Blood Pressure-lowering Drugs Research Articles

Adherence to anti-hypertensive therapy with perindopril-based single-pill versus free-pill combinations: a 10-year real-world analysis in Italy

Abstract Background/Introduction Despite the growing availability of blood pressure-lowering drugs, hypertension remains poorly controlled and a significant mortality cause worldwide. The silent course of the disease, suboptimal adherence, and complexity of therapeutic schedules are important factors in reducing the effectiveness of anti-hypertensive treatments at the population level. With the purpose of simplifying patients’ medication self-management, guidelines have strongly endorsed the use of anti-hypertensive therapy with single-pill combinations (SPCs). Perindopril (PER)-based SPCs, including both two- and three-drug combinations, have been available since 2008. Purpose We explored treatment adherence over 10 years in patients receiving PER-based regimens (SPC or free-pill combination) in Italy. Methods A retrospective real-world analysis was conducted on administrative databases covering 6.7 million Italian health-assisted residents. Among adults with hospitalization discharge diagnosis or exemption code for hypertension between 2010 and 2021, those with PER-based prescriptions were identified, considering combinations with amlodipine (AML) and/or indapamide (IND), either as SPC or free-pill or mixed (SPC+separate pill). The index-date (ID) was that of the first prescription of a PER-based regimen throughout the inclusion period. All patients with at least 12 months of available data before and after the ID were included. A cross-sectional analysis evaluated the yearly adherence for the period 2012-2021, calculating the proportion of days covered (PDC) by drug prescriptions on 1-year follow-up (PDC≥80% indicated high-adherence). Results Over 2012-2021, of 121,397 patients on a PER-based therapy, those treated with SPC ranged from 87% (during 2012) to 94.4% (during 2021), while free-pill and SPC+separate pill cohorts represented, respectively, 10.6-3.5% and 2.4-2.1% of all hypertensive patients. Over the decade, the proportion of adherent patients in SPC users was markedly higher than in free-pill and SPC+separate pill cohorts (Fig. 1). The sudden reduction of adherent patients during 2018-2019 was possibly due to a temporary shortage of PER/AML/IND as SPC in Italy from Nov-2018 to Mar-2019. Multivariate analysis showed that over 2012-2021 decade, free-pill and SPC+separate pill regimens resulted in significantly lower adherence (more than 80% reduction) than SPC formulation, while male gender and older age were predictive of better adherence (Table 1). Conclusions These findings from real clinical practice in Italy highlighted a growing attitude from clinicians to prescribe more manageable anti-hypertensive schemes based on SPC formulations, in line with current guidelines. The higher proportion of adherent patients among the users of PER-based SPCs corroborates the importance of alleviating pill burden, that is a key component in blood pressure control, and so in the reduction of hypertensive complications and cardiovascular risk.

Spironolactone in modern cardiology: from many years of experience to the latest evidence of effectiveness (literature review)

Spironolactone is a drug that plays an important role in the treatment of various diseases, especially in the field of cardiology and endocrinology. First synthesized in 1957, spironolactone gained widespread recognition due to its unique ability to block the action of aldosterone, a hormone that plays an important role in the pathogenesis of many cardiovascular diseases and increases the risk of severe cardiovascular complications. Spironolactone is included in the list of essential medicines of the World Health Organization. In cardiology, it is one of the universal remedies, because it is prescribed for resistant or secondary hypertension, heart failure, as part of hormonal therapy and in a number of other clinical conditions and situations. Resistant hypertension is a complex and serious medical problem, which is a significant challenge for doctors and patients, as it requires a specialized and individualized approach to treatment. Clinical studies found that spironolactone was the most effective adjunctive drug for the management of resistant hypertension, and this superiority of spironolactone confirmed the central role of sodium retention in the development of treatment resistance. Studies have shown that the addition of spironolactone to initial combination therapy resulted in a more potent antihypertensive effect compared to the addition of doxazosin or bisoprolol. The proportion of patients in whom spironolactone was the optimal blood pressure-lowering drug appeared to be the largest, according to the analysis on the prediction of the effect of each drug on the blood pressure level using plasma renin and the probability that different drugs will be best at different points of renin distribution in the blood plasma. Spironolactone has been used in modern cardiology for a long time to treat patients with heart failure and atrial fibrillation, but in this article, we have focused on another very important site for spironolactone administration, namely hypertension, especially in its resistant forms.

P082 HOW LONG DO BLOOD PRESSURE LOWERING DRUGS TAKE TO WORK? A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALS

Background: Evidence on the time course of antihypertensive drug (AHTD) efficacy is crucial to guide the frequency of visits recommended in guidelines and when it is appropriate to wait for further effects to accrue. Objective: To assess how quickly AHTD therapy works to lower blood pressure (BP). Methods: We systematically searched multiple electronic databases for relevant randomized, double-blind, placebo-controlled trials of untreated adults. These trials compared fixed doses of AHTDs from the five major classes to a placebo for a minimum of four weeks and reported BP data at baseline, and at least at weeks 2 and 4. Primary outcomes were systolic and diastolic BP reduction at weeks 2, 4, and 8. A fixed-effect meta-analysis was conducted, and a best-fit exponential association model was used to evaluate BP-lowering efficacy over time. Results: A total of 94 trials (25,637 participants) were included. Trial duration ranged from 4-16 (median 8) weeks. The best-fit exponential association model predicted that the reductions in systolic BP (SBP) at weeks 1, 2 and 3 were 64%, 79%, 85% of the reductions seen at week 4. There was no evidence of additional BP reduction after week 4. In absolute terms, after week 2 the additional reduction in BP averaged only 1.8/0.8 mmHg by week 4 and 0.4/0.2 mmHg between week 4 and week 8. This finding was consistent across trials by drug class, with no evidence that renin-angiotensin-aldosterone system inhibitors, diuretics, beta-blockers, calcium channel blockers, diuretics or combinations took longer to work. Baseline BP did appear to modify the effect, but still there was no additional benefit after 4 weeks. Conclusion: BP lowering drugs work quickly, with little additional BP lowering occurring after 2 weeks. These findings have relevance for guidelines and for addressing treatment inertia related to expectation of time needed for drugs to work fully.

Low-Dose Triple-Pill vs Standard-Care Protocols for Hypertension Treatment in Nigeria

With the high burden of hypertension in sub-Saharan Africa, there is a need for effective, safe and scalable treatment strategies. To compare, among Black African adults, the effectiveness and safety of a novel low-dose triple-pill protocol compared with a standard-care protocol for blood pressure lowering. Randomized, parallel-group, open-label, multicenter trial conducted in public hospital-based family medicine clinics in Nigeria. Black African adults with uncontrolled hypertension (≥140/90 mm Hg) who were untreated or receiving a single blood pressure-lowering drug. Participants were randomly allocated to low-dose triple-pill or standard-care protocols. The triple-pill protocol involved a novel combination of telmisartan, amlodipine, and indapamide in triple one-quarter, one-half, and standard doses (ie, 10/1.25/0.625 mg, 20/2.5/1.25 mg, and 40/5/2.5 mg), with accelerated up-titration. The standard-care protocol was the Nigeria hypertension treatment protocol starting with amlodipine (5 mg). The primary effectiveness outcome was the reduction in home mean systolic blood pressure, and the primary safety outcome was discontinuation of trial treatment due to adverse events, both from randomization to month 6. The first participant was randomized on July 19, 2022, and the last follow-up visit was on July 18, 2024. Among 300 randomized participants (54% female; mean age, 52 years; baseline mean home blood pressure, 151/97 mm Hg; and clinic blood pressure, 156/97 mm Hg), 273 (91%) completed the trial. At month 6, mean home systolic blood pressure was on average 31 mm Hg (95% CI, 28 to 33 mm Hg) lower in the triple-pill protocol group and 26 mm Hg (95% CI, 22 to 28 mm Hg) lower in the standard-care protocol group (adjusted difference, -5.8 mm Hg [95% CI, -8.0 to -3.6]; P < .001]). At month 6, clinic blood pressure control (<140/90 mm Hg) was 82% vs 72% (risk difference, 10% [95% CI, -2% to 20%]) and home blood pressure control (<130/80 mm Hg) was 62% vs 28% (risk difference, 33% [95% CI, 22% to 44%]) in the triple-pill compared with the standard-care protocol group; these were 2 of 21 prespecified secondary effectiveness end points. No participants discontinued trial treatment due to adverse events. Among Black African adults with uncontrolled hypertension, a low-dose triple-pill protocol achieved better blood pressure lowering and control with good tolerability compared with the standard-care protocol. Pan African Clinical Trials Registry Identifier: PACTR202107579572114.

Post-Ischemic Stroke Cardiovascular Risk Prevention and Management.

Cardiac death is the second most common cause of death among patients with acute ischemic stroke (IS), following neurological death resulting directly from acute IS. Risk prediction models and screening tools including electrocardiograms can assess the risk of adverse cardiovascular events after IS. Prolonged heart rate monitoring and early anticoagulation therapy benefit patients with a higher risk of adverse events, especially stroke patients with atrial fibrillation. IS and cardiovascular diseases have similar risk factors which, if optimally managed, may reduce the incidence of recurrent stroke and other major cardiovascular adverse events. Comprehensive risk management emphasizes a healthy lifestyle and medication therapy, especially lipid-lowering, glucose-lowering, and blood pressure-lowering drugs. Although antiplatelet and anticoagulation therapy are preferred to prevent cardiovascular events after IS, a balance between preventing recurrent stroke and secondary bleeding should be maintained. Optimization of early rehabilitation care comprises continuous care across environments thus improving the prognosis of stroke survivors.

Assessing Additive Interactions between Protective Factors Using Relative Risk Reduction Due to Interaction.

Background and Objectives: In the context of disease prevention, interaction on an additive scale is commonly assessed to determine synergistic effects between exposures. While the "Relative Excess Risk due to Interaction" represents the main measure of additive interaction between risk factors, in this study we aimed to extend this approach to assess additive interaction between factors known to prevent the event's occurrence, such as medical interventions and drugs. Materials and Methods: We introduced and described the "Relative Risk Reduction due to Interaction" (RRRI) as a key measure to assess additive interactions between preventive factors, such as therapeutic interventions and drug combinations. For RRRI values closer to 1, the combination of exposures has a greater impact on reducing the event risk due to their interaction. As a purely illustrative example, we re-evaluated a previous investigation of the synergistic effect between statins and blood pressure-lowering drugs in preventing major adverse cardiovascular events (MACE). Moreover, simulation studies were used to empirically evaluate the performance of a robust Poisson regression model to estimate RRRI across different scenarios. Results: In our example, the drug combination revealed a positive additive interaction in further reducing MACE risk (RRRI > 0), even if not statistically significant. This result is more straightforward to interpret as compared to the original one based on the RERI. Additionally, our simulations highlighted the importance of large sample sizes for detecting significant interaction effects. Conclusion: We recommend RRRI as the main measure to be considered when exploring additive interaction effects between protective exposures, such as the investigation of synergistic effects between drug combinations or preventive treatments.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease.

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I2 = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I2 = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.

Representation of Patients With Chronic Kidney Disease in Clinical Trials of Cardiovascular Disease Medications

Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease, but their systematic underrepresentation in cardiovascular randomized clinical trials (RCTs) limits the generation of appropriate evidence to guide cardiovascular risk management (CVRM). To evaluate the underrepresentation of patients with CKD in cardiovascular RCTs, and to highlight evidence gaps in CVRM medications in this population. A systematic search was conducted in ClinicalTrials.gov from February 2000 through October 2021 for RCTs with full-text publications. If no full-text publications were found in ClinicalTrials.gov, MEDLINE, Embase, and Google Scholar were also searched. Eligible RCTs were those evaluating the effectiveness of antiplatelets, anticoagulants, blood pressure-lowering drugs, glucose-lowering drugs, or cholesterol-lowering drugs in adults with cardiovascular disease or cardiovascular risk factors. Trials with a sample size of fewer than 100 patients were excluded. In total, 1194 RCTs involving 2 207 677 participants (mean [SD] age, 63 [6] years; 1 343 970 males [64%]) were included. Since 2000, the percentage of cardiovascular RCTs excluding patients with CKD has increased from 66% to 79% (74% overall [884 RCTs]). In 864 RCTs (72%), more patients were excluded than anticipated on safety grounds (63% [306] of trials required no dose adjustment, and 79% [561] required dose adjustment). In total, 158 RCTs (13%) reported results for patients with CKD separately (eg, in subgroup analyses). Significant evidence gaps exist in most CVRM interventions for patients with CKD, particularly for those with CKD stages 4 to 5. Twenty-three RCTs (2%) reported results for patients with an estimated glomerular filtration rate less than 30 mL/min/1.73 m2, 15 RCTs (1%) reported for patients receiving dialysis, and 1 RCT (0.1%) reported for recipients of kidney transplant. Results of this systematic review suggest that representation of patients with CKD in cardiovascular RCTs has not improved in the past 2 decades and that these RCTs excluded more patients with CKD than expected on safety grounds. Lack of reporting or underreporting of results for this patient population is associated with evidence gaps in the effectiveness of most CVRM medications in patients with all stages of CKD, particularly CKD stages 4 to 5.

Influence of renin-angiotensin system blockades on vascular access survival in patients on maintenance hemodialysis.

Results on the association between the use of renin-angiotensin system blockades (RASBs) and vascular access-related outcomes are inconsistent. We aimed to compare vascular access-related outcomes according to the use of RASBs in hemodialysis patients. This study used data from a national hemodialysis quality assessment program of the Republic of Korea (n = 54,903). Group 1 was not prescribed any blood pressure-lowering drugs (n = 28,521). Group 2 was prescribed other blood pressure-lowering agents except for RASBs (n = 9571). Group 3 was prescribed RASBs (n = 16,811). Vascular access-related outcomes were classified into intervention-free survival (IFS), thrombosis-free survival (TFS), and vascular access survival (VAS). No significant difference in the three access survival rates was identified among the three groups. The multivariate Cox regression analyses indicated that Group 3 had better outcomes in IFS and TFS than Group 1. The numbers of angioplasties performed were significantly greater in Group 1 than in the other two groups. The numbers of thrombectomies performed were significantly the lowest in Group 3 among all the groups. Our study revealed different results according to types of access survival in univariate or multivariate analyses. The association of RASBs with favorable outcomes in vascular access remains unclear.

Cardiovascular risk prediction in a New Zealand cohort of patients with known cardiovascular disease - a regional individual patient-level data linkage study

Abstract Background National health databases have been underutilised in the development of cardiovascular disease (CVD) risk prediction equations for people with known CVD, yet can inform population level practice and policy—including identification of health equity gaps, high-risk groups, and high-risk localities. With the recent introduction of novel and expensive preventive cardiovascular drugs, stratifying risk in patients with prior CVD could be required to inform cost-effective use of these medications in the future. Purpose We sought to develop 5-year CVD risk equations in adults with known history of CVD in Aotearoa New Zealand, using data from administrative health databases and characterize distribution of risk according to sex. Methods All people above 18 years of age with a history of CVD hospitalization, living in the Auckland and Northland regions of Aotearoa New Zealand (approximately one-third of the national population) on 1 January 2014 were included. Participants were followed for 5 years (31 December 2018) or until death or the outcome of interest, being any fatal or non-fatal CVD hospitalization (ischemic heart disease, heart failure, ischemic stroke, or peripheral artery disease) during follow-up. Sex-specific 5-year CVD risk prediction equations were developed using multivariable Fine and Gray models taking competing risk of non-cardiovascular death into account. Predictor variables included were age; ethnicity; deprivation level; time since most recent CVD hospitalization, history of smoking, heart failure, atrial fibrillation, chronic renal disease, and diabetes mellitus; use of anti-thrombotic, blood pressure-lowering, and lipid-lowering drugs; and blood levels of glycosylated hemoglobin (HbA1c), non-HDL cholesterol, and creatinine. Results The cohort comprised 42,130 men (median age: 68 years [interquartile range (IQR): 59–76]) and 31,717 women (median age: 70 years [IQR: 60–78]) with 12,875 and 8,734 observed events during follow-up, respectively. Sex-specific 5-year CVD risk prediction equations with excellent calibration (accuracy) were developed (Figure 1). Increasing age; high deprivation level; more recent CVD hospitalization; history of smoking, heart failure, atrial fibrillation, chronic renal disease, diabetes mellitus; use of blood-pressure lowering drugs; and high blood levels of HbA1c, non-HDL cholesterol, or creatinine were predictors of elevated risk. There was a wide range of predicted 5-year risk, with 15% of men and 24% of women having a predicted risk below 15%, and 24% and 20%, respectively, having a predicted risk of 40% or above (Figure 2). Conclusion This study demonstrates that it is possible to develop accurate CVD risk prediction equations from administrative health databases for patients with known CVD. Marked heterogeneity in 5-year risk of a subsequent CVD event emphasise that the current ‘one size fits all’ approach to secondary prevention of CVD requires review.Figure 1Figure 2

In-silico study of the Effectiveness of Allium sativum L. extract as an Angiotensin-Converting Enzyme (ACE) Inhibitor in Hypertension

Over the last decade, the global prevalence of hypertension rate has increased by 5.2% and, in Indonesia, the prevalence rate has increased significantly from 25.8% in 2013 to 34.1% in 2018. Hypertension treatments using blood pressure-lowering drugs, such as angiotensin-converting enzyme (ACE) inhibitors, often cause unpleasant side effects. These side effects increase the interest in using potentially effective natural remedies, such as garlic. This study aimed to determine which organosulfur compounds in garlic can act as an ACE inhibitor to reduce blood pressure in hypertension using a cheminformatics approach. Eighteen organosulfur compounds of Allium sativum L. were screened based on Lipinski’s rules and ADMET evaluation. Seven compounds passed the screening and were subjected to QSAR analysis, molecular docking analysis, and molecular dynamics simulations to assess the stability of the protein. The seven compounds then underwent molecular docking and QSAR analysis. Ajoene (4,5,9-trithiadodeca-1,6,11-triene-9-oxide) and S-allylmercaptocysteine (SAMC) were two compounds with better docking values compared to the positive control compound. The QSAR analysis also showed that SAMC had an activity as an ACE inhibitor. The ADMET evaluation showed that Ajoene and SAMC had good absorption and could not penetrate the blood-brain barrier. Molecular dynamics simulation of ACE complexes Ajoene, SAMC, and Captopril ranged from 0.05 to 5.61 Å but exhibited a pattern of synonymous fluctuations for most residues. Based on the simulation data, the organosulfur compounds from garlic, Ajoene, and SAMC are proven to have a mechanism of action as ACE inhibitors to reduce blood pressure in hypertension.

Development and validation of cardiovascular risk prediction equations in 76 000 people with known cardiovascular disease.

Multiple health administrative databases can be individually linked in Aotearoa New Zealand, using encrypted identifiers. These databases were used to develop cardiovascular risk prediction equations for patients with known cardiovascular disease (CVD). Administrative health databases were linked to identify all people aged 18-84 years with known CVD, living in Auckland and Northland, Aotearoa New Zealand, on 1 January 2014. The cohort was followed until study outcome, death, or 5 years. The study outcome was death or hospitalization due to ischaemic heart disease, stroke, heart failure, or peripheral vascular disease. Sex-specific 5-year CVD risk prediction equations were developed using multivariable Fine and Gray models. A total of 43 862 men {median age: 67 years [interquartile range (IQR): 59-75]} and 32 724 women [median age: 70 years (IQR: 60-77)] had 14 252 and 9551 cardiovascular events, respectively. Equations were well calibrated with good discrimination. Increasing age and deprivation, recent cardiovascular hospitalization, Mori ethnicity, smoking history, heart failure, diabetes, chronic renal disease, atrial fibrillation, use of blood pressure lowering and anti-thrombotic drugs, haemoglobin A1c, total cholesterol/HDL cholesterol, and creatinine were statistically significant independent predictors of the study outcome. Fourteen per cent of men and 23% of women had predicted 5-year cardiovascular risk <15%, while 28 and 24% had ≥40% risk. Robust cardiovascular risk prediction equations were developed from linked routine health databases, a currently underutilized resource worldwide. The marked heterogeneity demonstrated in predicted risk suggests that preventive therapy in people with known CVD would be better informed by risk stratification beyond a one-size-fits-all high-risk categorization.

First-line diuretics versus other classes of antihypertensive drugs for hypertension.

First-line diuretics versus other classes of antihypertensive drugs for hypertension.

Sex hormone-binding globulin levels and development of hypertension in middle-aged men and women.

To investigate the association between sex hormone-binding globulin (SHBG) levels, change in blood pressure and development of hypertension. In a community-based study, we examined 2816 middle-aged participants with focus on cardiometabolic risk factors in 2002-2005. A representative sample of 1954 men and women was invited to follow-up in 2012-2014 and 1327 were included in a second study visit. Mean follow-up time was 9.7 years. Blood pressure was measured according to the guidelines from the seventh Joint National Committee of Hypertension, and new cases of hypertension were recorded. SHBG was measured at baseline. The association between SHBG, blood pressure and new cases of hypertension was investigated using linear regression analyses and logistic regression analyses after excluding individuals treated with blood pressure-lowering drugs. Mean SBP and DBP at follow-up was 123 and 72 mmHg, respectively, and mean increase from baseline was 5.8 and 2.9 mmHg. During the follow-up time, 167 new cases of hypertension (16.1%) were identified. One standard deviation (SD) increase in SHBG at baseline was inversely associated with the risk to develop hypertension at follow-up (OR = 0.74, 95% CI 0.58-0.95) in the fully adjusted model. Moreover, one SD increase in SHBG was associated with a decrease in mean SBP (delta = -1.5 mmHg, 95% CI - 2.2 to -0.8) and DBP (delta = - 1.0 mmHg, 95% CI - 1.5 to -0.4), after adjusting for covariates. SHBG levels are inversely associated with development of hypertension and change in blood pressure levels independent of major risk factors.

Assessment and Diagnosis of Peripheral Artery Disease in Patients with Diabetes

Peripheral artery disease (PAD) is a chronic circulatory condition that occurs when the arteries that supply blood to the legs and feet are narrowed or blocked, leading to reduced blood flow to these areas. PAD is a common complication of type 2 diabetes, affecting up to 1 in 3 individuals with the condition. Assessment of PAD in individuals with diabetes typically involves a physical exam, ankle-brachial index (ABI) measurement, and imaging tests such as Doppler ultrasound or angiography. The ABI is a noninvasive measure that compares the blood pressure in the ankles and arms, with a lower ABI indicating a higher risk of PAD. Management of PAD in type 2 diabetes involves a multifaceted approach, including lifestyle modifications, medication, and revascularization procedures. Lifestyle changes such as smoking cessation and regular exercise can improve PAD symptoms and reduce the risk of disease progression. Medications such as antiplatelet agents, statins, and blood pressure-lowering drugs help to manage PAD and its associated risk factors. Revascularization procedures such as angioplasty or bypass surgery may be necessary in severe cases of PAD to restore blood flow to the affected limbs. In addition, these procedures should be considered in the feet of patients with diabetes if there is evidence of ischemia. Early detection and management of PAD in type 2 diabetes are critical to preventing complications such as non-healing wounds, infections, and amputations. Individuals with type 2 diabetes should undergo regular screening for PAD and work with their healthcare providers to develop a personalized treatment plan.

Pathogenesis and management of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in men) are monitored by imaging and large asymptomatic, symptomatic, and ruptured AAAs are considered for surgical repair. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. This review outlines research on AAA pathogenesis and therapies to limit AAA growth. Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. Mendelian randomization analyses suggest that treatments to reduce low-density lipoprotein cholesterol such as proprotein convertase subtilisin/kexin type 9 inhibitors and smoking reduction or cessation are also treatment targets. Thirteen placebo-controlled randomized trials have tested whether a range of antibiotics, blood pressure-lowering drugs, a mast cell stabilizer, an anti-platelet drug, or fenofibrate slow AAA growth. None of these trials have shown convincing evidence of drug efficacy and have been limited by small sample sizes, limited drug adherence, poor participant retention, and over-optimistic AAA growth reduction targets. Data from some large observational cohorts suggest that blood pressure reduction, particularly by angiotensin-converting enzyme inhibitors, could limit aneurysm rupture, but this has not been evaluated in randomized trials. Some observational studies suggest metformin may limit AAA growth, and this is currently being tested in randomized trials. In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.

Pharmacogenomics and the Concept of Personalized Medicine for the Management of Hypertension

Pharmacogenomics and the Concept of Personalized Medicine for the Management of Hypertension

#6463 IMPLEMENTATION OF CLINICAL ALARM SYSTEM IS ASSOCIATED WITH REDUCTION OF THE RISK OF INTRADIALYTIC HYPOTENSION

Abstract Background and Aims Intradialytic hypotension (IDH) plays an essential role in hemodialysis. IDH prevalence can be up to 8% to 40% [1], according to research. Furthermore, research shows that IDH positively correlates with severe complications such as non-occlusive mesenteric ischemia[2], critical limb ischemia[3] and tissue ischemia, which leads to irreversible damage, even increasing the chance of infection. Many causes and risk factors result in IDH, such as excessive weight gain during dialysis, cardiovascular dysfunction, and improper use of blood pressure-lowering drugs[1]. Therefore, it still relies on experienced medical professionals to monitor patients’ blood pressure to beware of the risk of developing IDH. However, this increases the workload on medical professionals and does not provide standard or more objective early warning indicators of hypotension for new medical professionals. Method Selection of experimental and control group: In this study, we included 81 subjects that received hemodialysis in Tainan City Municipal Annan Hospital from January 2021 to August 2022. The control group was retrospective data collected from January 2021 to August 2021. Then, from January 2022 to August 2022, we implemented our IDH predicting system and took subjects’ data from this interval as the experimental group to compare the incidence of IDH with the control group. IDH prediction system monitoring interface: After integrating with the hemodialysis dataset, our prediction system will predict patients’ systolic pressure and the likelihood of IDH in the next 30 minutes. As soon as the system detects that the patient will encounter hypotension, it sends warning signals, blood pressure and IDH incidence probability predictions to the monitoring interface to alert medical professionals. Furthermore, our system also supports multi-bed monitoring, which can significantly increase the efficiency of monitoring during hemodialysis. Results After implementing the IDH prediction system, the outcome yielded an IDH incidence of 6.12% in August 2022. Compared to the control group, when the IDH system was not yet implemented, which yielded an IDH incidence of 9.34%, it showed a reduction of 34.5% in IDH cases. Furthermore, the average reduction in IDH rate each month was 12%. Conclusion The present study demonstrated that implementing the IDH predicting model may efficiently reduce the incidence of IDH. However, along with the IDH warning multi-bed monitoring interface, medical professionals must develop a standard procedure to deploy when noticing the warning signals. As a result, this may further reduce the incidence of IDH during hemodialysis sessions.

The effect of blood pressure lowering medications on the prevention of episodic migraine: A systematic review and meta-analysis.

Currently, only a few specific blood pressure-lowering medications are recommended for migraine prevention. Whether benefits extend to other classes or drugs is uncertain. Embase, MEDLINE, and the Cochrane Central Registry of Controlled Trials were searched for randomized control trials on the effect of blood pressure-lowering medications compared with placebo in participants with episodic migraine. Data were collected on four outcomes - monthly headache or migraine days, and monthly headache or migraine attacks, with a standardised mean difference calculated for overall. Random effect meta-analysis was performed. In total, 50 trials (70% of which were crossover) were included, comprising 60 comparisons. Overall mean age was 39 years, and 79% were female. Monthly headache days were fewer in all classes compared to placebo, and this was statistically significant for all but one class: alpha-blockers -0.7 (95% CI: -1.2, -0.1), angiotensin-converting enzyme inhibitors -1.3 (95% CI: -2.9, 0.2), angiotensin II receptor blockers -0.9 (-1.6, -0.1), beta-blocker -0.4 (-0.8, -0.0) and calcium channel blockers -1.8 (-3.4, -0.2). Standardised mean difference was significantly reduced for all drug classes and was separately significant for numerous specific drugs: clonidine, candesartan, atenolol, bisoprolol, metoprolol, propranolol, timolol, nicardipine and verapamil. Among people with episodic migraine, a broader number of blood pressure-lowering medication classes and drugs reduce headache frequency than those currently included in treatment guidelines.Trial Registration: The study was registered at PROSPERO (CRD42017079176).

MEDICAL VERSUS SURGICAL TREATMENT IN PATIENTS WITH NON-FUNCTIONING KIDNEY

Objective: Non-functioning kidney (NFK) can be responsible in whole or in part for hypertension. Patients with a lateralized renin secretion can be treated either medically or surgically. Objective: assess the benefice of nephrectomy over medical treatment in the management of lateralized NFK in hypertensive patients diagnosed after renal vein sampling (RVS). The profit is based on the blood pressure (BP) control, the number of BP lowering drugs or the daily-defined dose (ddd). Design and method: We conducted an observational retrospective study at the Hypertension Unit at Georges-Pompidou European Hospital in France, between January 2004 and January 2021, that analyzes RVS in hypertensive patients. We studied the data (N = 68) at the time of diagnosis and at two follow up visits: the first after RVS or nephrectomy (V1) and the last visit (V2). Results: At V1, in patients with a lateralized NFK: - 18 underwent nephrectomy: 11 vascular disease, 4 urologic disease, 2 trauma and 1 another cause.- 5 were treated medically: all had a vascular disease In patients who underwent nephrectomy, between the diagnosis, V1 and V2 (N = 12) respectively: In patients with medical treatment, between the diagnosis, V1 and V2 (N = 4) respectively: a) systolic BP dropped from 189 to 170,33 to 133,33 mmHgb) number of molecules increased from 3 to 4,8 at V1 and V2c) ddd increased from 63,35 to 118,3 to 267d) at V1 and V2: 1 had a controlled HTN Conclusions: In patients with lateralized NFK, nephrectomy helps in the control of the BP and reduces systolic BP, number of drugs and ddd. The effect on the BP control seems not to be maintained on the long term. Further studies, with a bigger sample, are needed to define subgroups that can benefit the most from nephrectomy.