Μελέτη HOPE-3: ελπίδα η «στατινοποίηση» του πλανήτη;

[Argirios Argiriou]

14-04-2016
του Καρδιολόγου Χρήστου Ντέλλου.

Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

[Ορθοπαιδικός]

   Ήδη δημοσιεύματα και αναλύσεις για την Hope εμφανίστηκαν την προηγούμενη εβδομάδα. Αναρωτιόμουν αν έπρεπε να αρχίσω τις στατίνες...

[GirousisN]

Θα μας τρελάνουν εντελώς !! Η μελέτη δείχνει στο συμπληρωματικό παράρτημα που παρατίθεται ( πίνακες S9,S10 )ότι η ροσουβαστατίνη μόνη της ,είναι ανώτερη από τον συνδυασμό της με καντεσαρτάνη + HCTZ στην πρόληψη καρδιαγγειακών συμβαμάτων  . Κοινώς τα αντιυπερτασικά φάρμακα και η μείωση της ΑΠ να οδηγηθούν στον κάλαθο των αχρήστων, αφού όλοι θα παίρνουμε στατίνες.

Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

[Argirios Argiriou]

April 3, 2016

HOPE-3: A Primary Cardiovascular Prevention Trial in People at Intermediate Risk

Allan S. Brett, MD reviewing Lonn EM et al. N Engl J Med 2016 Apr 2. Yusuf S et al. N Engl J Med 2016 Apr 2. Yusuf S et al. N Engl J Med 2016 Apr 2. Cushman WC and Goff DC. N Engl J Med 2016 Apr 2.

Rosuvastatin lowered the incidence of CV-related death, myocardial infarction, or stroke by 1 percentage point during 5 years of treatment.

The Heart Outcomes Prevention Evaluation (HOPE)-3 is an international randomized trial conducted in 21 countries; China, India, Colombia, Argentina, and Canada contributed the most participants. The trial included 12,705 people (age, ≥65 for women, and ≥55 for men) without known cardiovascular (CV) disease who were considered to be at intermediate risk by virtue of meeting at least one inclusion criterion: Elevated waist–hip ratio, HDL cholesterol level <39 mg/dL (men) or <50 mg/dL (women), current or recent smoking, prediabetes or diet-controlled diabetes, premature coronary disease in first-degree relatives, or early renal dysfunction. Most participants had at least two risk factors.

In a 2×2 factorial design, each participant received daily rosuvastatin (10 mg) or placebo, plus daily candesartan/hydrochlorothiazide (16 mg/12.5 mg) or placebo. At baseline, mean LDL cholesterol level was 128 mg/dL and mean blood pressure (BP) was 138/82 mm Hg. During median follow-up of 5.6 years, key findings were as follows:

Compared with placebo, rosuvastatin lowered mean LDL cholesterol level by 35 mg/dL, and the antihypertensive drugs lowered mean systolic/diastolic BP by 6/3 mm Hg.

The first coprimary outcome (CV-related death, nonfatal stroke, or nonfatal myocardial infarction [MI]) occurred significantly less frequently with rosuvastatin than with placebo (3.7% vs. 4.8%); absolute reductions were 0.3%, 0.4%, and 0.5% for CV-related death, MI, and stroke, respectively.

Overall, candesartan/hydrochlorothiazide did not significantly lower the incidence of the first coprimary outcome compared with placebo (4.1% vs. 4.4%); however, it did lower the incidence in a subgroup with highest baseline systolic BP (>143 mm Hg; 4.8% vs. 6.5%).

Overall, outcomes with rosuvastatin plus candesartan/hydrochlorothiazide were not significantly better than outcomes with rosuvastatin alone.

All-cause mortality was not lowered by active therapies compared with placebo.

Neither treatment increased risk for diabetes; a small excess of muscle pain was noted with rosuvastatin and dizziness with candesartan/hydrochlorothiazide.

COMMENT — GENERAL MEDICINE

Allan S. Brett, MD
Interestingly, HOPE-3 had no LDL cholesterol or BP thresholds for enrollment (although people with “symptomatic hypotension” were excluded). For intermediate-risk patients like those in the trial (whose 10-year risk for adverse cardiovascular events is roughly 10%), the subgroup analysis of the trial's antihypertensive arm suggested potential benefit when systolic BP was >143 mm Hg. For the cholesterol-lowering arm, the 1 percentage-point difference in CV-related death, MI, or stroke that favored rosuvastatin (vs. placebo) means that about 100 people were treated for 5 years to benefit 1 person. In the U.S., the retail cost of rosuvastatin (Crestor) — for which a generic form is not available — is about US$3,600 annually. Patient preferences obviously will be important to guide these decisions. HOPE-3 was funded in part by the maker of Crestor.

COMMENT — CARDIOLOGY

Harlan M. Krumholz, MD, SM
In my opinion, this study shows that antihypertensive medications did not benefit this cohort. This finding is certain to unsettle further the ongoing discussion about what patients and their doctors should do about this common risk factor — mildly elevated blood pressure — and runs counter to the findings of the SPRINT trial, albeit with a different population and less-aggressive treatment (NEJM JW Gen Med Dec 15 2015 and N Engl J Med 2015; 373:2174). This study provides little help in determining the threshold to begin treatment. It suggests that the subgroup in the upper tertile of BP (mean BP, 153 mm Hg) might have benefited from BP reduction (which was about 6 mm Hg systolic in this group) — but this secondary analysis with borderline significance is only exploratory.

EDITOR DISCLOSURES AT TIME OF PUBLICATION

Disclosures for Allan S. Brett, MD at time of publication
Nothing to disclose

CITATION(S):

Lonn EM et al. Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med 2016 Apr 2; [e-pub]. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)
Yusuf S et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med 2016 Apr 2; [e-pub]. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)
Yusuf S et al. Blood-pressure and cholesterol lowering in persons without cardiovascular disease. N Engl J Med 2016 Apr 2; [e-pub]. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)
Cushman WC and Goff DC.More HOPE for prevention with statins. N Engl J Med 2016 Apr 2; [e-pub]. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)
- See more at: Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος

[GirousisN]

1) Overall, candesartan/hydrochlorothiazide did not significantly lower the incidence of the first coprimary outcome compared with placebo (4.1% vs. 4.4%); however, it did lower the incidence in a subgroup with highest baseline systolic BP (>143 mm Hg; 4.8% vs. 6.5%).

2) Overall, outcomes with rosuvastatin plus candesartan/hydrochlorothiazide were not significantly better than outcomes with rosuvastatin alone.

3) All-cause mortality was not lowered by active therapies compared with placebo.


Άρα τι κάνουμε ? Να μειώσουμε την ΑΥ και πότε ? Ως τι θα έχουμε στόχο ? Να δώσουμε στατίνες και πότε ?  Με τι στόχο ?
Αν πάρουμε υπ' όψιν μας και τις SPRINT , IMPROVE IT που κυκλοφόρησαν προ 6μήνου κλάφ'τα Χαράλαμπε.
Μήπως θα έπρεπε να θεωρήσουμε ότι η μεθοδολογία των μελετών αυτών ,έχει σοβαρά θέματα και αντί να ακολουθούμε αμφίβολης αξίας συμπεράσματα, να σκύψουμε εξατομικευμένα πάνω από τις πραγματικές ανάγκες των ασθενών μας ?

[GirousisN]

Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review.

Our review provides the first comprehensive analysis of the literature about the association between LDL-C and mortality in the elderly. Since the main goal of prevention of disease is prolongation of life, all-cause mortality is the most important outcome, and is also the most easily defined outcome and least subject to bias. The cholesterol hypothesis predicts that LDL-C will be associated with increased all-cause and CV mortality. Our review has shown either a lack of an association or an inverse association between LDL-C and both all-cause and CV mortality.
Our review provides the basis for more research about the cause of atherosclerosis and CVD and also for a re-evaluation of the guidelines for cardiovascular prevention, in particular because the benefits from statin treatment have been exaggerated.

Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος