Updates 30 May 2016

Late development of left ventricular hypertrophy in familial hypertrophic cardiomyopathy
Adults who test positive for a mutation associated with the development of hypertrophic cardiomyopathy (HCM) but who have not manifested left ventricular hypertrophy (LVH) at the time of that diagnosis are now commonly identified in the era of genetic testing. The subsequent clinical course of these individuals has been unclear.

A study by McTaggart and colleagues, published in Heart Lung and Circulation, documents the late development of overt hypertrophy during adult life in three such individuals, harbouring mutations in the MTBPC3 gene. Each of these individuals was identified as having the mutation without hypertrophy in adult life. During follow up to 18 years, they developed abnormal ventricular hypertrophy. These findings highlight the need for ongoing surveillance of all individuals with a known HCM mutation, as well as those at risk in whom mutation status is unknown.

See: https://member.heartone.com.au/learning/resource/detail/1901

Utility of the DAPT score for determining antiplatelet therapy after coronary stenting
Patients with a history of myocardial infarction (MI) or presenting with acute coronary syndrome (ACS) have higher rates of recurrent ischemia following percutaneous coronary intervention (PCI) than those presenting with stable angina. Use of dual antiplatelet therapy beyond one year reduces later recurrent events, however risk of bleeding is also increased. The DAPT score is a decision tool, developed to determine, among patients eligible for long-term dual antiplatelet therapy, those more likely to derive benefit (vs. harm) from long-term therapy.

The recent study by Keriakes et al investigated whether the decision tool (DAPT score) aids prescription of dual antiplatelet therapy duration in patients with or without prior myocardial infarction (MI) treated with coronary stents. Rates of MI were 3.8% versus 2.4% (p = 0.01) for patients with any MI versus no MI. Continued thienopyridine reduced late MI compared with placebo regardless of MI history (hazard ratio [HR] for any MI: 0.46; p < 0.001; HR for no MI: 0.60; p = 0.003) and increased bleeding (HR: 1.86, p = 0.01 any MI; HR: 1.58, p = 0.01 no MI). DAPT scores ≥2 were associated with reductions in MI/stent thrombosis with continued thienopyridine compared with placebo (2.7% vs. 6.0%, p < 0.001 any MI; 2.6% vs. 5.2%, p = 0.002 no MI), with comparable bleeding rates. Among patients with DAPT scores ≤2 in both groups, continued thienopyridine was associated with significantly increased bleeding but similar rates of ischemia.

The authors conclude that the DAPT score improves prediction of patient benefit and harm from continued dual antiplatelet therapy beyond assessment of MI history alone.

See: https://member.heartone.com.au/learning/resource/detail/1902

Blood-pressure lowering does not affect outcomes for individuals at intermediate risk without cardiovascular disease
High blood pressure is the leading risk factor for cardiovascular disease globally. Observational studies in persons without cardiovascular disease show a graded increase in risk at systolic blood-pressure levels >115 mm Hg. It has been suggested that lowering blood pressure at any level above this value will reduce the risk of cardiovascular events.

This study, from the HOPE-3 investigators, examined the benefit or otherwise of treatment with candesartan 16 mg daily plus hydrochlorothiazide on cardiovascular outcomes in 12,705 participants at intermediate risk (annual risk adverse event 1%) during a 5.6 years follow-up.

The mean decreases in systolic blood pressure from baseline during the trial were 10.0±13.1 mm Hg in the active-treatment group and 4.0±12.9 mm Hg in the placebo group and the average difference between the groups was 6.0±13.0 mm Hg.

The two coprimary outcomes were a composite of cardiovascular death, nonfatal MI, or nonfatal stroke and the composite of these events plus resuscitated cardiac arrest, heart failure, or revascularization. There were two secondary outcomes: the composite of events comprising the second coprimary outcome plus angina with evidence of ischemia, and for the comparison of blood-pressure lowering, fatal or nonfatal stroke.

There were no significant differences between the active-treatment group and the placebo group in the incidence of the first coprimary outcome or the second coprimary outcome nor in the incidence of the secondary outcomes and the components of the coprimary outcomes, in total mortality, in the incidence of new-onset diabetes, or in the post hoc outcome of total cardiovascular events.

The authors conclude that their findings contradict the “lower is better” hypothesis that has been derived from epidemiologic studies, and the findings support the concept that a J-curve phenomenon exists for major cardiovascular events, other than for stroke, in this population. They further concluded that the data are compatible with the hypothesis that treating persons without cardiovascular disease who have a systolic blood pressure > 140 mm Hg appears to be beneficial, but treatment would not be of benefit and may be even harmful in persons with lower systolic blood-pressure levels.

See: http://www.nejm.org/doi/full/10.1056/NEJMoa1600175

Cholesterol lowering does affect outcomes for individuals at intermediate risk without cardiovascular disease
This report from the HOPE-3 investigators describes the benefit of treatment with rosuvastatin 10 mg daily for individuals with intermediate risk of cardiovascular events (estimated adverse event rate 1% per annum) who do not have known cardiovascular disease.

The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years.

The LDL cholesterol level was 1.02 mmol per liter lower in the rosuvastatin group than in the placebo group at 1 year; 0.90 mmol per liter lower at 3 years; and 0.76 mmol per liter lower at the end of the trial (overall mean difference = 0.90 mmol per liter or 26.5%; P<0.001).

The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P=0.002; number needed to treat with rosuvastatin to prevent one coprimary outcome event=91). The second coprimary outcome occurred in 277 participants (4.4%) in the rosuvastatin group and in 363 participants (5.7%) in the placebo group (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001; number need to treat=73).

The authors concluded that cholesterol lowering with the use of a low dose of rosuvastatin in a population of persons, who did not have cardiovascular disease and who were at intermediate risk, was associated with a significant reduction in the risk of cardiovascular events.

See: http://www.nejm.org/doi/full/10.1056/NEJMoa1600176

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