AMEA vs ATII

[deleteduser]

Cardiovascular Mortality in Contemporary Hypertension Trials
A Review

Roberto Ferrari, Eric Boersma
Disclosures

Expert Rev Cardiovasc Ther. 2013;11(6):705-717.


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Conclusion

The most recent meta-analysis of mortality reduction with RAAS inhibition in hypertension demonstrated a statistically significant 10% reduction in all-cause mortality (p = 0.004) and a trend towards a 12% reduction in cardiovascular mortality with ACE inhibitors (p = 0.051), while no significant mortality reduction was observed with ARBs. Interestingly, a recent meta-analysis of 26 randomized controlled trials comparing ACE inhibitors or ARBs versus placebo in a different population, patients at high cardiovascular risk (n = 108, 212), confirmed this absence of mortality reduction with ARBs, showing that they did not significantly reduce cardiovascular or all-cause death.[63] By concluding that ARBs represent a practical treatment option for patients intolerant to ACE inhibitors, the authors endorsed the first-line use of ACE inhibitors.

Significant heterogeneity among ACE inhibitors was observed in our meta-analysis; treatment with perindopril was associated with a further significant 13% reduction in all-cause mortality, mainly due to a 22% reduction in cardiovascular mortality. The balance of mortality evidence now suggests that in hypertension, ACE inhibitors should be considered ahead of ARBs, and ARBs should be restricted to patients intolerant of ACE inhibitors.

[deleteduser]

... το οποίο ως γνωστόν εχει πάρει ενδειξη για ΣΝ.
Ενα άρθρο που τσιμπησα απο το medscape που αναφερεται στο σκανδαλο που εχει ξεσπάσει σχετικά με 5 κατασκευασμενες δημοσιευσεις που εδειχναν ότι η βαλσαρτανη βελτιωνει τους καρδιαγγειακους στοχους πέραν της αντι-υπερτασικης δρασης της

Παρεμπιπτόντως στις τελευταιες οδηγιες της AHA/ACCF ορίζεται σαφως ότι σε ΣΝ οι ΑΑΙΙ εχουν θέση στη θεραπεία μόνο σε δυσανεξια σε ΑΜΕΑ. Οι λόγοι προφανώς δεν είναι μόνο οικονομικοι.

Heartwire
Diovan Data-Manipulation Scandal Touches Novartis in Japan

Shelley Wood
Jul 19, 2013

Last year, the American Heart Association (AHA) issued anotice of concern about five papers appearing in three AHA-published journals--Circulation, Circulation Research, andHypertension--between 2001 and 2004, as reported byheartwire .

Concerns about Dr Hiroaki Matsubara ultimately spread to the Kyoto Heart Study , the >3000 patient, postmarketing study Matsubara presented to some fanfare at the European Society of Cardiology 2009 Congress and subsequently published in the European Heart Journal ( EHJ). The EHJ later retracted that article, a move the AHA opted to follow this May after concluding its review of the studies published in a number of the association's journals. Matsubara resigned from his post at Kyoto Prefectural University earlier this year.

Last Friday, Japan's minister of health, Norihisa Tamura, as well as university officials at Kyoto Prefectural University announced that the Kyoto Heart Study data were "very likely" fabricated, according to AFP. "Incomplete" patient data were used in the study, which concluded the blood-pressure drug could also reduce other cardiovascular end points via mechanisms unrelated to blood-pressure lowering. Had "complete patient records" been used, the study would have reached "a different conclusion," the university concluded.

Finally, it has also emerged that two Novartis employees were involved in the conduct and analysis of the Kyoto Heart Study and a second investigator-initiated trial, the Jikei Heart study , although their participation was not acknowledged in publications and presentations of the data. Those employees are no longer with Novartis.

Novartis has issued a statement saying that it had launched a third-party investigation into allegations of conflict of interest (COI) relating to the two Novartis employees back in April.

"At the time these Japanese valsartan [investigator-initiated trials] IITs started between 2001 and 2004, there were no specific guidelines for COI in IITs," the statement reads. "The former employees and their managers misunderstood the appropriate level of involvement in IITs of employees of a pharmaceutical company. However, there are now COI guidelines for in place across the industry, which are followed by all Novartis Pharma Japan employees."

In June, after its investigation concluded, the company implemented "preventive and corrective measures . . . to address the causes identified in the third-party investigation, demonstrating our social and ethical accountability," the statement notes.

According to AFP, Novartis has also stressed that the university "was not able to conclude that there was intentional wrongdoing" and that it remains possible that the "inconsistencies" may have been unintentional.

The retractions, Matsubara's resignation, the Novartis announcement, and other details have been followed in detail on blog sites Retraction Watch and Cardiobrief , as well as on PharmaTimes .

[schumifer]

το έχω διαβάσει στο medscape, αλλά είναι χρήσιμο να υπάρχει κι εδώ

[Zachariadis]

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

Circulatory and tissue renin-angiotensin systems (RAS) play a central role in cardiovascular (CV) and renal pathophysiology,
making RAS inhibition a logical therapeutic approach in the prevention of CV and renal disease in patients with hypertension.
The cardio- and renoprotective effects observed with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) monotherapy,
together with the availability of a direct renin inhibitor (DRI), led to the investigation of the potential benefits of dual RAS inhibition.
In small studies, ARB and ACE inhibitor combinations were shown to be beneficial in patients with CV or renal disease, with improvement in surrogate markers.
However, in larger outcome trials, involving combinations of ACE inhibitors, ARBs or DRIs, dual RAS inhibition did not show reduction in mortality in patients
with diabetes, heart failure, coronary heart disease or after myocardial infarction, and was in fact, associated with increased harm.
A recent meta-analysis of all major trials conducted over the past 22 years involving dual RAS inhibition has clearly shown that
the risk-benefit ratio argues against the use of dual RAS inhibition.
Hence, the recent evidence clearly advocates against the use of dual RAS inhibition, and single RAS inhibition appears to be the most suitable approach
to controlling blood pressure and improving patient outcomes.
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Conclusions:
Although some small studies demonstrate benefits of combinations of ARBs with ACE inhibitors,
larger clinical trials such as ONTARGET® and VA NEPHRON-D indicate that this approach to dual RAS inhibition does not improve outcomes across most patient groups,
and in fact, increases the risk of AEs. Similarly, dual RAS inhibition involving aliskiren has been reported in large trials such as ALTITUDE and ASTRONAUT
to increase the risk of AEs with no clinical benefits.
A recent meta-analysis of all major trials involving dual RAS inhibition has clearly shown that the risk-benefit ratio argues against the use of dual RAS inhibition
Based on these results, the EMA currently is reviewing the use of dual RAS blockade in the treatment of hypertension and congestive heart failure.