Haitham Ahmed

Cardioprotective anti-hyperglycaemic medications: a review of clinical trials

Despite extensive clinical efforts to achieve stricter glycaemic control over the past few decades, cardiovascular (CV) disease remains the leading cause of death among diabetic patients. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor (GLP-1-R) agonists have gained attention due to their apparent effects in reducing CV mortality. Four CV randomized controlled trials: EMPA-REG, CANVAS, LEADER, and SUSTAIN-6, found a decrease in CV events among patients with type 2 diabetes on empagliflozin, canagliflozin, liraglutide, and semaglutide, respectively. In light of this data, the US Food and Drug Administration has recently approved empagliflozin for CV mortality reduction in type 2 diabetic patients, making it the first diabetes medication approved for such an indication. The purpose of this review is to summarize the results of novel anti-hyperglycaemic medication trials, and shed light on their mode of action and cardioprotective pathways.

Six-Year Changes in Physical Activity and the Risk of Incident Heart Failure: The Atherosclerosis Risk in Communities (ARIC) Study

Background —Higher physical activity (PA) is associated with lower heart failure (HF) risk. However, the impact of changes in PA on HF risk is unknown. Methods —We evaluated 11,351 ARIC participants (mean age 60 years) who attended Visit 3 (1993-95) and did not have a history of cardiovascular disease. Exercise PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines as recommended, intermediate, or poor. We used Cox regression models to characterize the association of 6-year changes in PA between the first (1987-1989) and third ARIC visits and HF risk. Results —During a median of 19 years of follow-up, there were 1,750 HF events. Compared to those with poor activity at both visits, the lowest HF risk was seen for those with persistently recommended activity (HR 0.69; 95% CI: 0.60, 0.80). However, those whose PA increased from poor to recommended also had reduced HF risk (HR 0.77; 95% CI: 0.63, 0.93). Among participants with poor baseline activity, each 1-SD higher PA at 6 years (512.5 METS*minutes/week; corresponding to approximately 30 minutes of brisk walking 4 times per week) was associated with significantly lower future HF risk (HR: 0.89, 95% CI: 0.82, 0.96). Conclusions —While maintaining recommended activity levels is associated with the lowest HF risk, initiating and increasing PA, even in late middle age, are also linked to lower HF risk. Augmenting PA may be an important component of strategies to prevent HF.Background: Higher physical activity (PA) is associated with lower heart failure (HF) risk; however, the effect of changes in PA on HF risk is unknown. Methods: We evaluated 11u2009351 ARIC study (Atherosclerosis Risk in Communities) participants (mean age 60 years) who attended visit 3 (1993–1995) and did not have a history of cardiovascular disease. Exercise PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines as recommended, intermediate, or poor. We used Cox regression models to characterize the association of 6-year changes in PA between the first (1987–1989) and third ARIC visits and HF risk. Results: During a median of 19 years of follow-up, 1750 HF events occurred. Compared with those with poor activity at both visits, the lowest HF risk was seen for those with persistently recommended activity (hazard ratio, 0.69; 95% confidence interval, 0.60–0.80). However, those whose PA increased from poor to recommended also had reduced HF risk (hazard ratio, 0.77; 95% confidence interval 0.63–0.93). Among participants with poor baseline activity, each 1 SD higher PA at 6 years (512.5 METS*minutes/week, corresponding to ≈30 minutes of brisk walking 4 times per week) was associated with significantly lower future HF risk (hazard ratio, 0.89, 95% confidence interval, 0.82–0.96). Conclusions: Although maintaining recommended activity levels is associated with the lowest HF risk, initiating and increasing PA, even in late middle age, are also linked to lower HF risk. Augmenting PA may be an important component of strategies to prevent HF.

A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes

Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception – September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibeu2009+u2009statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55–0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62–0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49–0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83–0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77–0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibeu2009+u2009statin (SUCRA, 50%). Conclusion PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.

Meta-Analysis of Placebo-Controlled Randomized Controlled Trials on the Prevalence of Statin Intolerance

The prevalence of intolerance varies widely. Stopping statin therapy is associated with worse outcomes in patients with cardiovascular disease. Despite extensive studies, the benefits and risks of statins continue to be debated by clinicians and the lay public. We searched the PubMed, Medline, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials of statins compared with placebo. Studies were included if they had ≥1,000 participants, had patients who were followed up for ≥1 year, and reported rates of drug discontinuation. Studies were pooled as per the random effects model. A total of 22 studies (statinsu2009=u200966,024, placebou2009=u200963,656) met the inclusion criteria. The pooled analysis showed that, over a mean follow-up of 4.1 years, the rates of discontinuation were 13.3% (8,872 patients) for statin-treated patients and 13.9% (8,898 patients) for placebo-treated patients. The random effects model showed no significant difference between the placebo and statin arms (odds ratio [OR]u2009=u20090.99, 95% confidence interval [CI]u2009=u20090.93 to 1.06). The results were similar for both primary prevention (ORu2009=u20090.98, 95% CIu2009=u20090.92 to 1.05, pu2009=u20090.39) and secondary prevention (ORu2009=u20090.92, 95% CIu2009=u20090.83 to 1.05, pu2009=u20090.43) studies. The pooled analysis suggested that the rates of myopathy were also similar between the statins and placebos (ORu2009=u20091.2, 95% CIu2009=u20090.88 to 1.62, pu2009=u20090.25). In conclusion, this meta-analysis of >125,000 patients suggests that the rate of drug discontinuation and myopathy does not significantly differ between statin- and placebo-treated patients in randomized controlled trials. These findings are limited by the heterogeneity of results, the variable duration of follow-up, and the lower doses of statins compared with contemporary clinical practice.

Cardiac Rehabilitation: Current Review of the Literature and Its Role in Patients with Heart Failure

Purpose of reviewCardiovascular (CV) disease remains the leading cause of death in the USA despite major advances in its treatment. With time, cardiac rehabilitation (CR) programs have gathered interest to help increase CV health and improve functional status after a CV event. Patients with heart failure have also been shown to benefit. In this review, we will evaluate the current literature showcasing the benefits of CR, particularly in patients with heart failure, discuss current limitations, and avenues for future investigation.Recent findingsStudies have shown that CR is beneficial in reducing morbidity, mortality, hospitalizations, activity-related symptoms, and increasing quality of life. Similar findings have also been observed in patients with heart failure who underwent CR in addition to optimal medical management.SummaryThe positive effects of CR are well established in patients with coronary disease. Recent literature is also showing a trend to benefit in patients with heart failure, though much of the evidence is limited to patients with systolic dysfunction. Despite recommendations by professional societies, the use of CR remains underutilized. Further investigation is needed to better understand the impact of CR in heart failure. Moreover, strategies to increase CR utilization must be explored.

PREDICTORS OF CARDIORESPIRATORY FITNESS IMPROVEMENT IN PHASE II CARDIAC REHABILITATION

Cardiac rehabilitation (CR) improves cardiorespiratory fitness (CRF) and has been shown to reduce cardiovascular events and death. However, data about predictors of fitness improvement during CR are limited and conflicting. The objective of this study was to determine predictors of improvement in metabolic equivalents of task (METs) based on formal exercise testing throughout phase II CR.