Jennie Smith

The drug sildenafil reduced the frequency of attacks of Raynaud's phenomenon secondary to limited cutaneous systemic sclerosis in a small, randomized, placebo-controlled trial that was reported in Arthritis & Rheumatism.

The study enrolled 57 men and women aged 18-75 years, all of whom both had a diagnosis of Raynaud's phenomenon (RP) secondary to limited cutaneous systemic sclerosis and experienced at least 7 attacks per week. Patients were randomized to receive modified-release sildenafil (100 mg once daily for 3 days, titrated to 200 mg once daily for 25 days) or placebo, reported Dr. Ariane Herrick of the University of Manchester (England) and her associates (Arthritis Rheum. 2011;63:775-82).

Of the 57 people originally enrolled, 20 in the treatment group and 25 controls completed the 28-day study and were entered into analysis. Patients kept treatment diaries before and during the study period, recording the duration and pain intensity of each attack; serum samples were taken on days 1, 7, and 28.

The primary end point was the percent change in the number of weekly RP attacks. Secondary end points measured the severity and duration of attacks.

After 28 days, the mean number of RP attacks per week lessened from 25 at baseline to 19 in the control arm, and from 31 at baseline to 19 in the treatment arm, with a mean percent reduction of 44% in the treatment arm, compared with 18% in the control arm (P = .034). Statistically insignificant differences were noted between the groups for Raynaud’s Condition Score, duration of attacks, pain score, endothelial dysfunction, or serum biomarkers associated with RP. The most frequent adverse events reported were headache and dyspepsia.

Dr. Ulf Müller-Ladner, professor of internal medicine and rheumatology at Justus-Liebig University Giessen (Germany), said in an interview that this "is a very important study, as we do not have too many controlled clinical trials for Raynaud’s, and every controlled study showing efficacy is very helpful for daily practice." The investigators acknowledged the study’s small size and high attrition from the intention-to-treat sildenafil arm as limitations, particularly as the study was no longer powered to detect secondary end points. Also disappointing, they wrote, was that the endothelial dysfunction measures and the serum levels of biomarkers were similar between the groups.

The study's short duration was another possible limitation. The findings from an earlier, longer (5.2-month) study of sildenafil in 16 patients with systemic sclerosis – of whom 7 had limited cutaneous involvement – showed statistically significant lessening of attack pain associated with RP with the maximum tolerated dose of sildenafil (Ann. Rheum. Dis. 2010;69:1475-8).

Finally, they noted, the modified-release formulation of sildenafil may not have provided the most effective dose for the patient population studied.

Dr. Müller-Ladner agreed with the description of the study's design weaknesses: "The shortcomings of the present study are its placebo arm and its short duration. These results must be confirmed through the initiation of a large, multinational, longer-term trial."

The trial was funded by Pfizer, the drug's manufacturer. Dr. Herrick acknowledged financial relationships with Actelion, Mediquest, Pfizer, and United Therapeutics. Several of the coinvestigators also made relevant financial disclosures. Dr. Müller-Ladner had no relevant financial disclosures.

The drug sildenafil reduced the frequency of attacks of Raynaud's phenomenon secondary to limited cutaneous systemic sclerosis in a small, randomized, placebo-controlled trial that was reported in Arthritis & Rheumatism.

The study enrolled 57 men and women aged 18-75 years, all of whom both had a diagnosis of Raynaud's phenomenon (RP) secondary to limited cutaneous systemic sclerosis and experienced at least 7 attacks per week. Patients were randomized to receive modified-release sildenafil (100 mg once daily for 3 days, titrated to 200 mg once daily for 25 days) or placebo, reported Dr. Ariane Herrick of the University of Manchester (England) and her associates (Arthritis Rheum. 2011;63:775-82).

Of the 57 people originally enrolled, 20 in the treatment group and 25 controls completed the 28-day study and were entered into analysis. Patients kept treatment diaries before and during the study period, recording the duration and pain intensity of each attack; serum samples were taken on days 1, 7, and 28.

The primary end point was the percent change in the number of weekly RP attacks. Secondary end points measured the severity and duration of attacks.

After 28 days, the mean number of RP attacks per week lessened from 25 at baseline to 19 in the control arm, and from 31 at baseline to 19 in the treatment arm, with a mean percent reduction of 44% in the treatment arm, compared with 18% in the control arm (P = .034). Statistically insignificant differences were noted between the groups for Raynaud’s Condition Score, duration of attacks, pain score, endothelial dysfunction, or serum biomarkers associated with RP. The most frequent adverse events reported were headache and dyspepsia.

Dr. Ulf Müller-Ladner, professor of internal medicine and rheumatology at Justus-Liebig University Giessen (Germany), said in an interview that this "is a very important study, as we do not have too many controlled clinical trials for Raynaud’s, and every controlled study showing efficacy is very helpful for daily practice." The investigators acknowledged the study’s small size and high attrition from the intention-to-treat sildenafil arm as limitations, particularly as the study was no longer powered to detect secondary end points. Also disappointing, they wrote, was that the endothelial dysfunction measures and the serum levels of biomarkers were similar between the groups.

The study's short duration was another possible limitation. The findings from an earlier, longer (5.2-month) study of sildenafil in 16 patients with systemic sclerosis – of whom 7 had limited cutaneous involvement – showed statistically significant lessening of attack pain associated with RP with the maximum tolerated dose of sildenafil (Ann. Rheum. Dis. 2010;69:1475-8).

Finally, they noted, the modified-release formulation of sildenafil may not have provided the most effective dose for the patient population studied.

Dr. Müller-Ladner agreed with the description of the study's design weaknesses: "The shortcomings of the present study are its placebo arm and its short duration. These results must be confirmed through the initiation of a large, multinational, longer-term trial."

The trial was funded by Pfizer, the drug's manufacturer. Dr. Herrick acknowledged financial relationships with Actelion, Mediquest, Pfizer, and United Therapeutics. Several of the coinvestigators also made relevant financial disclosures. Dr. Müller-Ladner had no relevant financial disclosures.

The drug sildenafil reduced the frequency of attacks of Raynaud's phenomenon secondary to limited cutaneous systemic sclerosis in a small, randomized, placebo-controlled trial that was reported in Arthritis & Rheumatism.

The study enrolled 57 men and women aged 18-75 years, all of whom both had a diagnosis of Raynaud's phenomenon (RP) secondary to limited cutaneous systemic sclerosis and experienced at least 7 attacks per week. Patients were randomized to receive modified-release sildenafil (100 mg once daily for 3 days, titrated to 200 mg once daily for 25 days) or placebo, reported Dr. Ariane Herrick of the University of Manchester (England) and her associates (Arthritis Rheum. 2011;63:775-82).

Of the 57 people originally enrolled, 20 in the treatment group and 25 controls completed the 28-day study and were entered into analysis. Patients kept treatment diaries before and during the study period, recording the duration and pain intensity of each attack; serum samples were taken on days 1, 7, and 28.

The primary end point was the percent change in the number of weekly RP attacks. Secondary end points measured the severity and duration of attacks.

After 28 days, the mean number of RP attacks per week lessened from 25 at baseline to 19 in the control arm, and from 31 at baseline to 19 in the treatment arm, with a mean percent reduction of 44% in the treatment arm, compared with 18% in the control arm (P = .034). Statistically insignificant differences were noted between the groups for Raynaud’s Condition Score, duration of attacks, pain score, endothelial dysfunction, or serum biomarkers associated with RP. The most frequent adverse events reported were headache and dyspepsia.

Dr. Ulf Müller-Ladner, professor of internal medicine and rheumatology at Justus-Liebig University Giessen (Germany), said in an interview that this "is a very important study, as we do not have too many controlled clinical trials for Raynaud’s, and every controlled study showing efficacy is very helpful for daily practice." The investigators acknowledged the study’s small size and high attrition from the intention-to-treat sildenafil arm as limitations, particularly as the study was no longer powered to detect secondary end points. Also disappointing, they wrote, was that the endothelial dysfunction measures and the serum levels of biomarkers were similar between the groups.

The study's short duration was another possible limitation. The findings from an earlier, longer (5.2-month) study of sildenafil in 16 patients with systemic sclerosis – of whom 7 had limited cutaneous involvement – showed statistically significant lessening of attack pain associated with RP with the maximum tolerated dose of sildenafil (Ann. Rheum. Dis. 2010;69:1475-8).

Finally, they noted, the modified-release formulation of sildenafil may not have provided the most effective dose for the patient population studied.

Dr. Müller-Ladner agreed with the description of the study's design weaknesses: "The shortcomings of the present study are its placebo arm and its short duration. These results must be confirmed through the initiation of a large, multinational, longer-term trial."

The trial was funded by Pfizer, the drug's manufacturer. Dr. Herrick acknowledged financial relationships with Actelion, Mediquest, Pfizer, and United Therapeutics. Several of the coinvestigators also made relevant financial disclosures. Dr. Müller-Ladner had no relevant financial disclosures.

The drug sildenafil reduced the frequency of attacks of Raynaud’s phenomenon secondary to limited cutaneous systemic sclerosis in a small, randomized, placebo-controlled trial that was reported in Arthritis & Rheumatism.

The study enrolled 57 men and women aged 18-75 years, all of whom both had a diagnosis of Raynaud’s phenomenon (RP) secondary to limited cutaneous systemic sclerosis and experienced at least 7 attacks per week. Patients were randomized to receive modified-release sildenafil (100 mg once daily for 3 days, titrated to 200 mg once daily for 25 days) or placebo, reported Dr. Ariane Herrick of the University of Manchester (England) and her associates (Arthritis Rheum. 2011;63:775-82).

Of the 57 people originally enrolled, 20 in the treatment group and 25 controls completed the 28-day study and were entered into analysis. Patients kept treatment diaries before and during the study period, recording the duration and pain intensity of each attack; serum samples were taken on days 1, 7, and 28.

The primary end point was the percent change in the number of weekly RP attacks. Secondary end points measured the severity and duration of attacks.

After 28 days, the mean number of RP attacks per week lessened from 25 at baseline to 19 in the control arm, and from 31 at baseline to 19 in the treatment arm, with a mean percent reduction of 44% in the treatment arm, compared with 18% in the control arm (P = .034). Statistically insignificant differences were noted between the groups for Raynaud’s Condition Score, duration of attacks, pain score, endothelial dysfunction, or serum biomarkers associated with RP. The most frequent adverse events reported were headache and dyspepsia.

Dr. Ulf Müller-Ladner, professor of internal medicine and rheumatology at Justus-Liebig University Giessen (Germany), said in an interview that this "is a very important study, as we do not have too many controlled clinical trials for Raynaud’s, and every controlled study showing efficacy is very helpful for daily practice." The investigators acknowledged the study’s small size and high attrition from the intention-to-treat sildenafil arm as limitations, particularly as the study was no longer powered to detect secondary end points. Also disappointing, they wrote, was that the endothelial dysfunction measures and the serum levels of biomarkers were similar between the groups.

The study’s short duration was another possible limitation. The findings from an earlier, longer (5.2-month) study of sildenafil in 16 patients with systemic sclerosis – of whom 7 had limited cutaneous involvement – showed statistically significant lessening of attack pain associated with RP with the maximum tolerated dose of sildenafil (Ann. Rheum. Dis. 2010;69:1475-8).

Finally, they noted, the modified-release formulation of sildenafil may not have provided the most effective dose for the patient population studied.

Dr. Müller-Ladner agreed with the description of the study’s design weaknesses: "The shortcomings of the present study are its placebo arm and its short duration. These results must be confirmed through the initiation of a large, multinational, longer-term trial."

The trial was funded by Pfizer, the drug’s manufacturer. Dr. Herrick acknowledged financial relationships with Actelion, Mediquest, Pfizer, and United Therapeutics. Several of the coinvestigators also made relevant financial disclosures. Dr. Müller-Ladner had no relevant financial disclosures.

The drug sildenafil reduced the frequency of attacks of Raynaud’s phenomenon secondary to limited cutaneous systemic sclerosis in a small, randomized, placebo-controlled trial that was reported in Arthritis & Rheumatism.

The study enrolled 57 men and women aged 18-75 years, all of whom both had a diagnosis of Raynaud’s phenomenon (RP) secondary to limited cutaneous systemic sclerosis and experienced at least 7 attacks per week. Patients were randomized to receive modified-release sildenafil (100 mg once daily for 3 days, titrated to 200 mg once daily for 25 days) or placebo, reported Dr. Ariane Herrick of the University of Manchester (England) and her associates (Arthritis Rheum. 2011;63:775-82).

Of the 57 people originally enrolled, 20 in the treatment group and 25 controls completed the 28-day study and were entered into analysis. Patients kept treatment diaries before and during the study period, recording the duration and pain intensity of each attack; serum samples were taken on days 1, 7, and 28.

The primary end point was the percent change in the number of weekly RP attacks. Secondary end points measured the severity and duration of attacks.

After 28 days, the mean number of RP attacks per week lessened from 25 at baseline to 19 in the control arm, and from 31 at baseline to 19 in the treatment arm, with a mean percent reduction of 44% in the treatment arm, compared with 18% in the control arm (P = .034). Statistically insignificant differences were noted between the groups for Raynaud’s Condition Score, duration of attacks, pain score, endothelial dysfunction, or serum biomarkers associated with RP. The most frequent adverse events reported were headache and dyspepsia.

Dr. Ulf Müller-Ladner, professor of internal medicine and rheumatology at Justus-Liebig University Giessen (Germany), said in an interview that this "is a very important study, as we do not have too many controlled clinical trials for Raynaud’s, and every controlled study showing efficacy is very helpful for daily practice." The investigators acknowledged the study’s small size and high attrition from the intention-to-treat sildenafil arm as limitations, particularly as the study was no longer powered to detect secondary end points. Also disappointing, they wrote, was that the endothelial dysfunction measures and the serum levels of biomarkers were similar between the groups.

The study’s short duration was another possible limitation. The findings from an earlier, longer (5.2-month) study of sildenafil in 16 patients with systemic sclerosis – of whom 7 had limited cutaneous involvement – showed statistically significant lessening of attack pain associated with RP with the maximum tolerated dose of sildenafil (Ann. Rheum. Dis. 2010;69:1475-8).

Finally, they noted, the modified-release formulation of sildenafil may not have provided the most effective dose for the patient population studied.

Dr. Müller-Ladner agreed with the description of the study’s design weaknesses: "The shortcomings of the present study are its placebo arm and its short duration. These results must be confirmed through the initiation of a large, multinational, longer-term trial."

The trial was funded by Pfizer, the drug’s manufacturer. Dr. Herrick acknowledged financial relationships with Actelion, Mediquest, Pfizer, and United Therapeutics. Several of the coinvestigators also made relevant financial disclosures. Dr. Müller-Ladner had no relevant financial disclosures.

The drug sildenafil reduced the frequency of attacks of Raynaud’s phenomenon secondary to limited cutaneous systemic sclerosis in a small, randomized, placebo-controlled trial that was reported in Arthritis & Rheumatism.

The study enrolled 57 men and women aged 18-75 years, all of whom both had a diagnosis of Raynaud’s phenomenon (RP) secondary to limited cutaneous systemic sclerosis and experienced at least 7 attacks per week. Patients were randomized to receive modified-release sildenafil (100 mg once daily for 3 days, titrated to 200 mg once daily for 25 days) or placebo, reported Dr. Ariane Herrick of the University of Manchester (England) and her associates (Arthritis Rheum. 2011;63:775-82).

Of the 57 people originally enrolled, 20 in the treatment group and 25 controls completed the 28-day study and were entered into analysis. Patients kept treatment diaries before and during the study period, recording the duration and pain intensity of each attack; serum samples were taken on days 1, 7, and 28.

The primary end point was the percent change in the number of weekly RP attacks. Secondary end points measured the severity and duration of attacks.

After 28 days, the mean number of RP attacks per week lessened from 25 at baseline to 19 in the control arm, and from 31 at baseline to 19 in the treatment arm, with a mean percent reduction of 44% in the treatment arm, compared with 18% in the control arm (P = .034). Statistically insignificant differences were noted between the groups for Raynaud’s Condition Score, duration of attacks, pain score, endothelial dysfunction, or serum biomarkers associated with RP. The most frequent adverse events reported were headache and dyspepsia.

Dr. Ulf Müller-Ladner, professor of internal medicine and rheumatology at Justus-Liebig University Giessen (Germany), said in an interview that this "is a very important study, as we do not have too many controlled clinical trials for Raynaud’s, and every controlled study showing efficacy is very helpful for daily practice." The investigators acknowledged the study’s small size and high attrition from the intention-to-treat sildenafil arm as limitations, particularly as the study was no longer powered to detect secondary end points. Also disappointing, they wrote, was that the endothelial dysfunction measures and the serum levels of biomarkers were similar between the groups.

The study’s short duration was another possible limitation. The findings from an earlier, longer (5.2-month) study of sildenafil in 16 patients with systemic sclerosis – of whom 7 had limited cutaneous involvement – showed statistically significant lessening of attack pain associated with RP with the maximum tolerated dose of sildenafil (Ann. Rheum. Dis. 2010;69:1475-8).

Finally, they noted, the modified-release formulation of sildenafil may not have provided the most effective dose for the patient population studied.

Dr. Müller-Ladner agreed with the description of the study’s design weaknesses: "The shortcomings of the present study are its placebo arm and its short duration. These results must be confirmed through the initiation of a large, multinational, longer-term trial."

The trial was funded by Pfizer, the drug’s manufacturer. Dr. Herrick acknowledged financial relationships with Actelion, Mediquest, Pfizer, and United Therapeutics. Several of the coinvestigators also made relevant financial disclosures. Dr. Müller-Ladner had no relevant financial disclosures.

The drug sildenafil reduced the frequency of attacks of Raynaud’s phenomenon secondary to limited cutaneous systemic sclerosis in a small, randomized, placebo-controlled trial that was reported in Arthritis & Rheumatism.

The study enrolled 57 men and women aged 18-75 years, all of whom both had a diagnosis of Raynaud’s phenomenon (RP) secondary to limited cutaneous systemic sclerosis and experienced at least 7 attacks per week. Patients were randomized to receive modified-release sildenafil (100 mg once daily for 3 days, titrated to 200 mg once daily for 25 days) or placebo, reported Dr. Ariane Herrick of the University of Manchester (England) and her associates (Arthritis Rheum. 2011;63:775-82).

Of the 57 people originally enrolled, 20 in the treatment group and 25 controls completed the 28-day study and were entered into analysis. Patients kept treatment diaries before and during the study period, recording the duration and pain intensity of each attack; serum samples were taken on days 1, 7, and 28.

The primary end point was the percent change in the number of weekly RP attacks. Secondary end points measured the severity and duration of attacks.

After 28 days, the mean number of RP attacks per week lessened from 25 at baseline to 19 in the control arm, and from 31 at baseline to 19 in the treatment arm, with a mean percent reduction of 44% in the treatment arm, compared with 18% in the control arm (P = .034). Statistically insignificant differences were noted between the groups for Raynaud’s Condition Score, duration of attacks, pain score, endothelial dysfunction, or serum biomarkers associated with RP. The most frequent adverse events reported were headache and dyspepsia.

Dr. Ulf Müller-Ladner, professor of internal medicine and rheumatology at Justus-Liebig University Giessen (Germany), said in an interview that this "is a very important study, as we do not have too many controlled clinical trials for Raynaud’s, and every controlled study showing efficacy is very helpful for daily practice." The investigators acknowledged the study’s small size and high attrition from the intention-to-treat sildenafil arm as limitations, particularly as the study was no longer powered to detect secondary end points. Also disappointing, they wrote, was that the endothelial dysfunction measures and the serum levels of biomarkers were similar between the groups.

The study’s short duration was another possible limitation. The findings from an earlier, longer (5.2-month) study of sildenafil in 16 patients with systemic sclerosis – of whom 7 had limited cutaneous involvement – showed statistically significant lessening of attack pain associated with RP with the maximum tolerated dose of sildenafil (Ann. Rheum. Dis. 2010;69:1475-8).

Finally, they noted, the modified-release formulation of sildenafil may not have provided the most effective dose for the patient population studied.

Dr. Müller-Ladner agreed with the description of the study’s design weaknesses: "The shortcomings of the present study are its placebo arm and its short duration. These results must be confirmed through the initiation of a large, multinational, longer-term trial."

The trial was funded by Pfizer, the drug’s manufacturer. Dr. Herrick acknowledged financial relationships with Actelion, Mediquest, Pfizer, and United Therapeutics. Several of the coinvestigators also made relevant financial disclosures. Dr. Müller-Ladner had no relevant financial disclosures.

The drug sildenafil reduced the frequency of attacks of Raynaud’s phenomenon secondary to limited cutaneous systemic sclerosis in a small, randomized, placebo-controlled trial that was reported in Arthritis & Rheumatism.

The study enrolled 57 men and women aged 18-75 years, all of whom both had a diagnosis of Raynaud’s phenomenon (RP) secondary to limited cutaneous systemic sclerosis and experienced at least 7 attacks per week. Patients were randomized to receive modified-release sildenafil (100 mg once daily for 3 days, titrated to 200 mg once daily for 25 days) or placebo, reported Dr. Ariane Herrick of the University of Manchester (England) and her associates (Arthritis Rheum. 2011;63:775-82).

Of the 57 people originally enrolled, 20 in the treatment group and 25 controls completed the 28-day study and were entered into analysis. Patients kept treatment diaries before and during the study period, recording the duration and pain intensity of each attack; serum samples were taken on days 1, 7, and 28.

The primary end point was the percent change in the number of weekly RP attacks. Secondary end points measured the severity and duration of attacks.

After 28 days, the mean number of RP attacks per week lessened from 25 at baseline to 19 in the control arm, and from 31 at baseline to 19 in the treatment arm, with a mean percent reduction of 44% in the treatment arm, compared with 18% in the control arm (P = .034). Statistically insignificant differences were noted between the groups for Raynaud’s Condition Score, duration of attacks, pain score, endothelial dysfunction, or serum biomarkers associated with RP. The most frequent adverse events reported were headache and dyspepsia.

Dr. Ulf Müller-Ladner, professor of internal medicine and rheumatology at Justus-Liebig University Giessen (Germany), said in an interview that this "is a very important study, as we do not have too many controlled clinical trials for Raynaud’s, and every controlled study showing efficacy is very helpful for daily practice." The investigators acknowledged the study’s small size and high attrition from the intention-to-treat sildenafil arm as limitations, particularly as the study was no longer powered to detect secondary end points. Also disappointing, they wrote, was that the endothelial dysfunction measures and the serum levels of biomarkers were similar between the groups.

The study’s short duration was another possible limitation. The findings from an earlier, longer (5.2-month) study of sildenafil in 16 patients with systemic sclerosis – of whom 7 had limited cutaneous involvement – showed statistically significant lessening of attack pain associated with RP with the maximum tolerated dose of sildenafil (Ann. Rheum. Dis. 2010;69:1475-8).

Finally, they noted, the modified-release formulation of sildenafil may not have provided the most effective dose for the patient population studied.

Dr. Müller-Ladner agreed with the description of the study’s design weaknesses: "The shortcomings of the present study are its placebo arm and its short duration. These results must be confirmed through the initiation of a large, multinational, longer-term trial."

The trial was funded by Pfizer, the drug’s manufacturer. Dr. Herrick acknowledged financial relationships with Actelion, Mediquest, Pfizer, and United Therapeutics. Several of the coinvestigators also made relevant financial disclosures. Dr. Müller-Ladner had no relevant financial disclosures.

The drug sildenafil reduced the frequency of attacks of Raynaud’s phenomenon secondary to limited cutaneous systemic sclerosis in a small, randomized, placebo-controlled trial that was reported in Arthritis & Rheumatism.

The study enrolled 57 men and women aged 18-75 years, all of whom both had a diagnosis of Raynaud’s phenomenon (RP) secondary to limited cutaneous systemic sclerosis and experienced at least 7 attacks per week. Patients were randomized to receive modified-release sildenafil (100 mg once daily for 3 days, titrated to 200 mg once daily for 25 days) or placebo, reported Dr. Ariane Herrick of the University of Manchester (England) and her associates (Arthritis Rheum. 2011;63:775-82).

Of the 57 people originally enrolled, 20 in the treatment group and 25 controls completed the 28-day study and were entered into analysis. Patients kept treatment diaries before and during the study period, recording the duration and pain intensity of each attack; serum samples were taken on days 1, 7, and 28.

The primary end point was the percent change in the number of weekly RP attacks. Secondary end points measured the severity and duration of attacks.

After 28 days, the mean number of RP attacks per week lessened from 25 at baseline to 19 in the control arm, and from 31 at baseline to 19 in the treatment arm, with a mean percent reduction of 44% in the treatment arm, compared with 18% in the control arm (P = .034). Statistically insignificant differences were noted between the groups for Raynaud’s Condition Score, duration of attacks, pain score, endothelial dysfunction, or serum biomarkers associated with RP. The most frequent adverse events reported were headache and dyspepsia.

Dr. Ulf Müller-Ladner, professor of internal medicine and rheumatology at Justus-Liebig University Giessen (Germany), said in an interview that this "is a very important study, as we do not have too many controlled clinical trials for Raynaud’s, and every controlled study showing efficacy is very helpful for daily practice." The investigators acknowledged the study’s small size and high attrition from the intention-to-treat sildenafil arm as limitations, particularly as the study was no longer powered to detect secondary end points. Also disappointing, they wrote, was that the endothelial dysfunction measures and the serum levels of biomarkers were similar between the groups.

The study’s short duration was another possible limitation. The findings from an earlier, longer (5.2-month) study of sildenafil in 16 patients with systemic sclerosis – of whom 7 had limited cutaneous involvement – showed statistically significant lessening of attack pain associated with RP with the maximum tolerated dose of sildenafil (Ann. Rheum. Dis. 2010;69:1475-8).

Finally, they noted, the modified-release formulation of sildenafil may not have provided the most effective dose for the patient population studied.

Dr. Müller-Ladner agreed with the description of the study’s design weaknesses: "The shortcomings of the present study are its placebo arm and its short duration. These results must be confirmed through the initiation of a large, multinational, longer-term trial."

The trial was funded by Pfizer, the drug’s manufacturer. Dr. Herrick acknowledged financial relationships with Actelion, Mediquest, Pfizer, and United Therapeutics. Several of the coinvestigators also made relevant financial disclosures. Dr. Müller-Ladner had no relevant financial disclosures.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

A modest, 12-week collaborative care intervention alleviated depression symptoms – at least in the short term – in depressed patients hospitalized for a wide spectrum of cardiovascular diseases.

The findings, from a randomized, controlled trial in 175 depressed patients hospitalized for acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure, , published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, suggest that a collaborative care depression management program begun in the hospital could have benefits in these groups even when follow-up is limited to a few phone calls from a care coordinator after discharge. 

The current study, published March 8 in the journal Circulation: Cardiovascular Quality and Outcomes, and led by Dr. Jeff C. Huffman and his colleagues at Harvard Medical School and Massachusetts General Hospital, both in Boston, differed from earlier research by initiating the intervention during hospitalization instead of shortly afterward, by enrolling people admitted for a wide range of cardiovascular diseases and by having relatively light postdischarge follow-up, with a maximum of three phone conversations between care coordinators and patients over 12 weeks (Circ. Cardiovasc. Qual. Outcomes 2011;4:198-205).

Also, for baseline and subsequent mental health analyses, Dr. Huffman and his colleagues used clinical depression measures recommended by the American Heart Association (Circulation 2008;188:1768-75): a Patient Health Questionnaire-2 on admission, with patients with positive screens further evaluated using Patient Health Questionnaire-9 (PHQ-9).

Hospital-started interventions have been generally avoided for this type of study, commented Dr. Bruce L. Rollman of the University of Pittsburgh, because some mood symptoms may be related to the hospitalization itself or resolve shortly following hospital discharge. However, for the their study, Dr. Huffman and his colleagues noted, subjects were highly selected, with more than 70% having a prior episode of depression and ongoing symptoms for 1 month before enrollment.

The 85 patients randomized to usual care had a mean age of 62.6 years; 55% were women and 91% were white. In that treatment, a care manager first informed the hospital team of each patient’s depression, then placed follow-up phone calls intermittently until 12 weeks after discharge to assess the patient’s depression status. If the manager determined that depression was ongoing, he or she informed the patient’s primary care physician.

For the 90 subjects in the treatment arm (mean age 62.1, 42% women, 92% white) the care manager provided more elaborate coordination and follow up that included in-hospital tutorials about depression and cardiac disease, help planning postdischarge activities, and postdischarge phone calls to determine whether changes were needed. The coordinator and psychiatrist developed depression treatment recommendations that were then prescribed by the psychiatrist, and the care manager worked to coordinate treatment with all providers.

Patients in both arms were evaluated again 6 weeks, 12 weeks, and 6 months after discharge.

The collaborative care subjects saw significantly greater rates of depression response, as measured by PHQ-9, at 6 weeks, compared with usual care (59.7%, and 33.7%, respectively). At 12 weeks, the difference remained significant but began to narrow, with 51.5% in the intervention, compared with 34.4% in the control arm. No statistically significant difference in depression response was found between the arms at 6 months. Cardiac symptoms were not significantly different at either 6 or 12 weeks between the arms, and hospital readmission outcomes for cardiac symptoms were similar – about 40% – for both groups after 6 months.

Collaborative care programs use nonphysician coordinators to facilitate communication and treatment plans among patients, their primary care doctors, and specialists. Part of the programs’ appeal, said Dr. Rollman in an interview, is that they can be performed on the phone for relatively little cost: “You could potentially do this from a call center in India, or on Skype.”

Several studies have evaluated collaborative care after hospitalization for depressed patients with specific cardiac diseases: Dr. Rollman’s recent 302-patient randomized controlled trial, called Bypassing the Blues, found telephone-administered collaborative care programs associated with significantly better self-reported mental and physical outcomes depressed patients 8 months after coronary artery surgery, compared with standard care (JAMA 2009;302:2095-103).

Dr. Roy Ziegelstein, of Johns Hopkins University’s Center for Mind-Body Research in Baltimore, called the current study important, and pointed to the difference in antidepressant use between the two groups. Of the patients in usual care, 46% were taking an antidepressant on admission, compared with 56% by hospital discharge, he said in an interview. Of patients in the treatment arm, 42% were taking an antidepressant on admission, compared with 83% at discharge, a near-doubling.

This shows “that without comprehensive depression care and follow-up, very little seems to happen even after screening and assessment,” Dr. Ziegelstein said, adding that, given the differences in medication use between the groups, it was “somewhat disappointing” that the differences in depression response did not also persist after the 12-week intervention.

Thomas Rutledge, Ph.D., of the department of psychiatry the University of California, San Diego, lauded the low-cost and low-intensity nature of the trial intervention but cautioned that as the mental health benefits appeared to drop after 12 weeks, continued effectiveness might require longer term treatment protocols, “or phasing patients into some sort of aftercare maintenance treatment.”

Dr. Rutledge also pointed to the study’s use of PHQ screening to help identify subjects as important, and potentially hard to replicate. “Screening for depression in cardiac populations is recommended by the American Heart Association but is often impractical without staff and care managers such as this study employed to accomplish this task,” he said. “Any effort to implement this study protocol in clinic would require that staff be identified for the administration and scoring of depression screening instruments.”

Dr. Huffman’s study was funded by the American Heart Association. Neither he nor his colleagues declared conflicts of interest.

* UPDATE, 3/9/2011: This article has been edited to reflect updated comments from Dr. Rollman and Dr. Ziegelstein.

The Food and Drug Administration has approved 17-alpha-hydroxyprogesterone caproate, a progesterone injection also known as 17P, for the prevention of recurrent preterm birth in women with singleton pregnancies.

The FDA said in a press statement that it had approved 17P (Makena) under the agency's accelerated approval regulations that allow drugs to be approved based on a surrogate end point benefit that is “reasonably likely to predict a clinical benefit.”

Hydroxyprogesterone caproate was initially approved in 1956 for the treatment and prevention of recurrent miscarriage, among other indications, but was withdrawn in 2000 because of manufacturing problems. Hospital pharmacies continued to mix the compound, and it remained available in many settings.

The March of Dimes said in a statement that it welcomed 17P's approval. “Prior to today's approval of Makena, health care providers ordered prescriptions of 17P from compounding pharmacies; however, many eligible patients faced logistical and financial barriers to access. FDA approval means the drug now will be widely available.”

It also should raise patient confidence. “Patients are much more accepting and comfortable when you can tell them it's FDA approved,” Dr. Laura E. Riley, medical director of labor and delivery at Massachusetts General Hospital in Boston, said in an interview.

The drug was first marketed in the 1950s as Delalutin. It was resubmitted to the FDA in 2006 as Gestiva by a California firm, and will now be marketed by its current manufacturer, the Massachusetts-based Hologic, as Makena.

The approval comes nearly 5 years after an FDA advisory panel voted in 17P's favor, based on results from a publicly funded, randomized, double-blind, placebo-controlled trial of 463 women with at least one preterm delivery (N. Engl. J. Med. 2003;348:2379-85).

That trial showed that women receiving weekly injections of 250 mg of 17P, starting at 20 weeks and continuing to 36 weeks or delivery, saw a 24% reduced risk of delivery before 37 weeks, compared with the control group.

The study also showed reductions in the rates of preterm delivery before 35 weeks and before 32 weeks in the treatment arm.

After the FDA panel's vote in August 2006, the agency demanded further safety studies, including now-completed studies of children born to women taking 17P, from the medicine's then-developer, which later sold its rights to 17P. In 2010 the drug's current developer, Hologic, resubmitted its filing for 17P.

The FDA said that the drug's approval comes with the manufacturer's responsibility to complete ongoing confirmatory studies, including a new infant follow-up study, expected to end in 2018 and to include between 580 and 750 infants.

View on the News

Availability a 'Great Advancement'

Dr. Sarah J. Kilpatrick called the FDA approval of 17-alpha-hydroxyprogesterone caproate a “great advancement.” Before the approval, special pharmacies had to compound the drug, also known as 17P. She said that she's “very confident” with the amount of long-term data about progesterone, which is a normal hormone that the body produces during pregnancy.

“It was not as accessible as presumably it will be now,” Dr. Kilpatrick said in an interview.

In addition to wider availability, another advantage is greater accuracy in dosage, because with compounding pharmacies there was always the potential for error, she said.

Before the drug's approval, insurance did not cover the cost in some states, according to Dr. Kilpatrick. “Hopefully, with an FDA approval, that will not be a problem now.” Even so, she added that the cost of 20 weeks of progesterone injections is still less than the cost of a preterm baby in the hospital.

There may be a possible downside to the drug's approval. “If it's easier to obtain, it could be used for the wrong people,” she said. Progesterone should only be used to prevent preterm delivery – not treat it – and only for women who have had prior preterm deliveries.

DR. KILPATRICK is the chair of the department of obstetrics and gynecology at Cedars-Sinai Medical Center in Los Angeles. She is also a past president of the Society for Maternal-Fetal Medicine. Dr. Kilpatrick reported having no relevant financial disclosures.

The Food and Drug Administration has approved 17-alpha-hydroxyprogesterone caproate, a progesterone injection also known as 17P, for the prevention of recurrent preterm birth in women with singleton pregnancies.

The FDA said in a press statement that it had approved 17P (Makena) under the agency's accelerated approval regulations that allow drugs to be approved based on a surrogate end point benefit that is “reasonably likely to predict a clinical benefit.”

Hydroxyprogesterone caproate was initially approved in 1956 for the treatment and prevention of recurrent miscarriage, among other indications, but was withdrawn in 2000 because of manufacturing problems. Hospital pharmacies continued to mix the compound, and it remained available in many settings.

The March of Dimes said in a statement that it welcomed 17P's approval. “Prior to today's approval of Makena, health care providers ordered prescriptions of 17P from compounding pharmacies; however, many eligible patients faced logistical and financial barriers to access. FDA approval means the drug now will be widely available.”

It also should raise patient confidence. “Patients are much more accepting and comfortable when you can tell them it's FDA approved,” Dr. Laura E. Riley, medical director of labor and delivery at Massachusetts General Hospital in Boston, said in an interview.

The drug was first marketed in the 1950s as Delalutin. It was resubmitted to the FDA in 2006 as Gestiva by a California firm, and will now be marketed by its current manufacturer, the Massachusetts-based Hologic, as Makena.

The approval comes nearly 5 years after an FDA advisory panel voted in 17P's favor, based on results from a publicly funded, randomized, double-blind, placebo-controlled trial of 463 women with at least one preterm delivery (N. Engl. J. Med. 2003;348:2379-85).

That trial showed that women receiving weekly injections of 250 mg of 17P, starting at 20 weeks and continuing to 36 weeks or delivery, saw a 24% reduced risk of delivery before 37 weeks, compared with the control group.

The study also showed reductions in the rates of preterm delivery before 35 weeks and before 32 weeks in the treatment arm.

After the FDA panel's vote in August 2006, the agency demanded further safety studies, including now-completed studies of children born to women taking 17P, from the medicine's then-developer, which later sold its rights to 17P. In 2010 the drug's current developer, Hologic, resubmitted its filing for 17P.

The FDA said that the drug's approval comes with the manufacturer's responsibility to complete ongoing confirmatory studies, including a new infant follow-up study, expected to end in 2018 and to include between 580 and 750 infants.

View on the News

Availability a 'Great Advancement'

Dr. Sarah J. Kilpatrick called the FDA approval of 17-alpha-hydroxyprogesterone caproate a “great advancement.” Before the approval, special pharmacies had to compound the drug, also known as 17P. She said that she's “very confident” with the amount of long-term data about progesterone, which is a normal hormone that the body produces during pregnancy.

“It was not as accessible as presumably it will be now,” Dr. Kilpatrick said in an interview.

In addition to wider availability, another advantage is greater accuracy in dosage, because with compounding pharmacies there was always the potential for error, she said.

Before the drug's approval, insurance did not cover the cost in some states, according to Dr. Kilpatrick. “Hopefully, with an FDA approval, that will not be a problem now.” Even so, she added that the cost of 20 weeks of progesterone injections is still less than the cost of a preterm baby in the hospital.

There may be a possible downside to the drug's approval. “If it's easier to obtain, it could be used for the wrong people,” she said. Progesterone should only be used to prevent preterm delivery – not treat it – and only for women who have had prior preterm deliveries.

DR. KILPATRICK is the chair of the department of obstetrics and gynecology at Cedars-Sinai Medical Center in Los Angeles. She is also a past president of the Society for Maternal-Fetal Medicine. Dr. Kilpatrick reported having no relevant financial disclosures.

The Food and Drug Administration has approved 17-alpha-hydroxyprogesterone caproate, a progesterone injection also known as 17P, for the prevention of recurrent preterm birth in women with singleton pregnancies.

The FDA said in a press statement that it had approved 17P (Makena) under the agency's accelerated approval regulations that allow drugs to be approved based on a surrogate end point benefit that is “reasonably likely to predict a clinical benefit.”

Hydroxyprogesterone caproate was initially approved in 1956 for the treatment and prevention of recurrent miscarriage, among other indications, but was withdrawn in 2000 because of manufacturing problems. Hospital pharmacies continued to mix the compound, and it remained available in many settings.

The March of Dimes said in a statement that it welcomed 17P's approval. “Prior to today's approval of Makena, health care providers ordered prescriptions of 17P from compounding pharmacies; however, many eligible patients faced logistical and financial barriers to access. FDA approval means the drug now will be widely available.”

It also should raise patient confidence. “Patients are much more accepting and comfortable when you can tell them it's FDA approved,” Dr. Laura E. Riley, medical director of labor and delivery at Massachusetts General Hospital in Boston, said in an interview.

The drug was first marketed in the 1950s as Delalutin. It was resubmitted to the FDA in 2006 as Gestiva by a California firm, and will now be marketed by its current manufacturer, the Massachusetts-based Hologic, as Makena.

The approval comes nearly 5 years after an FDA advisory panel voted in 17P's favor, based on results from a publicly funded, randomized, double-blind, placebo-controlled trial of 463 women with at least one preterm delivery (N. Engl. J. Med. 2003;348:2379-85).

That trial showed that women receiving weekly injections of 250 mg of 17P, starting at 20 weeks and continuing to 36 weeks or delivery, saw a 24% reduced risk of delivery before 37 weeks, compared with the control group.

The study also showed reductions in the rates of preterm delivery before 35 weeks and before 32 weeks in the treatment arm.

After the FDA panel's vote in August 2006, the agency demanded further safety studies, including now-completed studies of children born to women taking 17P, from the medicine's then-developer, which later sold its rights to 17P. In 2010 the drug's current developer, Hologic, resubmitted its filing for 17P.

The FDA said that the drug's approval comes with the manufacturer's responsibility to complete ongoing confirmatory studies, including a new infant follow-up study, expected to end in 2018 and to include between 580 and 750 infants.

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Availability a 'Great Advancement'

Dr. Sarah J. Kilpatrick called the FDA approval of 17-alpha-hydroxyprogesterone caproate a “great advancement.” Before the approval, special pharmacies had to compound the drug, also known as 17P. She said that she's “very confident” with the amount of long-term data about progesterone, which is a normal hormone that the body produces during pregnancy.

“It was not as accessible as presumably it will be now,” Dr. Kilpatrick said in an interview.

In addition to wider availability, another advantage is greater accuracy in dosage, because with compounding pharmacies there was always the potential for error, she said.

Before the drug's approval, insurance did not cover the cost in some states, according to Dr. Kilpatrick. “Hopefully, with an FDA approval, that will not be a problem now.” Even so, she added that the cost of 20 weeks of progesterone injections is still less than the cost of a preterm baby in the hospital.

There may be a possible downside to the drug's approval. “If it's easier to obtain, it could be used for the wrong people,” she said. Progesterone should only be used to prevent preterm delivery – not treat it – and only for women who have had prior preterm deliveries.

DR. KILPATRICK is the chair of the department of obstetrics and gynecology at Cedars-Sinai Medical Center in Los Angeles. She is also a past president of the Society for Maternal-Fetal Medicine. Dr. Kilpatrick reported having no relevant financial disclosures.

Body mass index rose in all parts of the globe over the past 3 decades, and the proportion of obese people worldwide doubled.

Meanwhile, mean systolic blood pressure dropped worldwide, and total cholesterol levels stayed roughly the same, but with huge regional differences.

Cholesterol levels fell in some regions, particularly in the United States and other English-speaking nations, and increased in others, such as East Asia, according to three papers by collaborating research teams.

Blood pressure was similarly variable by region, with upward trends in parts of Asia and Africa that were countered by downward trends in North America, Australia, and much of Europe.

“We've got this massive wave of obesity happening, but particularly in English-speaking countries we have had this really large decline [in cholesterol and blood pressure]. The good news is, we are mitigating some of the obesity effects,” Majid Ezzati, Ph.D., of Harvard School of Public Health, Boston, and Imperial College London, the papers' senior author, said in an interview. But obesity “is a serious rise that we should become serious about combating.”

Dr. Ezzati and colleagues' research, which was funded by the World Health Organization and the Bill and Melinda Gates Foundation, sought to map global trends for the main cardiovascular disease indicators – BMI, systolic blood pressure, and total serum cholesterol – in 199 countries and territories during 1980–2008.

The BMI team used data on 960 country-years with 9.1 million people aged 20 years and older (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62037-5]). Dr. Ezzati and colleagues found that in 2008, 9.8% of men and 13.8% of women worldwide were obese (defined as having a BMI greater than 30 kg/m

Mean BMI worldwide increased by 0.4 per decade for men and 0.5 per decade for women. A group of countries in the tropical Pacific region saw an increase of 2 per decade for women, and higher still for men. A handful of countries in South Asia, sub-Saharan Africa, and Europe, meanwhile, registered very slight or no increases, or even declines.

Among high-income countries, the English-speaking countries – including the United States, the United Kingdom, Australia, and New Zealand – saw some of the most pronounced increases, which put them in sharp contrast to some Western European nations.

The United States had both the highest worldwide BMI among high-income countries (mean, 28 for both men and women) and the highest rise in BMI over 28 years (1.1 per decade), followed by male BMI in the United Kingdom (1 per decade) and Australia (0.9 per decade). In 2008, mean BMI in men was highest in North America (28.4) and Australia and New Zealand (27.6). Also among high-income countries, the United States, New Zealand, and Australia saw the most gains in female BMI over 30 years, with increases of 1.2 per decade.

Changes in blood pressure and cholesterol in these nations, however, did not correspond to these trends but rather seemed to run counter to them.

The English-speaking countries that saw substantial increases in BMI also recorded significant decreases in total cholesterol levels and blood pressure over the same period, according to a linked study, suggesting an effect from cholesterol-lowering drugs. And Asian countries, which had some of the world's lowest cholesterol levels in 1980, saw dramatic rises.

The cholesterol study examined published and unpublished records encompassing 3 million participants aged 25 years and older in 199 countries (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62038-7]). Worldwide, the mean, age-standardized, total serum cholesterol level was 4.64 mmol/L for men and 4.76 mmol/L for women, a slight decrease of 0.1 mmol/L per decade since 1980.

Cholesterol fell in Australia, New Zealand, North America, and Western Europe by 0.19 mmol/L per decade for men and by 0.21 mmol/L for women.

However, levels remained high in these regions, with a mean of 5.24 for men and 5.23 for women in 2008, with Germany, Greenland, and Iceland having mean, age-standardized levels of 5.5 or greater.

Mean total cholesterol increased in East and Southeast Asia by 0.08 mmol/L per decade in men and by 0.09 mmol/L per decade in women, and was lowest in sub-Saharan Africa at 4.08 for men and 4.27 for women. Cholesterol levels in Japan, which were relatively low in 1980, were close to levels in Western Europe in 2008. Singapore and China also registered substantial increases.

Globally, the news on blood pressure was also mixed. Mean, age-standardized, systolic blood pressure decreased by 0.8 mm Hg per decade in men and by 1.0 mm Hg per decade in women since 1980, with Western Europe, Australia, New Zealand, and North America seeing steep declines, according to a study of 5.4 million people aged 25 years and older in 199 countries. (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62036-3])

However, blood pressure rose in the tropical Pacific, East Africa, and South and Southeast Asia for both sexes, and in West Africa for women in the same period. Female systolic blood pressure was highest in some East and West African countries in 2008, with means of 135 mm Hg or greater – numbers that, the investigators noted, were not unlike those seen in Europe and North America at the beginning of the study period in 1980.

“The decline we have seen is [primarily] in high-income countries and also parts of Latin America, so really we are dividing the world into the high-income nations that are mitigating the effects,” Dr. Ezzati said. “Middle-income countries, such as those in Latin America, have shown that they can do it, too, but in lower-income countries the infrastructure is really absent.”

The good news on blood pressure and cholesterol, he said, should be interpreted with caution. With drug interventions, “we are either mitigating or delaying the effects of obesity – we don't know,” he said.

Dr. Ezzati and colleagues are now working on a diabetes study of similar global scope.

Two researchers reported holding stock in Johnson & Johnson and Pfizer.

Body mass index rose in all parts of the globe over the past 3 decades, and the proportion of obese people worldwide doubled.

Meanwhile, mean systolic blood pressure dropped worldwide, and total cholesterol levels stayed roughly the same, but with huge regional differences.

Cholesterol levels fell in some regions, particularly in the United States and other English-speaking nations, and increased in others, such as East Asia, according to three papers by collaborating research teams.

Blood pressure was similarly variable by region, with upward trends in parts of Asia and Africa that were countered by downward trends in North America, Australia, and much of Europe.

“We've got this massive wave of obesity happening, but particularly in English-speaking countries we have had this really large decline [in cholesterol and blood pressure]. The good news is, we are mitigating some of the obesity effects,” Majid Ezzati, Ph.D., of Harvard School of Public Health, Boston, and Imperial College London, the papers' senior author, said in an interview. But obesity “is a serious rise that we should become serious about combating.”

Dr. Ezzati and colleagues' research, which was funded by the World Health Organization and the Bill and Melinda Gates Foundation, sought to map global trends for the main cardiovascular disease indicators – BMI, systolic blood pressure, and total serum cholesterol – in 199 countries and territories during 1980–2008.

The BMI team used data on 960 country-years with 9.1 million people aged 20 years and older (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62037-5]). Dr. Ezzati and colleagues found that in 2008, 9.8% of men and 13.8% of women worldwide were obese (defined as having a BMI greater than 30 kg/m

Mean BMI worldwide increased by 0.4 per decade for men and 0.5 per decade for women. A group of countries in the tropical Pacific region saw an increase of 2 per decade for women, and higher still for men. A handful of countries in South Asia, sub-Saharan Africa, and Europe, meanwhile, registered very slight or no increases, or even declines.

Among high-income countries, the English-speaking countries – including the United States, the United Kingdom, Australia, and New Zealand – saw some of the most pronounced increases, which put them in sharp contrast to some Western European nations.

The United States had both the highest worldwide BMI among high-income countries (mean, 28 for both men and women) and the highest rise in BMI over 28 years (1.1 per decade), followed by male BMI in the United Kingdom (1 per decade) and Australia (0.9 per decade). In 2008, mean BMI in men was highest in North America (28.4) and Australia and New Zealand (27.6). Also among high-income countries, the United States, New Zealand, and Australia saw the most gains in female BMI over 30 years, with increases of 1.2 per decade.

Changes in blood pressure and cholesterol in these nations, however, did not correspond to these trends but rather seemed to run counter to them.

The English-speaking countries that saw substantial increases in BMI also recorded significant decreases in total cholesterol levels and blood pressure over the same period, according to a linked study, suggesting an effect from cholesterol-lowering drugs. And Asian countries, which had some of the world's lowest cholesterol levels in 1980, saw dramatic rises.

The cholesterol study examined published and unpublished records encompassing 3 million participants aged 25 years and older in 199 countries (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62038-7]). Worldwide, the mean, age-standardized, total serum cholesterol level was 4.64 mmol/L for men and 4.76 mmol/L for women, a slight decrease of 0.1 mmol/L per decade since 1980.

Cholesterol fell in Australia, New Zealand, North America, and Western Europe by 0.19 mmol/L per decade for men and by 0.21 mmol/L for women.

However, levels remained high in these regions, with a mean of 5.24 for men and 5.23 for women in 2008, with Germany, Greenland, and Iceland having mean, age-standardized levels of 5.5 or greater.

Mean total cholesterol increased in East and Southeast Asia by 0.08 mmol/L per decade in men and by 0.09 mmol/L per decade in women, and was lowest in sub-Saharan Africa at 4.08 for men and 4.27 for women. Cholesterol levels in Japan, which were relatively low in 1980, were close to levels in Western Europe in 2008. Singapore and China also registered substantial increases.

Globally, the news on blood pressure was also mixed. Mean, age-standardized, systolic blood pressure decreased by 0.8 mm Hg per decade in men and by 1.0 mm Hg per decade in women since 1980, with Western Europe, Australia, New Zealand, and North America seeing steep declines, according to a study of 5.4 million people aged 25 years and older in 199 countries. (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62036-3])

However, blood pressure rose in the tropical Pacific, East Africa, and South and Southeast Asia for both sexes, and in West Africa for women in the same period. Female systolic blood pressure was highest in some East and West African countries in 2008, with means of 135 mm Hg or greater – numbers that, the investigators noted, were not unlike those seen in Europe and North America at the beginning of the study period in 1980.

“The decline we have seen is [primarily] in high-income countries and also parts of Latin America, so really we are dividing the world into the high-income nations that are mitigating the effects,” Dr. Ezzati said. “Middle-income countries, such as those in Latin America, have shown that they can do it, too, but in lower-income countries the infrastructure is really absent.”

The good news on blood pressure and cholesterol, he said, should be interpreted with caution. With drug interventions, “we are either mitigating or delaying the effects of obesity – we don't know,” he said.

Dr. Ezzati and colleagues are now working on a diabetes study of similar global scope.

Two researchers reported holding stock in Johnson & Johnson and Pfizer.

Body mass index rose in all parts of the globe over the past 3 decades, and the proportion of obese people worldwide doubled.

Meanwhile, mean systolic blood pressure dropped worldwide, and total cholesterol levels stayed roughly the same, but with huge regional differences.

Cholesterol levels fell in some regions, particularly in the United States and other English-speaking nations, and increased in others, such as East Asia, according to three papers by collaborating research teams.

Blood pressure was similarly variable by region, with upward trends in parts of Asia and Africa that were countered by downward trends in North America, Australia, and much of Europe.

“We've got this massive wave of obesity happening, but particularly in English-speaking countries we have had this really large decline [in cholesterol and blood pressure]. The good news is, we are mitigating some of the obesity effects,” Majid Ezzati, Ph.D., of Harvard School of Public Health, Boston, and Imperial College London, the papers' senior author, said in an interview. But obesity “is a serious rise that we should become serious about combating.”

Dr. Ezzati and colleagues' research, which was funded by the World Health Organization and the Bill and Melinda Gates Foundation, sought to map global trends for the main cardiovascular disease indicators – BMI, systolic blood pressure, and total serum cholesterol – in 199 countries and territories during 1980–2008.

The BMI team used data on 960 country-years with 9.1 million people aged 20 years and older (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62037-5]). Dr. Ezzati and colleagues found that in 2008, 9.8% of men and 13.8% of women worldwide were obese (defined as having a BMI greater than 30 kg/m

Mean BMI worldwide increased by 0.4 per decade for men and 0.5 per decade for women. A group of countries in the tropical Pacific region saw an increase of 2 per decade for women, and higher still for men. A handful of countries in South Asia, sub-Saharan Africa, and Europe, meanwhile, registered very slight or no increases, or even declines.

Among high-income countries, the English-speaking countries – including the United States, the United Kingdom, Australia, and New Zealand – saw some of the most pronounced increases, which put them in sharp contrast to some Western European nations.

The United States had both the highest worldwide BMI among high-income countries (mean, 28 for both men and women) and the highest rise in BMI over 28 years (1.1 per decade), followed by male BMI in the United Kingdom (1 per decade) and Australia (0.9 per decade). In 2008, mean BMI in men was highest in North America (28.4) and Australia and New Zealand (27.6). Also among high-income countries, the United States, New Zealand, and Australia saw the most gains in female BMI over 30 years, with increases of 1.2 per decade.

Changes in blood pressure and cholesterol in these nations, however, did not correspond to these trends but rather seemed to run counter to them.

The English-speaking countries that saw substantial increases in BMI also recorded significant decreases in total cholesterol levels and blood pressure over the same period, according to a linked study, suggesting an effect from cholesterol-lowering drugs. And Asian countries, which had some of the world's lowest cholesterol levels in 1980, saw dramatic rises.

The cholesterol study examined published and unpublished records encompassing 3 million participants aged 25 years and older in 199 countries (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62038-7]). Worldwide, the mean, age-standardized, total serum cholesterol level was 4.64 mmol/L for men and 4.76 mmol/L for women, a slight decrease of 0.1 mmol/L per decade since 1980.

Cholesterol fell in Australia, New Zealand, North America, and Western Europe by 0.19 mmol/L per decade for men and by 0.21 mmol/L for women.

However, levels remained high in these regions, with a mean of 5.24 for men and 5.23 for women in 2008, with Germany, Greenland, and Iceland having mean, age-standardized levels of 5.5 or greater.

Mean total cholesterol increased in East and Southeast Asia by 0.08 mmol/L per decade in men and by 0.09 mmol/L per decade in women, and was lowest in sub-Saharan Africa at 4.08 for men and 4.27 for women. Cholesterol levels in Japan, which were relatively low in 1980, were close to levels in Western Europe in 2008. Singapore and China also registered substantial increases.

Globally, the news on blood pressure was also mixed. Mean, age-standardized, systolic blood pressure decreased by 0.8 mm Hg per decade in men and by 1.0 mm Hg per decade in women since 1980, with Western Europe, Australia, New Zealand, and North America seeing steep declines, according to a study of 5.4 million people aged 25 years and older in 199 countries. (Lancet 2011 Feb. 4 [doi:10.1016/S0140-6736(10)62036-3])

However, blood pressure rose in the tropical Pacific, East Africa, and South and Southeast Asia for both sexes, and in West Africa for women in the same period. Female systolic blood pressure was highest in some East and West African countries in 2008, with means of 135 mm Hg or greater – numbers that, the investigators noted, were not unlike those seen in Europe and North America at the beginning of the study period in 1980.

“The decline we have seen is [primarily] in high-income countries and also parts of Latin America, so really we are dividing the world into the high-income nations that are mitigating the effects,” Dr. Ezzati said. “Middle-income countries, such as those in Latin America, have shown that they can do it, too, but in lower-income countries the infrastructure is really absent.”

The good news on blood pressure and cholesterol, he said, should be interpreted with caution. With drug interventions, “we are either mitigating or delaying the effects of obesity – we don't know,” he said.

Dr. Ezzati and colleagues are now working on a diabetes study of similar global scope.

Two researchers reported holding stock in Johnson & Johnson and Pfizer.

Being obese may significantly increase the risk of having a fatal coronary heart disease event independent of known obesity-associated cardiovascular risk factors such as high blood pressure and high cholesterol, investigators in Scotland have found.

By contrast, obesity alone was not seen as significantly increasing the risk of nonfatal CHD events.

The findings, derived from the long-term follow-up of a large pharmaceutical trial, and published in the journal Heart (doi:10.1136/hrt.2010.211201), suggest that fatal and nonfatal CHD events could have separate causes – and that CHD death might not be preventable by mitigating traditional cardiovascular risk factors in obese men.

“It's assumed that nonfatal and fatal events occur along an index of severity – but maybe there's something different going on,” Dr. Jennifer Logue of the University of Glasgow, the study's lead investigator, said in an interview.

With the fatal events, she said, “we found an almost 60% higher risk from obesity alone.” The risk was seen after modeling for obesity-associated cardiovascular risks such as high blood pressure and high cholesterol level, along with factors such as smoking, low socioeconomic status, and medications.

“If you've got a middle-aged man in front of you with a [body mass index] of 35 – and that's not an uncommon sight nowadays – yes, you can treat his blood pressure and cholesterol and help him stop smoking,” Dr. Logue said. “But his weight itself is still making him at significant risk.”

Dr. Logue and her colleagues examined data from 6,082 men, with a mean age of 55, who had moderate hypercholesterolemia but who were without a history of diabetes or cardiovascular disease. The men had originally been enrolled in a manufacturer-sponsored, 5-year, randomized, placebo-controlled controlled trial to determine the effectiveness of the statin drug pravastatin in preventing cardiovascular events (N. Engl. J. Med. 1995; 333:1301-7), and the follow-up period ran to 15 years.

The researchers excluded from their analysis men who had had a fatal or nonfatal CHD event in the first 2 years of the study, or those who had diabetes. A total of 1,027 nonfatal and 214 fatal CHD events were included in the analysis.

Dr. Logue and her colleagues created two models in an attempt to isolate the role played by obesity alone in the fatal and nonfatal CHD events. One adjusted for age, sex, and statin treatment only. The other adjusted for these factors plus known cardiovascular risk factors, including blood pressure, elevated cholesterol, smoking status, high blood pressure, and use of a host of medications affecting blood pressure or the cardiovascular system. A standard social deprivation score, a measure of socioeconomic status, was also incorporated into the model.

The risk of fatal CHD events, the investigators found, was significantly increased in men with a body mass index of between 30 and 39.9 kg/m

“This link was not seen for non-fatal CHD events and therefore, owing to large relative numbers of such events, also not seen for composite CHD events,” the investigators wrote in their analysis. “In other words, our data suggest that obesity may give greater risk for fatal CHD events than nonfatal events, even after accounting for classical CHD risk factors.”

The investigators cautioned that their results were not conclusive, but “should be considered hypothesis generating.”

Among the weaknesses of their study, they wrote, was the fact that it evaluated only men, and that the percentage of participants who were obese was relatively small, limiting its statistical power.

Among the study's strengths, they wrote, was “the large cohort with a high number of events; this has allowed significant results to be generated while still allowing participants with events in the first 2 years to be excluded, along with those with known diabetes.” A further strength, they wrote, was having details of each death, thanks to standardized government records. “Had we combined fatal and nonfatal CHD events we would have missed this important association.”

Dr. Logue and her colleagues cited in their analysis a study highlighting inflammation as a possible culprit in fatal CHD events (PLoS Med. 2009 Aug. 6;6: e1000099) and another exploring the effects of adiposity on inflammation (J. Clin. Endocrinol. Metab. 2010;95:93-9).

“Recent work has shown that inflammatory markers, namely, IL-6, CRP, and fibrinogen, are more strongly related to fatal than nonfatal cardiovascular events. As obesity is increasingly recognized as an inflammatory state, this is a potential etiological pathway to account for the increased risk of fatal CHD events seen with obesity,” the investigators wrote.

Dr. Logue said in an interview, however, that the culprit was far from clear. “It could be inflammation,” she said. “But there's also upcoming evidence around structural changes to the heart caused by obesity, which could mean your heart can't cope as well when you're having a heart attack.” But more important in any case, she said, is to learn whether the risk of a fatal CHD event is mitigated by weight loss.

“I'd rather see the resources put into looking to see if we can get people's weight down and preventing people getting to this weight in the first place,” Dr. Logue said.

The pravastatin trial and the first 5 years of follow-up were funded by the drug's manufacturer, Bristol-Myers Squibb and Sankyo. The final years of follow-up and Dr. Logue and her colleagues' analysis were funded by the Scottish government and a grant from Scotland's Chest, Heart, and Stroke Association, respectively. Dr. Logue and her colleagues said they had no financial disclosures.

Being obese may significantly increase the risk of having a fatal coronary heart disease event independent of known obesity-associated cardiovascular risk factors such as high blood pressure and high cholesterol, investigators in Scotland have found.

By contrast, obesity alone was not seen as significantly increasing the risk of nonfatal CHD events.

The findings, derived from the long-term follow-up of a large pharmaceutical trial, and published in the journal Heart (doi:10.1136/hrt.2010.211201), suggest that fatal and nonfatal CHD events could have separate causes – and that CHD death might not be preventable by mitigating traditional cardiovascular risk factors in obese men.

“It's assumed that nonfatal and fatal events occur along an index of severity – but maybe there's something different going on,” Dr. Jennifer Logue of the University of Glasgow, the study's lead investigator, said in an interview.

With the fatal events, she said, “we found an almost 60% higher risk from obesity alone.” The risk was seen after modeling for obesity-associated cardiovascular risks such as high blood pressure and high cholesterol level, along with factors such as smoking, low socioeconomic status, and medications.

“If you've got a middle-aged man in front of you with a [body mass index] of 35 – and that's not an uncommon sight nowadays – yes, you can treat his blood pressure and cholesterol and help him stop smoking,” Dr. Logue said. “But his weight itself is still making him at significant risk.”

Dr. Logue and her colleagues examined data from 6,082 men, with a mean age of 55, who had moderate hypercholesterolemia but who were without a history of diabetes or cardiovascular disease. The men had originally been enrolled in a manufacturer-sponsored, 5-year, randomized, placebo-controlled controlled trial to determine the effectiveness of the statin drug pravastatin in preventing cardiovascular events (N. Engl. J. Med. 1995; 333:1301-7), and the follow-up period ran to 15 years.

The researchers excluded from their analysis men who had had a fatal or nonfatal CHD event in the first 2 years of the study, or those who had diabetes. A total of 1,027 nonfatal and 214 fatal CHD events were included in the analysis.

Dr. Logue and her colleagues created two models in an attempt to isolate the role played by obesity alone in the fatal and nonfatal CHD events. One adjusted for age, sex, and statin treatment only. The other adjusted for these factors plus known cardiovascular risk factors, including blood pressure, elevated cholesterol, smoking status, high blood pressure, and use of a host of medications affecting blood pressure or the cardiovascular system. A standard social deprivation score, a measure of socioeconomic status, was also incorporated into the model.

The risk of fatal CHD events, the investigators found, was significantly increased in men with a body mass index of between 30 and 39.9 kg/m

“This link was not seen for non-fatal CHD events and therefore, owing to large relative numbers of such events, also not seen for composite CHD events,” the investigators wrote in their analysis. “In other words, our data suggest that obesity may give greater risk for fatal CHD events than nonfatal events, even after accounting for classical CHD risk factors.”

The investigators cautioned that their results were not conclusive, but “should be considered hypothesis generating.”

Among the weaknesses of their study, they wrote, was the fact that it evaluated only men, and that the percentage of participants who were obese was relatively small, limiting its statistical power.

Among the study's strengths, they wrote, was “the large cohort with a high number of events; this has allowed significant results to be generated while still allowing participants with events in the first 2 years to be excluded, along with those with known diabetes.” A further strength, they wrote, was having details of each death, thanks to standardized government records. “Had we combined fatal and nonfatal CHD events we would have missed this important association.”

Dr. Logue and her colleagues cited in their analysis a study highlighting inflammation as a possible culprit in fatal CHD events (PLoS Med. 2009 Aug. 6;6: e1000099) and another exploring the effects of adiposity on inflammation (J. Clin. Endocrinol. Metab. 2010;95:93-9).

“Recent work has shown that inflammatory markers, namely, IL-6, CRP, and fibrinogen, are more strongly related to fatal than nonfatal cardiovascular events. As obesity is increasingly recognized as an inflammatory state, this is a potential etiological pathway to account for the increased risk of fatal CHD events seen with obesity,” the investigators wrote.

Dr. Logue said in an interview, however, that the culprit was far from clear. “It could be inflammation,” she said. “But there's also upcoming evidence around structural changes to the heart caused by obesity, which could mean your heart can't cope as well when you're having a heart attack.” But more important in any case, she said, is to learn whether the risk of a fatal CHD event is mitigated by weight loss.

“I'd rather see the resources put into looking to see if we can get people's weight down and preventing people getting to this weight in the first place,” Dr. Logue said.

The pravastatin trial and the first 5 years of follow-up were funded by the drug's manufacturer, Bristol-Myers Squibb and Sankyo. The final years of follow-up and Dr. Logue and her colleagues' analysis were funded by the Scottish government and a grant from Scotland's Chest, Heart, and Stroke Association, respectively. Dr. Logue and her colleagues said they had no financial disclosures.

Being obese may significantly increase the risk of having a fatal coronary heart disease event independent of known obesity-associated cardiovascular risk factors such as high blood pressure and high cholesterol, investigators in Scotland have found.

By contrast, obesity alone was not seen as significantly increasing the risk of nonfatal CHD events.

The findings, derived from the long-term follow-up of a large pharmaceutical trial, and published in the journal Heart (doi:10.1136/hrt.2010.211201), suggest that fatal and nonfatal CHD events could have separate causes – and that CHD death might not be preventable by mitigating traditional cardiovascular risk factors in obese men.

“It's assumed that nonfatal and fatal events occur along an index of severity – but maybe there's something different going on,” Dr. Jennifer Logue of the University of Glasgow, the study's lead investigator, said in an interview.

With the fatal events, she said, “we found an almost 60% higher risk from obesity alone.” The risk was seen after modeling for obesity-associated cardiovascular risks such as high blood pressure and high cholesterol level, along with factors such as smoking, low socioeconomic status, and medications.

“If you've got a middle-aged man in front of you with a [body mass index] of 35 – and that's not an uncommon sight nowadays – yes, you can treat his blood pressure and cholesterol and help him stop smoking,” Dr. Logue said. “But his weight itself is still making him at significant risk.”

Dr. Logue and her colleagues examined data from 6,082 men, with a mean age of 55, who had moderate hypercholesterolemia but who were without a history of diabetes or cardiovascular disease. The men had originally been enrolled in a manufacturer-sponsored, 5-year, randomized, placebo-controlled controlled trial to determine the effectiveness of the statin drug pravastatin in preventing cardiovascular events (N. Engl. J. Med. 1995; 333:1301-7), and the follow-up period ran to 15 years.

The researchers excluded from their analysis men who had had a fatal or nonfatal CHD event in the first 2 years of the study, or those who had diabetes. A total of 1,027 nonfatal and 214 fatal CHD events were included in the analysis.

Dr. Logue and her colleagues created two models in an attempt to isolate the role played by obesity alone in the fatal and nonfatal CHD events. One adjusted for age, sex, and statin treatment only. The other adjusted for these factors plus known cardiovascular risk factors, including blood pressure, elevated cholesterol, smoking status, high blood pressure, and use of a host of medications affecting blood pressure or the cardiovascular system. A standard social deprivation score, a measure of socioeconomic status, was also incorporated into the model.

The risk of fatal CHD events, the investigators found, was significantly increased in men with a body mass index of between 30 and 39.9 kg/m

“This link was not seen for non-fatal CHD events and therefore, owing to large relative numbers of such events, also not seen for composite CHD events,” the investigators wrote in their analysis. “In other words, our data suggest that obesity may give greater risk for fatal CHD events than nonfatal events, even after accounting for classical CHD risk factors.”

The investigators cautioned that their results were not conclusive, but “should be considered hypothesis generating.”

Among the weaknesses of their study, they wrote, was the fact that it evaluated only men, and that the percentage of participants who were obese was relatively small, limiting its statistical power.

Among the study's strengths, they wrote, was “the large cohort with a high number of events; this has allowed significant results to be generated while still allowing participants with events in the first 2 years to be excluded, along with those with known diabetes.” A further strength, they wrote, was having details of each death, thanks to standardized government records. “Had we combined fatal and nonfatal CHD events we would have missed this important association.”

Dr. Logue and her colleagues cited in their analysis a study highlighting inflammation as a possible culprit in fatal CHD events (PLoS Med. 2009 Aug. 6;6: e1000099) and another exploring the effects of adiposity on inflammation (J. Clin. Endocrinol. Metab. 2010;95:93-9).

“Recent work has shown that inflammatory markers, namely, IL-6, CRP, and fibrinogen, are more strongly related to fatal than nonfatal cardiovascular events. As obesity is increasingly recognized as an inflammatory state, this is a potential etiological pathway to account for the increased risk of fatal CHD events seen with obesity,” the investigators wrote.

Dr. Logue said in an interview, however, that the culprit was far from clear. “It could be inflammation,” she said. “But there's also upcoming evidence around structural changes to the heart caused by obesity, which could mean your heart can't cope as well when you're having a heart attack.” But more important in any case, she said, is to learn whether the risk of a fatal CHD event is mitigated by weight loss.

“I'd rather see the resources put into looking to see if we can get people's weight down and preventing people getting to this weight in the first place,” Dr. Logue said.

The pravastatin trial and the first 5 years of follow-up were funded by the drug's manufacturer, Bristol-Myers Squibb and Sankyo. The final years of follow-up and Dr. Logue and her colleagues' analysis were funded by the Scottish government and a grant from Scotland's Chest, Heart, and Stroke Association, respectively. Dr. Logue and her colleagues said they had no financial disclosures.