changes in simvastatin prescribing systems and processes are needed to improve compliance with FDA labeling to improve medication and patient safety.

[Postregistration study of comparative assessment efficacy of the use of fixed combination of nebivolol and amlodipine for the treatment of patients with moderate and high degree of arterial hypertension].

AIM: of the study was to assess efficacy of the use of fixed combination of nebivolol and amlodipine in patients with moderate and high degree of arterial hypertension (AH). MATERIAL AND METHODS: Patients with diagnosis of primary AH (n=124) were divided into 2 groups by random sample method. Patients of group 1 (n=62) received of fixed combination of nebivolol and amlodipine, while those of group 2 (n=62) received free combination of nebivolol and amlodipine. Study drugs were administered both as initial therapy and replacement of preceding treatment. Duration of observation was 3 months with visits after first 2 weeks and in 1, 2, and 3 months after enrollment. RESULTS: Starting from 2nd week visit of fixed combination of nebivolol and amlodipine treated patients had significantly lower levels of systolic and diastolic AP. Already after 2 weeks of combined two-component therapy 60% of group 1 and 52% of group 2 patients achieved target AP. Target AP was achieved by the end of month 1 by 86 and 71%, of month 2 - by 93 and 78% of patients in groups 1 and 2, respectively. In 3 months almost all patients had target AP, but in 1.6% of group 1 and 2.3% of group 2 patients this level was achieved after addition of a thiazide diuretic. Patients receiving of fixed combination of nebivolol and amlodipine achieved noromosyslolia more quickly compared with patients who received free combination of nebivolol and amlodipine. CONCLUSION: Combined therapy with fixed combination of nebivolol and amlodipine appears to be one of effective approaches to treatment of patients with moderate and high degree AH.

A review of the efficacy and tolerability of combination amlodipine/valsartan in non-white patients with hypertension.

This article discusses racial/ethnic disparities in hypertension, with particular focus on non-white populations including blacks, Hispanics/Latinos, and Asians. Hypertension and its related morbidity and mortality affect a disproportionate number of black patients compared with white patients. Blacks, Hispanics/Latinos, and Asians have poor rates of hypertension awareness, treatment, and control. Given the high prevalence of comorbidities (e.g., obesity, diabetes, and metabolic syndrome) in these populations, renin-angiotensin-aldosterone system blockers are a good choice for foundation therapy. This review also discusses the importance of adherence and persistence with antihypertensive medication, which remain suboptimal in these non-white populations. Evidence suggests improvement with the use of single-pill combination therapy. Lastly, clinical trial data on the antihypertensive efficacy and safety of the combination of a dihydropyridine calcium channel blocker and an angiotensin receptor blocker, a widely utilized combination, in non-white populations are presented. PubMed was searched using the title/abstract key words (amlodipine AND valsartan AND [hypertension OR hypertensive] AND [black(s) OR African American(s) OR Hispanic(s) OR Latino(s) OR Mexican(s) OR Asian(s)]). In total, eight studies in patients with stage 1 or 2 hypertension were identified (n = 1,111 black, n = 389 Hispanic/Latino, and n = 3,094 Asian). Results showed that treatment with the combination of amlodipine plus valsartan is a reasonable choice for initial therapy or in patients who fail to respond to monotherapy. These drug classes have complementary mechanisms of action and, when used concomitantly, the magnitude of blood pressure lowering in these non-white populations is generally comparable with that seen in non-Hispanic white patients.

I-ADD study: assessment of efficacy and safety profile of irbesartan/amlodipine fixed-dose combination therapy compared with irbesartan monotherapy in hypertensive patients uncontrolled with irbesartan 150 mg monotherapy: a multicenter, phase III, prospective, randomized, open-label with blinded-end point evaluation study.

BACKGROUND: Hypertension guidelines recommend the use of 2 agents with synergistic action when >1 agent is needed to achieve blood pressure goals. Newer antihypertensive treatment combinations include fixed-dose combinations of an angiotensin receptor blocker and a calcium channel blocker. OBJECTIVE: The I-ADD study aimed to demonstrate whether the antihypertensive efficacy of fixed-dose combination irbesartan 300 mg/amlodipine 5 mg (I300/A5) was superior to that of irbesartan (I300) monotherapy in lowering home systolic blood pressure after 10 weeks' treatment. METHODS: The I-ADD study was a 10-week, multicenter, Phase III, prospective, randomized, parallel-group, open-label with blinded-end point study. The main inclusion criterion was essential uncontrolled hypertension (systolic blood pressure ≥145 mm Hg at office after at least 4 weeks of irbesartan 150 mg [I150] monotherapy administered once daily). Patients continued to receive I150 for 7 to 10 days and were randomized to either monotherapy with I150 for 5 weeks then I300 for the next 5 weeks, or to a fixed-dose combination therapy (I150/A5, then I300/A5). Safety profile was assessed by recording adverse events reported by patients or observed by the investigator. RESULTS: Following enrollment, 325 patients were randomized to treatment, and 320 (mean [SD] age, 56.7 [11.4] years; 41% male) were included in the intention-to-treat analysis: 155 patients treated with I150/A5 then I300/A5, and 165 patients treated with I150 then I300. At randomization, mean home systolic blood pressure was similar in both groups: 152.7 (11.8) mm Hg in the I150/A5 group and 150.4 (10.1) mm Hg in the I150 group. At week 10, the adjusted mean difference in home systolic blood pressure between groups was -8.8 (1.1) mm Hg (P < 0.001). The percentage of controlled patients (mean home blood pressure <135 and 85 mm Hg) was nearly 2-fold higher in the I300/A5 group versus the I300 group (P < 0.001). Treatment-emergent adverse events were experienced by 10.5% of I300/A5-treated patients and 6.6% of I300-treated patients during the second 5-week period. Three serious adverse events were reported; 2 with monotherapy (1 with I150 and 1 with I300) and 1 with fixed-dose combination I300/A5. All patients affected by serious adverse events made a full recovery. CONCLUSIONS: These 10-week data from this patient population suggest a greater antihypertensive efficacy of the fixed-dose combination I300/A5 over I300 alone in lowering systolic blood pressure. Both treatments were well tolerated throughout the study. ClinicalTrials.gov identifier: NCT00957554.

I-COMBINE study: assessment of efficacy and safety profile of irbesartan/amlodipine fixed-dose combination therapy compared with amlodipine monotherapy in hypertensive patients uncontrolled with amlodipine 5 mg monotherapy: a multicenter, phase III, prospective, randomized, open-label with blinded-end point evaluation study.

BACKGROUND: Hypertension guidelines recommend the use of 2 agents with synergistic action when >1 agent is needed to achieve blood pressure goals. Newer antihypertensive treatment combinations include fixed-dose combinations of an angiotensin receptor blocker and a calcium channel blocker. OBJECTIVE: The I-COMBINE study aimed to determine whether the antihypertensive efficacy of the fixed-dose combination irbesartan 150 mg/amlodipine 5 mg (I150/A5) was superior to that of amlodipine 5 mg (A5) monotherapy in lowering home systolic blood pressure (HSBP) after 5 weeks' treatment. METHODS: The I-COMBINE study was a 10-week, multicenter, Phase III, prospective, randomized, parallel-group, open-label with blinded-endpoint study. The main inclusion criterion was essential uncontrolled hypertension (SBP ≥145 mm Hg at office, after at least 4 weeks of A5 monotherapy administered once daily). Patients continued to receive A5 for 7 to 10 days and were randomized to either monotherapy with A5 for 5 weeks then amlodipine 10 mg (A10) for the next 5 weeks or to a fixed-dose combination therapy (I150/A5 then I150/A10). Safety profile was assessed by recording adverse events reported by patients or observed by the investigator. RESULTS: Following enrollment, 290 patients were randomized to treatment, and 287 (mean [SD] age, 57.3 [11.2] years; 48% male) were included in the intention-to-treat analysis: 144 patients treated with I150/A5 then I150/A10, and 143 patients treated with A5 then A10. At randomization, mean HSBP was similar in both groups: 148.5 (10.3) mm Hg in the I150/A5 group and 149.2 (9.7) mm Hg in the A5 group. At week 5, the adjusted mean difference in HSBP between groups was -6.2 (1.0) mm Hg (P < 0.001). The proportion of controlled patients (mean home blood pressure <135 and 85 mm Hg) was significantly higher in the I150/A5 group than in the A5 group (P < 0.001). Treatment-emergent adverse events were experienced by 13.8% of I150/A5-treated patients and 11.9% of A5-treated patients during the first 5-week period, and by 15.8% of I150/A10-treated patients and 17.0% of A10-treated patients during the second 5-week period. Two serious adverse events were reported with the fixed-dose combination; both patients recovered. CONCLUSIONS: Data from this adult population with essential hypertension suggest greater efficacy with the fixed-dose combination I150/A5 over A5 monotherapy in lowering SBP after 5 weeks. Both treatment regimens were well tolerated throughout the study. ClinicalTrials.gov identifier: NCT00956644.

Proactive cardiovascular risk management versus usual care in patients with and without diabetes mellitus: CRUCIAL trial subanalysis.

UNLABELLED: Patients with diabetes mellitus (DM) and additional cardiovascular (CV) risk factors are at very high risk for future CV events. This study investigated the efficacy and safety of a proactive, multifactorial CV risk factor-management strategy based on single-pill amlodipine/atorvastatin (SPAA) versus continuing physicians' usual care (UC) over 52 weeks in patients with and without DM. Patients with hypertension and ≥ 3 additional CV risk factors from the Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-Term-Risk (CRUCIAL) trial--an open-label, cluster-randomized trial conducted in 19 countries--were enrolled and randomized to receive proactive intervention (based on SPAA 5/10 to 10/20 mg) or UC (based on investigators' best clinical judgment). Patients were analyzed according to baseline DM status. Six hundred patients had DM. Patients with DM in the SPAA and UC arms had mean ages of 61.8 and 61.5 years, respectively, and an absolute coronary heart disease (CHD) risk of 25.2% and 21.5%, respectively. Among non-DM patients, mean ages were 58.6 and 59.5 years, respectively, and CHD risk was 16.0% vs 15.7%, respectively. Least-squares mean treatment differences in percentage change from baseline in calculated 10-year Framingham CHD risk were -26.3% vs -27.3% among DM and non-DM patients (adjusted for respective baseline values) (both P < 0.0001). Among DM and non-DM patients, adverse events were reported in 52.8% versus 45.6% in the SPAA and 49.6% versus 41.6% in the UC arms, respectively. This global risk-management approach, simultaneously targeting blood pressure and lipids, was more effective for reducing calculated 10-year Framingham CHD risk than UC in patients with DM. While blood pressure changes were of smaller magnitude among patients with DM, this strategy reduced overall risk to an extent comparable with that observed in non-DM patients. Further studies are thus warranted to study this proactive risk factor intervention on CV or mortality endpoints in patients with and without DM. TRIAL REGISTRATION: www.ClinicalTrials.gov identifier NCT00407537.

[Medical mistakes due to generic substitution]. / Medicineringsfejl ved generisk substitution.

Generic substitution is a major cause of medical mistakes in the general population. Danish legislation obligates pharmacies to substitute prescribed medicine with the cheapest equivalent formulation, despite variations in product name, packaging, shape and colour. Consequently, medical mistakes occur. Scientific evidence on the consequences of generic substitution is sparse. Call upon fellow health workers to report medical mistakes to the national entities and scientific peers, in order to increase awareness and scientific evidence about the problem.

An economic evaluation of antihypertensive therapies based on clinical trials.

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.

An economic evaluation of antihypertensive therapies based on clinical trials

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.

Using primary care prescribing databases for pharmacovigilance.

AIMS: In the UK, adverse drug reactions (ADRs) are responsible for over 6.5% of all hospital admissions, representing a significant morbidity and cost burden to the health service. We aimed to develop an ADR monitoring system capable of identifying the reasons for patient discontinuation of drug therapy within 6 months of the index prescription. METHODS: Patients first prescribed amlodipine between 1 March 2004 and 28 February 2007 who discontinued their amlodipine medication within 6 months of the index prescription were identified from the practice team information (PTI) database. Once identified, reasons for amlodipine discontinuation were assessed by an electronic database search using relevant Readcodes and key words and by a direct approach to the primary care medical records. RESULTS: The PTI database identified 995 patients [61.4% females, mean age 65.9 years (SD 12.4 years)] who discontinued amlodipine within 6 months of an index prescription. An electronic search of the database, using Readcodes, identified that 19.4% (193) of patients who discontinued their medication had an ADR recorded in the database. Six (20%) of 30 participating primary care practices, contributing to the PTI database, agreed to be approached directly and supply the reasons for discontinuation for the 51 patients identified as having discontinued amlodipine in their practices. Completed data were returned for all 51 patients, 98% of whom discontinued amlodipine due to an ADR or adverse drug event. CONCLUSIONS: The results of this study confirm that primary care prescribing databases can be easily used to identify the frequency and nature of ADRs occurring in an ADR-enriched population identified through medication discontinuation.

Fixed combination of amlodipine and atorvastatin in cardiovascular risk management: patient perspectives.

Hypertension and dyslipidemia are two of the most commonly co-occurring cardiovascular risk factors which together cause an increase in coronary heart disease-related events that is more than simply additive for anticipated event rates with each condition. Data have shown that even relatively small reductions in both blood pressure and cholesterol levels can lead to large reductions in the risk for cardiovascular events. However, though there are robust data on the beneficial effect of concomitant reduction in these risk factors, the reality is that this is achieved in <10% of patients. There is nonadherence with prescribed therapies with up to 50% of patients stopping their medications of their own volition for a variety of reasons. There is a reasonable evidence base to suggest that simplifying drug regimens and reducing pill burden will enhance patient adherence. The fixed-dose combination containing the antihypertensive agent amlodipine besylate and the statin atorvastatin is the first combination of its kind, which is both efficacious and safe and could potentially improve medication compliance, thereby improving the outcomes in these patients.

Amlodipine/atorvastatin fixed-dose combination: a review of its use in the prevention of cardiovascular disease and in the treatment of hypertension and dyslipidemia.

Amlodipine/atorvastatin (Caduet) is a once-daily fixed-dose combination of the dihydropyridine calcium channel antagonist amlodipine and the HMG-CoA reductase inhibitor atorvastatin. In Europe, the combination is indicated for the prevention of cardiovascular events in hypertensive patients with three concomitant cardiovascular risk factors and, in the US, it is indicated for the management of hypertension and dyslipidemia in patients for whom treatment with both agents is appropriate. In clinical trials, the fixed-dose combination of amlodipine/atorvastatin effectively managed two important risk factors simultaneously in hypertensive patients at risk of cardiovascular disease or in those with concomitant hypertension and dyslipidemia. The combination is bioequivalent to amlodipine and atorvastatin given alone and does not modify the efficacy of either single agent. Amlodipine/atorvastatin is generally well tolerated, with a tolerability profile consistent with that of each single agent. Compared with the coadministration of each single agent, the convenience of single-pill amlodipine/atorvastatin has the potential to improve patient adherence and the management of cardiovascular risk in selected patients, thereby improving clinical outcomes.