Users Of Calcium Channel Blockers Research Articles

Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy

Animal and human studies have suggested that the use of angiotensin receptor blockers (ARBs) may be associated with a lower risk of incident epilepsy compared with other antihypertensive medications. However, observational data from the US are lacking. To evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension. This retrospective cohort study used data from a national health administrative database from January 2010 to December 2017 with propensity score (PS) matching. The eligible cohort included privately insured individuals aged 18 years or older with diagnosis of primary hypertension and dispensed at least 1 ARB, angiotensin-converting enzyme inhibitor (ACEI), β-blocker, or calcium channel blocker (CCB) from 2010 to 2017. Patients with a diagnosis of epilepsy at or before the index date or dispensed an antiseizure medication 12 months before or 90 days after initiating the study medications were excluded. The data analysis for this project was conducted from April 2022 to April 2024. Propensity scores were generated based on baseline covariates and used to match patients who received ARBs with those who received either ACEIs, β-blockers, CCBs, or a combination of these antihypertensive medications. Cox regression analyses were used to evaluate epilepsy incidence during follow-up comparing the ARB cohort with other antihypertensive classes. Subgroup and sensitivity analyses were conducted to examine the association between ARB use and epilepsy incidence in various subgroups. Of 2 261 964 patients (mean [SD] age, 61.7 [13.9] years; 1 120 630 [49.5%] female) included, 309 978 received ARBs, 807 510 received ACEIs, 695 887 received β-blockers, and 448 589 received CCBs. Demographic and clinical characteristics differed across the 4 comparison groups prior to PS matching. Compared with ARB users, patients receiving ACEIs were predominantly male and had diabetes, CCB users were generally older (eg, >65 years), and β-blocker users had more comorbidities and concurrent medications. The 1:1 PS-matched subgroups included 619 858 patients for ARB vs ACEI, 619 828 patients for ARB vs β-blocker, and 601 002 patients for ARB vs CCB. Baseline characteristics were equally distributed between comparison groups after matching with propensity scores. Use of ARBs was associated with a decreased incidence of epilepsy compared with ACEIs (adjusted hazard ratio [aHR], 0.75; 95% CI, 0.58-0.96), β-blockers (aHR, 0.70; 95% CI, 0.54-0.90), and a combination of other antihypertensive classes (aHR, 0.72; 95% CI, 0.56-0.95). Subgroup analyses revealed a significant association between ARB use (primarily losartan) and epilepsy incidence in patients with no preexisting history of stroke or cardiovascular disease. This cohort study found that ARBs, mainly losartan, were associated with a lower incidence of epilepsy compared with other antihypertensive agents in hypertensive patients with no preexisting stroke or cardiovascular disease. Further studies, such as randomized clinical trials, are warranted to confirm the comparative antiepileptogenic properties of antihypertensive medications.

Evaluating calcium channel blockers and bisphosphonates as otoprotective agents in cochlear implantation hearing preservation candidates

Objectives: Evaluate potential effects of calcium channel blockers (CCB) and bisphosphonates (BP) on residual hearing following cochlear implantation. Methods: Medications of 303 adult hearing preservation (HP) candidates (low frequency pure tone average [LFPTA] of 125, 250, and 500 Hz ≤80 dB HL) were reviewed. Postimplantation LFPTA of patients taking CCBs and BPs were compared to controls matched by age and preimplantation LFPTA. Results: Twenty-six HP candidates were taking a CCB (N = 14) or bisphosphonate (N = 12) at implantation. Median follow-up was 1.37 years (range 0.22–4.64y). Among subjects with initial HP, 29% (N = 2 of 7) CCB users compared to 50% (N = 2 of 4) controls subsequently lost residual hearing 3–6 months later (OR = 0.40, 95% CI = 0.04–4.32, p = 0.58). None of the four BP patients with initial HP experienced delayed loss compared to 50% (N = 2 of 4) controls with initial HP (OR = 0.00, 95% CI = 0.00–1.95, P = 0.43). Two CCB and one BP patients improved to a LFPTA <80 dB HL following initial unaided thresholds that suggested loss of residual hearing. Discussion: There were no significant differences in the odds of delayed loss of residual hearing with CCBs or BPs. Conclusion: Further investigation into potential otoprotective adjuvants for maintaining residual hearing following initial successful hearing preservation is warranted, with larger cohorts and additional CCB/BP agents.

Beta-blockers reduce severe exacerbation in patients with mild chronic obstructive pulmonary disease with atrial fibrillation: a population-based cohort study

Background and objectiveBeta-blockers (BBs) decrease mortality and acute exacerbation (AE) rates in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular disease; however, information on their effects in patients with...

The Effect of Antihypertensive Therapy on Skeletal Muscle Mass and Bone Mineral Density in Patients With End-Stage Kidney Disease

ObjectiveSarcopenia and osteoporosis substantially influence health and lifespan. However, the variables affecting skeletal muscle mass (SMM) or bone mineral density (BMD) remain unknown. Design and MethodsFrom August 1, 2018, to July 31, 2019, we conducted a single-center, observational cohort study with 291 Japanese adult patients on maintenance hemodialysis due to end-stage kidney disease (ESKD), who had their femoral neck BMD measured using dual-energy X-ray absorptiometry. After 1-year follow-up, we measured annual changes of BMD (ΔBMD) and SMM (ΔSMM), which was calculated through a modified creatinine index (mg/kg/day) using age, sex, serum creatinine, and single-pooled Kt/V for urea. The factors associated with ΔSMM/ΔBMD or progressive loss of SMM/BMD, defined as ΔSMM/ΔBMD <0 per year respectively, were analyzed with multivariable, linear regression or logistic regression models. ResultsThe median age of the patients was 66 years and 33% were female. Dialysis vintage and β-blocker-use were inversely correlated to ΔSMM. In comparison to nonusers, β-blockers users had 2.5-fold-higher SMM loss odd ratios [95% confidence interval (CI), 1.3–4.8]. The risk for SMM loss caused by β-blockers was not increased in users of renin-angiotensin system inhibitors (RASis). The ΔBMD was negatively correlated to the usage of calcium channel blockers (CCBs). The risk of developing osteosarcopenia, which was defined as annual loss of both SMM and BMD, increased in CCBs users. ConclusionThe use of β-blockers is associated with an elevated risk of developing sarcopenia, whereas RASis may minimize this effect in patients with ESKD. The CCB therapy was associated with a faster decline of BMD.

Impact of calcium channel blockers and angiotensin receptor blockers on hematological parameters in type 2 diabetic patients.

Antihypertensive medications have been associated with a reduction in hemoglobin (Hb) levels, leading to clinically significant anemia. We aimed to provide valuable insights into the impact of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) on hematological parameters by measuring the levels of erythropoietin (EPO), ferritin, and complete blood count (CBC) in individuals with type 2 diabetes mellitus (T2DM), particularly considering the duration of the antihypertensives use. In addition to comparing their effects on blood pressure, glycemic status, and renal function, a retrospective cohort study was conducted at the consultation unit of Alsalam Teaching Hospital, Mosul, Nineveh Province, between October 2022 and February 2023. A total of 160 participants were enrolled after being fully examined by the consultants to detect their eligibility for inclusion in the study and to rule out any abnormality. They consisted of 40 healthy controls, 30 T2DM patients (T2DM group), 30 T2DM patients with newly diagnosed hypertension (HT) (T2DM+HT group), 30 type 2 diabetic-hypertensives on ARBs (T2DM+HT+ARBs group), and 30 type 2 diabetic-hypertensives on CCBs (T2DM+HT+CCBs group). Five milliliters of blood was drawn from a vein and divided into two parts. Two milliliters was transferred into an anticoagulant tube for the measurement of HbA1c and complete blood picture. Serum was obtained from the remaining blood and used for assessment of ferritin, EPO, FSG, creatinine, urea, and uric acid. Significantly reduced FSG and HbA1c levels were observed in T2DM+HT+CCBs and T2DM+HT+ARBs groups vs T2DM+HT group (p < 0.05). The T2DM+HT+CCBs group had statistically higher urea levels than the T2DM group (p < 0.05). Both CCBs and ARBs use resulted in reduced creatinine clearance (CrCl). T2DM+HT+CCBs group exhibited slightly higher uric acid levels compared to controls (p < 0.05). Prolonged use of CCBs and ARBs led to disturbances in hematological parameters, with CCBs users showing the lowest levels of hemoglobin (Hb), RBCs, and hematocrit (Hct) among the groups. ARBs users displayed the lowest values of EPO and ferritin compared to other patient groups, along with reduced levels of Hb, RBCs, and Hct, albeit slightly higher than CCBs users. Our study highlights the importance of a balanced approach in prescribing ARBs and CCBs to patients with T2DM, given their potential to induce blood abnormalities, particularly with prolonged usage.

Calcium Channel Blocker Use and Associated Glaucoma and Related Traits Among UK Biobank Participants

Calcium channel blocker (CCB) use has been associated with an increased risk of glaucoma in exploratory studies. To examine the association of systemic CCB use with glaucoma and related traits among UK Biobank participants. This population-based cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis of glaucoma status, intraocular pressure (IOP), and optical coherence tomography (OCT)-derived inner retinal layer thicknesses. Data analysis was conducted in January 2023. Calcium channel blocker use was assessed in a baseline touchscreen questionnaire and confirmed during an interview led by a trained nurse. The primary outcome measures included glaucoma status, corneal-compensated IOP, and 2 OCT-derived inner retinal thickness parameters (macular retinal nerve fiber layer [mRNFL] and macular ganglion cell-inner plexiform layer [mGCIPL] thicknesses). We performed logistic regression and linear regression analyses to test for associations with glaucoma status and IOP and OCT-derived inner retinal thickness parameters, respectively. This study included 427 480 adults. Their median age was 58 (IQR, 50-63) years, and more than half (54.1%) were women. There were 33 175 CCB users (7.8%). Participants who had complete data for glaucoma status (n = 427 480), IOP (n = 97 100), and OCT-derived inner retinal layer thicknesses (n = 41 023) were eligible for respective analyses. After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, use of CCBs (but not other antihypertensive agents) was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001). Calcium channel blocker use was also associated with thinner mGCIPL (-0.34 μm [95% CI, -0.54 to -0.15 μm]; P = .001) and mRNFL (-0.16 μm [95% CI, -0.30 to -0.02 μm]; P = .03) thicknesses but not IOP (-0.01 mm Hg [95% CI, -0.09 to 0.07 mm Hg]; P = .84). In this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39% higher odds of glaucoma. Calcium channel blocker use was also associated with thinner mGCIPL and mRNFL thicknesses, providing a structural basis that supports the association with glaucoma. The lack of association of CCB use with IOP suggests that an IOP-independent mechanism of glaucomatous neurodegeneration may be involved. Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.

PSYCHIATRIC SEQUELAE OF CALCIUM CHANNEL BLOCKERS – PRELIMINARY RESULTS FROM A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Objective: L-type Calcium Channel Blockers (CCB) are widely used in the treatment of hypertension and other cardiovascular diseases. The risk of adverse events such as hypotension and edema for dihydropyridine-CCB (DHP), and bradycardia, atrioventricular block, and constipation for non-dihydropyridine-CCB (non-DHP) is well known. In addition, CCB have also been suspected of causing psychiatric adverse events (PAE). In our study, we evaluate the risk of PAE during CCB therapy. Design and method: We conducted a systematic search in literature databases and clinical trial registries to identify placebo-controlled randomized controlled trials (RCT) that reported frequencies of PAE during CCB therapy. We extracted data on frequencies of PAE and reviewed them, taking into account the total number of exposed patients. We separately calculated odds ratios (OR) with a 95% confidence interval (CI) for PAE in users of DHP or non-DHP CCB. Results: We retrieved 86 eligible placebo-controlled studies, encompassing 14,585 patients exposed to CCB. Main indications for CCB use were hypertension (64 studies) and angina pectoris (11 studies). PAE were reported in 1,425 patients, with fatigue, depression, agitation, and insomnia accounting for most of cases (299, 272, 113, and 105 respectively). Meta-analyses were possible for eight symptoms in DHP studies and for two symptoms in non-DHP studies, with a total of 73 RCT contributing data. We found no significant differences between the risk of PAE during DHP (anxiety (OR = 0.85; CI = 0.47–1.54; p = 0.58), depression (OR = 0.87; CI = 0.73–1.03; p = 0.11), unusual dreams (OR = 0.92; CI = 0.47–1.80; p = 0.80), fatigue (OR = 1.15; CI = 0.91–1.46; p = 0.24), insomnia (OR = 0.90; CI = 0.62–1.29; p = 0.55), nervousness (OR = 1.18; CI = 0.87–1.59; p = 0.29), sleep disorders (OR = 1.26; CI = 0.68–2.33; p = 0.47), and somnolence (OR = 1.15; CI = 0.77–1.71; p = 0.49) or non-DHP (fatigue (OR = 1.32; CI = 0.76–2.27; p = 0.32) and insomnia (OR = 0.94; CI = 0.31–2.86; p = 0.92)) compared to placebo. Conclusions: PAE are occasionally reported during CCB therapy but not more frequently than during placebo. Therefore, CCB do not impose a risk of psychiatric sequelae and can be considered safe regarding mental health.

Use of calcium channel blockers and risk of breast cancer among women aged 55 years and older: a nationwide population-based cohort study.

This retrospective cohort study was aimed to compare the incidence of breast cancer among women aged ≥55 who received calcium channel blockers and angiotensin converting enzyme inhibitors/angiotensin II receptor blockers. We used the 2002-2015 Health and Welfare Database in Taiwan. Women 55 years and older who initiated antihypertensive treatment were included. Breast cancer risk for patients receiving calcium channel blockers was compared to those receiving angiotensin converting enzyme inhibitors/angiotensin II receptor blockers. Cox proportional hazards models were used to generate adjusted hazard ratios for breast cancer. We found that the risk of breast cancer was similar between calcium channel blockers users and angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (adjusted hazard ratio [aHR] and 95% CI = 1.03 [0.80 to 1.34]). No significant risk increase was observed in the stratified analysis by dihydropyridine (aHR = 1.02 [0.78 to 1.33]) and non-dihydropyridine calcium channel blockers (aHR = 1.23 [0.48 to 3.20]). No difference in the risk of breast cancer associated with calcium channel blockers exposure was observed in patients who used hormone replacement therapy (aHR = 1.02 [0.29 to 3.58]). The risk for breast cancer was observed to be significantly lower in patients receiving calcium channel blockers than in those receiving angiotensin converting enzyme inhibitors/angiotensin II receptor blockers at a treatment duration of 5 or more years (aHR = 0.57 [0.33 to 0.98]). In conclusion, the risk for breast cancer is similar for calcium channel blockers and angiotensin converting enzyme inhibitors/angiotensin II receptor blocker users in an Asian population.

Differential Cardiovascular Outcomes of Each Antihypertensive Drug Class in Patients With Hypertension and Breast Cancer Undergoing Doxorubicin-Containing Chemotherapy.

The preemptive use of renin-angiotensin system (RAS) inhibitors may reduce doxorubicin (DOX)-related cardiotoxicity. Using the national insurance claims data of Korea, this study compared cardiovascular (CV) outcomes following the use of four major antihypertensive drug classes in patients with hypertension and breast cancer who underwent DOX-containing chemotherapy. A total of 4,722 patients with hypertension and breast cancer who underwent DOX-containing chemotherapy were included. The outcomes were compared between patients who used RAS inhibitors, calcium channel blockers (CCBs), beta-blockers (BBs), and thiazide and thiazide-like diuretics (TDs). The primary outcome was a composite of incident heart failure and serious ventricular arrhythmias, including ventricular tachycardia and fibrillation, ischemic heart disease, and stroke. In the propensity score-matched population, there were no significant differences in the primary outcome between RAS inhibitor and CCB users; however, patients with diabetes who used CCBs had a worse primary outcome than those who used RAS inhibitors (adjusted hazard ratio [aHR], 1.93; 95% confidence interval [CI], 1.06-3.51). BB and TD users had a worse primary outcome compared with RAS inhibitor (aHR, 1.88; 95% CI, 1.30-2.71 in BB users and aHR, 2.55; 95% CI, 1.37-4.75 in TD users) or CCB (aHR, 1.54; 95% CI, 1.09-2.16 in BB users and aHR, 2.08; 95% CI, 1.13-3.82 in TD users) users. RAS inhibitors are preferred for the treating hypertension and improving CV outcomes in patients with hypertension and breast cancer undergoing DOX-containing chemotherapy, particularly in patients with comorbid diabetes. However, CCBs are equivalent to RAS inhibitors and are more favorable than BBs and TDs in terms of improving CV outcomes.

Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension.

AimsSeveral observational studies have examined the potential protective effect of angiotensin‐converting enzyme inhibitor (ACE‐I) use on the risk of age‐related macular degeneration (AMD) and have reported contradictory results owing to confounding and time‐related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE‐I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK.MethodsIn this study, 53 832 and 43 106 new users of ACE‐I and CCB were included between 1995 and 2019, respectively. In an on‐treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow‐up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE‐I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD.ResultsDuring a median follow‐up of 2 years (interquartile range 1–5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2–2.6) and 2.2 (2.0–2.4) per 1000 person‐years among the weighted new users of ACE‐I and CCB, respectively. There was no association of ACE‐I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on‐treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90–1.27] and 0.87 [0.71–1.07], respectively).ConclusionWe found no evidence that the use of ACE‐I is associated with risk of AMD in patients with hypertension.

Calcium Channel Blocker Use and the Risk for Breast Cancer: A Population-Based Nested Case-Control Study.

Simple SummaryCalcium channel blockers (CCBs) are widely used among hypertension and heart disease patients. These drugs are effective and well-tolerated. Some studies have found that patients who used CCBs have a higher incidence of breast cancer (BCa). However, other studies did not find such an association. We investigate whether exposure to CCBs in patients with hypertension is associated with an increased risk of BCa. From a cohort of patients prescribed their first antihypertensive medication between 2000 and 2016, we detected 4875 BCa cases. For each case, we matched ten patients without BCa (controls). We found no association between CCB users and an increased risk of BCa compared to the use of other antihypertensive medications. There was no increase in risk even with longer exposure to CCBs (above eight years) and high doses. Considering that CCBs are a widely used antihypertensive drug class, our results provide important safety information on a population level, especially for patients with increased BCa risk.We investigated whether long-term exposure to calcium channel blockers (CCBs) is associated with an increased risk of breast cancer (BCa). We designed a nested case–control study based on data from the Clalit electronic database, the largest Israeli Health Services organization. All newly diagnosed breast cancer (BCa) cases were selected from a cohort of patients with hypertension. Ten controls were matched for each BCa case. The odds ratios (ORs) of BCa among CCBs users were calculated using multivariate conditional logistic regression analyses. A total of 4875 patients with newly diagnosed BCa were identified from the cohort with a median follow-up of 5.15 years. The exposure to CCBs was not associated with an increased risk of BCa (OR = 0.98; 95% CI, 0.92–1.04). Additionally, there was no association between long-term exposure to CCBs (above eight years) and increased BCa risk (OR = 0.91; 95% CI, 0.67–1.21). Higher cumulative doses of CCBs were not associated with an elevated risk of BCa (OR = 0.997; 95% CI, 0.962–1.034, calculated per 1000 DDD). Based on this large population-based study, long-term exposure to CCBs was not associated with an increased risk of BCa. Considering that CCBs are widely used medications, our results provide important safety information on a population level, especially for patients with an increased risk of BCa.

Association of renin-angiotensin-aldosterone system inhibition with Covid-19 hospitalization and all-cause mortality in the UK biobank.

With growing evidence on the protective effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (Covid-19), we aimed to thoroughly investigate the association between the use of major classes of antihypertensive medications and Covid-19 outcomes in comparison with the use of ACEIs and ARBs. We conducted a population-based study in patients with pre-existing hypertension in the UK Biobank with data from the first 2 SARS-CoV-2 waves prior population-based vaccination. Multivariable logistic regression analysis was performed adjusting for a wide range of confounders. The use of either β-blockers (BBs), calcium-channel blockers (CCBs) or diuretics was associated with a higher risk of Covid-19 hospitalization compared to ACEI use (adjusted OR (95%CI): 1.66 [1.43-1.93]) and ARB use (1.53 [1.30-1.81]). The risk of 28-day mortality among Covid-19 patients was also increased among users of BBs, CCBs or diuretics when compared to ACEI users (1.74 [1.30-2.33]) but not when compared to ARB users (1.26 [0.93-1.71]). The association between BB, CCB or diuretic use (compared to ACEI use) and 28-day mortality among hospitalized Covid-19 patients narrowly missed statistical significance (1.47 [0.99-2.18]) but it was statistically significant when the analysis was restricted to patients hospitalized during the second SARS-CoV-2 wave (1.80 [1.15-2.83]). Our results suggest protective effects of inhibition of the renin-angiotensin-aldosterone system on Covid-19 hospitalization and mortality, particularly with ACEI, among patients with pharmaceutically treated hypertension. If confirmed by randomized controlled trials, this finding could have high clinical relevance for treating hypertension during the SARS-CoV-2 pandemic.

Renal outcomes of diabetic patients treated with combination therapy of ACE inhibitors plus either thiazide diuretics or calcium channel blockers: comparative retrospective cohort study in Northwestern Ethiopia

ObjectiveThe study determined the comparative renal functions on patients with diabetes treated with ACE inhibitors (ACEIs) plus either thiazide diuretics or calcium channel blockers (CCBs) in Northwestern Ethiopia.DesignRetrospective cohort study...

Effects of angiotensin II receptor blockers on serum potassium level and hyperkalemia risk: retrospective single-centre analysis

ObjectiveTo examine the effect of angiotensin II receptor blocker (ARB) treatment on serum potassium level and hyperkalaemia risk in a clinical setting with inpatients and outpatients using calcium channel blockers...

Risk of skin cancer in new users of thiazides and thiazide-like diuretics: a cohort study using an active comparator group.

Case-control studies report a dose-dependent increased risk of skin cancer in users of hydrochlorothiazide (HCTZ) vs. nonusers. The degree to which other thiazides and thiazide-like diuretics (TZs) are associated with skin cancer is less certain. To assess the risk of skin cancer in new users of different TZs compared with new users of calcium channel blockers (CCBs). We conducted a cohort study using a UK primary-care database (1998-2017), including 271154 new TZ users [87·6% bendroflumethiazide (BFT), 5·8% indapamide and 3·6% HCTZ] and 275263 CCB users. The outcomes were basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). We estimated incidence rates (IRs) and IR ratios (IRRs) in short-term (< 20 prescriptions) and long-term (≥ 20 prescriptions) users of TZs and CCBs using negative binomial regression, and calculated rate differences (RDs) for selected results. We used fine stratification on the propensity score (PS) to control for 23 baseline covariates. Long-term use of HCTZ increased absolute and relative risks of SCC [PS-weighted IRR 1·95; 95% confidence interval (CI) 1·87-2·02; RD per 100000 person-years 87.4], but not of BCC or CMM. Long-term use of indapamide was associated with an increased incidence of CMM (IRR 1·43; 95% CI 1·35-1·50). BFT was not meaningfully associated with the risk of any type of skin cancer. Our results corroborate the previously reported increased risk of SCC (but not of BCC or CMM) for long-term use of HCTZ. BFT may be a safer alternative for patients at increased risk of skin cancer.

Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care

IntroductionRenin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality.MethodsWe conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome.ResultsThe incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality.ConclusionUse of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.

Association of Antihypertensive Agents with the Risk of In-Hospital Death in Patients with Covid-19.

PurposeThe role of angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), or other antihypertensive agents in the case of Covid-19 remains controversial. We aimed to investigate the association between antihypertensive agent exposure and in-hospital mortality in patients with Covid-19.MethodsWe performed a retrospective multicenter cohort study on patients hospitalized between February 1 and May 15, 2020. All patients had been followed up for at least 30 days.ResultsOf the 8078 hospitalized patients for Covid-19, 3686 (45.6%) had hypertension and were included in the study. In this population, the median age was 75.4 (IQR, 21.5) years and 57.1% were male. Overall in-hospital 30-day mortality was 23.1%. The main antihypertensive pharmacological classes used were calcium channel blockers (CCB) (n=1624, 44.1%), beta-blockers (n=1389, 37.7%), ARB (n=1154, 31.3%), and ACEi (n=998, 27.1%). The risk of mortality was lower in CCB (aOR, 0.83 [0.70–0.99]) and beta-blockers (aOR, 0.80 [0.67–0.95]) users and non-significant in ARB (aOR, 0.88 [0.72–1.06]) and ACEi (aOR, 0.83 [0.68–1.02]) users, compared to non-users. These results remain consistent for patients receiving CCB, beta-blocker, or ARB as monotherapies.ConclusionThis large multicenter retrospective of Covid-19 patients with hypertension found a reduced mortality among CCB and beta-blockers users, suggesting a putative protective effect. Our findings did not show any association between the use of renin-angiotensin-aldosterone system inhibitors and the risk of in-hospital death. Although they need to be confirmed in further studies, these results support the continuation of antihypertensive agents in patients with Covid-19, in line with the current guidelines.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10557-021-07155-5.

Assessment of lower urinary tract symptoms among calcium channel blocker-users and its impact on quality of life

To investigate the prevalence and severity of lower urinary tract symptoms among calcium channel blocker users, and the impact on patients' quality of life. The cross-sectional study was conducted at one hospital and 2 community pharmacies in Lahore, Pakistan, from November 2017 to July 2018, and comprised patients using calcium channel blockers. Data was collected using standardised scales to assess lower urinary tract symptoms and quality of life. Data was analysed using SPSS 22. Of the 410 subjects, 315 (76.8%) were males. The overall median age was 50.84 years, IQR 19 with 126 (30.7%) aged 41-50 years. Of the total, 108 (26.3%) patients were on calcium channel blockers alone, while the rest were taking it in combination with other drugs. Prevalence of lower urinary tract symptoms was 307 (74.9%); mild 103 (25.1%), moderate 201 (49.1%) and severe 106 (25.9%). The symptoms were significantly associated with reduced quality of life (p<0.05). Majority calcium channel blockers users had clinically significant lower urinary tract symptoms which significantly reduced patients' quality of life.

Antihypertensive Drugs and COVID-19 Risk: A Cohort Study of 2 Million Hypertensive Patients.

After initially hypothesizing a positive relationship between use of renin-angiotensin-aldosterone system inhibitors and risk of coronavirus disease 2019 (COVID-19), more recent evidence suggests negative associations. We examined whether COVID-19 risk differs according to antihypertensive drug class in patients treated by ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) compared with calcium channel blockers (CCBs). Three exclusive cohorts of prevalent ACE inhibitors, ARB and CCB users, aged 18 to 80 years, from the French National Health Insurance databases were followed from February 15, 2020 to June 7, 2020. We excluded patients with a history of diabetes, known cardiovascular disease, chronic renal failure, or chronic respiratory disease during the previous 5 years, to only consider patients treated for uncomplicated hypertension and to limit indication bias. The primary end point was time to hospitalization for COVID-19. The secondary end point was time to intubation/death during a hospital stay for COVID-19. In a population of almost 2 million hypertensive patients (ACE inhibitors: 566 023; ARB: 958 227; CCB: 358 306) followed for 16 weeks, 2338 were hospitalized and 526 died or were intubated for COVID-19. ACE inhibitors and ARBs were associated with a lower risk of COVID-19 hospitalization compared with CCBs (hazard ratio, 0.74 [95% CI, 0.65-0.83] and 0.84 [0.76-0.93], respectively) and a lower risk of intubation/death. Risks were slightly lower for ACE inhibitor users than for ARB users. This large observational study may suggest a lower COVID-19 risk in hypertensive patients treated over a long period with ACE inhibitors or ARBs compared with CCBs. These results, if confirmed, tend to contradict previous hypotheses and raise new hypotheses.

Renin–angiotensin system inhibitors and COVID-19: overwhelming evidence against an association

Renin–angiotensin system inhibitors and COVID-19: overwhelming evidence against an association