Pregnancy outcome after in utero exposure to angiotensin converting enzyme inhibitors or angiotensin receptor blockers

ObjectiveTo examine first trimester safety of angiotensin-converting-enzyme-inhibitors (ACEIs) or angiotensin-receptor-blockers (ARBs).Study designProspective observational cohort regarding pregnancy ACEI/ARBs-exposure including contacts to two Teratology Information Services in Israel (1994–2007) and Italy (1990–2008), with two comparison groups: (1) exposed to other antihypertensives (OAH) (2) after non-teratogenic exposure (NTE) in similar time frames.Results252 ACEI/ARBs-exposed, 256 OAH-exposed and 495 NTE-exposed pregnancies were followed-up. The rate of major congenital anomalies was comparable between the groups (8/190, 4.2%, ACEI/ARB; 9/212, 4.2%, OAH; 18/471, 3.8% NTE; p = 0.954) among first trimester exposed pregnancies. The median gestational age at delivery was two weeks earlier, rate of preterm deliveries more than 2-fold higher, and median birth weight more than 200 g lower in the ACEI/ARB and OAH groups compared to the NTE group.ConclusionThe present study suggests that ACEI/ARBs are not major teratogens when used in the first trimester, and can reassure women with similar exposures.     

Using group-based trajectory modeling to characterize the association of past ACEIs/ARBs adherence with subsequent statin adherence patterns among new statin users

BackgroundDespite well-documented benefits, statin adherence remains suboptimal. Studies have suggested that previous adherence to other chronic medications is a strong predictor of future adherence to newly initiated statins. Group-based trajectory modeling (GBTM) has been applied as a method to longitudinally depict the dynamic nature of adherence.ObjectivesThis study aimed to examine the association between patients’ adherence patterns to newly initiated statins and previous adherence trajectories of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) using GBTM.MethodsThis retrospective cohort study was conducted among continuously enrolled statin initiators using claims data. Patients were included if they had ACEI/ARB use within 1 year before statin initiation (preindex period). Monthly adherence to ACEIs/ARBs was calculated during the preindex period and monthly adherence to statins was assessed 1 year after statin initiation using proportion of days covered (PDC). The monthly PDCs were modeled as a longitudinal response in a logistic GBTM to provide distinct patterns of adherence for ACEIs/ARBs and statins, separately. A multinomial logistic regression was conducted to determine an association between ACEI/ARB adherence trajectories and future statin trajectories, controlling for patient characteristics.ResultsA total of 1078 patients were categorized into 4 distinct statin adherence trajectories: adherent (40.8%), gradual decline (37.4%), gaps in adherence (13.9%), and rapid decline (7.9%). Patients were further categorized into 4 groups on the basis of their distinct past ACEIs/ARBs trajectories: adherent (43%), gaps in adherence (29%), delayed nonadherence (15.2%), and gradual decline (12.8%). In the multinomial logistic regression, patients in the gaps in adherence or gradual decline groups were more likely to follow similar trajectories for future statin use than the adherent trajectory.ConclusionPrevious adherence trajectories of ACEIs/ARBs may predict future adherence patterns for newly initiated statins. Knowledge of past medication-taking behavior could provide valuable information for developing tailored interventions to improve adherence.     

A review of chemical therapies for treating diabetic hypertension

Introduction: Hypertension and diabetes are two of the most important modifiable risk factors for cardiovascular and renal disease. The majority of patients with diabetes also have high blood pressure (BP) and the presence of hypertension in these patients dramatically increases cardiovascular and renal risk.

Areas covered: This article will discuss chemical therapies for hypertension in patients with diabetes, based on currently available evidence on the effects of antihypertensive treatment on metabolic profile and renal endpoints that are the factors mostly influencing drug choice.

Expert opinion: Several lines of evidence suggest that angiotensin-converting-enzyme-inhibitors (ACEIs), angiotensin-receptor-blockers (ARBs) and calcium-channel-blockers (CCBs) have beneficial or neutral effects on carbohydrate metabolism, whereas old β-blockers and thiazide diuretics have not. Renal outcome trials clearly suggest that in proteinuric diabetic CKD ACEIs and ARBs reduce the rate of disease progression. Thus, an ACEI or an ARB, if tolerated, should be the first choice in diabetic individuals, followed by CCBs, vasodilating β-blockers and diuretics, depending on the individual patient characteristics. Recent studies suggest that the novel antidiabetic class of sodium-glucose co-transporter 2 inhibitors may offer a small reduction in BP together with important decrease in incidence of cardiovascular and renal events in patients with type 2 diabetes.     

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in women of childbearing age: risks versus benefits

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are effective and widely used antihypertensive drugs. Exposure to these agents is known to be harmful to the fetus in the second and third trimesters of pregnancy. Concerns have also been raised about the risk of congenital malformations if ACEIs or ARBs are taken during the first trimester of pregnancy. The evidence to date, however, is conflicting and observed malformations may be due to confounders such as undiagnosed diabetes or maternal obesity, other antihypertensive medications or the hypertension itself. Nonetheless, in women who become pregnant while taking an ACEI or ARB, the drug should be stopped as soon as possible. In women with chronic kidney disease and proteinuria, it may be appropriate to continue taking an ACEI or ARB until the pregnancy is confirmed because of the significant benefit to their kidney function and the lower fertility rate in these patients.     

Angiotensin II reactivation and aldosterone escape phenomena in renin-angiotensin-aldosterone system blockade: is oral renin inhibition the solution?

This editorial considers the use of the first selective oral renin inhibitor, aliskiren, in reducing angiotensin (Ang) II reactivation or aldosterone (ALDO) escape during renin-angiotensin-aldosterone system (RAAS) inhibition. RAAS blockade with angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor AT(1) blockers (ARBs) is very useful for the treatment of arterial hypertension, chronic heart failure (CHF), atherosclerosis and diabetes. 'Ang II reactivation' and 'ALDO escape' or 'breakthrough' have been observed during either ACEI or ARB treatment, and may attenuate the clinical benefit of RAAS blockade. Renin and Ang I accumulate during ACE inhibition, and might overcome the ability of an ACEI to effectively suppress ACE activity. There is also data suggesting that 30 - 40% of Ang II formation in the healthy human during RAAS activation is formed via renin-dependent, but ACE-independent, pathways. Moreover, ACE gene polymorphisms contribute to the modulation and adequacy of the neurohormonal response to long-term ACE inhibition, at least in patients with CHF (up to 45% of CHF patients have elevated Ang II levels despite the long-term use of an ACEI) or diabetes. The reactivated Ang II promotes ALDO secretion and sodium reabsorption. ALDO breakthrough also occurs during long-term ARB therapy, mainly by an AT(2)-dependent mechanism. This was related to target-organ damage in animal models. Oral renin inhibition with aliskiren has showed excellent efficacy and safety in the treatment of hypertension. Aliskiren can be co-administered with ACEIs, ARBs or hydrochlorothiazide. Furthermore, there is evidence suggesting that aliskiren reduces Ang II reactivation in ACE inhibition and ALDO escape during treatment with an ACEI or an ARB, at least to the degree that this is associated with the RAAS. For RAAS-independent ALDO production, the combination of aliskiren with eplerenone might prove useful.     

Effect of certain angiotensin-converting enzyme inhibitors on mortality in heart failure: A multiple-propensity analysis

BackgroundHeart failure is a major and growing public health problem in United States. There is a substantial evidence about efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in heart failure (HF); however, there is no conclusive evidence on the relative effectiveness of individual ACEIs.ObjectiveTo evaluate the effect of individual ACEIs on mortality using multiple-propensity score analysis in a large real-world population.MethodsThe study was a retrospective analysis of a national cohort of patients with HF identified from the Department of Veterans Affairs. A multiple-propensity score analysis was used to balance 47 baseline patient characteristics between different nontissue ACEIs. The effect of different ACEIs on time to death was assessed using a propensity score-weighted, multivariable Cox proportional hazard model.ResultsThe study included 139,994 patients with 69.50% (97,293) on lisinopril, 21.79% (30,503) on fosinopril, 8.41% (11,775) on captopril, and 0.30% (423) on enalapril. Propensity scores balanced nearly all differences between different ACEI groups. Fosinopril (hazard ratio [HR] = 0.739, 95% confidence interval [CI]: 0.686-0.797) and lisinopril (HR = 0.818, 95% CI: 0.766-0.874) were significantly associated with reduced mortality as compared with captopril. Similar mortality was observed with enalapril (HR = 0.944, 95% CI: 0.675-1.320) as compared with captopril.ConclusionsIn patients with HF, fosinopril and lisinopril were associated with lower mortality as compared with captopril. However, the results of this observational study should be interpreted with caution, and need to be replicated and confirmed in studies for which HF severity data are available.     

Incidence of and Risk Factors for Severe Adverse Events in Elderly Patients Taking Angiotensin‐Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers after an Acute Myocardial Infarction

Study Objective

To assess the incidence of and risk factors associated with severe adverse events in elderly patients who used angiotensin‐converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) after an acute myocardial infarction (AMI).

Design

Retrospective cohort study.

Data Sources

Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse (Medicare service claims database), American Community Survey of the U.S. Census Bureau, and Multum Lexicon Drug database.

Patients

A total of 101,588 eligible Medicare fee‐for‐service beneficiaries 66 years or older, who were hospitalized for AMI between January 1, 2008, and December 31, 2009, and used ACEIs or ARBs within 30 days after discharge.

Measurements and Main Results

Primary outcomes were hospitalizations for acute renal failure (ARF) and hyperkalemia. The secondary outcome was discontinuation or suspension of ACEI/ARB therapy after a visit to a health care provider. The primary risk factors of interest were age, sex, race/ethnicity, and chronic kidney disease (CKD). Cumulative incidence curves and multivariable Fine‐Gray proportional hazards models with 95% confidence intervals (CIs) were used with death as a competing risk in both intention‐to‐treat (ITT) and as‐treated (AT) analyses. In the study cohort, 2.8% experienced ARF, 0.5% experienced hyperkalemia, and 63.7% discontinued ACEI/ARB therapy within 1 year after hospital discharge. Approximately half of the incidence of ARF and hyperkalemia occurred within 6 months after hospital discharge, but the cumulative incidence increased after 6 months. Patients older than 85 years had a higher rate of ARF (ITT hazard ratio [HR] 1.15, 95% CI 1.04–1.28) and hyperkalemia (ITT HR 1.33, 95% CI 1.05–1.68) compared with those aged 65–74 years. Patients with baseline CKD had higher rates of ARF (ITT HR 1.61, 95% CI 1.42–1.82), hyperkalemia (ITT HR 1.41, 95% CI 1.11–1.77), and ACEI/ARB therapy discontinuation or suspension (ITT HR 1.05, 95% CI 1.02–1.09).

Conclusion

We found a low incidence of ARF and hyperkalemia in elderly patients treated with ACEIs or ARBs after AMI hospitalization. However, a high rate of treatment discontinuation might prevent a higher rate of occurrence of these events. Long‐term careful monitoring of severe adverse events and timely discontinuation of ACEIs or ARBs among elderly patients with advancing age and CKD after an AMI is warranted in clinical practice.     

Antihypertensive agents acting on the renin–angiotensin system and the risk of sepsis

AimsIn response to safety concerns from two large randomized controlled trials, we investigated whether the use of telmisartan, an angiotensin receptor blocker (ARB), ARBs as a class and angiotensin-converting enzyme inhibitors (ACEIs) increase the risk of sepsis, sepsis-associated mortality and renal failure in hypertensive patients.MethodsWe performed a nested case–control study from a retrospective cohort of adults with hypertension from the UK General Practice Research Database diagnosed between 1 January 2000 and 30 June 2009. All subjects hospitalized with sepsis during follow-up were matched for age, sex, practice and duration of follow-up with 10 control subjects. Exposure was defined as current use of antihypertensive drugs.ResultsFrom the cohort of 550 436 hypertensive patients, 1965 were hospitalized with sepsis during follow-up (rate 6.9 per 10 000 per year), of whom 824 died and 346 developed acute renal failure within 30 days. Compared with use of β-blockers, calcium-channel blockers or diuretics, use of ARBs, including telmisartan, was not associated with an elevated risk of sepsis (relative risk 1.09; 95% confidence interval 0.83–1.43); but use ACEIs was (relative risk 1.65; 95% confidence interval 1.42–1.93). Users of ARBs, β-blockers, calcium-channel blockers or diuretics, but not users of ACEIs, had lower rates of hospitalization for sepsis compared with untreated hypertensive patients. Findings were similar for sepsis-related 30 day mortality and renal failure.ConclusionsHypertensive patients treated with ARBs, including telmisartan, do not appear to be at increased risk of sepsis or sepsis-related 30 day mortality or renal failure. On the contrary, users of ACEIs may have an increased risk.     

Elevated serum HMGB1 in pulmonary arterial hypertension secondary to congenital heart disease

AimsThis study investigated the potential value of serum high mobility group box-1 (HMGB1) level in the diagnosis, staging and treatment response of patients with pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD).Methods and resultsThis was a single-center prospective study in 106 CHD patients. Serum HMGB1 levels were measured by enzymelinked immunosorbent assay. HMGB1 levels were significantly increased in patients with PAH compared to patients without PAH (P < 0.01) and healthy controls (P < 0.001). HMGB1 levels significantly correlated with pulmonary arterial pressure (P < 0.001) and pulmonary vascular resistance (PVR) (P < 0.001). In patients with severe PAH, HMGB1 levels were significantly higher in patients with Eisenmenger syndrome (ES) than in patients exhibiting low PVR (P < 0.001). Severe PAH and ES was identified by serum HMGB1 with a cutoff value of 13.62 ng/mL (P < 0.001) with a specificity of 82.8% and a sensitivity of 90%, and a cutoff value of 21.62 ng/mL (P = 0.001) with a specificity of 85.2% and a sensitivity of 64.3%, respectively. HMGB1 levels were significantly decreased after sildenafil therapy for 6 months (P < 0.01).ConclusionsOur study suggests that serum HMGB1 level may be used as a biomarker to identify PAH in CHD patients, assess pulmonary vascular remodeling, and evaluate the treatment response to sildenafil.     

Role of antihypertensive therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in combination with calcium channel blockers for stroke prevention

ObjectiveTo review the available literature on the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and calcium channel blockers (CCBs) or combinations of these agents on stroke outcomes in hypertensive patients.Data sourcesA Medline search was conducted using the search terms stroke and antihypertensives, calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers from 1985 to August 17, 2009.Study selectionRandomized controlled clinical trials with at least 400 randomized patients were selected if at least one of the treatment arms used a CCB, ACEI, or ARB to evaluate stroke outcomes in hypertensive patients.Data synthesisThe prevalence of stroke is high in the United States, accounting for approximately 150,000 deaths per year. Early identification and treatment of hypertension to quickly achieve blood pressure reduction is critical in the prevention of stroke. Many trials have provided evidence that CCBs, ACEIs, and ARBs are effective in stroke prevention. Most patients require two or more antihypertensive drugs to achieve blood pressure goals. Because of their complementary actions, combination antihypertensive therapy with a renin–angiotensin–aldosterone system (RAAS) blocker and a CCB may help reduce stroke incidence to a greater extent than either of the monotherapies.ConclusionA growing body of clinical trial data suggest that aggressive combination antihypertensive therapy, including a RAAS blocker and CCB, may help reduce stroke incidence. Fixed-dose combination therapy is an important consideration in optimizing blood pressure control and patient adherence to therapy in stroke prevention.     

Pharmacovigilance in patients with diabetes: A data-driven analysis identifying specific RAS antagonists with adverse pulmonary safety profiles that have implications for COVID-19 morbidity and mortality

ObjectivesThe current demographic information from China reports that 10%-19% of patients hospitalized with coronavirus disease (COVID-19) were diabetic. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are considered first-line agents in patients with diabetes because of their nephroprotective effects, but administration of these drugs leads to upregulation of angiotensin-converting enzyme 2 (ACE2), which is responsible for the viral entry of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). Data are lacking to determine what pulmonary effects ACEIs or ARBs may have in patients with diabetes, which could be relevant in the management of patients infected with SARS-CoV-2. This study aims to assess the prevalence of pulmonary adverse drug effects (ADEs) in patients with diabetes who were taking ACEI or ARBs to provide guidance as to how these medications could affect outcomes in acute respiratory illnesses such as SARS-CoV-2 infection.Methods1DATA, a unique data platform resulting from collaboration across veterinary and human health care, used an intelligent medicine recommender system (1DrugAssist) developed using several national and international databases to evaluate all ADEs reported to the Food and Drug Administration for patients with diabetes taking ACEIs or ARBs.ResultsMining of this data elucidated the proportion of a cluster of pulmonary ADEs associated with specific medications in these classes, which may aid health care professionals in understanding how these medications could worsen or predispose patients with diabetes to infections affecting the respiratory system, specifically COVID-19. Based on this data mining process, captopril was found to have a statistically significantly higher incidence of pulmonary ADEs compared with other ACEIs (P = 0.005) as well as ARBs (P = 0.012), though other specific drugs also had important pulmonary ADEs associated with their use.ConclusionThese analyses suggest that pharmacists and clinicians will need to consider the specific medication’s adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19.     

Cardiovascular Outcomes in High-Risk Patients without Heart Failure Treated with ARBs

Background and objective

Angiotensin II type 1 receptor antagonists (ARBs) are widely used as a substitute for angiotensin-converting enzyme inhibitors (ACEIs) to treat patients without heart failure, but their effect on cardiovascular morbidity and mortality has not been clearly determined. A systematic review and metaanalysis was undertaken to determine the impact of ARBs on cardiovascular outcomes in high-risk patients without heart failure.

Methods

A computerized literature search was carried out using PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, and EMBASE, from January 1990 to April 2008. The following search terms were used: ‘hypertension’, ‘clinical trial’, ‘sartan’, ‘ARB’, ‘angiotensin receptor antagonist’, ‘losartan’, ‘candesartan’, ‘valsartan’, ‘irbesartan’, ‘eprosartan’, ‘telmisartan’, ‘olmesartan’, ‘coronary disease’, ‘coronary heart disease’, ‘myocardial infarction’, ‘cardiovascular disease’, ‘cerebrovascular disease’, and ‘stroke’. Criteria for inclusion of clinical trials in our meta-analysis were the use of a randomized control group not receiving an ARB and the availability of outcome data for any one of four endpoints: myocardial infarction (MI), stroke, cardiovascular death, and all-cause death (these were not always pre-specified endpoints in all trials). Out of 45 potentially relevant studies, 37 trials met the inclusion criteria. We tabulated all occurrences of these four adverse outcomes.

Results

Homogenous subgroups were combined by means of a fixed-effects model, while heterogenous subgroups were not combined. In the subgroup without heart failure, ARBs, when compared with the control group, had an odds ratio of 1.09 (95% CI 1.00, 1.18; p = 0.05) for MI. Other endpoints, namely, cardiovascular death and all-cause death, did not reach statistical significance. There was a clear trend for fewer strokes in the ARB group, but these studies were clearly heterogenous, and therefore a pooled risk estimate was not computed.

Conclusion

After pooling more than 89 000 patients, there is no evidence to suggest that ARBs confer cardiovascular protection akin to ACEIs, and the results that emerged are not in favor of ARB therapy in terms of its use as a substitute for ACEIs in non-heart failure patients. ARBs may have a small benefit in terms of stroke risk, but the studies are heterogenous, making it very difficult to quantify this effect. Given that ACEIs protect against both stroke and MI, caution is advised in the use of ARBs as a substitute for ACEIs in patients without a heart failure indication, who are tolerant of an ACEI.     

Do ACE Inhibitors/Angiotensin II type 1 receptor antagonists reduce hospitalisations in older patients with heart failure? A propensity analysis

BACKGROUND: Randomised controlled trials have shown a reduced risk of heart failure (HF) hospitalisation among users of ACE inhibitors (ACEIs) or angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), but these results have limited generalisability. Some observational studies have also demonstrated reductions in hospitalisation but are potentially affected by non-random treatment selection. OBJECTIVE: To assess the effect of ACEI/ARB therapy on all-cause and HF-related hospitalisations among older adults using a propensity model to adjust for treatment-selection bias and focusing on consistent medication use as the exposure of interest. METHODS: A retrospective cohort study of continuously enrolled, older (age > or =60 years) Kansas Medicaid beneficiaries with HF, using data from May 1999 to April 2000. A propensity analysis was used to identify a comparison group of untreated persons that were otherwise clinically similar to treated persons. The effect of regular ACEI/ARB use on hospitalisations was estimated using multivariable logistic regression models. The HF sample included 887 subjects, of whom 235 (27%) received regular ACEI/ARB therapy. To be considered a regular user of ACEI/ARB therapy ('treated'), we required evidence that a subject obtained at least 80% of their intended daily supply. The main outcome measure was the effect of regular ACEI/ARB use on all-cause and HF-related hospitalisations. RESULTS: Treated subjects were matched against an equal number of untreated persons, for a final sample of 470 persons. The mean age of both treated and untreated subjects was 81 years. Regular ACEI/ARB use did not alter the adjusted odds ratio (AOR) of all-cause hospitalisation (AOR = 1.04, 95% CI 0.71, 1.52), which occurred in 40% of the sample, or the odds of an HF-related hospitalisation (AOR = 1.01, 95% CI 0.65, 1.57), which occurred in 22.6% of both groups. CONCLUSION: Although randomised controlled trials have shown that ACEI/ARB treatment is associated with reduced hospitalisations in patients with HF, this benefit was not observed in our study. Further study of ACEI/ARB outcomes is needed in a larger sample of older subjects with HF.     

Rurality and other factors associated with adherence to immunosuppressant medications in community-dwelling solid-organ transplant recipients

BackgroundData on immunosuppressant adherence of community-dwelling adult solid-organ transplant recipients (SOTRs) from rural populations in the United States are limited. Therefore, understanding the association of rurality and other factors of immunosuppressant adherence will help providers design and deliver patient-centered adherence enhancing interventions.ObjectivesThe objective was to examine factors associated with a previously validated 4-item Immunosuppressant Therapy Adherence Scale (ITAS) score in community-dwelling adult SOTRs who received a transplant from an academic center in the Midwestern United States.MethodsFor this observational study, cross-sectional survey data (patient demographic, medical condition, immunosuppressant therapy, and self-reported ITAS) received from adult SOTRs aged 19 years or older with other data from an academic transplant center’s database were merged. Using multivariate logistic regression, significant SOTR characteristics associated with being adherent (ITAS score = 12) versus nonadherent (ITAS score <12) were examined.ResultsThe survey response rate was 30% (n = 556/1827). Those SOTRs responding (n = 556) had a kidney (48%), liver (47%), or other (4.5%) transplant. They were more likely to be 50- to 64-year olds (52%), men (55%), white (90%), metroresident (59%), with an annual income less than $55,000. The SOTRs were living with a transplant for 6.3 years (median), reported excellent-to-good health status (77%), and received different immunosuppressant regimens. More than half of the SOTRs (58%) were adherent. In multivariate analyses, compared with patients aged 65 years or older, younger patients, nonmetro rural- versus metroresident, and those having more (≥6) versus less (<6) comorbidities were significantly less likely to report adherence. SOTRs receiving tacrolimus-based combination immunosuppressant versus tacrolimus alone were more likely to report adherence.ConclusionsWhen designing and delivering patient care-centered interventions including those that use technology to increase immunosuppressant adherence, providers need to consider rural residence besides other well-established patient factors (younger age, immunosuppressant drug, and comorbidities) of nonadherence.     

Platelet reactivity in patients with impaired renal function receiving dual antiplatelet therapy with clopidogrel or ticagrelor

BackgroundSuboptimal platelet inhibition still represents an important challenge, especially for patients undergoing percutaneous coronary interventions (PCI). Chronic kidney disease (CKD) is a common comorbidity of patients with coronary artery disease, and may potentially influence platelet reactivity. So far only few studies have assessed the role of CKD on response to dual antiplatelet therapy (DAPT) with conflicting results. Therefore, the aim of our study was to evaluate the impact of CKD on platelet function in patients treated with DAPT after a recent acute coronary syndrome (ACS) or PCI.MethodsPatients treated with DAPT, acetylsalicylic acid (ASA) + adenosine diphosphate antagonist (ADP-antagonist) such as clopidogrel or ticagrelor, for ACS or elective patients undergoing PCI were scheduled for platelet function assessment at 30–90 days post-discharge. Platelet function was assessed by whole blood impedance aggregometry (Multiplate®- Roche Diagnostics AG), high residual platelet reactivity (HRPR) was considered for ASPI test > 862 AU*min (for ASA) and ADP test values ≥ 417 AU*min (for ADP-antagonists). Chronic renal failure was defined as an estimated glomerular filtration rate of 60 mol/min/1.73m² or less, calculated by applying MDRD (Modification of Diet in renal Disease) formula.ResultsOur population included a total of 537 patients of which 308 (57.3%) received ASA and clopidogrel and 229 (42.6%) received ASA and ticagrelor. Patients with renal failure at baseline (101 out of 537, 18.8%) were older, with higher prevalence of hypertension, previous myocardial infarction and coronary artery bypass graft surgery. Moreover, they had a lower ejection fraction at baseline and were more often in therapy with diuretics, but less often with statins at admission. They had lower haemoglobin and higher glycated haemoglobin. HRPR was observed in 1.5% of patients treated with ASA with no difference according to renal function (p = 0.18). HRPR for ADP-antagonists was observed in 23.7% of patients, with no difference according to renal function (p = 0.50). This result was confirmed either with clopidogrel (31.9% versus 38%, p = 0.41) and ticagrelor (13.1% versus 10.8%, p = 0.99), also after correction for all baseline confounders (clopidogrel: adjusted OR[95%CI] = 1.26 [0.60–2.63], p = 0.54) (ticagrelor: adjusted OR[95%CI] = 0.95 [0.54–1.65], p = 0.84). The absence of association between renal function and platelet reactivity was confirmed at linear regression analysis both with clopidogrel (r = − 0.04, p = 0.52) and ticagrelor (r = 0.006, p = 0.92).ConclusionIn patients receiving DAPT, chronic renal failure did not influence ADP-mediated platelet reactivity, with both ticagrelor or clopidogrel. No influence of chronic renal failure was found on the effectiveness of ASA.