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Comparison of the Efficacy and Safety of Sacubitril/Valsartan versus Ramipril in Patients With ST-Segment Elevation Myocardial Infarction.
Rezq, A, Saad, M, El Nozahi, M
The American journal of cardiology. 2021;:7-13
Abstract
The role of sacubitril and/or valsartan in patient with heart failure (HF) is established. Whether sacubitril and/or valsartan plays a role in improving outcomes in patients after ST-segment elevation myocardial infarction (STEMI) is unknown. The current study aims to comparing the efficacy and safety of sacubitril and/or valsartan versus ramipril in post-STEMI patients. Patients presenting with STEMI were randomized to receive either sacubitril and/or valsartan or ramipril after primary percutaneous coronary intervention. The main efficacy endpoint was major adverse cardiac events (MACE) at 30 days and 6 months, defined as a composite of cardiac death, myocardial infarction, and HF hospitalizations. Multiple secondary clinical safety and efficacy endpoints were examined. A total of 200 patients were randomized from January 2018 to March 2019, mean age 54.5±10.4, 87% men, 75% presented with anterior wall STEMI. Baseline clinical and echocardiographic characteristics were comparable between groups. The primary endpoint of MACE was similar with sacubitril/valsartan versus ramipril at 30 days (p = 0.18); however, at 6 months, sacubitril/valsartan was associated with significant reduction of MACE (p = 0.005), mainly driven by reduction in HF hospitalizations (18% vs 36%, OR 0.40, 95% 0.22 to 0.75; p = 0.004). At 6 months, LV ejection fraction was higher with sacubitril/valsartan (46.8±12.5% vs 42.09±13.8%; p = 0.012), with improved LV remodelling (LV end diastolic dimension 50.6±3.9 mm vs 53.2±2.7 mm, p = 0.047; and LV end systolic dimension 36.1±3.4 mm versus 39.9±6.3 mm, p = 0.001) compared with ramipril. No difference in other efficacy or safety clinical endpoints was observed. In conclusion, early initiation of sacubitril/valsartan may offer clinical benefit and improvement in myocardial remodelling in post-STEMI patients.
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Comparative Effectiveness of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in Individuals With Advanced CKD: A Nationwide Observational Cohort Study.
Fu, EL, Clase, CM, Evans, M, Lindholm, B, Rotmans, JI, Dekker, FW, van Diepen, M, Carrero, JJ
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2021;(5):719-729.e1
Abstract
RATIONALE & OBJECTIVE It is unknown whether initiating renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs). We compared the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD in routine nephrology practice who were initiating either RAS inhibitor or CCB therapy. STUDY DESIGN Observational study in the Swedish Renal Registry, 2007 to 2017. SETTINGS & PARTICIPANTS 2,458 new users of RAS inhibitors and 2,345 CCB users with estimated glomerular filtration rates<30mL/min/1.73m2 (CKD G4-G5 without KRT) who were being followed up by a nephrologist. As a positive control cohort, new users of the same drugs with CKD G3 (estimated glomerular filtration rate, 30-60mL/min/1.73m2) were evaluated. EXPOSURES RAS inhibitor versus CCB therapy initiation. OUTCOME Initiation of KRT (maintenance dialysis or transplantation), all-cause mortality, and MACE (composite of cardiovascular death, myocardial infarction, or stroke). ANALYTICAL APPROACH HRs with 95% CIs were estimated using propensity score-weighted Cox proportional hazards regression adjusting for demographic, clinical, and laboratory covariates. RESULTS Median age was 74 years, 38% were women, and median follow-up was 4.1 years. After propensity score weighting, there was significantly lower risk for KRT after new use of RAS inhibitors compared with new use of CCBs (adjusted HR, 0.79 [95% CI, 0.69-0.89]) but similar risks for mortality (adjusted HR, 0.97 [95% CI, 0.88-1.07]) and MACE (adjusted HR, 1.00 [95% CI, 0.88-1.15]). Results were consistent across subgroups and in as-treated analyses. The positive control cohort of patients with CKD G3 showed similar KRT risk reduction (adjusted HR, 0.67 [95% CI, 0.56-0.80]) with RAS inhibitor therapy compared with CCBs. LIMITATIONS Potential confounding by indication. CONCLUSIONS Our findings provide evidence from real-world clinical practice that initiation of RAS inhibitor therapy compared with CCBs may confer kidney benefits among patients with advanced CKD, with similar cardiovascular protection.
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Comparison of Percutaneous Coronary Intervention, Coronary Artery Bypass Grafting and Medical Therapy in Non-ST Elevation Acute Coronary Syndrome Patients With 3-Vessel Disease.
Jia, S, Zhang, C, Jiang, L, Xu, L, Tian, J, Zhao, X, Feng, X, Wang, D, Zhang, Y, Sun, K, et al
Circulation journal : official journal of the Japanese Circulation Society. 2020;(10):1718-1727
Abstract
BACKGROUND The aim of this study is to compare the long-term prognosis of non-ST elevation acute coronary syndrome (NSTE-ACS) patients with 3-vessel disease (3VD) who underwent percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical therapy (MT).Methods and Results:Overall, 3,928 NSTE-ACS patients with 3VD were consecutively enrolled from April 2004 to February 2011 at Fu Wai Hospital. Patients were followed up for a median of 7.5 years, and were divided into PCI, CABG or MT groups according to their treatment. Compared with patients undergoing PCI, CABG patients had lower rates of myocardial infarction (MI), unplanned revascularization, major adverse cardiovascular and cerebrovascular events (MACCE) and a higher rate of stroke (all P<0.05). Compared with MT, PCI and CABG had lower incidences of all adverse outcomes (all P<0.05), except for a similar rate of stroke between PCI and MT. Kaplan-Meier analysis showed similar results. After adjusting for confounders, CABG was independently associated with a lower risk of cardiac death, revascularization and MACCE compared with PCI (all P<0.05). Compared with MT, PCI reduced long-term risk of death, whereas CABG reduced long-term risk of death, revascularization and MACCE events (all P<0.05). CONCLUSIONS In NSTE-ACS patients with 3VD, CABG is independently associated with a lower risk of long-term cardiac death, revascularization and MACCE compared with PCI. Patients who received MT alone had the highest risk of long-term MACCE.
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PAIT-Survey Follow-Up: Changes in Albuminuria in Hypertensive Diabetic Patients with Mild-Moderate Chronic Kidney Disease.
Fici, F, Ari Bakir, E, Ilkay Yüce, E, Kanuncu, S, Makel, W, Tarim, BA, Robles, NR
High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension. 2020;(1):43-49
Abstract
INTRODUCTION Albuminuria is an early marker of kidney disease and reduction of albuminuria translates into a decreased occurrence of cardiovascular and renal outcomes. AIMS To evaluate the changes in the prevalence of albuminuria in diabetic hypertensive patients treated with several combinations of renin-angiotensin aldosterone system with calcium channel blockers. METHODS We analysed data from 668 unselected patients from the PAIT survey (mean age 60.4 ± 10.2 years, prevalence of males 38%), with and without albuminuria, maintained for 6 months with the previous treatment with amlodipine-valsartan, amlodipine perindopril, lercanidipine-enalapril, verapamil-trandolapril, nitrendipine-enalapril and felodipine-ramipril Albuminuria was assessed, as urinary albumin-creatinine ratio, using a Multistic-Clinitek device analyzer. Microalbuminuria was defined as a loss of 3.4-33.9 mg albumin/mmol creatinine (30-300 mg/g) and macroalbuminuria as a loss of > 33.9 mg albumin/mmol creatinine (> 300 mg/g). Blood pressure was measured with a validated digital device. RESULTS At baseline, albuminuria was present in 310 subjects (46.4%) (microalbuminuria in 263 (84.8%), macroalbuminuria in 15.2%), and normoalbuminuria in 53.6% 358. After 6 months, the prevalence of subjects with albuminuria was significantly lowered (p < 0.01) by 23.5% (microalbuminuria - 23.9%, p < 0.01 and macroalbuminuria - 21.3%). The prevalence of subjects with microalbuminuria was reduced with all treatments: amlodipine-valsartan - 15.6%, amlodipine-perindopril - 11.8%, lercanidipine-enalapril - 41.3% and verapamil-trandolapril - 19.2%. Data with nitrendipine-enalapril and felodipine-ramipril were not analyzed, due to the low number of patients. The frequency of patients with normoalbuminuria was significantly higher (p < 0.01) with lercanidipine-enalapril compared with any other treatment. Blood pressure was significantly (p < 0.01) reduced, with a similar effect between treatments. CONCLUSIONS The treatments decrease the prevalence of subjects with albuminuria, showing a significant difference among the different drug combinations, favoring the use of new dihydropyridine calcium channel blockers, such as lercanidipine, combined with RAAS inhibitors, to control albuminuria in diabetic hypertensive patients.
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Comparative Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Response to a Physical Activity Intervention in Older Adults: Results From the Lifestyle Interventions and Independence for Elders Study.
Brown, JD, Smith, SM, Strotmeyer, ES, Kritchevsky, SB, Gill, TM, Blair, SN, Fielding, RA, Buford, TW, Pahor, M, Manini, TM
The journals of gerontology. Series A, Biological sciences and medical sciences. 2020;(5):1010-1016
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BACKGROUND Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) may protect against aging-related decline. This study directly compared ACEis and ARBs on associations with risk of mobility disability in older adults when combined with a physical activity intervention. METHODS This was a secondary analysis of the Lifestyle Interventions and Independence for Elders (LIFE) trial. Participants aged 70-89 years were randomized to a physical activity or health education intervention. Outcomes included incident and persistent major mobility disability, injurious falls, short physical performance battery, and gait speed. For this analysis, only participants who reported ACEi or ARB use at baseline were included. Baseline differences between ACEi and ARB groups were adjusted for using inverse probability of treatment weights. Weighted Cox proportional hazard models and analysis of covariance models were used to evaluate the independent effects of medications and interaction effects with the intervention on each outcome. RESULTS Of 1,635 participants in the Lifestyle Interventions and Independence for Elders study, 796 used either an ACEi (496, 62.3%) or ARB (300, 37.7%). Compared with ACEi users, ARB users had 28% lower risk (hazard ratio [HR] = 0.72 [0.60-0.85]) of incident major mobility disability and 35% (HR = 0.65 [0.52-0.82]) lower risk of persistent major mobility disability whereas no interaction between medication use and intervention was observed. Risk of injurious falls and changes in short physical performance battery or gait speed were not different between ARB and ACEi users. CONCLUSIONS These results suggest that ARBs may protect from major mobility disability by other mechanisms than improving physical performance.
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Prior Heart Failure Hospitalization, Clinical Outcomes, and Response to Sacubitril/Valsartan Compared With Valsartan in HFpEF.
Vaduganathan, M, Claggett, BL, Desai, AS, Anker, SD, Perrone, SV, Janssens, S, Milicic, D, Arango, JL, Packer, M, Shi, VC, et al
Journal of the American College of Cardiology. 2020;(3):245-254
Abstract
BACKGROUND The period shortly after hospitalization for heart failure (HF) represents a high-risk window for recurrent clinical events, including rehospitalization or death. OBJECTIVES This study sought to determine whether the efficacy and safety of sacubitril/valsartan varies in relation to the proximity to hospitalization for HF among patients with HF with preserved ejection fraction (HFpEF). METHODS In this post hoc analysis of PARAGON-HF (Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ARB [Angiotensin Receptor Blocker] Global Outcomes in HFpEF), we assessed the risk of clinical events and response to sacubitril/valsartan in relation to time from last HF hospitalization among patients with HFpEF (≥45%). The primary outcome was composite total HF hospitalizations and cardiovascular death, analyzed by using a semiparametric proportional rates method, stratified by geographic region. RESULTS Of 4,796 validly randomized patients in PARAGON-HF, 622 (13%) were screened during hospitalization or within 30 days of prior hospitalization, 555 (12%) within 31 to 90 days, 435 (9%) within 91 to 180 days, and 694 (14%) after 180 days; 2,490 (52%) were never previously hospitalized. Over a median follow-up of 35 months, risk of total HF hospitalizations and cardiovascular death was inversely and nonlinearly associated with timing from prior HF hospitalization (p < 0.001). There was a gradient in relative risk reduction in primary events with sacubitril/valsartan from patients hospitalized within 30 days (rate ratio: 0.73; 95% confidence interval: 0.53 to 0.99) to patients never hospitalized (rate ratio: 1.00; 95% confidence interval: 0.80 to 1.24; trend in relative risk reduction: pinteraction = 0.15). With valsartan alone, the rate of total primary events was 26.7 (≤30 days), 24.2 (31 to 90 days), 20.7 (91 to 180 days), 15.7 (>180 days), and 7.9 (not previously hospitalized) per 100 patient-years. Compared with valsartan, absolute risk reductions with sacubitril/valsartan were more prominent in patients enrolled early after hospitalization: 6.4% (≤30 days), 4.6% (31 to 90 days), and 3.4% (91 to 180 days), whereas no risk reduction was observed in patients screened >180 days or who were never hospitalized (trend in absolute risk reduction: pinteraction = 0.050). CONCLUSIONS Recent hospitalization for HFpEF identifies patients at high risk for near-term clinical progression. In the PARAGON-HF trial, the relative and absolute benefits of sacubitril/valsartan compared with valsartan in HFpEF appear to be amplified when initiated in the high-risk window after hospitalization and warrant prospective validation. (PARAGON-HF; NCT01920711).
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Comparisons of Three Main Treatments on Renoprotective Effects in Diabetes Mellitus.
Huang, Q, Li, K, Li, M, Xu, G
Iranian journal of kidney diseases. 2019;(1):36-47
Abstract
INTRODUCTION Antihypertension, intensive glucose control (IGC), and lipid lowering were the main therapeutic strategies in diabetes mellitus. However, the comparative effects of them on renoprotection remain unclear. MATERIALS AND METHODS We searched the PubMed, EMBase, and Cochrane Library up to May 18, 2017, for studies with comparative interventions on regression, end-stage renal disease and all-cause death in diabetes mellitus. Statistical analysis was done using the Bayesian network meta-analysis (NMA). The surface under the cumulative ranking area and median rank were calculated to rank the interventions. RESULTS A total of 73 randomized controlled trials with 13 3703 participants were included for the comparisons of 14 interventions. Angiotensin-converting enzyme inhibitor plus angiotensin receptor blocker (ACEI-ARB) ranked first in regression (odds ratio, 62; 95% confidence interval, 5.2 to > 999); ACEI-ARB also ranked first in end-stage renal disease decline (odds ratio, 0.58, 95% confidence interval, 0.39 - 0.85), followed by IGC hemoglobin A1c less than 6.5% (odds ratio, 0.58, 95% confidence interval, 0.36 - 0.90). The ACEI plus calcium channel blocker reduced all-cause death leaving other interventions insignificant (odds ratio, < 0.001; 95% confidence interval, < 0.001 to 0.30). ). The surface under the cumulative ranking area analyses also matched the result ranks. CONCLUSIONS Compared with antihypertension interventions, IGC including IGC hemoglobin A1c less than 6.5% and lipid lowering, ACEI-ARB showed the best renoprotective effects.
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Angiotensin-Converting Enzyme Inhibitors vs. Angiotensin Receptor Blockers for the Treatment of Hypertension in Adults With Type 2 Diabetes: Why We Favour Angiotensin Receptor Blockers.
Mavrakanas, TA, Lipman, ML
Canadian journal of diabetes. 2018;(2):118-123
Abstract
Cardiovascular disease is the principal cause of morbidity and mortality in patients with diabetes mellitus. The incidence or progression of kidney disease is also common in these patients. Several clinical trials have established the efficacy of angiotensin receptor blockers for the prevention of adverse cardiovascular and renal outcomes in this population and are summarized in this review article. Head-to-head comparison of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors has shown similar cardioprotective and renoprotective properties of both medication classes. However, angiotensin receptor blockers have an improved safety profile with fewer episodes of cough and angioedema and may be the agent of choice in patients with diabetes and hypertension. Novel therapeutic strategies, such as those that include a mineralocorticoid receptor blocker or a selective sodium-glucose cotransporter type 2 inhibitor, may further protect patients with diabetes from cardiovascular and renal complications.
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Add-On Antihypertensive Medications to Angiotensin-Aldosterone System Blockers in Diabetes: A Comparative Effectiveness Study.
Schroeder, EB, Chonchol, M, Shetterly, SM, Powers, JD, Adams, JL, Schmittdiel, JA, Nichols, GA, O'Connor, PJ, Steiner, JF
Clinical journal of the American Society of Nephrology : CJASN. 2018;(5):727-734
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BACKGROUND AND OBJECTIVES In individuals with diabetes, the comparative effectiveness of add-on antihypertensive medications added to an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker on the risk of significant kidney events is unknown. DESIGN, SETTING PARTICIPANTS, & MEASUREMENTS We used an observational, multicenter cohort of 21,897 individuals with diabetes to compare individuals who added β-blockers, dihydropyridine calcium channel blockers, loop diuretics, or thiazide diuretics to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. We examined the hazard of significant kidney events, cardiovascular events, and death using Cox proportional hazard models with propensity score weighting. The composite significant kidney event end point was defined as the first occurrence of a ≥30% decline in eGFR to an eGFR<60 ml/min per 1.73 m2, initiation of dialysis, or kidney transplant. The composite cardiovascular event end point was defined as the first occurrence of hospitalization for acute myocardial infarction, acute coronary syndrome, stroke, or congestive heart failure; coronary artery bypass grafting; or percutaneous coronary intervention, and it was only examined in those free of cardiovascular disease at baseline. RESULTS Over a maximum of 5 years, there were 4707 significant kidney events, 1498 deaths, and 818 cardiovascular events. Compared with thiazide diuretics, hazard ratios for significant kidney events for β-blockers, calcium channel blockers, and loop diuretics were 0.81 (95% confidence interval, 0.74 to 0.89), 0.67 (95% confidence interval, 0.58 to 0.78), and 1.19 (95% confidence interval, 1.00 to 1.41), respectively. Compared with thiazide diuretics, hazard ratios of mortality for β-blockers, calcium channel blockers, and loop diuretics were 1.19 (95% confidence interval, 0.97 to 1.44), 0.73 (95% confidence interval, 0.52 to 1.03), and 1.67 (95% confidence interval, 1.31 to 2.13), respectively. Compared with thiazide diuretics, hazard ratios of cardiovascular events for β-blockers, calcium channel blockers, and loop diuretics compared with thiazide diuretics were 1.65 (95% confidence interval, 1.39 to 1.96), 1.05 (95% confidence interval, 0.80 to 1.39), and 1.55 (95% confidence interval, 1.05 to 2.27), respectively. CONCLUSIONS Compared with thiazide diuretics, calcium channel blockers were associated with a lower risk of significant kidney events and a similar risk of cardiovascular events.
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First-line renin-angiotensin system inhibitors vs. other first-line antihypertensive drug classes in hypertensive patients with type 2 diabetes mellitus.
Wang, G, Chen, Y, Li, L, Tang, W, Wright, JM
Journal of human hypertension. 2018;(7):494-506
Abstract
First-line renin-angiotensin system (RAS) inhibitors are recommended for diabetic patients because of their potential nephron-protective properties. For hypertensive patients with type 2 diabetes mellitus, little is known about first-line RAS inhibitors vs. other first-line antihypertensive agents in terms of cardiovascular outcomes. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the comparative efficacy of first-line RAS inhibitors vs. other first-line antihypertensive drug classes in hypertensive patients with type 2 diabetes mellitus. We identified RCTs by searching the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE up to December 15, 2015. Eighteen RCTs involving 18,862 participants were included. First-line RAS inhibitors were not different from first-line diuretics for all the primary outcomes. First-line RAS inhibitors reduced major cardiovascular events (2 RCTs, relative risk [RR] 0.78, 95% confidence interval [CI] 0.66, 0.91) and heart failure (4 RCTs, RR 0.72, 95% CI 0.61, 0.83) compared to first-line calcium channel blockers. Compared to β-blockers, RAS inhibitors reduced the risk of all-cause mortality (1 RCT, RR 0.63, 95% CI 0.47, 0.84), major cardiovascular events (1 RCT, RR 0.76, 95% CI 0.62, 0.93) and heart failure (1 RCT, RR 0.60, 95% CI 0.40, 0.92). Our meta-analysis indicates that, in patients with type 2 diabetes mellitus and hypertension, first-line RAS inhibitors reduced adverse cardiovascular events to the same degree as first-line diuretics but to a greater degree than first-line calcium channel blockers and first-line beta blockers.