Tag: Reduced

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Clopidogrel monotherapy linked with reduced risk of net adverse clinical events, study finds

Clopidogrel monotherapy linked with reduced risk of net adverse clinical events, study finds

Results from a real-world study investigating safety and effectiveness of clopidogrel versus aspirin monotherapy beyond 12 months after PCI in high-risk patients during the chronic maintenance period. This study found that clopidogrel monotherapy was associated with reduced risk of net adverse clinical events (NACE; all-cause death, MI, stent thrombosis, stroke, or BARC type 2, 3, or 5 bleeding) and MACCE (death, MI, stent thrombosis, stroke), and a numerical decrease in major or clinically relevant nonmajor bleeding (BARC type 2, 3, or 5 bleeding), compared with aspirin monotherapy. The findings were presented today as late-breaking clinical research at the Society for Cardiovascular Angiography & Interventions (SCAI) 2022 Scientific Sessions.

P2Y12 inhibitor monotherapy reduces bleeding risk without increasing the risk of ischemic events compared with dual antiplatelet therapy (DAPT), especially in the first 12 months following percutaneous coronary intervention (PCI). Recent research showed that among patients who were event free for six to 18 months post-PCI and successfully received the intended duration of DAPT, clopidogrel monotherapy was superior compared with aspirin monotherapy in terms of NACE. However, optimal antiplatelet monotherapy during the chronic maintenance period beyond 12 months after PCI with drug-eluting stents in high-risk patients in real-world settings is previously unknown.

In total, 8,377 consecutive patients at high risk for both bleeding and thrombosis were identified from the prospective Fuwai PCI Registry if they satisfied one clinical and one angiographic criterion. Patients who received antiplatelet (aspirin or clopidogrel) monotherapy longer than 12 months and were free from ischemic and bleeding events at 12-month post-PCI without extended duration of DAPT were included. The primary endpoint was net adverse clinical events (NACE) from 12 to 30 months. The key secondary endpoints were major adverse cardiac or cerebral events (MACCE) and major or clinically relevant nonmajor bleeding (BARC type 2, 3 or 5).

“These findings show for the first time clopidogrel monotherapy is associated with reduced risk of long-term NACE and MACCE,” said Hao-Yu Wang, Cardiometabolic Medicine Center, Coronary Heart Disease Center, Department of Cardiology, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. “Our results may have important practical implications for determining the optimal treatment for patients requiring a single antiplatelet drug, either aspirin or clopidogrel, for secondary prevention of ischemic events in high-risk PCI population.”

Of 7,392 high-risk patients that were event-free after the first year and adherent to DAPT, 5,664 patients who received antiplatelet monotherapy (clopidogrel monotherapy: n=1,974 and aspirin monotherapy: n=3690) were included in the present analysis. Researchers found that between 12 and 30 months, the net adverse clinical events were lower with clopidogrel monotherapy compared to aspirin monotherapy (Kaplan-Meier estimate: 2.5% vs. 5.0%; adjusted HR:0.566, 95% CI: 0.403-0.795). Clopidogrel monotherapy was associated with lower risk for MACCE (Kaplan-Meier estimate: 1.0% vs. 3.1%, log-rank p = 0.001 ), as well as lower incidence rates of all-cause death, MI, and stroke. The difference in risk between the groups was statistically similar for major or clinically relevant nonmajor bleeding (Kaplan-Meier estimate: 1.5% vs. 2.1%, log-rank p = 0.199).

Researchers recommended that their findings should be further investigated through a randomized clinical trial.

Source:

Society for Cardiovascular Angiography and Interventions

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WPIC: Events in Q1’22 hit platinum supply harder than demand, with previous surplus forecast for 2022 reduced to 627 koz

  • Platinum supply forecast to fall 5% in 2022, while demand to increase 2%
  • Despite unprecedented headwinds, annual automotive demand in 2022 forecast to rise 16%
  • Strong jewellery demand in Europe, North America, Japan and India unable to offset falls in pandemic-affected China
  • Strong underlying platinum industrial demand masked by reduced expansions in glass

LONDON, May 16, 2022 /CNW/ — The World Platinum Investment Council (WPIC) today publishes its Platinum Quarterly for the first quarter of 2022, with a revised full year forecast for 2022.

Unprecedented events in Q1’22 had a huge impact on both the supply of and demand for platinum, adding a layer of complexity on top of pre-existing issues, which will continue well into 2022. During the quarter, both demand (-26%) and supply (-13%) fell year-on-year leaving the market in surplus of 167 koz. However, for the full year, supply is expected to be 5% less than in 2021, yet demand to be 2% greater.

The surplus forecast for 2022 has now been reduced to 627 koz, which is also notably down on the surplus in 2021 (1,128 koz).

Constrained supply

Q1’22 saw confirmation that the processing of semi-finished inventory built up during the 2020 Anglo American platinum converter plant (ACP) shutdown had been completed. With mine production no longer receiving the one-off supply boost from the ACP inventory unwind, a clearer picture of underlying production levels emerged this quarter. South African production in Q1’22 fell 16% (-167 koz) year-on-year, to quarterly levels below those seen in 2019. Platinum mine supply in South Africa is forecast to decline 9% in 2022 (-421 koz) and is at risk of potential strike action related to three-yearly wage negotiations. Russian output also declined in Q1’22, down 11% year-on-year (-21 koz) with the operating environment in Russia becoming increasingly challenging due to the geopolitical situation and sanctions against Russia. Overall, global refined mine production is forecast to decline 7% (-425 koz) year-on-year to 5,872 koz.

Recycling supply was constrained during Q1’22 (-20% year-on-year) due to reduced volumes of end-of-life vehicles as a result of fewer new vehicles being sold – an issue that will persist yet ease throughout 2022. Full year platinum recycling supply is forecast to decline by 2% (-43 koz).

Notable automotive demand despite severe challenges

Against a backdrop of shortages of semiconductor chips and other parts, zero-COVID protocols in China, and disruption in Europe due to Russia’s invasion of Ukraine, total platinum automotive demand this quarter was remarkably strong. Demand was flat on Q1’21 (725 koz), and is expected to increase by 16% (+412 koz) in 2022, due to a rise in light duty vehicles produced, higher loadings due to tighter emissions regulations and continued platinum substitution to partially replace palladium in gasoline vehicle catalysts.

Jewellery demand rises in all regions except China

A jump in the number of weddings, price-led gains from gold in bridal and further growth for luxury brands saw platinum jewellery demand rise in Europe and North America in Q1’22 – a trend which is forecast to continue throughout the year. Jewellery demand also grew in Japan, albeit from a low base. In India, platinum jewellery demand rose in Q1’22, with fabrication expected to grow to a record high in 2022.

However, this could not offset a fall in jewellery demand in China, where platinum fabrication fell by 36% year-on-year in Q1’22, partly due to the negative impact of the Omicron outbreak. Sales are expected to gradually pick up in the second half of the year as the pandemic-related impact is expected to ease. Overall global platinum jewellery demand declined by 9% (-42 koz) year-on-year in Q1’22, and is forecast to decline 2% (-37 koz) to 1,886 koz in 2022.

Underlying industrial demand above 2019 levels

Petroleum demand in Q1’22 rose by 21% (+8 koz) year-on-year, especially in Europe and North America, where refining output had picked up considerably as the recovery from COVID continued. Similarly, as health service utilisation is recovering towards pre-pandemic levels, demand for platinum in the medical sector was up by 15% (+8 koz). Both sectors are forecast to see demand growth in 2022.

Meanwhile, platinum glass demand fell 56% (-179 koz) year-on-year in Q1 22 as expected. This seemingly dramatic drop was due to unusually high demand in Q1’21, as significant investment in new plant capacity was completed and plants were commissioned. This reduced requirement from the glass sector was a significant factor in overall industrial demand falling by 25% (-175 koz) in Q1’22 year-on-year, and the forecast of a 16% decline in 2022, albeit that 2022 industrial demand is still expected to be the third strongest year on record.

Investment demand affected by yen weakness and ETF liquidations

Bar and coin demand increased from 21 koz in Q1’21 to 60 koz in Q1’22. However, despite particularly strong demand in North America, global demand growth was limited by US dollar price strength sustained by a significant subsequent weakening in the yen which drove local platinum prices to their highest since May last year and which encouraged profit-taking among Japanese investors. This trend is expected to continue into the next quarter, with global bar and coin demand for the full year forecast to decline by 23%.

For ETFs, liquidations in Q1’22 stemmed primarily from one European ETF issuer and were contrary to investors’ finding hard assets attractive due to surging inflationary worries and elevated geopolitical and economic uncertainties. A modest inflow in ETF holdings over the remainder of this year is forecast, resulting in a 50 koz full-year outflow.

Paul Wilson, CEO of the World Platinum Investment Council commented:

“At the start of Q1’22, most regions were at various stages of a post-COVID economic recovery. However, Russia’s invasion of Ukraine at the end of February sent shockwaves through the markets, which will be felt for months and years to come. This new layer of complexity, on top of existing COVID-related factors and operational challenges, will add to the wider markets’ volatility.

“With the backlog of semi-finished inventory built up during the 2020 Anglo American Platinum converter plant (ACP) outages now processed, we are left with the stark reality that South African production is actually below where it was in 2019. This, combined with a massive drop in recycled material, points to constrained supply for the coming months, as demand continues to grow.

“While the cost of the tragic war in Ukraine will not be known for some time, the potential indirect impact it could have on platinum is considerable. Security-of-supply concerns, particularly for palladium have arisen in the wake of Russia’s invasion of Ukraine and given Russia’s importance to the global supplies of mined palladium and, to a much lesser extent, platinum. This could increase platinum for palladium substitution efforts and modify the procurement and inventory management strategies of a wide range of market participants.

“In addition to decarbonisation, security of energy supply for all Governments is now a far greater issue than it was. The role of green hydrogen in reducing European gas imports could drive a strategic acceleration of electrolyser construction, which would benefit platinum directly but also support the infrastructure needed for broad-based commercial adoption of FCEVs. Investors looking for green opportunities are becoming increasingly aware of platinum’s key strategic role in unlocking hydrogen’s crucial contribution to achieving global net zero targets; being used in both electrolysers to produce green hydrogen and in hydrogen fuel cells.”

Disclaimer

Neither the World Platinum Investment Council nor Metals Focus is authorised by any regulatory authority to give investment advice. Nothing within this document is intended or should be construed as investment advice or offering to sell or advising to buy any securities or financial instruments and appropriate professional advice should always be sought before making any investment. For further information, please visit www.platinuminvestment.com.

SOURCE World Platinum Investment Council (WPIC)

For further information: Charlotte Raisbeck, +44 (0)7908 551605 – [email protected]

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Paris Olympics | Boxing events for male reduced, changes also in weightlifting and shooting

Paris Olympics | Boxing events for male reduced, changes also in weightlifting and shooting

While the preceding Tokyo Games had eight events for men and five for women, in Paris there will be seven events for the male pugilists and six for the female

While the preceding Tokyo Games had eight events for men and five for women, in Paris there will be seven events for the male pugilists and six for the female

Aiming to achieve gender equality, the International Olympic Committee (IOC) has increased the number of boxing events for women in the 2024 Paris Olympics from five to six as per a revised list.

While the preceding Tokyo Games had eight events for men and five for women, in Paris there will be seven events for the male pugilists and six for the female, according to an update shared by Indian Olympic Association (IOA) president Narinder Batra.

The new categories for men are 51kg, 57kg, 63.5kg, 71kg, 80kg, 92kg and +92kg.

While the new women’s weight classes include 50kg, 54kg, 57kg, 60kg, 75kg.

The changes are in line with the trend of increasing women’s weight classes as the Rio Olympics only had three, which was increased by two for the Tokyo Games.

In shooting, the trap mixed team event has been replaced with skeet mixed team event.

As far as weightlifting is concerned, as PTI reported last December the number of events has come down to 10 (5 men and 5 women) from 14 events in Tokyo.

The competition schedule for the Paris Olympic Games was unveiled on April 1, after being approved by the IOC executive board.

In total 32 sports are set to be contested across 19 days of action, with 329 events due to take place across 762 sessions.

Action is scheduled to begin on July 24, two days before the Opening Ceremony is due to be held.

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Reduced kidney function caused by antithrombotic therapy can influence bleeding events

Reduced kidney function caused by antithrombotic therapy can influence bleeding events

Antithrombotic therapy is prescribed to prevent thrombotic (blood clotting inside a blood vessel) events but the treatment also increases the likelihood of experiencing a bleeding event, which can be extremely serious if it occurs in a vital organ. Aging societies tend to have an increased number of patients undergoing antithrombotic therapy, and the drugs used in this treatment can affect kidney function. In particular, reduced kidney function caused by antithrombotic medications can significantly influence bleeding events. It is highly recommended that patients, especially those with decreased kidney function, have a detailed discussion with their doctor about the possible risks and benefits of proceeding with antithrombotic therapy.

Patients with heart arrythmia (atrial fibrillation) have a high risk for thrombotic events in blood vessels that could lead to permanent organ damage-;such as cerebral infarction-;and are prescribed antithrombotic therapy to lower their risk of developing blood clots. However, the risk of bleeding events simultaneously increases due to the nature of these medications. The severity of these bleeding events is highly variable, ranging from epistaxis (nosebleeds) to fatal brain hemorrhage.

While kidney function is known to be related to bleeding event risk, researchers at Kumamoto, Miyazaki, and Tohoku Universities in Japan conducted a post-hoc subgroup analysis of the Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial to determine the impact of kidney function on the risk of recurrent bleeding events during antithrombotic therapy. Their analysis revealed that the effect of kidney function on recurrent bleeding risk events was quite large for patients undergoing this treatment. They also found that the bleeding risk decreased with time for patients with healthy kidney function but remained high for patients with decreased kidney function. Clearly, the decision to use such a therapy should be balanced between the expected antithrombotic effects and bleeding risks.

In most cases, it is considered better to continue antithrombotic therapies even after bleeding events as long as the event was not severe. However, it is not surprising that both patients and physicians hesitate to continue the therapy after any bleeding event. To assess for drug safety and efficacy, these drugs are usually measured by the numbers of bleeding and thrombotic events. Unfortunately, in the assessment of antithrombotic therapy, most studies only consider the first event in their analyses even though patients could experience multiple events throughout their lifetime. This study revealed that the impact of kidney function on bleeding risk during antithrombotic therapy is larger than estimated in previous studies. Furthermore, patients with healthy kidney function appear to have a decreased risk of experiencing a bleeding event over time, but the risk for patients with reduced kidney function remains high as time continues.

A detailed discussion between patients and physicians based on all current scientific evidence about the risks and benefits of antithrombotic therapy is highly recommended. Our analysis should be quite useful in facilitating this type of discussion.”


Dr. Kunihiko Matsui, Study Leader, Kumamoto University Hospital’s Department of General Medicine and Primary Care

Source:

Journal reference:

Matsui, K., et al. (2022) The impact of kidney function in patients on antithrombotic therapy: a post hoc subgroup analysis focusing on recurrent bleeding events from the AFIRE trial. BMC Medicine. doi.org/10.1186/s12916-022-02268-6.

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Hemophilia A Gene Therapy Reduced Bleeding Events, Need for Clotting Factors

Hemophilia A Gene Therapy Reduced Bleeding Events, Need for Clotting Factors

The phase 3 trial of valoctocogene roxaparvovec for severe hemophilia A showed it reduced bleeding events as well as the use of factor VIII concentrates.

A phase 3 trial of valoctocogene roxaparvovec, a gene therapy for severe hemophilia A, showed it reduced bleeding events as well as the use of factor VIII concentrates and increased endogenous production of clotting factors.

Severe hemophilia A, defined as a factor VIII level of 1 IU/dL or lower, carries the highest risk of spontaneous and traumatic bleeding, resulting in loss of limbs, chronic pain, decreased quality of life, and higher risk of mortality. About 1 in 5000 males is born with the rare disease, and about 60% have the most severe form, according to the National Organization for Rare Disorders.

Outcomes for individuals with hemophilia A, caused by a deficient F8 gene, have improved with factor VIII concentrates that are used prophylactically, but bleeding events are not eliminated.

If approved by the FDA, the adeno-associated virus (AAV) vector gene therapy would be sold as Roctavian by BioMarin, which funded the study. The FDA has granted valoctocogene roxaparvovec Regenerative Medicine Advanced Therapy and Breakthrough Therapy designations; according to press reports, it could be priced as high as $3 million, making it the most expensive therapy to date.

Writing in The New England Journal of Medicine, the authors said the gene therapy enables steady production of factor VIII without additional prophylactic measures. However, the authors also said, “The expression of the transferred gene appears to decline over time; further study is needed to address whether repeat treatment will be necessary or possible.”1

Participants in the trial (GENEr8-1) were 134 adult men 18 years or older who had previously been treated with clotting-factor prophylaxis for at least 1 year, 2 of whom were living with HIV. At baseline, 61.9% of the participants were receiving factor VIII prophylaxis with standard half-life products, 27.6% with extended half-life products, and 17.9% with plasma-derived products. None of the participants were receiving emicizumab (Helimbra), a humanized bispecific monoclonal antibody that joins both factor IXa and X, which are proteins necessary to activate the natural coagulation cascade and restore the blood clotting process.

Exclusion criteria for the open-label, single-group, multicenter, phase 3 study included those who had preexisting anti-AAV5 antibodies, factor VIII inhibitors, or significant liver disease.

Patients received a single infusion of valoctocogene roxaparvovec at a dose of 6×1013 vector genomes per kilogram of body weight, and investigators examined the change from baseline in factor VIII activity (measured with a chromogenic substrate assay) during weeks 49 through 52 after infusion.

Secondary end points included the change in annualized factor VIII concentrate use and bleeding rates.

Overall, 134 participants received an infusion and completed more than 51 weeks of follow-up. The analysis included data from 132 HIV-negative participants, including 112 participants enrolled from a prospective noninterventional study.

Results showed:

  • A decline in annualized rates of factor VIII use of 98.6% and treated bleeding of 83.8% (P <.001 for both comparisons)
  • A median factor VIII activity level of 5 IU/dL or higher in 88.1% of participants

As for safety, all participants had at least 1 adverse event (AE); 22 of 134 (16.4%) reported serious AEs.

Elevations in alanine aminotransferase levels occurred in 115 of 134 participants (85.8%) and were managed with glucocorticoids. The other most common AEs were headache (38.1%), nausea (37.3%), and elevations in aspartate aminotransferase levels (35.1%).

There were no deaths in the trial or withdrawals due to AEs, and there was no thrombosis or development of factor VIII inhibitors.

The investigators wrote that “intra- and interindividual variability in factor VIII activity after gene transfer were notable.” Seven participants had a median factor VIII activity level of greater than 150 IU/dL; 12 participants had a median factor VIII activity level of less than 3 IU/dL, measured by chromogenic assay; and 2 participants, measured by a 1-stage assay, had a factor VIII activity level of less than 1 IU/dL.

The causes of the variability are not fully known; the authors said biologic variables and molecular events related to gene transfer and expression may impact endogenous factor VIII production.

There were a few limitations to the study. The 2 participants with HIV were excluded from the primary analysis, and so generalizing the results to that population may be constrained. In addition, direct comparisons to emicizumab cannot be made because the participants had previously been using factor VIII concentrates, but the authors said “the annualized rates of treated bleeding here were similar to those reported with long-term emicizumab prophylaxis.”

In an accompanying editorial, the author called valoctocogene roxaparvovec “a new choice for care that could be truly transformative and liberating for eligible men with hemophilia” and called on payers, policymakers, and others to get ready for its entrance.2

Reference

1. Ozelo MC, Mahlangu J, Pasi KJ, et al; GENEr8-1 Trial Group. Valoctocogene roxaparvovec gene therapy for hemophilia A. N Engl J Med. 2022;386:1013-1025. doi:10.1056/NEJMoa2113708

2. Thornberg CD. Prepare the way for hemophilia A gene therapy. N Engl J Med. 2022;386:1081-1082. doi:10.1056/NEJMe2200878