Users Of Calcium Channel Blockers Research Articles

Calcium Channel Blockers in Secondary Cardiovascular Prevention and Risk of Acute Events: Real-World Evidence from Nested Case-Control Studies on Italian Hypertensive Elderly.

Antihypertensive treatment with calcium channel blockers (CCBs) is consolidated in clinical practice; however, different studies observed increased risks of acute events for short-acting CCBs. This study aimed to provide real-world evidence on risks of acute cardiovascular (CV) events, hospitalizations and mortality among users of different CCB classes in secondary CV prevention. Three case-control studies were nested in a cohort of Italian elderly hypertensive CV-compromised CCBs users. Cases were subjects with CV events (n=25,204), all-cause hospitalizations (n=19,237), or all-cause mortality (n=17,996) during the follow-up. Up to four controls were matched for each case. Current or past exposition to CCBs at index date was defined based on molecule, formulation and daily doses of the last CCB delivery. The odds ratio (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Compared to past users, current CCB users had significant reductions in risks of CV events [OR 0.88 (95% CI: 0.84-0.91)], hospitalization [0.90 (0.88-0.93)] and mortality [0.48 (0.47-0.49)]. Current users of long-acting dihydropyridines (DHPs) had the lowest risk [OR 0.87 (0.84-0.90), 0.86 (0.83-0.90), 0.55 (0.54-0.56) for acute CV events, hospitalizations and mortality], whereas current users of short-acting CCBs had an increased risk of acute CV events [OR 1.77 (1.13-2.78) for short-acting DHPs; 1.19 (1.07-1.31) for short-acting non-DHPs] and hospitalizations [OR 1.84 (0.96-3.51) and 1.23 (1.08-1.42)]. The already-existing warning on short-acting CCBs should be potentiated, addressing clinicians towards the choice of long-acting formulations.

Antiarrhythmic drug usage and prostate cancer: a population-based cohort study

Even though the relationship between antiarrhythmic drug usage and subsequent prostate cancer (PCa) risk has recently been highlighted, relevant findings in the previous literature are still inconsistent. In addition, very few studies have attempted to investigate the association between sodium channel blockers or potassium channel blockers for arrhythmia and the subsequent PCa risk. Therefore, this cohort study aimed to find the relationship between antiarrhythmic drug usage and the subsequent PCa risk using a population-based dataset. The data used in this study were derived from the Longitudinal Health Insurance Database 2005, Taiwan, China. We respectively identified 9988 sodium channel blocker users, 3663 potassium channel blocker users, 65 966 beta-blocker users, 23 366 calcium channel blockers users, and 7031 digoxin users as the study cohorts. The matched comparison cohorts (one comparison subject for each antiarrhythmic drug user) were selected from the same dataset. Each patient was tracked for a 5-year period to define those who were subsequently diagnosed with PCa. After adjusting for sociodemographic characteristics, comorbidities, and age, Cox proportional hazard regressions found that the hazard ratio (HR) of subsequent PCa for sodium channel blocker users was 1.12 (95% confidence interval [CI]: 0.84–1.50), for potassium channel blocker users was 0.89 (95% CI: 0.59–1.34), for beta-blocker users was 1.08 (95% CI: 0.96–1.22), for calcium channel blocker users was 1.14 (95% CI: 0.95–1.36), and for digoxin users was 0.89 (95% CI: 0.67–1.18), compared to their matched nonusers. We concluded that there were no statistical associations between different types of antiarrhythmic drug usage and subsequent PCa risk.

Prior Use of Calcium Channel Blockers Is Associated With Decreased Mortality in Critically Ill Patients With Sepsis: A Prospective Observational Study.

Experimental studies suggest that calcium channel blockers can improve sepsis outcome. The aim of this study was to determine the association between prior use of calcium channel blockers and the outcome of patients admitted to the ICU with sepsis. A prospective observational study. The ICUs of two tertiary care hospitals in the Netherlands. In total, 1,060 consecutive patients admitted with sepsis were analyzed, 18.6% of whom used calcium channel blockers. None. Considering large baseline differences between calcium channel blocker users and nonusers, a propensity score matched cohort was constructed to account for differential likelihoods of receiving calcium channel blockers. Fifteen plasma biomarkers providing insight in key host responses implicated in sepsis pathogenesis were measured during the first 4 days after admission. Severity of illness over the first 24 hours, sites of infection and causative pathogens were similar in both groups. Prior use of calcium channel blockers was associated with improved 30-day survival in the propensity-matched cohort (20.2% vs 32.9% in non-calcium channel blockers users; p = 0.009) and in multivariate analysis (odds ratio, 0.48; 95% CI, 0.31-0.74; p = 0.0007). Prior calcium channel blocker use was not associated with changes in the plasma levels of host biomarkers indicative of activation of the cytokine network, the vascular endothelium and the coagulation system, with the exception of antithrombin levels, which were less decreased in calcium channel blocker users. Prior calcium channel blocker use is associated with reduced mortality in patients following ICU admission with sepsis.

Effect of contraindicated drugs for heart failure on hospitalization among seniors with heart failure: A nested case-control study.

Little is known about the effect of nonsteroidal anti-inflammatory drugs (NSAIDs), thiazolidinediones (TZDs), nifedipine and nondihydropyridine calcium channel blockers (CCBs) usage on the risk of all-cause hospitalization among seniors with heart failure (HF). We assessed the risk of all-cause hospitalization associated with exposure to each of these drug classes, in a population of seniors with HF.Using the Quebec provincial databases, we conducted a nested case-control study in a population of individuals aged ≥65 with a first HF diagnosis between 2000 and 2009. Patients were considered users of a potentially inappropriate drug class if their date of hospital admission occurred in the interval between the date of the last drug claim and the end date of its days’ supply. The risks of hospitalization were estimated using multivariate conditional logistic regression.Of the 128,853 individuals included in the study population, 101,273 (78.6%) were hospitalized. When compared to nonusers, users of NSAIDs (adjusted odds ratio: 1.16; 95% confidence interval: 1.13–1.20), TZD (1.09; 1.04–1.14), and CCBs (1.03; 1.01–1.05) had an increased risk of all-cause hospitalization, but not the users of nifedipine (1.00; 0.97–1.03).Seniors with HF exposed to a potentially inappropriate drug class are at increased risk of worse health outcomes. Treatment alternatives should be considered, as they are available.

Effect of Calcium Channel Blockers on Gingival Tissues in Hypertensive Patients in Lagos, Nigeria: A Pilot Study.

Background:Long-term treatment of common chronic cardiac conditions such as hypertension with calcium channel blockers (CCBs) has long been associated with gingival hyperplasia. This oral side effect may affect esthetics and function, yet often overlooked and therefore underreported among Nigerians.Aim:This study aimed to determine the association of CCBs with gingival overgrowth (GO) in hypertensive patients.Methods:This was a hospital-based, case–control study conducted among 116 hypertensive patients (58 CCB and 58 non-CCB age-matched controls) attending the medical outpatient clinic of a tertiary health institution in Lagos, Nigeria. Data collection tools included interviewer-administered questionnaires and periodontal examination. Sociodemographic details, medical history, and periodontal indices (gingival index, plaque index, class of GO according to drug-induced GO [DIGO] Clinical Index) were recorded.Results:The mean age was 59.4 ± 12.6 years, females representing 50.9%. In the CCB group, 39 (67.2%) participants were on amlodipine and 19 (32.8%) were on nifedipine. The mean duration of CCB use was 55.6 ± 53 months. DIGO was higher in CCB (36.2%) than that in non-CCB participants (17.2%) (χ2 = 4.4, P = 0.036). The risk of GO was higher in CCB users (odds ratio [OR] 2.7, [95% confidence interval (CI)]: 1.1–6.5). Amlodipine users had higher DIGO (37.5%) than that of nifedipine users (21.1%) (OR 2.3, [95% CI]: 1.0–5.3). The predominant class of DIGO among the CCB users was Class 2 DIGO Clinical Index (90.5%).Conclusion:The study reveals that the risk of GO is nearly three times in CCB than that of non-CCB users and twice higher in amlodipine than nifedipine users in Nigeria.

Preadmission Use of Calcium Channel Blockers and Outcomes After Hospitalization With Pneumonia: A Retrospective Propensity-Matched Cohort Study.

In sepsis, an overwhelming immune response, as mediated by the release of various inflammatory mediators, can lead to shock, multiple organ damage, and even death. Pneumonia is the leading cause of sepsis. In animal septic models, sepsis could induce uncontrolled calcium (Ca) leaking, raising cytosolic Ca to a toxic level, causing irreversible cellular injuries and organ failure. All types of calcium channel blockers (CCBs), by inhibiting Ca influx, have been shown to decrease overall mortality in various septic animal models. However, to our best knowledge, no clinical study had been conducted to investigate the beneficial effect(s) of CCBs in sepsis. We conducted a retrospective propensity-matched cohort study after screening 2214 patients hospitalized for pneumonia from year 2012 to 2014 at our institution. We identified 387 preadmission CCB users and 387 nonusers by propensity score matching. Logistic regression analysis was then used to determine the association between preadmission CCB use and outcomes in pneumonia. Our study showed that the odds for development of severe sepsis was significantly lower in the CCB user group [odds ratio (OR), 0.466; 95% confidence interval (CI), 0.311-0.697; P = 0.002]. Preadmission CCB use was associated with a lower risk of contracting bacteremia (OR, 0.498; 95% CI, 0.262-0.99; P = 0.0327), lower risk of acute respiratory insufficiency (OR, 0.573; 95% CI, 0.412-0.798; P = 0.001), lower risk of intensive care unit admission (OR, 0.602; 95% CI, 0.432-0.840; P = 0.0028). In conclusion, our study suggested preadmission CCB use was associated with a reduction in the risks of development of respiratory insufficiency, bacteremia, and severe sepsis in patients admitted to the hospital with pneumonia.

QTc interval in young Gujarati hypertensives: Effect of disease, antihypertensive monotherapy, and coexisting risk factors.

Objectives:To study the effect of disease duration, treatment and risk factors on QTc interval among young hypertensives.Materials and Methods:A case–control study was conducted on 142 hypertensives (60 males, 82 females) taking calcium channel blocker (CCB) or angiotensin-converting enzyme inhibitor (ACEI) as monotherapy. After blood pressure measurement, we recorded lead II electrocardiograph with minimum ten waveforms. QTc was derived from average of ten values using Bazett's formula. QTc interval >0.43 s in male and >0.45 s in female was considered abnormal.Results:Cases had mean duration of hypertension 5 years, mean age of 40 years, and poor blood pressure control (systolic blood pressure >140 and diastolic blood pressure >90 mm of Hg). Newly diagnosed hypertensives had significantly higher QTc values than the matched known cases (0.44 vs. 0.42 s, P < 0.05). Known hypertensives did not differ significantly in QTc values by the duration of disease. CCB users showed small, insignificant disadvantage for abnormally prolonged QTc values than ACEI users. With coexisting diabetes, smoking, and positive family history of hypertension, there was odds risk of 7.69, 2.75, and 2.54, respectively for prolonged QTc.Conclusion:Our study showed prolonged QTc in hypertensives more so in newly diagnosed, unaffected by duration or use of ACEI, or CCB but associated with modifiable risk factors. This underscores high risk of repolarization abnormality-induced future events, suggesting early screening of hypertension, strict blood pressure control, optimum use of QTc measurement, and preventive pharmacotherapy to reduce this aftermath.

Risk of Parkinson's Disease in the Users of Antihypertensive Agents: An Evidence from the Meta-Analysis of Observational Studies.

Background. Antihypertensive agents have been shown to inhibit oxidative stress and inflammatory response and thus neuroprotection in Parkinson's disease (PD). Epidemiological evidence suggests inconsistency between use of antihypertensives and risk of PD. This study is aimed to examine the association between antihypertensive use and risk of PD. Methods. Literature search in PubMed, EMBASE, and PsycINFO database was undertaken through February 2012 looking for observational studies evaluating the association between antihypertensive drug use and risk of PD. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects model (DerSimonian and Laird method). Subgroup analyses and sensitivity analysis were also performed. Results. Seven relevant studies including a total of 28,32,991 subjects were included. Pooled RR of overall use of antihypertensive agents was found to be 0.95 (95% CI 0.84–1.05). A significant reduction in the risk of PD was observed among users of calcium channel blockers (RR 0.82, 95% CI 0.71–0.93). Significant heterogeneity (I 2 = 76.2%) but no publication bias was observed. Conclusions. Overall use of antihypertensive agents showed no significant association with the risk of PD. CCBs provided significant protective role. However, studies with large sample size and dose relationships are required to strengthen our hypothesis.

Long-term use of calcium channel blocking drugs and breast cancer risk in a prospective cohort of US and Puerto Rican women

BackgroundIn a recent case–control study, long-term use of calcium channel blocking drugs was associated with a greater-than-twofold increased breast cancer risk. If prospectively collected data confirm that calcium channel blocker use increases breast cancer risk, this would have major implications for hypertension treatment. The objective of this study was to determine whether women using calcium channel blockers for 10 years or more were at increased risk of developing breast cancer compared with women not using calcium channel blockers.MethodsThe Sister Study is a prospective volunteer cohort study of women from the USA and Puerto Rico designed to evaluate environmental and genetic risk factors for breast cancer. Beginning in 2003, women between the ages of 35 and 74 were recruited. They were eligible to participate if they had a sister with breast cancer but had not been diagnosed with breast cancer themselves. In total, 50,884 women enrolled in the cohort between 2003 and 2009; 50,757 women with relevant baseline data and available follow-up data are included in this study. The exposure of interest is current use of calcium channel blocking drugs and the reported duration of use at entry into the cohort. Secondary exposures of interest were the duration and frequency of use for all other subclasses of antihypertensive drugs. Our main outcome is a self-reported diagnosis of breast cancer during the study follow-up period. With patient permission, self-reported diagnoses were confirmed using medical records.ResultsResults showed 15,817 participants were currently using an antihypertensive drug, and 3316 women were currently using a calcium channel blocker at study baseline; 1965 women reported a breast cancer diagnosis during study follow-up. Using Cox proportional hazards modeling, we found no increased risk of breast cancer among women who had been using calcium channel blockers for 10 years or more compared with never users of calcium channel blockers (HR 0.88, 95 % CI 0.58–1.33).ConclusionsWe saw no evidence of increased risk of breast cancer from 10 years or more of current calcium channel blocker use. Our results do not support avoiding calcium channel blocking drugs in order to reduce breast cancer risk.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0720-6) contains supplementary material, which is available to authorized users.

Antihypertensive Drugs and Diabetic Retinopathy in Patients with Type 2 Diabetes

Objective: To evaluate the association between the development of sight-threatening diabetic retinopathy (STDR) and antihypertensive drugs (AHDs) use among type 2 diabetic patients with concomitant hypertension. Methods: Type 2 diabetic patients aged 20-100 years who had at least one prescription for AHDs between 2000 and 2011 were identified from the Longitudinal Health Insurance Database (LHID) 2005. The incidence rates of STDR were followed and Cox proportional hazard models were used to analyze the risk associated with AHDs. Results: Users of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) were associated with a significantly higher risk than users of calcium channel blockers (CCBs), independent of baseline characteristics. After adjusting for time-varying use of concomitant medications for propensity score-matched or -unmatched cohorts, the results showed that patients receiving ACEIs/ARBs and CCBs were associated with a significantly greater risk compared with β-blocker users. Conclusions: Our study did not support a superiority of ACEIs/ARBs and CCBs over β-blockers for lowering the progression of diabetic retinopathy.

Calcium Channel Blockers and Outcomes in Pneumonia

SESSION TITLE: Chest Infections Posters I SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: Calcium channel blockers(CCBs) have been shown to decrease overall mortality in septic animal models. However, to our best knowledge, no study had been conducted in human subjects to asses their impact in sepsis. Here we investigated the potential protective effect of pre-hospital CCB use against severe sepsis in patients with pneumonia. METHODS: Retrospective study of hospitalized patients with diagnosis code of 481, 482, 485 or 486 from the year of 2012 to 2014. Patient data were extracted from the EPIC electronic database. Chest radiography and clinical presentation were reviewed for the presence of clinically compatible pneumonia at the first 72 hours of admission. Certain inclusion and exclusion criteria were applied. Continuous outcomes were analyzed by multivariate analysis of variance and dichotomous outcomes by logistic regression. RESULTS: RESULTS: Total 2214 patients were admitted with pneumonia during this period of time. Among total 2214 patients, 1230 patients were included into the study, of which included 373 CCB users and 857 non-CCB users. After adjusting age, gender, statin use and Charleston Comorbidity Index (CCI), our study revealed CCB use was associated with less severity of disease on arrival by pneumonia severity scores(Standardized Coefficients β(β) of -0.135, p<0.05). Meanwhile, there was a significant difference in the Length of Stay (LOS) between CCB group and non-CCB group (β -0.119, p<0.05). Moreover, CCB use was associated with less chance to be admitted to Intensive Care Unit (p: 0.029) for the whole hospital stay. Regarding the outcomes, CCB use seems to have no association with the development of acute renal failure and in-hospital mortality (p>0.05). However, it is associated with less respiratory failure needing high flow oxygen (p: 0.008), less bacteremia (p<0.037) as well as less chances of developing severe sepsis or septic shock (p: 0.001). CONCLUSIONS: Pre-hospital CCB use is inversely associated with the development of respiratory failure, bacteremia and severe sepsis in patients with pneumonia. CLINICAL IMPLICATIONS: Pneumonia is one of leading causes for hospital admission, sepsis and death. CCBs have been shown to be beneficial in animal sepsis syndrome models as an immunomodulator. As the first study to asses the beneficial effect(s) of CCBs in severe infections in human subjects, our study adds to the accumulating evidences from animal studies that CCB use is associated with better outcomes in severe infections like pneumonia. DISCLOSURE: The following authors have nothing to disclose: Lin Zheng, Sameer Poddar No Product/Research Disclosure Information

Comparative Effectiveness of Ranolazine Versus Traditional Therapies in Chronic Stable Angina Pectoris and Concomitant Diabetes Mellitus and Impact on Health Care Resource Utilization and Cardiac Interventions

Comparative studies evaluating traditional versus newer antianginal (AA) medications in chronic stable angina pectoris (CSA) on cardiovascular (CV) outcomes and utilization are limited, particularly in patients with diabetes mellitus (DM). Claims data (2008 to 2012) were analyzed using a commercial database. Patients with CSA receiving a β blocker (BB), calcium channel blocker (CCB), long-acting nitrate (LAN), or ranolazine were identified and followed for 12 months after a change in AA therapy. Patients on traditional AA medications were required to have concurrent sublingual nitroglycerin. Therapy change was defined as adding or switching to another traditional AA medication or ranolazine to identify patients whose angina was inadequately controlled with previous therapy. Four groups were identified (BB, CCB, LAN, or ranolazine users) and matched on relevant characteristics. A DM subset was identified. Logistic regression compared revascularization at 30, 60, 90, 180, and 360 days. Negative binomial regression compared all-cause, CV-, and DM-related (in the DM cohort) health care utilization. A total of 8,008 patients were identified with 2,002 patients in each matched group. Majority were men (mean age 66 years). A subset of 3,724 patients with DM (BB, n = 933; CCB, n = 940; LAN, n = 937; and ranolazine, n = 914) resulted from this cohort. Compared to ranolazine in the overall cohort, traditional AA medication exhibited greater odds for revascularization and higher rates in all-cause outpatient, emergency room visits, inpatient length of stay, and CV-related emergency room visits. In the DM cohort, ranolazine demonstrated similar benefits over traditional AA medication. In conclusion, ranolazine use in patients with inadequately controlled chronic angina is associated with less revascularization and all-cause and CV-related health care utilization compared to traditional AA medication.

Systematic review with meta-analysis: the association between the use of calcium channel blockers and gastrointestinal bleeding.

Due to their potential anti-platelet effect, it is suggested that calcium channel blockers (CCBs) are associated with gastrointestinal bleeding (GIB). However, results from previous studies are conflicting. To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) and observational studies to clarify the association between CCBs and GIB. We conducted a systematic search of PubMed, EMBASE, Cochrane library and Trial Register databases up to January 2015. Studies that evaluated exposure to CCBs reporting GIB outcomes were included in the meta-analysis. The inverse variance method with random effects model was used to calculate the pooled estimates. Seventeen studies (four RCTs, eleven case-control and two cohort studies) were included in the meta-analysis. The summary risk ratio (RR) for GIB was 1.17 (95% CI 1.01-1.36) for CCB users vs. non-users. Subgroup analysis showed that CCB use was associated with a moderately higher risk of lower GIB (RR=1.83, 95% CI 1.17-2.84) but not upper GIB. However, data from four RCTs did not support association between CCBs and GIB (RR=0.93, 95% CI 0.82-1.05). Subgroup analyses further showed that the increased risk of GIB among CCB users was only observed in studies that failed to adjust for prior history of GIB (RR=1.67, 95% CI 1.34-2.08) or use of anti-ulcer drugs (RR=1.40, 95% CI 1.19-1.65). Our meta-analysis showed a marginal association between calcium channel blocker use and the risk of gastrointestinal bleeding. This association is of dubious clinical significance, as the effects of different comparators or adjustment for confounding factors render this association nonsignificant.

Calcium channel blocker use and risk of Parkinson's disease: a meta-analysis.

Whether calcium channel blocker (CCB) use contributes to a low risk of developing a first time diagnosis of Parkinson's disease (PD) remains controversial. We conducted a meta-analysis to investigate the relationship between CCB use and PD risk. Pubmed, EMBASE, China National Knowledge Infrastructure, and WanFang databases were searched for papers through May 2014. Studies investigating the association between CCB use and the risk of first time diagnosis of PD were included. Pooled adjusted risk ratio (RR) and 95% confidence interval (CI) were calculated using a fixed-effect model. Five studies involving 208 248 CCB users were identified. Overall, CCB use was associated with a reduction in PD risk (RR = 0.76, 95%CI = 0.68-0.84) compared with the controls. Subgroup analysis showed that dihydropyridine CCB use reduced by 27% PD risk (RR = 0.73, 95%CI = 0.64-0.83) and non-dihydropyridine CCB use reduced by 30% PD risk (RR = 0.70, 95%CI = 0.50-0.93). Overall, CCB use as a class is associated with a reduction in PD risk. Both of dihydropyridine and non-dihydropyridine CCB use appear to reduce the risk of developing a first time diagnosis of PD. More well-designed prospective studies are needed to investigate the difference of the subtype of CCB user on PD risk.

Impact of preadmission treatment with calcium channel blockers or beta blockers on short-term mortality after stroke: a nationwide cohort study.

BackgroundThe prognostic impact of preadmission use of calcium channel blockers (CCBs) and beta blockers (BBs) on stroke mortality remains unclear. We aimed to examine whether preadmission use of CCBs or BBs was associated with improved short-term mortality following ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH).MethodsWe conducted a nationwide population-based cohort study using Danish medical registries. We identified all patients with a first-time inpatient diagnosis of stroke between 2004 and 2012 and their comorbidities. We defined CCB/BB use as current use, former use, or non-use. Current use was further classified as new or long-term use. We used Cox regression modeling to compute 30-day mortality rate ratios (MRRs) with 95% confidence intervals (CIs), controlling for potential confounders.ResultsWe identified 100,043 patients with a first-time stroke. Of these, 83,736 (83.7%) patients had ischemic stroke, 11,779 (11.8%) had ICH, and 4,528 (4.5%) had SAH. Comparing current users of CCBs or BBs with non-users, we found no association with mortality for ischemic stroke [adjusted 30-day MRR = 0.99 (95% CI: 0.94-1.05) for CCBs and 1.01 (95% CI: 0.96-1.07) for BBs], ICH [adjusted 30-day MRR = 1.05 (95% CI: 0.95-1.16) for CCBs and 0.95 (95% CI: 0.87-1.04) for BBs], or SAH [adjusted 30-day MRR = 1.05 (95% CI: 0.85-1.29) for CCBs and 0.89 (95% CI: 0.72-1.11) for BBs]. Former use of CCBs or BBs was not associated with mortality.ConclusionsPreadmission use of CCBs or BBs was not associated with 30-day mortality following ischemic stroke, ICH, or SAH.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-015-0279-3) contains supplementary material, which is available to authorized users.

Reduced Risk of Parkinson's Disease in Users of Calcium Channel Blockers: A Meta-Analysis.

Aim. To pool the data currently available to determine the association between calcium channel blockers (CCBs) and risk of Parkinson's disease (PD). Methods. Literature search in PubMed, EBSCO, and Cochrane library was undertaken through March 2014, looking for observational studies evaluating the association between CCBs use and PD. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using random-effects model. Subgroup analyses, sensitivity Analysis, and cumulative meta-analysis were also performed. Results. Six studies were included in our meta-analysis according to the selection criteria, including three cohort studies and three case-control studies involving 27,67,990 subjects including 11,941 PD cases. We found CCBs use was associated with significant decreased risk of PD, compared with not using CCBs (random effects model pooled RR, 0.81 (95% CI, 0.69–0.95)); a significant heterogeneity was found between studies (P = 0.031; I 2 54.6%). Both the classes of CCB, that is, dihydropyridine calcium channel blockers (DiCCB) (0.80 (95% CI, 0.65–0.98) P = 0.032) and non-DiCCB (0.70 (95% CI, 0.53–0.92) P = 0.013), were found to be reducing the risk of PD. Conclusion. In our analysis, we found that CCBs use was associated with a Significantly decreased risk of PD compared with non-CCB use.

Calcium channel blockers and risk of breast cancer: a meta-analysis of 17 observational studies.

PurposeStudies on the association between the use of calcium channel blockers (CCBs) and breast cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on the evidence from observational studies.MethodsWe searched PubMed, MEDLINE, EMBASE and the Cochrane Library for relevant studies published up to and including December 31, 2013. We calculated pooled risk ratios (RRs) for cancer risk.ResultsA total of 17 studies (9 cohort studies, 8 case-control studies) were selected for further study. These studies included 149,607 female subjects, of which 53,812 were CCBs users, who were followed for 2–16 years. The risks of breast cancer among patients receiving CCBs were significantly different for the pooled RRs (95% confidence interval) of cohort studies 1.08 (0.95, 1.20) and case-control studies 0.98 (0.86, 1.09). Differences were also noted for cancer risk, for CCBs use of <5 years 0.96 (0.78, 1.15), and for >5 years 1.01 (0.74, 1.28), as well as for ever used 1.08 (0.95, 1.20), and for current use 1.13 (0.83, 1.42). The RR for studies longer than 10 years was 1.71 (1.01, 2.42), and for studies evaluating nifedipine was 1.10 (0.87, 1.33) and diltiazem was 0.75 (0.40, 1.10).ConclusionsThe long-term use of CCBs appears to have a significant relationship with breast cancer. Well-designed clinical trials are needed to optimize the doses and types of these drugs needed to minimize their carcinogenic potential.

Abstract 131: Ranolazine Improves Cardiovascular Outcomes and Healthcare Utilization: A Comparative Effective Analysis with Traditional Antianginal Medications

Introduction: Real-world comparative studies evaluating traditional with newer antianginal medications in chronic stable angina (CSA) on cardiovascular (CV) outcomes and healthcare utilization are limited. Methods: Medical and pharmacy claims from 2008-2012 were analyzed using a large commercial database. Patients with a CSA diagnosis receiving ranolazine, beta blocker (BB), calcium channel blocker (CCB), or long-acting nitrates (nitrates) were identified and followed for 12 months after a change in antianginal therapy. Patients on traditional antianginal medication: BB, CCB, and nitrates were required to have concurrent sublingual nitroglycerin. Therapy change was defined as adding or switching to another traditional antianginal or ranolazine to identify patients who had failed prior therapy. Four groups were identified (BB, CCB, nitrates, or ranolazine users) and matched for age,gender, baseline Charlson Comorbidity Index (CCI), acute coronary syndrome,hypertension, diabetes, heart failure, hyperlipidemia, diabetes related complications, and cardiovascular healthcare costs. Rates for percutaneous intervention (PCI) and coronary bypass graft (CABG) at 30, 60, 90, 180 and 360 days, as well as, annual number of CV-related outpatient visits, emergency room (ER) visits, and inpatient admissions post therapy change were compared between groups. Results: A total of 8008 patients were identified with 2002 patients in each antianginal matched group. The majority (63-65%) were male with a mean age of 66 years and a CCI of 2.89-3.01. The Table summarizes the annual rate per 1000 for CV outcomes. Compared to other antianginal therapies, ranolazine consistently exhibited lower PCI and CABG rates at all time periods following therapy change. Compared to BB, CCB,and nitrates,ranolazine had a 21% (p=0.004), 4% (p=0.578), and 23% (p&lt;0.0001) lower mean number of annual CV inpatient admissions; and 15% (p&lt;0.0001), 4% (p=0.224), and 13% (p&lt;0.0001) lower mean number of annual CV outpatient visits,respectively.Ranolazine had a 17-21% lower mean annual number of CV ER visits compared to the other antianginal groups (p=0.073,p=0.079, p=0.106,respectively). Conclusion: Ranolazine improves CV outcomes and lowers healthcare utilization compared to traditional antianginal therapies.

Antihypertensive medications and diastolic dysfunction progression in an African American population.

There have been no studies examining the association between antihypertensive medications and progression of diastolic dysfunction. The purpose of this study is to determine whether there is an association between class of antihypertensive medication and diastolic dysfunction progression in an African American population. A retrospective cohort study of African American patients with at least two echocardiograms demonstrating diastolic dysfunction drawn from an echocardiogram database at an academic medical center. The main outcome measures were change in diastolic function grade as a function of time and association with hypertension medication classification. There were 96 African American patients in the database with 2 or more echocardiograms demonstrating diastolic dysfunction; representing 302 echocardiograms. The mean time between echocardiograms was 2.6 years. The mean age was 64.2 (±10.1) years, 78 % were women, and mean BMI 31.2 (±7.4) kg/m(2). The majority of subjects had Grade I diastolic dysfunction at their initial examination [N = 87 (90.6 %)]. Approximately 22.9 % (n = 22) of the study cohort demonstrated diastolic dysfunction progression. In multivariate analysis use of calcium channel blockers (CCB) was protective against diastolic dysfunction progression (OR for CCB users vs. non-users 0.28, 95 % confidence interval, 0.09-0.90, p < 0.05). These findings suggest that use of calcium channel blockers may have a protective effect against progression of diastolic dysfunction among African American patients. Further studies are required to confirm these findings and identify specific factors that can mediate disease progression among African American individuals with hypertension, who face substantial risk of complications such as diastolic heart failure.

CYP3A4 Genetic Status May Be Associated With Increased Vulnerability to the Inhibitory Effect of Calcium-Channel Blockers on Clopidogrel

Calcium-channel blockers (CCBs) inhibit the CYP3A4 enzyme, which is involved in clopidogrel activation. Studies have shown conflicting results regarding the effect of concomitant CCB administration on clopidogrel response. We investigated the relationship between CYP3A4 genotype and the inhibitory effect of CCBs on clopidogrel response. Clopidogrel on-treatment platelet reactivity (OPR) was measured and CYP3A4 (IVS10+12G>A) genotyped in 1,247 consecutive patients with drug-eluting stent implantation. The mean OPR was 231±83 (P2Y12 reaction units: PRU). In total, 332 (26.6%) CCB users had higher OPR compared with 915 (73.4%) non-CCB users (245±84 vs. 227±83 PRU, P=0.001). The distribution of CYP3A4 (IVS10+12G>A) genotype was 63.6%, 32.6% and 3.8% for GG, GA and AA genotypes, respectively. After adjustment for possible confounding factors, the number of A-alleles was associated with increased vulnerability to CCB use (effect of CCB use ΔPRU: +8 PRU, P=0.210, +24 PRU, P=0.012, +50 PRU, P=0.025, for patients with 0, 1, and 2 A-alleles, respectively, +24 PRU, P=0.005 for GA/AA genotypes). Furthermore, only in the GA/AA-genotype did CCB use result in a significantly increased risk for high-OPR (odds ratio 1.84, 95% confidence interval 1.15-2.92, P=0.010). CCB use is associated with increased OPR. The number of CYP3A4 (IVS10+12G>A) A-alleles may be associated with an increased vulnerability to the effects of CCBs on clopidogrel response variation.