A recent trial by Dr. Salim Yusuf, published in The New England Journal of Medicine, indicated that combination therapy with aspirin plus a polypill (consisting of a statin plus three blood-pressure-lowering drugs) can reduce the incidence of cardiovascular events compared with placebo among participants without established cardiovascular disease, but at moderate cardiovascular risk.

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A recent meta-analysis of clinical trials with more than 100,000 patients has shown that the carotid intima-media thickness (cIMT) progression can be used as a surrogate marker for cardiovascular risk in the clinical trials. The results of this study published in Circulation. According to Dr. Willeit, the assessment of cIMT progression can provide a link for the development and license of new therapies for cardiovascular disease. Continue reading →

Hypertrophic cardiomyopathy (HCM) is the most common inherited genetic disorder of the myocardium, and the number one culprit of sudden cardiac death in athletes, particularly African Americans.

“Is race associated with differential disease expression, inequitable care provision, or disparate clinical outcomes among patients with hypertrophic cardiomyopathy?”

In order to answer the above question, Lauren A. Eberly, et al. studied 2,467 patients with hypertrophic cardiomyopathy. In a retrospective cohort study, black and white patients with hypertrophic cardiomyopathy from the US-based sites of the Sarcomeric Human Cardiomyopathy Registry from 1989 through 2018 compared in terms of baseline characteristics; genetic architecture; adverse outcomes such as cardiac arrest, cardiac transplantation or left ventricular assist device implantation, cardioverter-defibrillator implantation, all-cause mortality, atrial fibrillation, stroke,  prevalence and likelihood of developing heart failure; and receiving septal reduction therapies.

According to the results of this study (8.3 percent black; 91.7 percent white), published in the JAMA CARDIOLOGY (December 2019), compared with white patients, black patients with HCM were younger (mean age, 36.5 versus 41.9 years), were less likely to have sarcomere mutations (26.1 versus 40.5 percent), had a higher prevalence of New York Heart Association (NYHA) class III or IV heart failure at presentation (22.6 versus 15.8 percent) and were more prone to developing heart failure (hazard ratio, 1.45). Lower rates of genetic testing (26.1 versus 40.5 percent) have been observed in black patients. Although there were no racial differences in implantation of implantable cardioverter-defibrillators, the invasive septal reduction was less common among African Americans (14.6 versus 23 percent). Nevertheless, Black patients had fewer incidents of atrial fibrillation (35 [17.1 percent] versus 608 [26.9 percent].

The results of this study were in accordance with the previous studies that mentioned a higher prevalence of complicated hypertrophic cardiomyopathy in African Americans in contrast to the lower prevalence of HCM in this community.  Eberly, et al. believe that racial differences in disease expression and adverse clinical outcomes are not only because of different characteristics of the disease in African Americans but also inequities in clinical care provision might be responsible for these observed differences.

A randomized parallel-group trial comparing intensive LDL-C lowering to modest lowering for prevention of major adverse cardiovascular events (MACE) in patients with recent ischemic stroke in the setting of atherosclerosis has shown that an aggressive LDL-C reduction strategy with a goal of < 70mg/dl is superior to modest reduction approach which targets a range of 90-110 mg/dl.

Results of the Treat Stroke to Target Trial (TST trial) which enrolled 2860 patients (32% females) with a median follow-up of 3.5 years were presented by Dr. Amarenco (Department of Neurology and Stroke Center, Bichat Hospital, France) at AHA 2019 and simultaneously published in The New England Journal of Medicine.

Patients with established atherosclerotic cardiovascular disease (ASCVD) and ischemic stroke within the past 3 months or transient ischemic stroke (TIA) within the past 15 days (modified Rankin score of 0-3) were randomized in 1:1 fashion to statin therapy with either a goal LDL-C of < 70 mg/dl (n =1430) or 90-110 mg/dl (n = 1430).

The primary efficacy endpoint of the trial was composite of MACE (nonfatal cerebral infarction or stroke of undetermined origin, nonfatal myocardial infarction, hospitalization for unstable angina followed by urgent coronary-artery revascularization, TIA treated with urgent carotid revascularization, or CV death). The primary outcome occurred in 8.5% of patients assigned to the group with intensive LDL lowering compared to 10.9% of patients in the modest control approach (adjusted hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.04). Mean LDL-C levels at baseline were 135 mg/dl for both groups and at 3.5 years for the intensive vs. modest treatment groups were 65 vs. 96 mg/dl (p < 0.05). Secondary outcomes were occurrence of MI, need for urgent revascularization, all-cause mortality, intracranial hemorrhage, and newly diagnosed diabetes mellitus. Rates of intracranial hemorrhage (1.3% vs. 0.9% [p > 0.05]) and new-onset diabetes mellitus (7.2% vs. 5.7% [p > 0.05]) were numerically higher with more aggressive control, but not statistically significant.

The present study highlights the clinical benefit obtained by a tighter control of plasma LDL levels for secondary prevention of stroke. Previously, the SPARCL trial showed that in patients who have had a stroke within the prior one to six months without coronary artery disease, treatment with 80 mg atorvastatin led to a lower incidence of recurrent MACE including fatal and nonfatal strokes. In the Heart Protection Study (HPS), simvastatin 40mg did not show benefit in secondary stroke protection, but in HPS, patients were enrolled after a mean of 4.3 years of having a cerebrovascular accident, whereas the greatest risk for recurrent strokes resides within the first year of suffering from a cerebrovascular accident.  Though findings from the current TST trial are in line with the SPARCL trial in terms of reduction of recurrent MACE, the SPARCL trial saw an increase in the incidence of hemorrhagic strokes in the treatment arm, while the present TST clinical trial revealed no rise in hemorrhagic stroke rates in patients despite achieving more aggressive reductions in their serum LDL-C levels.

The authors ask the readers to interpret the results of the TST trial while considering the fact that the study was stopped prematurely due to insufficient funding at 3.5 years and did not reach the goal of 385 events, instead, 277 primary events were recorded for the analysis. In addition, secondary endpoints could not be tested due to the failure of hierarchical clustering of endpoints.