Abstract 14373: Efficacy and Safety of Antihypertensive Drug Classes: The Systolic Blood Pressure Intervention Trial (SPRINT)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Christina Byrne ◽  
Anubodh Varshney ◽  
Zaid Almarzooq ◽  
Kristian H Kragholm ◽  
Maria L Krogager ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Systolic Blood Pressure ◽  
Antihypertensive Drug ◽  
Primary Outcome ◽  
Control Group ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Drug Classes ◽  
Safety Outcomes

Purpose: To assess the efficacy and safety of antihypertensive drug classes, including angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB), beta blockers (BB), calcium channel blockers (CCB), and thiazide diuretics (TD), in subjects at high cardiovascular (CV) risk. Methods: SPRINT was a randomized, controlled, open-label trial in which individuals without diabetes aged ≥50 years, at high CV risk, and with a systolic blood pressure (SBP) 130-180 mmHg were randomized to intensive (SBP target <120mmHg) or standard BP control (SBP target 135-139 mmHg). The primary outcome was the composite of acute coronary syndromes, stroke, heart failure, or CV death. Safety outcomes included serious adverse events, i.e., hypotension, syncope, electrolyte abnormalities, acute kidney injury or failure, and falls. Associations between baseline antihypertensive drug classes, efficacy, and safety outcomes, stratified by level of SBP control, were examined using Cox proportional-hazards regression. Results: Of 9361 participants, baseline use of antihypertensive agents was as follows: ACEi/ARB in 1317 (14%), BB in 911 (10%), CCB in 796 (9%), and TD in 979 (10%). A total of 1366 (15%) subjects did not have a record of being on an antihypertensive drug at baseline. In the intensive BP control group, use of a BB-based regimen at baseline was associated with a significantly higher risk of the primary outcome when compared with no medications ( Figure ). Similar patterns were observed for secondary efficacy endpoints. The risk of serious adverse events tended to be lower in patients receiving a treatment regimen containing either an ACEi/ARB or a TD compared with those receiving a regimen containing a BB or a CCB ( Figure ). Conclusions: In SPRINT, the risk of adverse events was lowest in patients who were not on an antihypertensive drug at baseline. ACEi/ARB-based and TD-based regimens appeared to have the best balance between efficacy and safety.

Abstract 13760: Intensive versus Standard Blood Pressure Control in Patients With Peripheral Artery Disease: The Systolic Blood Pressure Intervention Trial (SPRINT)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Johanna Frary ◽  
Christina Byrne ◽  
Muthiah Vaduganathan ◽  
Tor Biering-srensen ◽  
Michael H Olsen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Peripheral Artery Disease ◽  
Primary Outcome ◽  
Standard Group ◽  
Efficacy And Safety ◽  
Peripheral Artery ◽  
Serious Adverse Events ◽  
Risk Of Death ◽  
Artery Disease

Background: High blood pressure (BP) is the strongest modifiable risk factor for cardiovascular (CV) disease and is highly prevalent among individuals with peripheral artery disease (PAD). Purpose: To assess the efficacy and safety of intensive versus standard BP control in patients with PAD, and to assess if the presence of PAD modified treatment effect. Methods: SPRINT was a randomized, controlled, open-label trial in which individuals aged ≥50 years, at high CV risk, and with a systolic BP 130-180 mmHg were randomized to intensive (systolic BP target <120mmHg) or standard BP control (systolic BP target 135-139 mmHg). The primary outcome was the composite of acute coronary syndromes, stroke, heart failure, or CV death. Safety outcomes included serious adverse events, such as hypotension, syncope, electrolyte abnormalities, acute kidney injury or failure, or injurious falls. We assessed the risk of events in patients with PAD versus those without and assessed the efficacy and safety of intensive BP in patients with PAD. Subgroup heterogeneity was evaluated using interaction analyses. Results: Of 9361 participants, 503 (5.3%) had baseline PAD (intensive group 250 (5.3%) versus standard group 253 (5.4%); P=0.90). Median follow-up duration was 3.2 years (range 0-4.6 years). PAD was independently associated with a higher risk of both the primary outcome (hazard ratio (HR) 1.61, 95% confidence interval (CI): 1.23-2.12; P<0.001) and composite serious adverse events (HR 1.49, 95% CI: 1.32-1.69; P<0.001). The presence of PAD did not modify the efficacy and safety of intensive versus standard BP control (P≥0.05). However, due to the higher baseline risk in PAD patients, the absolute risk reduction of the primary outcome with intensive treatment was larger compared with patients without PAD (1.8% versus 1.6%), as was the risk of death from any cause (2.3% versus 1.1%) (Figure) . Conclusion: Intensive BP control reduced CV events and death in patients with hypertension and PAD.

Abstract P179: The Magnitude, And Not Direction, Of Blood Pressure Change Influences The Risk Of Serious Adverse Events In SPRINT

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Michael Buhnerkempe ◽  
Vivek Prakash ◽  
Albert Botchway ◽  
Oritsegbubemi Adekola ◽  
John M Flack
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Systolic Blood Pressure ◽  
Proportional Hazards ◽  
Pressure Change ◽  
Cox Proportional Hazards ◽  
Intensive Treatment ◽  
Atherosclerotic Cardiovascular Disease ◽  
Serious Adverse Events ◽  
Ascvd Risk

Background: The landmark Systolic Blood Pressure Intervention Trial (SPRINT) showed that more intensive systolic blood pressure treatment (SBP < 120 mm Hg) was associated with lower risk for cardiovascular events and mortality but higher risk for serious adverse events (SAEs). However, it is unclear if the magnitude and/or the direction of the BP change determines SAE risk. In this study, we aim to determine how the magnitude and direction of BP change impacts SAE risk. Methods: This is a secondary analysis of 7922 participants in SPRINT. Time-varying Cox proportional hazards models were used to explore the relationship between visit-to-visit BP change and SAE risk. BP change was categorized using five intervals: 1) decreases ≥30 mm Hg, 2) decreases 10-29 mm Hg, 3) increases or decreases <10 mm Hg (reference category), 4) increases 10-29 mm Hg, and 5) increases ≥30 mm Hg. Additional variables adjusted for in the model included: age, gender, race, estimated glomerular filtration rate, treatment group, and baseline atherosclerotic cardiovascular disease (ASCVD) risk. Hypotension was excluded as an SAE to prevent bias in SAE risk in the large BP decrease category. Results: The hazard ratio (HR) for SAEs compared to the minimal BP change category was greatest for BP increases above 30 mm Hg (HR = 1.62, 95% confidence interval [1.30, 2.01]). However, the HR was similar for sharp BP decreases over 30 mm Hg (HR = 1.52 [1.23, 1.87]). Milder BP increases and decreases were associated with lower SAE risk (HR = 1.18 [1.06, 1.32] and HR = 1.10 [0.98, 1.22] for BP changes 10 to 30 mm Hg and -30 to -10 mm Hg, respectively). There were no significant interactions between BP change, intensive treatment, and baseline ASCVD risk. Conclusions: SAE risk was similar for similarly sized increases and decreases in BP between visits, with higher magnitude changes associated with higher SAE risk. When accounting for the magnitude of BP change, no significant effect of intensive treatment or baseline ASCVD risk was found.

scholarly journals Intensive blood pressure lowering in different age categories: insights from the Systolic Blood Pressure Intervention Trial

2019 ◽  
Vol 6 (6) ◽  
pp. 356-363 ◽  
Author(s):  
Christina Byrne ◽  
Manan Pareek ◽  
Muthiah Vaduganathan ◽  
Tor Biering-Sørensen ◽  
Arman Qamar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Adverse Events ◽  
Systolic Blood Pressure ◽  
Primary Efficacy ◽  
Intervention Trial ◽  
Blood Pressure Lowering ◽  
Serious Adverse Events ◽  
Pressure Lowering ◽  
Intensive Blood Pressure

Abstract Aims The 2018 ESC/ESH guidelines for hypertension recommend differential management of patients who are &lt;65, 65–79, and ≥80 years of age. However, it is unclear whether intensive blood pressure lowering is well-tolerated and modifies risk uniformly across the age spectrum. Methods and results SPRINT randomized 9361 high-risk adults without diabetes and age ≥50 years with systolic blood pressure 130–180 mmHg to either intensive or standard antihypertensive treatment. The primary efficacy endpoint was the composite of acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. The primary safety endpoint was composite serious adverse events. We assessed whether age modified the efficacy and safety of intensive vs. standard blood pressure lowering using Cox proportional-hazards regression and restricted cubic splines. In all, 3805 (41%), 4390 (47%), and 1166 (12%) were &lt;65, 65–79, and ≥80 years. Mean age was similar between the two study groups (intensive group 67.9 ± 9.4 years vs. standard group 67.9 ± 9.5 years; P = 0.94). Median follow-up was 3.3 years. In multivariable models, age was linearly associated with the risk of stroke (P &lt; 0.001) and non-linearly associated with the risk of primary efficacy events, death from cardiovascular causes, death from any cause, heart failure, and serious adverse events (P &lt; 0.001). The safety and efficacy of intensive blood pressure lowering were not modified by age, whether tested continuously or categorically (P &gt; 0.05). Conclusion In SPRINT, the benefits and risks of intensive blood pressure lowering did not differ according to the age categories proposed by the ESC/ESH guidelines for hypertension. Trial Registration SPRINT (Systolic Blood Pressure Intervention Trial); ClinicalTrials.gov Identifier: NCT01206062, https://clinicaltrials.gov/ct2/show/NCT01206062.

scholarly journals MyTEMP: Statistical Analysis Plan of a Registry-Based, Cluster-Randomized Clinical Trial

2021 ◽  
Vol 8 ◽  
pp. 205435812110411
Author(s):  
Stephanie N. Dixon ◽  
Jessica M. Sontrop ◽  
Ahmed Al-Jaishi ◽  
Lauren Killin ◽  
Christopher W. McIntyre ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Primary Outcome ◽  
Intervention Group ◽  
Statistical Analysis Plan ◽  
Control Group ◽  
Trial Period ◽  
Primary Analysis ◽  
Cluster Randomized ◽  
Dialysate Temperature

Background: Major Outcomes with Personalized Dialysate TEMPerature (MyTEMP) is a 4-year cluster-randomized clinical trial comparing the effect of using a personalized, temperature-reduced dialysate protocol versus a dialysate temperature of 36.5°C on cardiovascular-related death and hospitalization. Randomization was performed at the level of the dialysis center (“the cluster”). Objective: The objective is to outline the statistical analysis plan for the MyTEMP trial. Design: MyTEMP is a pragmatic, 2-arm, parallel-group, registry-based, open-label, cluster-randomized trial. Setting: A total of 84 dialysis centers in Ontario, Canada. Patients: Approximately 13 500 patients will have received in-center hemodialysis at the 84 participating dialysis centers during the trial period (April 3, 2017, to March 1, 2021, with a maximum follow-up to March 31, 2021). Methods: Patient identification, baseline characteristics, and study outcomes will be obtained primarily through Ontario administrative health care databases held at ICES. Covariate-constrained randomization was used to allocate the 84 dialysis centers (1:1) to the intervention group or the control group. Centers in the intervention group used a personalized, temperature-reduced dialysate protocol, and centers in the control group used a fixed dialysate temperature of 36.5°C. Outcomes: The primary outcome is a composite of cardiovascular-related death or major cardiovascular-related hospitalization (defined as a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke) recorded in administrative health care databases. The key secondary outcome is the mean drop in intradialytic systolic blood pressure, defined as the patients’ predialysis systolic blood pressure minus their nadir systolic blood pressure during the dialysis treatment. Anonymized data on patients’ predialysis and intradialytic systolic blood pressure were collected at monthly intervals from each dialysis center. Analysis plan: The primary analysis will follow an intent-to-treat approach. The primary outcome will be analyzed at the patient level as the hazard ratio of time-to-first event, estimated from a subdistribution hazards model. Within-center correlation will be accounted for using a robust sandwich estimator. In the primary analysis, patients’ observation time will end if they experience the primary outcome, emigrate from Ontario, or die of a noncardiovascular cause (which will be treated as a competing risk event). The between-group difference in the mean drop in intradialytic systolic blood pressure obtained during the dialysis sessions throughout the trial period will be analyzed at the center level using an unadjusted random-effects linear mixed model. Trial status: The MyTEMP trial period is April 3, 2017, to March 31, 2021. We expect to analyze and report results by 2023 once the updated data are available at ICES. Trial registration: MyTEMP is registered with the US National Institutes of Health at clincaltrials.gov (NCT02628366). Statistical analytic plan: Version 1.1 June 15, 2021.

scholarly journals Quantitative analysis of efficacy and safety of LABA/LAMA fixed-dose combinations in the treatment of stable COPD

2022 ◽  
Vol 16 ◽  
pp. 175346662110660
Author(s):  
Yiwen Gong ◽  
Yinghua Lv ◽  
Hongxia Liu ◽  
Qingshan Zheng ◽  
Lujin Li
Keyword(s):  
Adverse Events ◽  
Rescue Medication ◽  
Primary Outcome ◽  
Medication Use ◽  
Fixed Dose ◽  
Efficacy And Safety ◽  
Copd Exacerbations ◽  
Safety Outcomes ◽  
Secondary Outcomes ◽  
Long Acting

Objective: This study aimed to quantitatively compare the efficacy and safety of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) for the treatment of stable chronic obstructive pulmonary disease (COPD), especially in terms of their loss of efficacy in lung function. Methods: Randomized controlled clinical trials of LABA/LAMA FDCs for the treatment of stable COPD were comprehensively searched for in public databases. Pharmacodynamic models were established to describe the time course of the primary outcome [trough forced expiratory volume in the first second (FEV1)]. Secondary outcomes [COPD exacerbations, St. George’s Respiratory Questionnaire (SGRQ), Transition Dyspnoea Index (TDI), and rescue medication use] and safety outcomes [mortality, serious adverse events (SAEs), and withdrawals due to adverse events (AEs)] were also compared via a meta-analysis. Results: A total of 22 studies involving 16,486 participants were included in this study. The results showed that in terms of primary outcome (change from baseline in trough FEV1), the efficacy of vilanterol/umeclidinium was the highest, while the efficacy of formoterol/aclidinium was the lowest, with a maximum effect value (Emax) of 0.185 L [95% confidence interval (CI): 0.173–0.197 L] and 0.119 L (95% CI: 0.103–0.135 L), respectively. The efficacy of other drugs, such as formoterol/glycopyrronium, indacaterol/glycopyrronium, and olodaterol/tiotropium, were comparable, and their Emax values were 0.150–0.177 L. Except for vilanterol/umeclidinium, the other four LABA/LAMA FDCs showed a certain degree of loss of efficacy. Compared with the efficacy at 2 days, the trough FEV1 (L) relative to baseline at 24 weeks decreased by 0.029–0.041 L. In terms of secondary outcomes, the efficacy of different LABA/LAMA FDCs was similar in TDI and rescue medication use. However, formoterol/aclidinium was better in preventing the COPD exacerbations, while vilanterol/umeclidinium was the best in terms of SGRQ. In addition, different LABA/LAMA FDCs and placebo had similar safety outcomes. Conclusion: The present findings may provide necessary quantitative information for COPD medication guidelines.

Intensive antihypertensive treatment and serious adverse events in older people

2018 ◽  
Vol 56 (12) ◽  
pp. 143-143
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Older People ◽  
Systolic Blood Pressure ◽  
Antihypertensive Treatment ◽  
Intervention Trial ◽  
Serious Adverse Events ◽  
Treatment Of Hypertension

Review of: Sink KM, et al. Syncope, hypotension and falls in the treatment of hypertension: results from the randomized clinical systolic blood pressure intervention trial. J Am Ger Soc 2018;66:679–86.

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