Although SWITCHD (Orth-Gomér et al. 2009) was not designed to study the interaction of the psychosocial–behavioral intervention with other treatment modalities, the finding that statin use had an independent protective effect on mortality (p = 0.01) prompted an exploratory analysis of the interaction between the psychosocial intervention and the effect of statins. Among the 70 women who received neither the psychosocial program nor statins, 15 women died (21.4 %). Of 54 women who did not receive the psychosocial program, but were on statins at baseline, 10 women died (18.5 %). Among the 45 women who received the psychosocial program, but not statins, 7 women died (15.5 %). Finally, of 65 women who received both the psychosocial program and statins, only 1 woman died (1.5 %). The Kaplan–Meier estimates of all-cause mortality by psychosocial intervention and statin therapy are shown in Fig. 15.2.

The design of the Orth-Gomér et al. (2009) RCT did not permit evaluation of the basis for the potentiation of the psychosocial intervention by statin use. These results, however, may have been due to an interaction of biological factors that reduced inflammation and delayed the progression of atherosclerosis. Thus, in animal experiments using the Watanabe heritable hyperlipidemic rabbit, both statins (Fukumoto et al. 2001) and affiliative prosocial behavior (McCabe et al. 2002) were found to attenuate the progression of atherosclerosis, possibly by decreasing inflammation. In a subsequent clinical trial conducted on patients with acute coronary syndrome, statins lowered the levels of LDL cholesterol and C-reactive protein, which is produced by the liver and becomes elevated in response to inflammation in the body (Ridker et al. 2005). Patients who had low CRP levels after statin therapy had better clinical outcomes than patients with a higher CRP level, regardless of the resultant level of LDL cholesterol. The results reported by Orth-Gomér and colleagues, therefore appear to be consistent with the findings described by Fukumoto and colleague, McCabe and collaborators, and Ridker and collaborators.

The third major RCT to use a group-based CBT psychosocial–behavioral intervention for the secondary prevention of CHD was SUPRIM (Gulliksson et al. 2011). This RCT was conducted in Uppsala, Sweden, on 362 women and men with the intervention carried out in sex-specific groups. There were 85 women and 277 men enrolled in the trial. Of these, 192 participants were randomized into the intervention condition and 170 participants into the usual care condition. As in SWITCHD, the intervention consisted of 20 two-hour sessions conducted over the course of a year; the mean follow-up period was 7.8 years. Median attendance at each intervention session was 85 %. There were 5–9 participants in each intervention group and each session had a specific theme, working material, and homework assignments. The session format included practicing brief progressive muscle relaxation, reflections on the previous session, homework assignments, introduction of a new theme, and preparation of homework. In-session work was supplemented by the keeping of a diary. Each therapist used a communication style that was oriented toward motivational interviewing rather than a didactic education approach. Gunilla Burell trained and certified the therapists in both SWITCHD and SUPRIM. The CBT aspect of the intervention included applying methods for self-monitoring, recognizing cognitive distortions, cognitive restructuring, skills training, and role playing. An education aspect of the intervention focused on cardiovascular pathophysiology manifestations and treatment procedures for CHD, health behaviors, and lifestyle. Another aspect of the program was concerned with spiritual development and examined life values in order to see the change process in the broader context of a future meaningful life. Particularly at the end of the program, group discussions focused on quality of life issues, goals and values, and the importance of significant others. The intervention intent was that the social and emotional support of the group would be instrumental for the development of self-esteem, optimism, trust, and emotional intimacy.

During the mean 94 months of follow-up in SUPRIM (Gulliksson et al. 2011) the psychosocial–behavioral intervention group compared to the usual care control group had a 41 % lower rate of fatal and nonfatal first recurrent CVD events (OR = 0.59 [CI 0.42–0.83], p = 0.002), 45 % fewer recurrent acute MI (OR = 0.59 [CI 0.42–0.83], p = 0.007), and a nonsignificant 28 % decrease in all-cause mortality (OR = 0.72 [CI 0.40–1.30], p = 0.28). There were no sex differences in any of the outcome analyses. In summary, SUPRIM indicated that a CBT psychosocial–behavioral intervention program can reduce the risk of recurrent CHD events.

In contrast to the three major RCT that reported positive results, the WALES Study (Jones and West 1996) reported null results in a trial that randomized 2,328 post-MI patients into either an intervention condition covering 7 weekly, 2-h psychological counseling and psychotherapy sessions that included relaxation training and stress management or into a usual care condition. The intervention program began soon after hospital discharge and was conducted by clinical psychologists and other health care providers. Spouses (or partners) were invited to the first two sessions. Intervention sessions included group and individual counseling sessions. The principal aims of the intervention were to (a) provide information about the cardiovascular system, MI and CHD treatment and management; (b) increase awareness about stress and stressful situations; (c) teach relaxation skills; (d) improve response to stressful situations and develop coping skills; (e) promote positive adjustment to illness; and (f) rebuild confidence in patients and spouses. Sessions included teaching practical exercises with patient participation, group discussion and individual counseling. The importance of practice between sessions was emphasized. Patients were asked to keep records of progress with diaries of activity, stress, and relaxation. However, other components of comprehensive rehabilitation including consideration of diet, physical activity, and weight control were explicitly omitted.

According to Jones and West (1996), 27 % of the participants (i.e., more than 200 patients) did not attend even a single session. Given that the investigators used an “intent-to-treat” analysis that included the 27 % of intervention participants who received no treatment, additional information is warranted concerning these participants, the informed consent procedure used, and details concerning how many of the possible seven sessions were attended by the remaining intervention patients. It would have been informative to know why almost all patients attended the 6- and 12-month check-ups, whereas many patients randomized to intervention did not participate in the psychosocial–behavioral intervention. Although some analyses did compare data from those “agreeing” to participate in the intervention group with those randomized into the control condition, it is impossible to unconfound potential major differences that may have existed between groups. In the absence of such information the possibility of reporting bias seems substantial. Given that this was a multi-center trial involving six district general hospitals, the lack of information concerning quality control procedures in conjunction with lack of intervention effects on anxiety and depression between baseline and 6 months suggest that the trial was not successful in demonstrating an efficacious psychological intervention. Finally, in comparing the results of the Jones and West trial with those of Friedman et al. (1986), Orth-Gomér et al. (2009), and Gulliksson et al. (2011), it should be noted that Jones and West used many fewer intervention sessions and followed participants for only 12 months, whereas the latter three studies followed patients for an average of 4.5, 7.1, and 7.8 years, respectively.

The second major RCT to report null findings for a psychosocial–behavioral intervention trial for secondary prevention of CHD was M-HART (Frasure-Smith et al. 1997). In this study 1,376 post-MI patients (473 women, 903 men) were randomized into an intervention program (n = 692) or a usual care condition (n = 684). Beginning 1 week after discharge for acute MI and then monthly for a year, intervention participants were telephoned by a research assistant. The assistant administered a 20-item General Health Questionnaire that assesses psychological distress from symptoms of depression, anxiety and impairment in the activities of daily living (Goldberg 1972). If a patient scored 5 or more out of 20 on this scale or was readmitted to the hospital, the research assistant contacted the project nurse responsible for that patient. The nurse arranged to visit the patient as soon as possible either at home or at another convenient location. During the initial 1-h visit, the nurse evaluated the patient’s psychosocial difficulties, needs, and cardiac status. Immediate difficulties were addressed. The nurse then scheduled a second visit within a month if the patient agreed. Intervention visits continued thereafter as required until the nurse and project team decided that there was no further need for contact. These visits were individually adjusted, but typically involved reassurance, emotional support, education, practical advice, and referral to other health care providers as needed. All patients completed a baseline interview that included assessment of anxiety and depression. Survivors were interviewed after 1 year. The nurses were all experienced in cardiology nursing but were explicitly not given special professional training concerning psychology, behavior change, or implementation of the research protocol.

About 75 % of intervention participants in M-HART (Frasure-Smith et al. 1997) received 5–6 1-h nursing visits. The program had no influence on psychological outcomes (e.g., depressive symptoms, anxiety, anger or perceived social support) between conditions nor upon cardiac or all-cause mortality over a 1-year period. Marginally greater all-cause mortality was observed in the intervention condition (10.3 % intervention vs. 5.4 % usual care, p = 0.051), suggesting that the intervention may have been harmful to women. The reasons for this marginal finding remain speculative.

The third major psychosocial RCT to report null findings for the secondary prevention of CHD was ENRICHD (Berkman et al. 2003). This trial randomized 2,481 post-MI patients (44 % women; 34 % race/ethnic minority participants) into a CBT condition or usual care. Post-MI patients were selected because they were depressed and/or had low perceived social support. Intervention-group patients with very high depression scores or failure to lower such scores after 5 weeks of the CBT intervention were referred to study psychiatrists for consideration of pharmacotherapy. In instances where group-based psychosocial–behavioral intervention was available, intervention participants were allowed to begin group-treatment provided they first completed at least three sessions of individual CBT. The maximum duration of the psychosocial–behavioral information was 6 months. Group therapy could extend an additional 12 weeks and adjunctive pharmacotherapy for up to 12 months. Approximately 30 % of intervention participants received group-based psychotherapy, whereas 70 % did not. The CBT was initiated at a median 17 days after the index MI for a median of 11 individual sessions throughout 6 months.

After an average follow-up of 29 months, there was no significant difference in event-free survival between the psychosocial intervention condition (75.8 %) and usual care (75.9 %). The intervention modestly improved depression and social support compared to usual care, but this was less than expected due to substantial improvements in usual care patients.

Although the ENRICHD intervention was designed to include both individual as well as group-based psychosocial–behavioral treatment, only 31 % of treated patients received group training and group training always began after exposure to several sessions of individual CBT. A secondary analysis, however, was conducted on 1,243 usual care, 781 individual therapy only, and 356 group plus individual therapy patients (Saab et al. 2009). In order to control for confounding of group participation with survival (because individual sessions invariably preceded group, risk set sampling was used to match minimal survival time of those receiving or not receiving group training. Analyses correcting for differential survival among comparison groups indicated that group plus individual therapy was associated with a 33 % reduction (OR = 0.67 [CI 0.49–0.92], p = 0.01) in event-free survival compared to usual care. No significant effect on medical outcome was associated with individual therapy alone. The group-based treatment benefit was reduced to 23 % (OR = 0.77 [CI 0.56–1.07], p = 0.11) in a multivariate-adjusted model. These findings suggest that adding group training to individual treatment may have an effect on event-free survival.

Several major psychosocial–behavioral RCT aimed at secondary prevention of CHD have obtained either positive or null results. The RCPP, SWITCHD, and SUPRIM trials reported by Friedman et al. (1986), Orth-Gomér et al. (2009) and Gulliksson et al. (2011), respectively, which found positive results had a number of features in common. All three trials, for example, used group-based CBT and also included relaxation, encouragement of specific lifestyle changes (e.g., diet and exercise), and medication adherence training. These three intervention studies all conducted sessions for at least a year (20 sessions during a year in SWITCHD and SUPRIM, and an average of 38 sessions over 4.5 years in RCPP). None of these studies attempted to engage intervention patients immediately during the acute phase of illness, but waited some months after the index event so that the emphasis could be on long-term lifestyle changes. The follow-up of patients was also long-term, being at least 7.1 years in SWITCHD and 7.4 years in SUPRIM. In all three studies, therapists trained in psychotherapy and behavior change used manualized treatment programs to engage participants.

In contrast to the RCPP, SWITCHD, and SUPRIM, which followed principles that favored multiple risk factor reduction, the studies that reported null results (Jones and West 1996; Frasure-Smith et al. 1997; Berkman et al. 2003) engaged patients soon after hospital discharge, provided fewer intervention sessions over a shorter period of time, followed up patients for much shorter periods of time, and did not focus on lifestyle changes or multiple risk factor reduction.