Prescribed Calcium Channel Blockers Research Articles

Trends of Antihypertensive Prescription Among US Adults From 2010 to 2019 and Changes Following Treatment Guidelines: Analysis of Multicenter Electronic Health Records.

Guidelines for the use of antihypertensives changed in 2014 and 2017. To understand the effect of these guidelines, we examined trends in antihypertensive prescriptions in the United States from 2010 to 2019 using a repeated cross-sectional design. Using electronic health records from 15 health care institutions for adults (20-85 years old) who had ≥1 antihypertensive prescription, we assessed whether (1) prescriptions of beta blockers decreased after the 2014 Eighth Joint National Committee (JNC 8) report discouraged use for first-line treatment, (2) prescriptions for calcium channel blockers and thiazide diuretics increased among Black patients after the JNC 8 report encouraged use as first-line therapy, and (3) prescriptions for dual therapy and fixed-dose combination among patients with blood pressure ≥140/90 mm Hg increased after recommendations in the 2017Hypertension Clinical Practice Guidelines. The study included 1 074 314 patients with 2 133 158 prescription episodes. After publication of the JNC 8 report, prescriptions for beta blockers decreased (3% lower in 2018-2019 compared to 2010-2014), and calcium channel blockers increased among Black patients (20% higher in 2015-2017 and 41% higher in 2018-2019, compared to 2010-2014), in accordance with guideline recommendations. However, contrary to guidelines, dual therapy and fixed-dose combination decreased after publication of the 2017 Hypertension Clinical Practice Guidelines(9% and 11% decrease in 2018-2019 for dual therapy and fixed-dose combination, respectively, compared to 2015-2017), and thiazide diuretics decreased among Black patients after the JNC8 report (6% lower in 2018-2019 compared to 2010-2014). Adherence to guidelines on prescribing antihypertensive medication was inconsistent, presenting an opportunity for interventions to achieve better blood pressure control in the US population.

Slow-flow phenomenon after drug-coated balloon angioplasty for lower-extremity arteries is associated with lack of prescribing of calcium channel blockers

This study aimed to investigate the relationship between prescription drugs and the slow-flow phenomenon after drug-coated balloon angioplasty. Of 30 patients, five (17%) presented with the slow-flow phenomenon. Patients with the slow-flow phenomenon were significantly less commonly prescribed calcium channel blockers than those without the slow-flow phenomenon (P = 0.03). There was no intergroup difference in the prescription of angiotensin II receptor blockers and β-blockers. The clinical outcomes, including restenosis, thrombosis, target lesion revascularization, and death, did not differ between groups during the 10-month observation period.

Verapamil inhibits TXNIP-NLRP3 inflammasome activation and preserves functional recovery after intracerebral hemorrhage in mice

Intracerebral hemorrhage (ICH) is the second most common type of stroke with no satisfactory treatment. Recent studies from our group and others indicated a potential positive effect of verapamil, a commonly prescribed calcium channel blocker, with thioredoxin-interacting protein (TXNIP) inhibitor properties, in ischemic stroke and cognitive disorders. It is unclear whether there would be a beneficial effect of verapamil administration in ICH. Therefore, this study was designed to determine the neuroprotective effects of verapamil in a murine ICH model. ICH was induced by stereotactic injection of collagenase type VII (0.075 U) into the right striatum of adult male C57BL/6 mice. Verapamil (0.15 mg/kg) or saline was administered intravenously at 1 h post-ICH followed by oral (1 mg/kg/d) administration in drinking water for 28 days. Motor and cognitive function were assessed using established tests for motor coordination, spatial learning, short- and long-term memory. A subset of animals was sacrificed at 72 h after ICH for molecular analysis. Verapamil treatment reduced expression of TXNIP and NOD-like receptor pyrin domain-containing-3 inflammasome activation in the perihematomal area. These protective effects of verapamil were associated with decreased proinflammatory mediators, microglial activation, and blood-brain barrier permeability markers and paralleled less phosphorylated nuclear factor kappa B level. Our findings also demonstrate that long-term low-dose verapamil effectively attenuated motor and cognitive impairments. Taken together, these data indicate that verapamil has therapeutic potential in improving acute motor function after ICH. Further investigations are needed to confirm whether verapamil treatment could be a promising candidate for clinical trials.

Blood Pressure Changes Following Antihypertensive Medication Reduction, by Drug Class and Dose Chosen for Withdrawal: Exploratory Analysis of Data From the OPTiMISE Trial.

Aims: Deprescribing of antihypertensive drugs is recommended for some older patients with polypharmacy, but there is little evidence to inform which drug (or dose) should be withdrawn. This study used data from the OPTiMISE trial to examine whether short-term outcomes of deprescribing vary by drug class and dose of medication withdrawn. Methods: The OPTiMISE trial included patients aged ≥80 years with controlled systolic blood pressure (SBP; <150 mmHg), receiving ≥2 antihypertensive medications. This study compared SBP control, mean change in SBP and frequency of adverse events after 12 weeks in participants stopping one medication vs. usual care, by drug class and equivalent dose of medication withdrawn. Equivalent dose was determined according to the defined daily dose (DDD) of each medication type. Drugs prescribed below the DDD were classed as low dose and those prescribed at ≥DDD were described as higher dose. Outcomes were examined by generalized linear mixed effects models. Results: A total of 569 participants were randomized, aged 85 ± 3 years with controlled blood pressure (mean 130/69 mmHg). Within patients prescribed calcium channel blockers, higher dose medications were more commonly selected for withdrawal (90 vs. 10%). In those prescribed beta-blockers, low dose medications were more commonly chosen (87 vs. 13%). Withdrawal of calcium channel blockers was associated with an increase in SBP (5 mmHg, 95%CI 0–10 mmHg) and reduced SBP control (adjusted RR 0.89, 95%CI 0.80–0.998) compared to usual care. In contrast, withdrawal of beta-blockers was associated with no change in SBP (−4 mmHg, 95%CI −10 to 2 mmHg) and no difference in SBP control (adjusted RR 1.15, 95%CI 0.96–1.37). Similarly, withdrawal of higher dose medications was associated with an increase in SBP but no change in BP control. Withdrawal of lower dose medications was not associated with a difference in SBP or SBP control. There was no association between withdrawal of specific drug classes and adverse events. Conclusion: These exploratory data suggest withdrawal of higher dose calcium channel blockers should be avoided if the goal is to maintain BP control. However, low dose beta-blockers may be removed with little impact on blood pressure over 12-weeks of follow-up. Larger studies are needed to confirm these associations.

POS-451 PROTEINURIA ≥ 10G/DAY AS A PROGNOSTIC FACTOR FOR GENERAL AND RENAL SURVIVAL IN PATIENTS WITH NEPHROTIC SYNDROME IN A PERUVIAN HOSPITAL

Chronic Kidney Disease (CKD) is a major health problem around the world. In Peru, it is considered to be among the first ten death causes during 2012, representing 3.3% of national deceases. In healthy adults, normal excretion of protein through urine (proteinuria) is less than 150 mg/day. However, values of proteinuria higher than 150 mg/day are considered to be pathological; furthermore, values higher than 3.5 g/day are denominated as nephrotic range proteinuria. In addition, it has been described that proteinuria values higher than 10 g/day, also called malignant proteinuria, has been related to higher CKD incidence and progression. The objective of this study was to compare the renal survival and the mortality among patients with proteinuria ≥ 10 g/day and patients with proteinuria between ≥ 3.5 g/day and < 10 g/day. A retrospective cohort study was accomplished. The exposed population was constituted by patients with proteinuria ≥ 10 g/day and the unexposed one by patients with proteinuria between ≥ 3.5 g/day and < 10 g/day. All patients enrolled were ≥ 18 years old, and the follow up of the population started up with the first proteinuria registered in the clinic history.Sample size was calculated through EPIDAT program, considering statistical significance level (α level) to be 0.05 (5%), β error to be 0.20 (20%) and study potency to be 0.80 (80%). For data collection, a collection form was used in order to register the variables. With this information, a database was created using Microsoft Excel 2018. At last, data was analyzed using STATA version 2015 software. A survival analysis with Cox Regression was performed to assess if proteinuria is an independent predictor of renal survival and mortality. 201 patients were selected, 94 were assigned to the exposed population and 107 to the unexposed one. Nephrotic syndrome etiology from both cohorts were equivalent; but some clinic, demographic and treatment characteristics were not. The mean age was 50.99 ± 16.06 (18-88) years old and 208 were men (53.73%). The principal CKD etiology was diabetes mellitus type II, constituted by 94 patients (46.77%). Diabetic etiology [HR: 2.82 (1.10 – 7.20)], prescription of calcium channel blockers [HR: 1.37 (1.15 – 2.07) p: 0.007], prescription of diuretic agents [HR: 1.39 (1.15 – 2.18) p:0.011] and no prescription of angiotensin II receptor blockers (ARBs) were considered factors related to bad prognosis. Only high values of Glomerular Filtration Rate (GFR) that were measured in the first consultation were consider a protective factor for the renal survival [HR: 0.94 (0.92 – 0.97) p:0.000]. Results did not show renal survival difference between both groups, even though confounding variables were excluded using Cox Regression [HR:1.54 (0.73 – 3.25) p:0.252]. The mortality rate was 0.005% and only 01 deceased was reported. Proteinuria values between ≥ 3.5 g/day to <10 g/day and ≥ 10 g/day were not independently related to renal survival nor mortality in this study. Thus, other variables were related to renal survival such as diabetic etiology, no prescription of ARBs, prescription of diuretic agents and calcium channel blockers, which were considered factors related to bad prognosis. On the other hand, a high value measured of GFR at the hospital admission was consider a protective factor.

Clinical outcomes between calcium channel blockers and angiotensin receptor blockers in hypertensive patients without established cardiovascular diseases during a 3-year follow-up

Although both angiotensin receptor blockers (ARBs) and dihydropyridine calcium channel blockers (CCBs) are all suitable for the initiation of antihypertensive treatment, studies investigating efficacy and safety between ARBs and CCBs are limited, and there is no previous study comparing their clinical outcomes during long-term follow-up periods in real world setting. We compared cardiovascular (CV) events between ARBs and CCBs in 464,948 hypertensive adults using the Korean National Health Insurance Service database during a 3-year follow-up. The patients with hypertension without heart failure, ischemic heart disease, cerebrovascular disease, or peripheral artery disease were enrolled. The CV events between only single prescription of CCBs and ARBs were finally compared. The primary endpoint for this study was the first occurrence of a major adverse CV events, defined as the composite of all-cause death, cardiac death, nonfatal myocardial infarction, or nonfatal stroke. ARB was significantly more administered in male and patients with higher income, diabetes mellitus, chronic kidney diseases, and higher Charlson comorbidity index. The primary endpoints occurred in 10,526 patients (5.2%) in the ARB group and in 19,363 patients (7.3%) in the CCB group (p < 0.001) during a 3-year follow-up (HR 0.96, 95% CI 0.93–0.98). All the components of CV events including all-cause death, cardiac death, nonfatal myocardial infarction, and nonfatal stroke occurred more frequently in the CCB group. With multivariable models adjusting age, sex, income, diabetes, chronic kidney disease, and Charlson comorbidity index, the primary endpoints less frequently developed in the ARB group than in the CCB group (HR 0.957, 95% CI 0.933–0.983, p < 0.001). After the propensity-score matching, baseline characteristics were similar and still showed significantly better primary endpoints in ARB group than CCB group (5.3% vs. 5.8%, p < 0.001). In this nationwide population-based simple hypertension study, administration of ARBs showed superior protection against CV events than CCBs during a 3-year follow-up. Our results suggest that ARBs could be preferred over CCBs as the initial choice of antihypertensive treatment regardless of age in real-world practice.

Changes in aortic pulse wave velocity in peritoneal dialysis do not mirror changes in extracellular water measured by bioimpedance.

Pulse wave velocity is a measurement of arterial stiffness and associated with increased cardiovascular mortality. Previous reports in peritoneal dialysis have linked increased pulse wave velocity with an expansion in extracellular water. As cardiovascular mortality is increased in peritoneal dialysis patient, we wished to determine whether changes in pulse wave velocity mirrored changes in extracellular water. We repeated aortic pulse wave velocity and bioimpedance-derived extracellular water measurements in peritoneal dialysis patients attending for assessment of peritoneal membrane function. Sixty-six patients, 41 males (62.1%), mean age of 66.2 ± 13.9 years, median duration of peritoneal dialysis treatment (14.3 (3.1-31.9) months) had repeated measurement 6.4 (5.8-10.2) months apart, with no significant change in aortic pulse wave velocity (10.1 ± 3.2 to 9.9 ± 2.8 m/s). In univariate analysis, the initial aortic pulse wave velocity was associated with extracellular water (r = 0.26, p = 0.034) and serum N-terminal pro brain-type natriuretic peptide (r = 0.25, p = 0.04), and on follow-up, aortic pulse wave velocity with N-terminal pro brain-type natriuretic peptide (r = 0.31, p = 0.01). Aortic pulse wave velocity increased in 50% of patients, and these patients had greater serum C-reactive protein 3(2-10) versus 2(1-4) mg/L, and ferritin (778(444-1099) versus 585(313-811), p < 0.05), but there were no differences in either absolute or adjusted extracellular water. Both log C-reactive protein (odds ratio 4.7 (95% confidence limits 1.3-17.1), p = 0.019) and prescription of calcium channel blockers (odds ratio 4.9 (95% confidence limits 1.2-19.1), p = 0.024) were independently associated with an increase in aortic pulse wave velocity. We did not find an independent association between a change in aortic pulse wave velocity and extracellular water, suggesting that changes in aortic stiffness in peritoneal dialysis patients are more complex than simply following changes in extracellular water.

Use of calcium channel blockers and myocardial infarction in hypertensive patients with rheumatoid arthritis – A nationwide cohort study

Rheumatoid arthritis (RA) should be regarded as a high risk factor for myocardial infarction (MI). In addition to anti-hypertensive effect, calcium channel blockers (CCBs) were frequently used as anti-angina drugs in patients with MI. However, the association between CCBs and MI in RA remains unclear. We investigated whether CCBs could decrease incidence of myocardial infarction in patients with hypertension and RA. We identified patients from the Registry for Catastrophic Illness, a nation-wide database encompassing almost all of the RA patients in Taiwan from 1995 to 2008. The primary endpoint was MI and the median duration of follow up was 3,050 days. Propensity score matching and Cox proportional hazards regression models were used to estimate hazard ratios for MI. Among 27,844 patients with hypertension, 17,317 (61.5%) subjects received CCBs (mean age=58.8 years, 72.1% female). The incidence of MI significantly decreased in patients treated with CCBs (hazard ratio [HR] 0.560; 95% confidence interval [CI] 0.494-0.634). After propensity match, subjects receiving CCBs had significantly lower risk of MI (HR 0.637, 95% CI 0.549-0.740). The protective effect of CCBs therapy was significantly better in patients taking longer duration. Of note, the effect remained robust in subgroup analyses, including dihydropyridine CCBs (HR 0.550; 95% CI 0.466-0.650) and non-dihydropyridine CCBs (HR 0.674, 95% CI 0.588-0.773). Therapy of CCBs is associated with a lower risk of MI among hypertensive patients with RA. Hence, the prescription of CCBs may be a compelling indication of BP lowering in RA population.

Analysis of prescription medications in elderly patients with cardiovascular diseases

Objective To analyze the clinical medications in elderly patients with cardiovascular diseases. Methods The medical records were extracted and statistically analyzed in 386 elderly patients with cardiovascular diseases in Department of Vasculocardiology of our hospital. Results The primary hypertension, coronary heart disease, and arrhythmias were the most common cardiovascular diseases in elderly patients.The most frequently prescribed medications were calcium channel blockers, angiotensin-converting enzyme inhibitors, and traditional Chinese medicine compound preparations, which accounted for 28.2%, 21.5% and 19.4%, respectively.The drug combination therapy is often used in clinical practice, and the proportion of four, five, ≥ six drugs combination therapy was 16.6%, 21.2% and 29.0%, respectively. Conclusions It is important to pay more attention to reducing adverse reactions and improving the rationality and safety of the drugs combination therapy in the treatment of senile cardiovascular diseases. Key words: Cardiovascular diseases; Clinical medications application

Prevalence and Predictors of Silent Gastroesophageal Reflux Disease in Patients with Hypertension.

Background Gastroesophageal reflux disease (GERD) without symptoms or silent GERD can be easily missed in patients with hypertension. We aimed to investigate the prevalence of GERD, specifically the prevalence of silent GERD in hypertensive patients, and to explore its possible predictors. Methods Consecutive patients with hypertension referred to the cardiovascular clinic of Suining Central Hospital in 2016 were screened for this study. A Reflux Disease Questionnaire (RDQ) and an esophagogastroduodenoscopy (EGD) were employed for the evaluation of silent GERD. Included patients were divided into silent-GERD group and non-GERD control group. The demographic characteristics and antihypertensive agent prescriptions were collected and compared between the two groups. Results The prevalence of silent GERD and GERD in patients with hypertension was 15.1% and 31.4%, respectively. 66 patients were included in the silent-GERD group, and 298 patients were included in the non-GERD control group. Abdominal obesity and untreated hypertension were positive predictors, while controlled hypertension was a negative predictor for silent GERD. The prescription of calcium channel blockers was not a predictor for it. Conclusions High prevalence of GERD, specifically silent GERD, could be found in patients with hypertension. Abdominal obesity and untreated hypertension were positive predictors for silent GERD, while controlled hypertension was a negative predictor for it.

Prevalence and treatment of diabetes mellitus and hypertension among older adults with intellectual disability in comparison with the general population

BackgroundDiabetes mellitus and hypertension are risk factors for cardiovascular disease, which is the most common cause of death in the world. People with intellectual disability (ID) have been reported to have high rates of both these disorders. The aim of this study was to describe and compare prevalence ratios of diabetes mellitus and hypertension between older adults with ID and their age peers in the general population, and to describe and compare treatment patterns in these two groups.MethodsThis is a Swedish register-based study, in which we established a cohort of people aged 55+ years and who had received support for those with ID in 2012 (n = 7936). We also established a same-sized referent cohort from the general population matched by sex and year of birth. Information on diagnoses of diabetes mellitus and hypertension, and prescription of drugs for these disorders, were collected from national registers for the period 2006–2012. The two cohorts were compared using generalized linear models (GLM).ResultsPeople with ID were 20% more likely than the general population to have a diagnosis of diabetes mellitus, and 26% more likely to have prescription of drugs for diabetes mellitus. People in the general population were 81% more likely to have a diagnosis of hypertension, and 9% more likely to have a prescription of drugs for hypertension. Among those with diabetes, ID was associated with higher occurrence of prescription of insulin combination drugs and sulfonylureas, but lower occurrence of prescription of dipeptidyl peptidase (DPP) 4-inhibitors and exenatide/liraglutide. Among those with hypertension, ID was associated with higher occurrence of prescription of diuretics, but lower occurrence of prescription of calcium channel blockers and angiotensin II antagonists.ConclusionsTreatment regimens among people with ID tended to include older types of medication compared with what was prescribed in the general population. To ensure that this is medically appropriate and not due to failure to update the treatment regimen, it is important to investigate if the people with ID and diabetes mellitus or hypertension are subjected to the same regular drug reviews that are recommended for older adults in general.

Residual Angina After Elective Percutaneous Coronary Intervention in Patients With Diabetes Mellitus.

Previous studies suggest that among patients with stable coronary artery disease, patients with diabetes mellitus (DM) have less angina and more silent ischemia when compared with those without DM. However, the burden of angina in diabetic versus nondiabetic patients after elective percutaneous coronary intervention (PCI) has not been recently examined. In a 10-site US PCI registry, we assessed angina before and at 1, 6, and 12 months after elective PCI with the Seattle Angina Questionnaire angina frequency score (range, 0-100, higher=better). We also examined the rates of antianginal medication prescriptions at discharge. A multivariable, repeated-measures Poisson model was used to examine the independent association of DM with angina over the year after treatment. Among 1080 elective PCI patients (mean age, 65 years; 74.7% men), 34.0% had DM. At baseline and at each follow-up, patients with DM had similar angina prevalence and severity as those without DM. Patients with DM were more commonly prescribed calcium channel blockers and long-acting nitrates at discharge (DM versus not: 27.9% versus 20.9% [P=0.01] and 32.8% versus 25.5% [P=0.01], respectively), whereas β-blockers and ranolazine were prescribed at similar rates. In the multivariable, repeated-measures model, the risk of angina was similar over the year after PCI in patients with versus without DM (relative risk, 1.04; range, 0.80-1.36). Patients with stable coronary artery disease and DM exhibit a burden of angina that is at least as high as those without DM despite more antianginal prescriptions at discharge. These findings contradict the conventional teachings that patients with DM experience less angina because of silent ischemia.

Antianginal medications and long-term outcomes after elective catheterization in patients with coronary artery disease.

Antianginal medications are a class I recommendation by the American College of Cardiology/American Heart Association guidelines for stable ischemic heart disease. We sought to better understand guidance in drug selection and real-life outcomes of antianginal medication use. In patients with stable ischemic heart disease, antianginal medications lower mortality. We evaluated 5608 patients with obstructive coronary artery disease (CAD) on elective cardiac catheterization with follow-up through self-administered questionnaires. Patients were classified as being prescribed a particular medication if they received that medication at index catheterization, or within 3 months postcatheterization. The association between antianginal medication use and outcomes was evaluated using Cox proportional hazards models. Compared with the 11% not prescribed any antianginal medication, patients prescribed antianginal medication were more likely to be older and female; have a history of hypertension, diabetes mellitus, peripheral vascular disease, or 3-vessel CAD; have lower adjusted mortality (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.63-0.89); and experience mortality or myocardial infarction (HR: 0.83, 95% CI: 0.71-0.98). Compared with patients not taking β-blockers (17%), those taking β-blockers had a lower risk of mortality (HR: 0.76, 95% CI: 0.66-0.88). Patients prescribed calcium channel blockers or long-acting nitrates had a higher risk of mortality compared with nonusers (HR: 1.16, 95% CI: 1.04-1.29; HR: 1.20, 95% CI: 1.08-1.34; respectively). Antianginal medications are not universally prescribed among obstructive CAD patients; nonuse was associated with higher mortality. For CAD patients with or without prior myocardial infarction, β-blockers were associated with improved long-term survival.

Abstract 177: Residual Angina Following Elective PCI in Patients with Diabetes

Background: While patients with diabetes (DM) have more diffuse coronary artery disease (CAD), the data on whether they experience more (or less) angina than patients without DM are conflicting. Although older studies suggested that patients with DM have less angina (due to silent ischemia), this has been contradicted by more recent work among patients after myocardial infarction. However, the prevalence of angina after PCI in patients with DM and stable CAD has not been examined. Methods: In a 10-site US PCI registry, we assessed angina in patients before elective PCI and at 1, 6, and 12 months after PCI with the Seattle Angina Questionnaire (SAQ) angina frequency (AF) score (range 0-100, higher=better). We also examined the rates of antianginal medication prescription at discharge. A multivariable, repeated measures Poisson model including demographic and clinical variables such as multivessel coronary disease was used to examine the association of diabetes with angina. Results: Among 1080 elective PCI patients (mean age 65, 74.7% male), 34.0% had DM. At baseline, 1, 6, and 12 months, patients with DM had similar angina prevalence as those without DM (Figure). In addition, when assessed as a continuous variable, SAQ AF scores were also similar at baseline and each follow-up for patients with DM vs. without DM (Figure). Patients with DM were more commonly prescribed calcium channel blockers and nitrates at discharge (DM vs. not: 27.9% vs 20.9% [p=0.01] and 32.8% vs. 25.5%, [p=0.01], respectively), while beta-blockers and ranolazine were prescribed at similar rates. In the multivariable, repeated measures model, the risk of angina remained similar at 1 and 12 months, and was slightly higher at 6 months in patients with vs. without diabetes (1 month: RR 1.10, 95% CI 0.84-1.44; 6 month: RR 1.24, 1.06-1.44; 12 months RR 1.04, 0.80-1.36). Conclusions: Patients with stable coronary artery disease and diabetes exhibit a burden of angina that is at least as high as those without diabetes, despite more aggressive antianginal prescription at discharge. These findings contradict the prevailing “conventional wisdom” which dictates that patients with diabetes experience less angina due to silent ischemia.

Calcium channel blockers and outcomes in older patients with heart failure and preserved ejection fraction.

Little is known about associations of calcium channel blockers (CCBs) with outcomes in patients with heart failure and preserved ejection fraction (EF). Of the 10 570 hospitalized patients with heart failure and preserved EF, ≥65 years, EF ≥40%, in the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF; 2003-2004), linked to Medicare data (through December 31, 2008), 7514 had no prior history of CCB use. Of these, 815 (11%) patients received new discharge prescriptions for CCBs. Propensity scores for CCB initiation, calculated for each of the 7514 patients, were used to assemble a matched cohort of 1620 (810 pairs) patients (mean age, 80 years; mean EF, 56%; 65% women; 10% black) receiving and not receiving CCBs, balanced on 114 baseline characteristics. The primary composite end point of all-cause mortality or heart failure hospitalization occurred in 82% and 81% of patients receiving and not receiving CCBs (hazard ratio for CCBs, 1.03; 95% confidence interval, 0.92-1.14). Hazard ratios (95% confidence intervals) for all-cause mortality, heart failure hospitalization, and all-cause hospitalization were 1.05 (0.94-1.18), 1.05 (0.91-1.21), and 1.03 (0.93-1.14), respectively. Similar associations were observed when we categorized patients into those receiving amlodipine and nonamlodipine CCBs. Among 7514 prematch patients, multivariable-adjusted and propensity-adjusted hazard ratios (95% confidence interval) for primary composite end point were 1.03 (0.95-1.12) and 1.02 (0.94-1.11), respectively. In hospitalized older patients with heart failure, new discharge prescriptions for CCBs had no associations with composite or individual end points of mortality or heart failure hospitalization, regardless of the class of CCBs.

Amlodipine Metabolism in Human Liver Microsomes and Roles of CYP3A4/5 in the Dihydropyridine Dehydrogenation

Amlodipine is a commonly prescribed calcium channel blocker for the treatment of hypertension and ischemic heart disease. The drug is slowly cleared in humans primarily via dehydrogenation of its dihydropyridine moiety to a pyridine derivative (M9). Results from clinical drug-drug interaction studies suggest that CYP3A4/5 mediate metabolism of amlodipine. However, attempts to identify a role of CYP3A5 in amlodipine metabolism in humans based on its pharmacokinetic differences between CYP3A5 expressers and nonexpressers failed. Objectives of this study were to determine the metabolite profile of amlodipine (a racemic mixture and S-isomer) in human liver microsomes (HLM), and to identify the cytochrome P450 (P450) enzyme(s) involved in the M9 formation. Liquid chromatography/mass spectrometry analysis showed that amlodipine was mainly converted to M9 in HLM incubation. M9 underwent further O-demethylation, O-dealkylation, and oxidative deamination to various pyridine derivatives. This observation is consistent with amlodipine metabolism in humans. Incubations of amlodipine with HLM in the presence of selective P450 inhibitors showed that both ketoconazole (an inhibitor of CYP3A4/5) and CYP3cide (an inhibitor of CYP3A4) completely blocked the M9 formation, whereas chemical inhibitors of other P450 enzymes had little effect. Furthermore, metabolism of amlodipine in expressed human P450 enzymes showed that only CYP3A4 had significant activity in amlodipine dehydrogenation. Metabolite profiles and P450 reaction phenotyping data of a racemic mixture and S-isomer of amlodipine were very similar. The results from this study suggest that CYP3A4, rather than CYP3A5, plays a key role in metabolic clearance of amlodipine in humans.

Outpatient calcium‐channel blockers and the risk of postpartum haemorrhage: a cohort study

To determine whether outpatient exposure to calcium-channel blockers (CCBs) at the time of delivery is associated with an increased risk for postpartum haemorrhage (PPH). Cohort study. United States of America. Medicaid beneficiaries. We identified a cohort of 9750 patients with outpatient prescriptions for CCBs, methyldopa, or labetalol for pre-existing or gestational hypertension whose days of supply overlapped with delivery; 1226 were exposed to CCBs. The risk of PPH was compared in those exposed to CCBs to those exposed to methyldopa or labetalol. Propensity score matching and stratification were used to address potential confounding. The occurrence of PPH during the delivery hospitalisation. There were 27 patients exposed to CCBs (2.2%) and 232 patients exposed to methyldopa or labetalol (2.7%) who experienced PPH. After accounting for confounders, there was no meaningful association between CCB exposure and PPH in the propensity score matched (odds ratio 0.77, 95% CI 0.50-1.18) or stratified (odds ratio 0.79, 95% CI 0.53-1.19) analyses. Similar results were obtained across multiple sensitivity analyses. The outpatient use of CCBs in late pregnancy for the treatment of hypertension does not increase the risk of PPH.

Ambulatory hypertensive patients treated by cardiologists in France

While general practitioners treat most hypertensive patients in France, hypertension is the most frequent pathology treated by cardiologists, raising questions about the differing profiles of such patients. Poor control of hypertension is commonly reported, and yet has not improved over time. Better understanding of the determinants of control, at both patient and physician levels, is necessary to implement improvements in practice. To describe the hypertensive population treated by independent cardiologists in France and to assess the prevalence and determinants of not-at-goal blood pressure (BP), at patient and physician levels. The COLHYGE study was an observational cross-sectional epidemiological study. Consecutive patients (n=5798) were selected by 371 independent cardiologists in France. Data concerning patients and physicians were assessed. Our study population had an elevated cardiovascular risk, high prevalence of patients in secondary cardiovascular prevention (27.5%) and a high proportion of diabetic patients (22.8%). Only 20.8% of the population presented controlled BP. At the patient level, the following variables were negatively and independently associated with BP control: age; body mass index; heart rate; recently diagnosed hypertension; left ventricular hypertrophy; patient belief that they are taking too many pills; prescription of calcium channel blockers, lipid-lowering agents and antiplatelet agents. Presence of atrial fibrillation and the prescription of renin-angiotensin system blockers and fixed combinations correlated positively with BP control. At the physician level, working in big cities and having an exclusive independent practice were associated with good BP control. There was high heterogeneity among physicians in terms of BP control, independent of the patient and physician characteristics assessed. The COLHYGE study has confirmed a high cardiovascular risk and poor BP control among hypertensive patients treated by cardiologists in France. Strategies aiming to control BP should focus on both patient and physician characteristics.

Does a Negative Ergonovine Provocation Test Truly Predict Freedom from Variant Angina?

Ergonovine provocation test is known to be very sensitive for diagnosing variant angina. The patient described in this study initially presented with atypical chest pain and underwent coronary angiography and ergonovine provocation tests, which were negative. The patient was subsequently prescribed a proton pump inhibitor and prokinetics for pain relief, but then presented with acute myocardial infarction and cardiogenic shock due to coronary artery vasospasm 5 years later. This case suggests that ergonovine provocation test generates false negative results, which can lead to unwanted outcomes. Even with a negative ergonovine provocation test, prescription of calcium channel blockers or nitrates should be considered in patients with a clinical history suggestive of variant angina.

The Frequency of Prescription of Immediate-Release Nifedipine for Elderly Patients in Germany

Immediate-release nifedipine is on the PRISCUS list of drugs that should not be given to elderly patients. We studied the use of this calcium-channel blocker under real-life conditions. In 2009, we carried out a cross-sectional study based on the Statutory Health Insurance Sample AOK Hesse/KV Hesse with a sample size of 260 672 insurees. We used an anatomic-therapeutic-chemical classification (C08) to identify prescriptions for calcium-channel blockers. We determined from brand names and dosage forms whether nifedipine was prescribed in an immediate-release or sustained-release formulation. Among insurees over age 65, the prevalence of treatment with immediate-release and sustained-release nifedipine was 0.9% and 1.0%, respectively. Immediate-release nifedipine was usually (75%) given in a single administration. 46% of patients receiving immediate-release nifedipine also received another calcium-channel blocker. Patients who received immediate-release nifedipine tended to take more cardiovascular drugs than those who received sustained-release nifedipine (6 or more cardiovascular drugs were taken by 30% and 16%, respectively). Among all medical diagnoses related to hypertension, two were significantly more common among patients taking immediate-release nifedipine than among those taking sustained-release nifedipine: hypertensive crisis (OR 4.26, 95% CI 2.45-7.40) and hypertensive heart disease (OR 1.82, 95% CI 1.04-3.19). Our analysis demonstrates that immediate-release nifedipine is being prescribed to elderly patients in Germany, albeit mostly in a single administration. In view of the risks and the availability of alternative drugs, stricter adherence to the PRISCUS recommendations in this case should be stressed in continuing medical education.