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Stopping statin therapy puts heart patients at risk
SCIENCE AND MEDICINE
Stopping statin therapy puts heart patients at risk
T
he use of statins in primary and secondary prevention of coronary events is well characterised, but a new study suggests that withdrawing therapy for a short time may have an unexpected and serious rebound effect. Statins reduce LDL cholesterol and reduce the risk of coronary events by affecting factors that contribute to inflammatory reactions. Animal studies have suggested that short-term withdrawal of statin therapy leads to impaired bioavailability of nitric oxide, which then cannot modify inflammatory responses in the vasculature. Christian Hamm (Kerchoff Heart Center, Bad Nauheim, Germany) and colleagues now confirm that discontinuation of statins after the onset of coronary symptoms leads to an increased risk of death from coronary events (Circulation 2002, published online March 4). The researchers investigated 1616 patients admitted to hospital with coronary artery disease and chest pain, and monitored them for 30 days to assess death and non-
fatal myocardial infarction (MI) rates. 1249 patients were not receiving statin therapy; 379 patients were already taking statins and continued therapy during the 30 days; and 86 patients discontinued their statin therapy on hospital admission. The risk of death or non-fatal MI in patients taking statins was half that in patients who were not receiving statin treatment (adjusted hazard ratio 0·49%), an unsurprising finding. However, if statin therapy was withdrawn after hospital admission, cardiac risk rose to almost three times that of patients who carried on taking their previously prescribed statins (adjusted hazard ration 2·93%). Jorge Plutzky, director of the Vascular Disease Prevention Program at the Brigham and Women’s Hospital (Harvard Medical School, Boston, MA, USA), says that this paper “offers data relevant to various emerging issues in both the basic science of atherosclerosis as well as the practice of preventive cardiology”. Plutzky points out that there
is currently a philosophical, and perhaps practical, movement away from the artificial concepts of “primary” versus “secondary” prevention of MI. He considers that Hamm and colleagues’ findings support the provocative notion that a patient may be better served if already on a statin when an acute coronary event occurs. “It is clear”, says Hamm, “that physicians should definitely not stop statin therapy in patients with acute coronary syndromes, since this may be harmful”. Plutzky agrees and goes further: “Although prior statin therapy is the best option, many preventive cardiologists might argue that it is worthwhile to initiate statin therapy at the time of hospital admission for an acute coronary event.” He concludes that this study shows that not do so is detrimental, and that it may mean the difference between life or death for some patients having their first MI. Kathryn Senior
Could polygenic analysis improve breast-cancer screening? K researchers believe that the estimation of breast-cancer risk on a polygenic basis may improve the efficacy of population-based intervention programmes. “If we could find all the susceptibility genes for breast cancer”, says Paul Pharoah (Strangeways Research Laboratories, Cambridge, UK), “our modelling predicts that the half of the population at highest risk would account for 88% of all breast-cancer cases”. Thus, women at low risk might decide not to have mammographic screening and chemopreventive agents could be given to women at greatest risk. However, warns Pharoah, “the key question is ‘are we going to be able to find all or even any of these genes?’”. The high penetrance breast-cancer susceptibility genes BRCA1 and BRCA2 account for less than 25% of excess familial breast-cancer risk, which suggests that other genes may be involved. But, says William Foulkes (McGill University, Montreal, Canada), “attempts to find a third high penetrance gene have been disappointing, greatly reducing researchers’ expectations that a size-
U
able fraction of the remaining familial susceptibility will be due to a single gene”.
No need to screen everyone?
Based on segregation analysis of women who developed breast cancer at a young age, the Cambridge researchers propose that an unknown number of common, unidentified genetic variants, each with a relatively low effect on breast-cancer risk, may account for the remaining excess familial risk. Their polygenic model yields an approximately log-normal risk distribution with a difference in risk between the lowest and highest quintiles of about 40-fold (Nat Genet 2002, published online March 3, DOI: 10.1038/ng853). By compari-
THE LANCET • Vol 359 • March 9, 2002 • www.thelancet.com
son, the current risk factor model, which includes reproductive and familial breast-cancer history, gives only a 3·5-fold difference in risk across the distribution. “This paper is thought provoking”, says Foulkes, “but it is a leap to go from here to talking about breast-cancer prevention when we have no idea of the genes involved”. Pharoah agrees that finding the genes is paramount. “I suspect that over the next 5–10 years we are going to get better at picking and testing the genes that are likely to be important”, he says. And if the susceptibility genes are found, would women then be willing to have their genotype tested to help them make informed decisions about screening and prevention? Both Pharoah and Foulkes think they would, and draw the parallel with colorectal cancer. “At the moment I would be reluctant to undergo colonoscopy as a screening procedure for colon cancer”, comments Pharoah, “but if I knew my risk was high it would very different”. Jane Bradbury
857
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Stopping statin therapy puts heart patients at risk
T
he use of statins in primary and secondary prevention of coronary events is well characterised, but a new study suggests that withdrawing therapy for a short time may have an unexpected and serious rebound effect. Statins reduce LDL cholesterol and reduce the risk of coronary events by affecting factors that contribute to inflammatory reactions. Animal studies have suggested that short-term withdrawal of statin therapy leads to impaired bioavailability of nitric oxide, which then cannot modify inflammatory responses in the vasculature. Christian Hamm (Kerchoff Heart Center, Bad Nauheim, Germany) and colleagues now confirm that discontinuation of statins after the onset of coronary symptoms leads to an increased risk of death from coronary events (Circulation 2002, published online March 4). The researchers investigated 1616 patients admitted to hospital with coronary artery disease and chest pain, and monitored them for 30 days to assess death and non-
fatal myocardial infarction (MI) rates. 1249 patients were not receiving statin therapy; 379 patients were already taking statins and continued therapy during the 30 days; and 86 patients discontinued their statin therapy on hospital admission. The risk of death or non-fatal MI in patients taking statins was half that in patients who were not receiving statin treatment (adjusted hazard ratio 0·49%), an unsurprising finding. However, if statin therapy was withdrawn after hospital admission, cardiac risk rose to almost three times that of patients who carried on taking their previously prescribed statins (adjusted hazard ration 2·93%). Jorge Plutzky, director of the Vascular Disease Prevention Program at the Brigham and Women’s Hospital (Harvard Medical School, Boston, MA, USA), says that this paper “offers data relevant to various emerging issues in both the basic science of atherosclerosis as well as the practice of preventive cardiology”. Plutzky points out that there
is currently a philosophical, and perhaps practical, movement away from the artificial concepts of “primary” versus “secondary” prevention of MI. He considers that Hamm and colleagues’ findings support the provocative notion that a patient may be better served if already on a statin when an acute coronary event occurs. “It is clear”, says Hamm, “that physicians should definitely not stop statin therapy in patients with acute coronary syndromes, since this may be harmful”. Plutzky agrees and goes further: “Although prior statin therapy is the best option, many preventive cardiologists might argue that it is worthwhile to initiate statin therapy at the time of hospital admission for an acute coronary event.” He concludes that this study shows that not do so is detrimental, and that it may mean the difference between life or death for some patients having their first MI. Kathryn Senior
Could polygenic analysis improve breast-cancer screening? K researchers believe that the estimation of breast-cancer risk on a polygenic basis may improve the efficacy of population-based intervention programmes. “If we could find all the susceptibility genes for breast cancer”, says Paul Pharoah (Strangeways Research Laboratories, Cambridge, UK), “our modelling predicts that the half of the population at highest risk would account for 88% of all breast-cancer cases”. Thus, women at low risk might decide not to have mammographic screening and chemopreventive agents could be given to women at greatest risk. However, warns Pharoah, “the key question is ‘are we going to be able to find all or even any of these genes?’”. The high penetrance breast-cancer susceptibility genes BRCA1 and BRCA2 account for less than 25% of excess familial breast-cancer risk, which suggests that other genes may be involved. But, says William Foulkes (McGill University, Montreal, Canada), “attempts to find a third high penetrance gene have been disappointing, greatly reducing researchers’ expectations that a size-
U
able fraction of the remaining familial susceptibility will be due to a single gene”.
No need to screen everyone?
Based on segregation analysis of women who developed breast cancer at a young age, the Cambridge researchers propose that an unknown number of common, unidentified genetic variants, each with a relatively low effect on breast-cancer risk, may account for the remaining excess familial risk. Their polygenic model yields an approximately log-normal risk distribution with a difference in risk between the lowest and highest quintiles of about 40-fold (Nat Genet 2002, published online March 3, DOI: 10.1038/ng853). By compari-
THE LANCET • Vol 359 • March 9, 2002 • www.thelancet.com
son, the current risk factor model, which includes reproductive and familial breast-cancer history, gives only a 3·5-fold difference in risk across the distribution. “This paper is thought provoking”, says Foulkes, “but it is a leap to go from here to talking about breast-cancer prevention when we have no idea of the genes involved”. Pharoah agrees that finding the genes is paramount. “I suspect that over the next 5–10 years we are going to get better at picking and testing the genes that are likely to be important”, he says. And if the susceptibility genes are found, would women then be willing to have their genotype tested to help them make informed decisions about screening and prevention? Both Pharoah and Foulkes think they would, and draw the parallel with colorectal cancer. “At the moment I would be reluctant to undergo colonoscopy as a screening procedure for colon cancer”, comments Pharoah, “but if I knew my risk was high it would very different”. Jane Bradbury
857
For personal use. Only reproduce with permission from The Lancet Publishing Group.