myocardial infarction

Therapeutic Use of Cannabis and Cannabinoids: A Review

RPR Commentary: Older patients with no history of CV disease who took a statin had fewer CV events but didn't live longer or have less disability. My conclusion is that statins should be used selectively in older people who are at increased risk of CV events. James W. Mold, MD, MPH

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Abstract
Background
The effectiveness and safety of statins for the primary prevention of cardiovascular events and the extension of disability-free survival among older adults remain uncertain.
Methods
We conducted a double-blind, randomized, placebo-controlled trial at general medical practices across Australia. Community-dwelling adults at least 70 years of age with no history of cardiovascular disease, diabetes, or dementia were randomly assigned in a 1:1 ratio to receive atorvastatin at a dose of 40 mg once daily or identical placebo. The two primary end points were a composite of death from cardiovascular causes, nonfatal myocardial infarction or stroke, or coronary revascularization (to assess effects on major cardiovascular events) and a composite of death from any cause, dementia, or persistent physical disability (to assess effects on disability-free survival). Analyses were performed according to a hierarchical testing plan.
Results
A total of 9971 participants were enrolled: 4984 were assigned to receive atorvastatin and 4987 to receive placebo. The mean (±SD) age of the participants was 74.7±4.5 years, and 51.9% were women. After a median of 5.9 years, a primary cardiovascular event had occurred in 297 participants (10.9 events per 1000 person-years) in the atorvastatin group and in 412 participants (15.5 events per 1000 person-years) in the placebo group (hazard ratio, 0.70; 95% confidence interval [CI], 0.61 to 0.82; P<0.001). Death from any cause, dementia, or persistent physical disability occurred in 637 participants (21.6 events per 1000 person-years) in the atorvastatin group and in 676 participants (23.0 events per 1000 person-years) in the placebo group (hazard ratio, 0.94; 95% CI, 0.84 to 1.05; P=0.25). Serious adverse events occurred in 131 participants (2.7%) in the atorvastatin group and in 129 (2.7%) in the placebo group, with musculoskeletal, hepatobiliary, and diabetes-related adverse events occurring more commonly in the atorvastatin group.
Conclusions
Treatment with atorvastatin led to a lower risk of major cardiovascular events than placebo at a median of 5.9 years but did not result in longer disability-free survival among community-dwelling older adults without clinical cardiovascular disease. (Funded by the National Health and Medical Research Council and others; STAREE ClinicalTrials.gov number, NCT02099123.)

Author/s:

Sophia Zoungas, Rory Wolfe, Chris Moran, Stephen J. Nicholls, Geoffrey C. Cloud, Christopher M. Reid, Andrew M. Tonkin, Lawrence Beilin, Anthony S. Wierzbicki, Trevor T.-J. Chong, Jonathan C. Broder, Andrea J. Curtis, Zachary Flanagan, Ingrid Hopper, Joanne Ryan, Simone Spark, John J. McNeil, Mark R. Nelson

Therapeutic Use of Cannabis and Cannabinoids: A Review

Megan George — Tue, 02 Dec 2025 16:11:48 +0000

Date Added:

December 2, 2025

Journal/Publication:

JAMA

Publication Date:

November 26, 2025

URL:

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1001/jama.2025.19433

Keywords

medical marijuana

cannabis

PMID (1):

41296368

MeSH

acquired immunodeficiency syndrome

Central Nervous System Depressants

united states food and drug administration

sleep initiation and maintenance disorders

Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation

anxiety disorders

A review of the therapeutic uses for cannabinoids. James W. Mold, MD, MPH

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Importance: Approximately 27% of adults in the US and Canada report having ever used cannabis for medical purposes. An estimated 10.5% of the US population reports using cannabidiol (CBD), a chemical compound extracted from cannabis that does not have psychoactive effects, for therapeutic purposes.

Observations: Conditions for which cannabinoids have approval from the US Food and Drug Administration include HIV/AIDS-related anorexia, chemotherapy-induced nausea and vomiting, and certain pediatric seizure disorders. A meta-analysis of randomized clinical trials reported a small but significant reduction in nausea and vomiting from various causes (eg, chemotherapy, cancer) when comparing prescribed cannabinoids (eg, dronabinol, nabilone) with placebo or active comparators (eg, alizapride, chlorpromazine; standardized mean difference [SMD], -0.29 [95% CI, -0.39 to -0.18]). A meta-analysis of randomized clinical trials among patients with HIV/AIDS reported that cannabinoids had a moderate effect on increasing body weight compared with placebo (SMD, 0.57 [95% CI, 0.22 to 0.92]). Evidence-based guidelines do not recommend the use of inhaled or high-potency cannabis (≥10% or 10 mg Δ9-tetrahydrocannabinol [Δ9-THC]) for medical purposes. High-potency cannabis compared with low-potency cannabis use is associated with increased risk of psychotic symptoms (12.4% vs 7.1%) and generalized anxiety disorder (19.1% vs 11.6%). A meta-analysis of observational studies reported that 29% of individuals who used cannabis for medical purposes met criteria for cannabis use disorder. Daily inhaled cannabis use compared with nondaily use was associated with an increased risk of coronary heart disease (2.0% vs 0.9%), myocardial infarction (1.7% vs 1.3%), and stroke (2.6% vs 1.0%). Evidence from randomized clinical trials does not support the use of cannabis or cannabinoids for most conditions for which it is promoted, such as acute pain and insomnia. Before considering cannabis or cannabinoids for medical use, clinicians should consult applicable institutional, state, and national regulations; evaluate for drug-drug interactions; and assess for contraindications (eg, pregnancy) or conditions in which risks likely outweigh benefits (eg, schizophrenia or ischemic heart disease). For patients using cannabis or cannabinoids for treatment of medical conditions, clinicians should discuss harm reduction strategies, including avoiding concurrent use with alcohol or other central nervous system depressants such as benzodiazepines, using the lowest effective dose, and avoiding use when driving or operating machinery.

Conclusions and relevance: Evidence is insufficient for the use of cannabis or cannabinoids for most medical indications. Clear guidance from clinicians is essential to support safe, evidence-based decision-making. Clinicians should weigh benefits against risks when engaging patients in informed discussions about cannabis or cannabinoid use.

Author/s:

Michael Hsu, Arya Shah, Ayana Jordan, Mark S Gold, Kevin P Hill

Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation

Megan George — Tue, 02 Sep 2025 13:36:10 +0000

Date Added:

September 2, 2025

Journal/Publication:

New England Journal of Medicine

Publication Date:

August 30, 2025

URL:

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2507532

Keywords

Chronic Coronary Syndrome

Oral Anticoagulation

aspirin

atherothrombotic risk

stent implantation

PMID (1):

40888725

MeSH

aspirin

Fibrinolytic Agents

follow-up studies

Clinical Trials Data Monitoring Committees

Confidence Intervals

random allocation

Early Invasive or Conservative Strategies for Older Patients With Acute Coronary Syndromes: A Meta-Analysis

In patients with high-risk CAD already on an anticoagulant, the addition of aspirin increases the risk of adverse events. James W. Mold, MD, MPH

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Background: The appropriate antithrombotic regimen for patients with chronic coronary syndrome who are at high atherothrombotic risk and receiving long-term oral anticoagulation remains unknown.

Methods: We conducted a multicenter, double-blind, randomized, placebo-controlled trial in France involving patients with chronic coronary syndrome who had undergone a previous stent implantation (>6 months before enrollment) and were at high atherothrombotic risk and currently receiving long-term oral anticoagulation. The patients were randomly assigned in a 1:1 ratio to receive aspirin (100 mg once daily) or placebo; all the patients continued to receive their current oral anticoagulation therapy. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia. The key safety outcome was major bleeding.

Results: A total of 872 patients underwent randomization; 433 were assigned to the aspirin group, and 439 to the placebo group. The trial was stopped early at the advice of the independent data and safety monitoring board after a median follow-up of 2.2 years because of an excess of deaths from any cause in the aspirin group. A primary efficacy outcome event occurred in 73 patients (16.9%) in the aspirin group and in 53 patients (12.1%) in the placebo group (adjusted hazard ratio, 1.53; 95% confidence interval [CI], 1.07 to 2.18; P = 0.02). Death from any cause occurred in 58 patients (13.4%) in the aspirin group and in 37 (8.4%) in the placebo group (adjusted hazard ratio, 1.72; 95% CI, 1.14 to 2.58; P = 0.01). Major bleeding occurred in 44 patients (10.2%) in the aspirin group and in 15 patients (3.4%) in the placebo group (adjusted hazard ratio, 3.35; 95% CI, 1.87 to 6.00; P<0.001). A total of 467 and 395 serious adverse events were reported in the aspirin group and placebo group, respectively.

Conclusions: Among patients with chronic coronary syndrome at high atherothrombotic risk who were receiving an oral anticoagulant, the addition of aspirin led to a higher risk of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia than placebo, as well as higher risks of death from any cause and major bleeding. (Funded by the French Ministry of Health and Bayer Healthcare; ClinicalTrials.gov number, NCT04217447.).

Author/s:

Gilles Lemesle, M.D., Ph.D., Romain Didier, M.D., Ph.D., Philippe Gabriel Steg, M.D., Tabassome Simon, M.D., Ph.D., Gilles Montalescot, M.D., Ph.D., Nicolas Danchin, M.D., Christophe Bauters, M.D., Ph.D.

Early Invasive or Conservative Strategies for Older Patients With Acute Coronary Syndromes: A Meta-Analysis

Hope Smashey — Tue, 01 Jul 2025 19:20:08 +0000

Date Added:

July 1, 2025

Journal/Publication:

JAMA Intern Medicine

Publication Date:

June 23, 2025

URL:

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamainternmed.2025.2058

Keywords

PMID (1):

40549394

MeSH

acute coronary syndrome

conservative treatment

What Is Atrial Fibrillation?

aged

In patients over the age of 70 who experience a heart attack, it appears that non-intervention is as good as early intervention considering the increased risk of bleeding. James W. Mold, MD, MPH

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Importance: The optimal management strategy for older patients who present with acute coronary syndrome (ACS) remains unclear due to a paucity of randomized evidence. New large and longer-term randomized data are available.

Objective: To test the association of an early invasive strategy vs a conservative strategy with clinical outcomes for patients 70 years or older who present with ACS.

Data sources: A literature search strategy was designed in collaboration with a medical librarian. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched ,with no language restrictions from inception through October 2024. Bibliographies of previous reviews and conference abstracts from major cardiovascular scientific meetings were handsearched.

Study selection: Studies were deemed eligible following review by 2 independent, masked investigators if they randomly allocated patients 70 years or older who presented with ACS to early invasive or conservative management and reported clinical end points. Observational analyses were excluded. No trials were excluded based on sample size or follow-up duration.

Data extraction and synthesis: Data were extracted independently and in triplicate. Clinical end points were pooled in meta-analyses that applied fixed-effects and random-effects modeling to calculate summary estimates for relative risks (RRs) and hazard ratios, along with their corresponding 95% CIs.

Main outcomes and measures: The prespecified primary end point was all-cause death. Secondary end points included recurrent myocardial infarction (MI), repeated coronary revascularization, major bleeding, cardiovascular death, death or MI, stroke, heart failure hospitalization, major adverse cardiac events, major adverse cardiovascular or cerebrovascular events, and length of hospital stay.

Results: The sample size-weighted mean age of participants across included trials was 82.6 years, and 46% were female. In the pooled analysis, there was no significant difference in all-cause death between the invasive and conservative strategies (RR, 1.05; 95% CI, 0.98-1.11; P = .15; I2 = 0%). An early invasive strategy was associated with a reduced risk of recurrent MI of 22% (RR, 0.78; 95% CI, 0.67-0.91; P = .001; I2 = 0%) and repeated coronary revascularization during follow-up of 57% (RR, 0.43; 95% CI, 0.30-0.60; P < .001; I2 = 33.3%). However, an invasive strategy was associated with an increased risk of major bleeding (RR, 1.60; 95% CI, 1.01-2.53; P = .05; I2 = 16.7). No differences were observed in secondary end points. Results in the non-ST-elevation ACS population were consistent with the overall findings.

Conclusions and relevance: The results of this systematic review and meta-analysis suggest that, in older patients with ACS, an early invasive strategy was not associated with reduced all-cause death compared with conservative management. An early invasive strategy was associated with reduced recurrent MI and repeated coronary revascularization during follow-up but increased risk of major bleeding. Competing risks associated with an early invasive strategy should be weighed in shared therapeutic decision-making for older patients with ACS.

Author/s:

Rohin K Reddy, David Koeckerling, Christian Eichhorn, Yasser Jamil, Maddalena Ardissino, Volker Braun, Haitham Abu Sharar, Norbert Frey, James P Howard, Yousif Ahmad

What Is Atrial Fibrillation?

Erin Blanchette — Wed, 30 Apr 2025 21:32:57 +0000

Date Added:

April 30, 2025

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

April 24, 2025

URL:

Type:

Patient Education Materials

Format:

Article

DOI (1):

10.1001/jama.2025.2888

Keywords

atrial fibrillation

Cardiology

Patient Information

jama Patient Information

Rhythm Disorders

PMID (1):

40272794

MeSH

Invasive Versus Conservative Treatment Strategy in Older Patients With Non-ST Segment Elevation Acute Coronary Syndromes: A Meta-Analysis of Randomized Controlled Trials

sleep apnea syndromes

Information for patients about atrial fibrillation. James W. Mold, MD, MPH

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Atrial fibrillation is an abnormal heart rhythm that can cause stroke, heart failure, heart attack, chronic kidney disease, dementia, and death.

Atrial fibrillation is classified as paroxysmal (intermittent episodes lasting 7 days or less), persistent (lasting more than 7 days), long-standing persistent (lasting more than 1 year), or permanent.1

In the US, atrial fibrillation affects about 10.55 million people and is more common among men than women. Other risk factors include older age, smoking, high blood pressure, diabetes, heart disease, high alcohol consumption, sleep apnea, an overactive thyroid gland, and possibly genetic factors.

Author/s:

Rebecca Voelker

Invasive Versus Conservative Treatment Strategy in Older Patients With Non-ST Segment Elevation Acute Coronary Syndromes: A Meta-Analysis of Randomized Controlled Trials

Alex Haga — Mon, 31 Mar 2025 13:51:29 +0000

Date Added:

March 31, 2025

Journal/Publication:

J Am Geriatr Soc .

Publication Date:

March 26, 2025

URL:

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1111/jgs.19447

Keywords

NSTEMI

Conservative treatment

invasive treatment

revascularization

unstable angina pectoris

PMID (1):

40135822

MeSH

acute coronary syndrome

conservative treatment

Aortic valve replacement versus conservative treatment in asymptomatic severe aortic stenosis: long-term follow-up of the AVATAR trial

Revascularization may reduce subsequent MI and invasive procedures but not mortality compared to conservative care in older patients following non-ST elevation MI. James W. Mold, MD, MPH

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Background
Non-ST segment elevation acute coronary syndromes (NSTE-ACS) are a common cause of hospital admission in older patients. Our study aims to synthesize the available evidence from randomized controlled trials (RCTs) to compare clinical outcomes with invasive versus conservative medical management in this population.

Methods
A literature search of online databases including PubMed/MEDLINE, Embase, and the Cochrane Library was conducted from inception to September 1, 2024. The search aimed to identify RCTs that reported clinical outcomes with invasive versus conservative strategies in older patients (≥ 70 years) with NSTE-ACS. The risk ratios (RRs) were used as summary estimates.

Results
Seven RCTs with 2998 patients were included; 1490 patients in the invasive group and 1508 patients in the conservatively managed group. The pooled analysis demonstrated no statistically significant difference between the two strategies for the risk of all-cause death (RR: 1.03, 95% CI: 0.92–1.15), cardiovascular death (RR: 1.04, 95% CI: 0.82–1.33), stroke (RR: 0.78, 95% CI: 0.53–1.15), and major bleeding (RR: 1.23, 95% CI: 0.90–1.69). However, the invasive strategy was associated with a significantly reduced risk of myocardial infarction (RR: 0.74, 95% CI: 0.57–0.96) and unplanned revascularization (RR: 0.29, 95% CI: 0.21–0.40) compared to the conservative strategy.

Conclusion
In older patients with NSTE-ACS, an invasive strategy reduces the risk of repeat myocardial infarction and unplanned revascularization without a significant increase in stroke or major bleeding. There was no associated reduction in all-cause or cardiovascular mortality with the invasive strategy compared to conservative management.

Author/s:

Mushood Ahmed, Areeba Ahsan, Aimen Shafiq, Tallal Mushtaq Hashmi

Aortic valve replacement versus conservative treatment in asymptomatic severe aortic stenosis: long-term follow-up of the AVATAR trial

Alex Haga — Tue, 08 Oct 2024 17:36:11 +0000

Date Added:

October 8, 2024

Journal/Publication:

European Heart Journal

Publication Date:

September 1, 2024

URL:

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1093/eurheartj/ehae585

Keywords

PMID (1):

39217448

MeSH

Aortic Valve

Stroke Volume

Kaplan-Meier Estimate

Avatar

Aortic Valve Stenosis

Hydroxychloroquine and Cardiovascular Events in Patients With Systemic Lupus Erythematosus

Contrary to prior recommendations, it looks like surgical repair of severely stenotic aortic valves produces better results when done early. James W. Mold, MD, MPH

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Background and aims: The question of when and how to treat truly asymptomatic patients with severe aortic stenosis (AS) and normal left ventricular (LV) systolic function is still subject to debate and ongoing research. Here, the results of extended follow-up of the AVATAR trial are reported (NCT02436655, clinical trials.gov).

Methods: The AVATAR trial randomly assigned patients with severe, asymptomatic AS and LV ejection fraction ≥50% to undergo either early surgical aortic valve replacement (AVR) or conservative treatment with watchful waiting strategy. All patients had negative exercise stress testing. The primary hypothesis was that early AVR will reduce a primary composite endpoint comprising all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure (HF), as compared to conservative treatment strategy.

Results: A total of 157 low-risk patients (mean age 67 years, 57% men, mean Society of Thoracic Surgeons score 1.7%) were randomly allocated to either early AVR group (n=78) or conservative treatment group (n=79). In an intention-to-treat analysis, after a median follow-up of 63 months, the primary composite endpoint outcome event occurred in 18/78 patients (23.1%) in the early surgery group and in 37/79 patients (46.8%) in the conservative treatment group (hazard ratio [HR] early surgery vs. conservative treatment 0.42; 95% confidence interval [CI] 0.24-0.73, p=0.002). The Kaplan-Meier estimates for individual endpoints of all-cause death and HF hospitalization were significantly lower in the early surgery compared with the conservative group (HR 0.44; 95% CI 0.23-0.85, p=0.012 for all-cause death, and HR 0.21; 95% CI 0.06-0.73, p=0.007 for HF hospitalizations).

Conclusions: The extended follow-up of the AVATAR trial demonstrates better clinical outcomes with early surgical AVR in truly asymptomatic patients with severe AS and normal LV ejection fraction compared with patients treated with conservative management on watchful waiting.

Author/s:

Marko Banovic, Svetozar Putnik, Bruno R Da Costa, Martin Penicka, Marek A Deja, Martin Kotrc

Hydroxychloroquine and Cardiovascular Events in Patients With Systemic Lupus Erythematosus

Alex Haga — Mon, 09 Sep 2024 23:19:03 +0000

Date Added:

September 9, 2024

Journal/Publication:

JAMA Network Open

Publication Date:

August 1, 2024

URL:

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2024.32190

Keywords

hydroxychloroquine

cardiovascular

systemic lupus erythematosis

lupus

PMID (1):

39212983

MeSH

Antirheumatic Agents* / therapeutic use

Cardiovascular Diseases* / epidemiology

Hydroxychloroquine* / therapeutic use

Lupus Erythematosus

Systemic* / drug therapy

Thromboembolism / epidemiology

Stroke / epidemiology

Hydroxychloroquine reduces the risk of cardiovascular events in patient with systemic lupus erythematosis. Prior research has suggested that it also increases their life expectancies. James W. Mold, MD, MPH

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Importance: Systemic lupus erythematosus (SLE) predisposes individuals to early cardiovascular (CV) events. While hydroxychloroquine is thought to mitigate CV risk factors, its protective role against CV events, particularly arterial ones, remains to be confirmed.

Objective: To evaluate the association between hydroxychloroquine and the risk of myocardial infarction (MI), stroke, and other thromboembolic events (OTEs) in patients with SLE.

Design, setting, and participants: This cohort study using a nested case-control design was conducted within the National French Healthcare Database (SNDS), which represents 99% of the French population, from 2010 to 2020. Participants were the cohort of all patients with SLE recorded in the SNDS. Patients with SLE experiencing CV events during the study period were the case group; those without CV events were controls. The analysis period was from February 2022 to September 2023.

Exposures: Hydroxychloroquine use within 365 days prior to the index date, defined as current (within 90 days), remote (91-365 days), or no exposure within the previous 365 days.

Main outcomes and measures: Outcomes of interest were MI, stroke, and OTE, analyzed individually and as a composite outcome (primary analysis). Controls were matched to patients with CV events by age, sex, time since SLE onset and entry into the SNDS database, index date, prior antithrombotic and CV medication, chronic kidney disease, and hospitalization. Multivariable conditional logistic regression was performed using hydroxychloroquine exposure as the main independent variable.

Results: The SLE cohort included 52 883 patients (mean [SD] age, 44.23 [16.09] years; 45 255 [86.6%] female; mean [SD] follow-up, 9.01 [2.51] years), including 1981 patients with eligible CV events and 16 892 matched control patients. There were 669 MI events, 916 stroke events, and 696 OTEs in the individual outcome studies. For current exposure to hydroxychloroquine, the adjusted odds were lower for composite CV events (odds ratio [OR], 0.63; 95% CI, 0.57-0.69) as well as for MI (OR, 0.72; 95% CI, 0.60-0.85), stroke (OR, 0.69; 95% CI, 0.60-0.81), and OTEs (OR, 0.58; 95% CI, 0.49-0.69) individually compared with no hydroxychloroquine exposure within 365 days.

Conclusions and relevance: In this nationwide cohort study of patients with SLE, a protective association was found between the current use of hydroxychloroquine and the occurrence of CV events, but not between remote use of hydroxychloroquine and CV outcomes, highlighting the value of continuous hydroxychloroquine treatment in patients with SLE.

Author/s:

Lamiae Grimaldi, Tom Duchemin, Yann Hamon, Albert Buchard, Jacques Benichou

Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment

Rowan Hutchins — Sat, 06 May 2023 05:00:00 +0000

Date Added:

May 6, 2023

Journal/Publication:

JAMA Intern Med

Publisher:

JAMA

Publication Date:

March 14, 2022

Issue:

Volume:

182

URL:

Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamainternmed.2022.0134

Keywords

adult

cholesterol

stroke prevention

PMID (1):

35285850

MeSH

Cardiovascular Disease

cholesterol, LDL

Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use

Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial

The modest reduction in all-cause mortality affected by statins is largely independent of the amount of LDL cholesterol reduction suggesting a somewhat lipid independent anti-inflammatory effect. Two caveats: 1)The 0.8% absolute risk reduction is per around 3 years, so longer term treatment will have more impact; 2) absolute risk reduction is directly proportional to baseline risk, so higher risk individuals will benefit more. James W. Mold, MD, MPH.

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Importance The association between statin-induced reduction in low-density lipoprotein cholesterol (LDL-C) levels and the absolute risk reduction of individual, rather than composite, outcomes, such as all-cause mortality, myocardial infarction, or stroke, is unclear.

Objective To assess the association between absolute reductions in LDL-C levels with treatment with statin therapy and all-cause mortality, myocardial infarction, and stroke to facilitate shared decision-making between clinicians and patients and inform clinical guidelines and policy.

Data Sources PubMed and Embase were searched to identify eligible trials from January 1987 to June 2021.

Study Selection Large randomized clinical trials that examined the effectiveness of statins in reducing total mortality and cardiovascular outcomes with a planned duration of 2 or more years and that reported absolute changes in LDL-C levels. Interventions were treatment with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) vs placebo or usual care. Participants were men and women older than 18 years.

Data Extraction and Synthesis Three independent reviewers extracted data and/or assessed the methodological quality and certainty of the evidence using the risk of bias 2 tool and Grading of Recommendations, Assessment, Development and Evaluation. Any differences in opinion were resolved by consensus. Meta-analyses and a meta-regression were undertaken.

Main Outcomes and Measures Primary outcome: all-cause mortality. Secondary outcomes: myocardial infarction, stroke.

Findings Twenty-one trials were included in the analysis. Meta-analyses showed reductions in the absolute risk of 0.8% (95% CI, 0.4%-1.2%) for all-cause mortality, 1.3% (95% CI, 0.9%-1.7%) for myocardial infarction, and 0.4% (95% CI, 0.2%-0.6%) for stroke in those randomized to treatment with statins, with associated relative risk reductions of 9% (95% CI, 5%-14%), 29% (95% CI, 22%-34%), and 14% (95% CI, 5%-22%) respectively. A meta-regression exploring the potential mediating association of the magnitude of statin-induced LDL-C reduction with outcomes was inconclusive.

Conclusions and Relevance The results of this meta-analysis suggest that the absolute risk reductions of treatment with statins in terms of all-cause mortality, myocardial infarction, and stroke are modest compared with the relative risk reductions, and the presence of significant heterogeneity reduces the certainty of the evidence. A conclusive association between absolute reductions in LDL-C levels and individual clinical outcomes was not established, and these findings underscore the importance of discussing absolute risk reductions when making informed clinical decisions with individual patients.

Author/s:

Byrne, P., Demasi, M., Jones, M.

Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial

Aubrey Delammermore — Sat, 22 Oct 2022 05:00:00 +0000

Date Added:

October 22, 2022

Journal/Publication:

The Lancet

Publisher:

Elsevier

Publication Date:

October 11, 2022

Issue:

10361

Volume:

400

Pages:

1417-1425

URL:

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1016/S0140-6736(22)01786-X

Keywords

Intention to Treat Analysis

Antihypertensive Agents

Cardiovascular Diseases

Surveys and Questionnaires

United Kingdom

PMID (1):

36240838

MeSH

antihypertensive agents

Time and Motion Studies

Final Report of a Trial of Intensive versus Standard Blood-Pressure Control

In this large RCT, evening dosing of antihypertensive drugs was no better than morning dosing in regard to cardiovascular outcomes. James W. Mold, MD, MPH

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Background: Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening (TIME) study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension.

Methods: The TIME study is a prospective, pragmatic, decentralised, parallel-group study in the UK, that recruited adults (aged ≥18 years) with hypertension and taking at least one antihypertensive medication. Eligible participants were randomly assigned (1:1), without restriction, stratification, or minimisation, to take all of their usual antihypertensive medications in either the morning (0600-1000 h) or in the evening (2000-0000 h). Participants were followed up for the composite primary endpoint of vascular death or hospitalisation for non-fatal myocardial infarction or non-fatal stroke. Endpoints were identified by participant report or record linkage to National Health Service datasets and were adjudicated by a committee masked to treatment allocation. The primary endpoint was assessed as the time to first occurrence of an event in the intention-to-treat population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants who submitted at least one follow-up questionnaire. The study is registered with EudraCT (2011-001968-21) and ISRCTN (18157641), and is now complete.

Findings: Between Dec 17, 2011, and June 5, 2018, 24 610 individuals were screened and 21 104 were randomly assigned to evening (n=10 503) or morning (n=10 601) dosing groups. Mean age at study entry was 65·1 years (SD 9·3); 12 136 (57·5%) participants were men; 8968 (42·5%) were women; 19 101 (90·5%) were White; 98 (0·5%) were Black, African, Caribbean, or Black British (ethnicity was not reported by 1637 [7·8%] participants); and 2725 (13·0%) had a previous cardiovascular disease. By the end of study follow-up (March 31, 2021), median follow-up was 5·2 years (IQR 4·9-5·7), and 529 (5·0%) of 10 503 participants assigned to evening treatment and 318 (3·0%) of 10 601 assigned to morning treatment had withdrawn from all follow-up. A primary endpoint event occurred in 362 (3·4%) participants assigned to evening treatment (0·69 events [95% CI 0·62-0·76] per 100 patient-years) and 390 (3·7%) assigned to morning treatment (0·72 events [95% CI 0·65-0·79] per 100 patient-years; unadjusted hazard ratio 0·95 [95% CI 0·83-1·10]; p=0·53). No safety concerns were identified.

Interpretation: Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimises any undesirable effects.

Funding: British Heart Foundation.

Author/s:

Mackenzie, I. S., Rogers, A., Poulter, N. R., Williams, B., Brown, M. J., Webb, D. J., Ford, I., Rorie, D. A., Guthrie, G., Grieve, J. W. K., Pigazzani, F., Rothwell, P. M., Young, R., McConnachie, A., Struthers, A. D., Lang, C. C., MacDonald, T. M.

Final Report of a Trial of Intensive versus Standard Blood-Pressure Control

Saige Blanchard — Fri, 21 May 2021 05:00:00 +0000

Date Added:

May 21, 2021

Journal/Publication:

New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

May 20, 2021

Issue:

Volume:

384

Pages:

1921-1930

URL:

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa1901281

Keywords

PMID (1):

34010531

MeSH

blood-pressure

cardiovascular diseases

acute coronary syndrome

hypotension

Screening for Hypertension in Adults

In patients at high risk for cardiovascular events, intensive BP control (target <120 systolic) reduced the rate of adverse CV events (CAD events, CVA, CHF, or death) by 0.63% per year. Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. James W. Mold, MD, MPH

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Background: In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected.

Methods: We randomly assigned 9361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analyzed post-trial observational follow-up data through July 29, 2016.

Results: At a median of 3.33 years of follow-up, the rate of the primary outcome and all-cause mortality during the trial were significantly lower in the intensive-treatment group than in the standard-treatment group (rate of the primary outcome, 1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; all-cause mortality, 1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92). Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. When trial and post-trial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and adverse events; however, rates of heart failure no longer differed between the groups.

Conclusions: Among patients who were at increased cardiovascular risk, targeting a systolic blood pressure of less than 120 mm Hg resulted in lower rates of major adverse cardiovascular events and lower all-cause mortality than targeting a systolic blood pressure of less than 140 mm Hg, both during receipt of the randomly assigned therapy and after the trial. Rates of some adverse events were higher in the intensive-treatment group. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062.).

Author/s:

Lewis, C. E., Fine, L. J., Beddhu, S., Cheung, A. K., Cushman, W. C., Cutler, J. A., Evans, G. W., Johnson, K. C., Kitzman, D. W., Oparil, S., Rahman, M., Reboussin, D. M., Rocco, M. V., Sink, K, M., Snyder, J. K., Whelton, P. K., Williamson, J. D., Wright Jr., J. T., Ambrosius, W. T.

Screening for Hypertension in Adults

Saige Blanchard — Wed, 05 May 2021 05:00:00 +0000

Date Added:

May 5, 2021

Journal/Publication:

Journal of the American Medical Association

Publisher:

U.S. Preventative Services Task Force

Publication Date:

April 27, 2021

Issue:

Volume:

325

Pages:

1650-1656

URL:

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Web Page

DOI (1):

10.1001/jama.2021.4987

Keywords

chronic kidney disease

MeSH

blood pressure

Mass Screening

Colchicine in Patients with Chronic Coronary Disease

No surprise that the USPSTF recommends in-office screening for hypertension. What seems interesting is that they suggest getting confirmatory readings from outside the office before making the diagnosis. James W. Mold, MD, MPH

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IMPORTANCE Hypertension is a prevalent condition that affects approximately 45% of the adult US population and is the most commonly diagnosed condition at outpatient office visits. Hypertension is a major contributing risk factor for heart failure, myocardial infarction, stroke, and chronic kidney disease. OBJECTIVE To reaffirm its 2015 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for hypertension in adults, the accuracy of office blood pressure measurement for initial screening, and the accuracy of various confirmatory blood pressure measurement methods. POPULATION Adults 18 years or older without known hypertension. EVIDENCE ASSESSMENT Using a reaffirmation deliberation process, the USPSTF concludes with high certainty that screening for hypertension in adults has substantial net benefit. RECOMMENDATION The USPSTF recommends screening for hypertension in adults 18 years or older with office blood pressure measurement. The USPSTF recommends obtaining blood pressure measurements outside of the clinical setting for diagnostic confirmation before starting treatment. (A recommendation)

Author/s:

U.S. Preventative Services Task Force

Colchicine in Patients with Chronic Coronary Disease

Brian Desmarais — Sat, 07 Nov 2020 22:20:46 +0000

Date Added:

November 7, 2020

Journal/Publication:

New England Journal of Medicine

Publication Date:

November 5, 2020

URL:

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2021372

MeSH

Heart Diseases

Myocardial Ischemia

Aspirin for Primary Atherosclerotic Cardiovascular Disease Prevention as Baseline Risk Increases: A Meta-Regression Analysis

In this RCT involving patients with chronic coronary artery disease, 0.5mg of colchicine daily reduce the risk of a composite endpoint of cardiovascular death, myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. James W. Mold, MD, MPH

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Abstract

Background: Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited.

Methods: In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke.

Results: A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31).

Conclusions: In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).

Author/s:

LoDoCo2 Trial Investigators

Aspirin for Primary Atherosclerotic Cardiovascular Disease Prevention as Baseline Risk Increases: A Meta-Regression Analysis

John Bayhi — Thu, 21 May 2020 16:39:36 +0000

Date Added:

May 21, 2020

Journal/Publication:

The American Journal of Medicine

Publisher:

Elsevier Inc

Publication Date:

May 20, 2020

Volume:

Article in Press

URL:

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1016/j.amjmed.2020.04.028

Keywords

aspirin

primary prevention

Atherosclerotic Cardiovascular Disease

MeSH

cardiovascular diseases

Brain Ischemia

follow-up studies

Initial Invasive or Conservative Strategy for Stable Coronary Disease

This analysis of 12 RCTs involving almost 1 million patients found that low-dose aspirin prevents major cardiovascular events (RRReduction 14%; ARR/1000 patient years 0.06%) but increases major bleeding events (RRIncrease 40%; ARR/1000 patient years 0.1%) across all levels of baseline risk. The researchers concluded that the absolute risk reduction and the risk: benefit ratio suggest that we should probably not prescribe low-dose aspirin for primary prevention even if the baseline risk of CV events is high and the risk of bleeding is low. James W. Mold, MD, MPH

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Background

Aspirin is often prescribed for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) however, recent randomized trials (RCTs) have challenged this practice. Despite this, aspirin is commonly recommended for high risk primary prevention. We tested the hypothesis that aspirin is more efficacious for the primary prevention of ASCVD, as the baseline risk increases.

Methods

RCTs that compared aspirin to control for primary prevention and evaluated ASCVD (composite of myocardial infarction and ischemic stroke) and major bleeding were included. Rate ratios (RR) and 95% confidence intervals (CI) were calculated. A regression analysis was performed using the ASCVD event rate in the control arm of each RCT as the moderator.

Results

Twelve RCTs were identified with 963,829 patient years of follow-up. Aspirin was associated with a reduction in ASCVD (4.7 versus 5.3 events per 1,000 patient years; RR 0.86; 95% CI 0.79-0.92). There was increased major bleeding among aspirin users (2.5 versus 1.8 events per 1000 patient years, RR 1.41 95% CI, 1.29-1.54). Regression analysis found no relationship between the log rate ratio of ASCVD or major bleeding and incidence of ASCVD in the control arm of each RCT.

Conclusion

Aspirin is associated with a reduction in ASCVD when used for primary prevention; however, it is unlikely to be clinically significant given the increase in bleeding. More importantly, aspirin's treatment effect does not increase as ASCVD risk increases as many hypothesize. There is no suggestion from this data that use of aspirin for higher risk primary prevention patients is beneficial.

Author/s:

Nudy, M, Cooper, J, Ghahramani, M, Ruzieh, M, Mandrola, J, Foy, AJ

Initial Invasive or Conservative Strategy for Stable Coronary Disease

John Bayhi — Thu, 02 Apr 2020 18:30:58 +0000

Date Added:

April 2, 2020

Journal/Publication:

The New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

March 30, 2020

Issue:

Online ahead of print

URL:

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/nejmoa1915922

Keywords

cardiac ischemia

cardiac interventions

PMID (1):

32227755

MeSH